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Utskriftsdato (22.9.2018)

Ovarian and fallopian tube cancer

Adnex, illustration

Ovarian cancer includes multiple tumor types:

  • Epithelial ovarian cancer of type: 
    • Invasive
    • Borderline
    • Primary peritoneal carcinoma
  • Non-epithelial ovarian cancer originates from:
    • Germinal cells (chyme cells)
    • Sex cord tumors
    • Stroma cells (thecomas/fibromas)

Fallopian tube cancer is clinically difficult to differentiate from ovarian cancer. Symptoms, diagnostics, and treatment are the same as ovarian cancer. The same applies for primary peritoneal carcinoma.

Criteria for diagnosing primary peritoneal carcinoma: 

  • Both ovaries should be of normal size or be enlarged from a benign disease. 
  • More tumor volume should be visible outside the ovaries than on the surface of the ovaries. 
  • Tumor cells should be limited to the surface of the ovaries, or have maximum stromal invasion of 5 millimeters. 

This disease diagnosis is not given to patients treated with chemotherapy before the operation.

Adnexa of uterus refer to the anatomical structures of the uterus including the ovaries, fallopian tubes and broad ligaments.

Incidence  

Ovarian cancer is relatively rare. Women with a family history of ovarian cancer have an increased risk for the disease. Approximately 1.3% of women in the United States will be diagnosed with ovarian cancer at some point during their lifetime. Ovarian cancer is most frequently diagnosed among women aged 55-64.

The number of new cases of ovarian cancer was 11.7 per 100,000 women per year based on 2010-2014 case. In 2017, it is estimated to be 22,440 new cases of ovarian cancer in the United States (23).

 

Age-specific incidence of ovarian cancer, 2010–2014.

Source: National Cancer Institute. Bethesda, MD, USA

 

 

Incidence of ovarian cancer, 1975–2014.

Source: National Cancer Institute. Bethesda, MD, USA

Etiology of ovarian and fallopian tube cancer

The etiology of cancer of the adnexa is uncertain. Several conditions have been hypothetically considered: incessant ovulation, excessive gonadotropin secretion, retrograde carcinogen transport (asbestos and talc), and estrogen/progesterone imbalance. Familial accumulation constitutes about 10% of the cases while the rest are spontaneous. Obese women have a higher frequency of borderline tumors. 

Increasing number of births and use of birth control pills provides a certain degree of protection, which is likely due to the reduced number of ovulations. Use of birth control pills for more than 5 years can reduce the risk of ovarian cancer by > 50%. Longer use reduces the risk even further, likely due to prevention of ovulation. Tobacco smoking may possibly also reduce the risk.

Risk factors

Repeated ovulation with repair of surface epithelium is assumed to be of significance for epithelial ovarian cancer. The risk appears to be related to the number of ovulations during a woman's fertile years. 

In a Norwegian study, it was found that 6% of patients with epithelial ovarian cancer had mutations in the BRCA 1 or BRCA 2 genes. 

For dysgerminomas, genetic conditions are of significance to a certain degree; around 5% occur in phenotypical women with abnormal gonads such as 46XY (bilateral streak gonads), 46X/46XY (unilateral streak gonad, contralateral testis) or 46XY (testicular feminization).

 

Histology of ovarian and fallopian tube cancer

Ovarian cancer

The malignant epithelial tumors (carcinomas) originate from the surface epithelium and account for about 90% of all ovarian cancers. The remaining 10% originate either from the germ cells or sex cord/stromal cells.

Invasive epithelial ovarian cancer

 

Ovarian specimen with serous epithelial cancer. Click to enlarge. Photomicrograph of the tumor in the left-hand picture. Click to enlarge.

There are several subtypes of ovarian carcinomas depending on cell type and malignancy grade (1-3). The invasive ovarian carcinomas must be separated from the non-invasive (borderline) tumors, since the treatment and prognosis is different. The serous and mucinous epitheial types are the most common subtypes.

Overview of the different subtypes of ovarian carcinomas and their incidence:

  • Serous 55%
  • Endometrioid 17%
  • Mucinous 13%
  • Clear cell 8%
  • Mixed 5%
  • Undifferentiated type 2%

Borderline ovarian tumors

Borderline tumors are epithelial tumors of low malignant potential also named low malignant potential  (LMP-tumors) tumors. These tumors are more frequent in younger women. They are often unilocular and can be smooth or with papillary projections in the lumen. These tumors can easily be misinterpreted as benign.

Borderline tumors differ from benign tumors by proliferation of atypical cells without infiltrating in the underlying stroma.

Contrary to invasive tumors, the atypical cells in borderline tumors are localized on the inside of ovarian cysts and have not penetrated the capsule. They are often limited to the ovary and thus Stage I, although they can spread outside the ovary.

 

Cystic ovarian tumor with papillary projections on inner surface. Click to enlarge. Photomicrograph from the serous borderline tumor in the left-hand picture. Click to enlarge.

 

Serous and mucinous are the most common ovarian borderline tumors, other types are unusual (infrequent).

  • Serous
  • Mucinous
  • Endometrioid
  • Clear cell
  • Transitional cell type

Non-epithelial ovarian cancer

Germ cell tumors

Germ cells can develop into embryonal or placental tissue and can grow undifferentiated (dysgerminoma) or simulated extraembryonal tissue (yolk sac tumor). Germ cell tumors account only for about 3% of all ovarian cancers and are a heterogenous group of tumors. The majority are benign teratomas. Malignant teratomas are very rare. Correct diagnosis is especially important since most patients with these tumors can be cured with adequate chemotherapy or radiation therapy.

 

Ovary with yolk sac tumor. Click to enlarge.

Photomicrograph of the yolk sac tumor in the left-hand picture. Click to enlarge.

 

  • Dysgerminoma is the most common type of malignant germ cell tumor. About 5% of these tumors appear in phenotypical women with abnormal gonads, for example 46XY (bilateral streak gonads), 46X/46XY (unilateral streak gonads, contralateral testis) or 46XY (testicular feminization). It is recommended to perform karyotyping when pelvic tumors are detected in premenarchal females.
  • Endodermal sinus tumor/yolk sac tumor . These tumors often produce alfa-feto protein (AFP).
  • Embryonal carcinoma
  • Polyembryoma
  • Choriocarcinomas usually originate from trophoblastic tissue. They can also originate from germ cell tumors as a pure tumor or as a component in a mixed.
  • Teratoma
    • Mature
    • Immature teratomas contain tissue developed from an embryo. It is graded according to differentiation and amount of immature tissue. A malignant transformation from a mature teratoma is seldom. The most common type of such malignant transformation is squamous cell carcinoma developed from a mature teratoma.
  • Secondary malignant transformation
  • Mixed forms
  • Mixed tumors are tumors that sometimes contain a mixture of different components in the same tumor.

Sex cord stromal tumors

Sex cord-stromal tumors are a mixed group of hormone-producing tumors. Surgery can often be limited to extirpation of one ovary and thus the woman can still be fertile. Omentectomy and lymph node staging should be considered.

Sex cord-stromal tumors account for only 8% of ovarian tumors. The dominating type of tumor is thecoma/fibroma (benign) followed by granulosa cell tumor (potentially malignant). The other types are very uncommon:

  • Granulosa stromal cell tumor
  • Granulosa cell tumor (adult and juvenile)
  • Thecoma/fibroma (thecoma , fibroma, variants of stromal cell tumors)
  • Sertolistromal cell tumor
  • Sertoli Leydig cell tumor (androblastoma/arrhenoblastoma)
  • Sertoli stromal cell tumors mixed or unclassified type
  • Leydig cell tumor
  • Gynandroblastoma
  • Unclassifiable tumor

Granulosa stromal cell tumors include granulosa cell tumors and thecomas. Fibrosarcoma can originate from ovarian stroma. These tumors produce estrogen and thus can induce endometrial hyperplasia and endometrial carcinoma. Granulosa cell tumors produce inhibin that can be detected by immunhistochemistry and thus support the microscopic diagnosis.

Sertoli-Leydig cell tumors (also named androblastoma/arrhenoblastoma, Sertoli cell, Sertoli-Leydig cell and Leydig cell tumors are rare tumors that often produce androgen. Gynandroblastoma is an extremly uncommon tumor demonstrating a mixture of ovarian and testicular differentiation often a mixture of granulosa cell elements and Sertoli-Leydig cell elements.

Primary peritoneal carcinoma

A peritoneal carcinoma can not microscopically be separated from serous epithelial ovarian carcinoma. The following criteria must be fulfilled for this diagnosis:

  • Both ovary should be of normal size or be enlarged because of a benign process.
  • There must be more tumor volume outside the ovaries than on their surfaces.
  • Ovarian carcinoma should not be present. Only tumor on the surface without stromal invasion is allowed or maximal cortical growth of 5 x 5 mm.

This diagnosis can only be given when the patient has had primary surgery without chemotherapy, since the above criteria cannot be evaluated for patients who have had chemotherapy.

Fallopian tube carcinoma

Photomicrograph demonstrating a serous papillary carcinoma of the fallopian tube. Click to enlarge.

Carcinomas of the fallopian tubes are microscopically similar to ovarian carcinomas. In order to establish the tumor as tubal in origin, there should limited tumor in the ovary and no similar type of carcinoma in the uterus.

Microscopically, serous carcinoma dominates completely. Less common subtypes are endometrioid, mucinous, clear cell, transitional cell and undifferenitiated carcinomas. The mixed epithelial and mesenchymal such as carcinosarcoma is sometime seen as primary tubal cancers.

DNA ploidy analysis

DNA ploidy analysis determines the amount of DNA in tumor cell nuclei in relation to normal diploid DNA content. DNA index 1 indicates DNA content corresponding to normal diploid nuclei. DNA index 2 corresponds to tetraploid nuclei, and everything in between as abnormal aneuploid nuclei.

DNA ploidy analysis can be performed from formalin-fixed paraffin-embedded material. At Oslo University Hospital, we prefer image analysis instead of flow cytometry for this type of investigation.
DNA ploidy results are useful to evaluate prognosis in stage I ovarian carcinomas.

Examples of DNA distributions:

  • Diploid
  • Tetraploid
  • Aneuploid

Staging of ovarian and fallopian tube cancer

Ovarian cancer

According to FIGO (The International Federation of Gynecology and Obstetrics), staging should be done surgically. A chest X-ray should be taken.

Staging according to FIGO

 

Stage I: Tumor limited to the ovaries.

  • Stage Ia: Tumor limited to one ovary. 
  • Stage Ib: Tumor in both ovaries.
  • Stage Ic: Tumor limited to one or both ovaries with any of the following: capsule ruptured, tumor on ovarian surface, malignant cells in ascites or peritoneal washings. 

 

 Stage II: Tumor involves one or both ovaries with pelvis extension

  • Stage IIa: Tumor invasion/metastasis to uterus and/tube(s)
  • Stage IIb: Tumor invasion/metastasis to other tissue pelvic tissues
  • Stage IIc: Tumor in stage IIa–IIb with tumor on surface of ovaries and/or capsule ruptured and/or tumor cells in ascites or peritoneal washings 

 

Stage III: Metastasis outside the pelvis but limited to the abdominal cavity and/or spreading to retroperitoneal lymph nodes (pelvis or paraaortal) or inguinal 

  • Stage IIIa: Microscopic tumor spreading to upper part of the abdominal cavity
  • Stage IIIb: Metastases smaller than 2 cm in upper abdominal cavity
  • Stage IIIc: Metastases larger than 2 cm in upper abdominal cavity to paraaortal or inguinal lymph nodes   

Stage IV: Distant metastasis and/or pleural fluid with malignant cells. Parenchymal liver metastases.  

Adnexa uteri Stadium IV 

Fallopian tube cancer

Staging according to FIGO

According to FIGO (The International Federation of Gynecology and Obstetrics), surgical staging should be done. A chest X-ray should be taken also. 

Stage 0: Carcinoma in situ (limited to tubal mucosa)

Stage I: Tumor limited to fallopian tubes

 

  • Stage Ia: Tumor confined to one fallopian tube with metastasis to submucosa and/or muscle, without penetrating serosal surface; no ascites.
  • Stage Ib: Tumor confined to both tubes, without penetrating the serosal surface; no ascites. 
  • Stage Ic: Tumor confined to one or both tube(s) with extension into or through the tubal serosa, or with malignant cells is ascites or peritoneal washings   

 

Stage II: Tumor in one or both fallopian tube(s) with metastasis in the pelvis  

  • Stage IIa: Tumor in one or both fallopian tube(s) with metastasis to the uterus and/or ovaries 
  • Stage IIb: Tumor in one or both ovaries with spreading to other pelvic structures
  • Stage IIc: Tumor stage IIa or IIb with malignant cells in ascites or peritoneal washings 

 

Stage III: Metastasis outside the pelvis, but confined to abdominal cavity and/or metastasis to retroperitoneal lymph nodes (pelvic or paraaortal) or inguinal

  • Stage IIIa: Microscopic metastasis to upper abdominal cavity
  • Stage IIIb: Metastases smaller than 2 cm in upper abdominal cavity
  • Stage IIIc: Metastases larger than 2 cm in upper abdominal cavity, or metastases to paraaortal or inguinal lymph nodes

Stage IV: Distant metastases and/or pleural fluid containing malignant cells. Parenchymal liver metastases. 

Metastatic patterns of ovarian and fallopian tube cancer

Ovarian cancer

Metastatic patterns of epithelial ovarian cancer: 

  • Intraperitoneal
  • Lymphatic to lymph nodes in the pelvis and along the aorta
  • Via blood to the liver and/or lungs
  • Can spread to pleura

There is often early intraperitoneal spreading in epithelial ovarian cancer via release of malignant cells from the ovarian surface, thereby spreading with fluid to the abdominal cavity, attaching to the abdominal membrane and growing as metastases. The ovaries can therefore have a normal or nearly normal size, even when there is extensive intraperitoneal metastasis. Extensive intraperitoneal disease will usually give rise to symptoms.  

Borderline tumors are usually diagnosed in stage I (85%), while 5% are in stage II, and 10% in stage III. The tumors are usually unilateral with 65% in stage Ia, 14% in stage Ib and 6% in stage Ic. Even though it is a characteristic of borderline tumors that they do not infiltrate the capsule, it is still possible, with involvement of the ovarian surface and further spread to the abdominal cavity. These tumors do not spread to lymph nodes and do not metastasize outside the abdominal cavity. 

Fallopian cancer

In fallopian cancer, metastasis occurs primarily by release of malignant cells from the tumor in the tube(s), which spread via fluid in the abdominal cavity, attach to the abdominal membrane and grow as metastases. These tumors have a prominent tendency to spread to lymph nodes, therefore, it is always recommended to remove the lymph nodes in the pelvis and along the aorta in cases where all tumor tissue can be removed by surgery. 

Primary peritoneal carcinoma

This form of tumor originates from the abdominal membrane's coelomic epithelium, and is thus primarily diffuse throughout the entire abdominal cavity. Extraperitoneal metastatic patterns are as in ovarian cancer. 

Symptoms of ovarian and fallopian tube cancer

Ovarian cancer

Epithelial ovarian cancer

Ovarian cancer has been known as the "hidden disease in the abdomen" because of few symptoms. Later research has shown that a majority of epithelial ovarian cancer has vague or unspecific pelvic, abdominal or menstrual symptoms. This can lead to a delay in the diagnosis.

90% of women with early ovarian cancer and 100% with advanced ovarian cancer have reported at least one of the following symptoms:

  • Often uncharacteristic abdominal problems
  • A feeling of pressure and bloating
  • Increase in abdominal circumference
  • Change in bowel or urination patterns (diarrhea, constipation, frequent urination)
  • Weight loss or weight gain
  • Loss of appetite
  • General symptoms 
  • Shortness of breath 
  • Vaginal bleeding - sporadic
  • Acute pains - can occur in cases of torsion or rupture/bleeding
  • Paraneoplastic syndromes

Borderline tumors cause at least one of the above symptoms in 70% of cases, as well as distention of the abdomen. Women with borderline tumors have a longer duration of different symptoms. Abdominal pain/discomfort, intestinal problems, lasting fatigue, and weight loss are less common. 

Non-epithelial ovarian cancer

In contrast to epithelial ovarian cancer, non-epithelial ovarian tumors are characterized by rapid growth and one or more of the following symptoms:  

  • Pelvic pain. Germ cell tumors grow rapidly often causing pelvic pain due to capsule distention, bleeding, necrosis, or tumor rupture.
  • Pressure symptoms from the bladder or bowel. 
  • Increase in abdominal circumference in you women may be due to this type of tumor. Some of these tumors produce HCG and can therefore falsely represent pregnancy. 
  • Irregular bleeding. Granulosa cell tumors often produce estrogen causing endometrial hyperplasia or cancer.
  • Precocious puberty. Granulosa cell tumor must be considered.
  • Virilization. Sertoli-Leydig cell tumors often produce androgens.
  • A pelvic tumor in a girl before menarche will most often be a germinal cell tumor. 
  • An ovarian tumor in pregnant woman may be a non-epithelial tumor. 

Fallopian tube cancer

In fallopian tube cancer, symptoms occur more frequently and in an earlier stage than ovarian cancer. Discharge and vaginal bleeding are typical symptoms of fallopian tube cancer. In advanced disease, symptoms are often the same as ovarian cancer. It is rarely possible to differentiate between the two cancers preoperatively.

Differential diagnosis of ovarian and fallopian tube cancer

Benign

  • Ovarian tumor
  • Ovarian cyst
  • Endometriosis
  • Abscess in fallopian tube/ovary
  • Myoma in uterus
  • Diverticulitis
  • Tuberculosis in the pelvis

Malignant

  • Sarcoma originating from ovaries or uterus
  • Metastasis to ovaries
  • Gastrointestinal tumor
  • Lymphoma

Prognosis of ovarian and fallopian tube cancer

Ovarian cancer

The prognosis depends on whether the ovarian cancer is localized, regional, or metastatic at the time of diagnosis. For ovarian cancer, 14.8% are diagnosed at the local stage and the 5-year survival for localized ovarian cancer is 92.5%. The overall 5-year survival rate for ovarian cancer patients during the period 2007-2013 was 46.5%.

The percent of ovarian cancer deaths is highest among women aged 65-74. Death rates have been falling on average 2.2% each year over 2005-2014.

In 2014, there were an estimated 222,060  women living with ovarian cancer in the United States and in 2017 there are an estimated 14,080 women will die of this disease (23).

Ploidy analysis

Multiple biological prognostic factors are correlated with prognosis of epithelial cancer types. Oslo University Hospital (The Norwegian Radium Hospital) has shown that epithelial ovarian cancers are often aneuploid. They have also shown a high correlation between FIGO stage and ploidy. That is, early early stage ovarian cancer has a tendency towards diploid and advanced tumors have a tendency to be aneuploid. Patients with diploid tumors have a significantly longer median survival time than those with aneuploid tumors, which are five and one year(s) respectively. Multivariant analyses have shown that ploidy is an independent prognostic factor.

 

Survival in 321 patients with ovarial border-line tumors related to ploidy and stage.

 

In vitro clonogenic assay

A significant inverse correlation has been reported between clonogenic growth in vitro and survival. Multivariant analysis has found that clonogenic growth in a semisolid culture medium is a significant independent variable. The prediction model "extreme drug resistance assay" has suggested that it is possible to decide chemotherapy by evaluating platinum-sensitive and resistant tumors in vitro. This technique is used at the department for gynecological cancer at Oslo University Hospital (The Norwegian Radium Hospital). It is still unknown whether this method alone can predict or change the outcome of a primary or recurrence situation.

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References on ovarian and fallopian tube cancer

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Diagnostics of ovarian and fallopian tube cancer

The primary examination of women with pelvic tumors includes:
  • Gynecological examination
  • Ultrasound, preferably combined vaginal-abdominal
  • Chest X-ray in cases where a specimen of pleural fluid is taken for a cytological examination
  • Measurement of s-CA125 and s-CEA. In younger women with ovarian tumors, s-AFP and s-HCG should also be measured. 
  • Calculation of risk of malignancy (RMI score). Scores over 200 are suspicious of ovarian cancer. The value of the risk of malignancy (RMI score) for non-epithelial ovarian cancer is unknown.
  • CT of abdomen/pelvis may provide supplementary information about the extent of the disease   

Ultrasound examination

  • Non-epithelial tumors are often more solid than epithelial ovarian tumors.
  • In a predominantly solid tumor in a younger woman, a germ cell tumor is the primary suspect. 
  • In a predominantly solid tumor in an elderly woman, a non-epithelial ovarian tumor, sarcoma, or metastasis-suspected. 

RMI score

With an RMI-score < 200, the likelihood the tumor represents cancer is relatively modest, and the patient can be operated at a regular gynecological clinic. The RMI score has about 50% sensitivity for predicting ovarian cancer in stage I.   

An RMI score ≥ 200 indicates a high likelihood that the tumor is malignant. It is crucial to survey the extent of the tumor adequately preoperatively. The pelvic tumor should also be evaluated to determine whether it represents epithelial ovarian cancer, non-epithelial ovarian cancer, metastasis, or possibly sarcoma.  

Tumor size

The size of the tumor is important. If a complex cystic tumor is more than 8 - 10 cm in diameter, the probability for cancer is great, if the patient has not taken chlomiphene or other drugs to induce ovulation. In premenopausal patients, a two month observation period is acceptable, unless the tumor is clinically suspect (should be cystic, mobile, unilateral, and without septa or excrescences). If the tumor increases in size and complexity, one should suspect cancer. In postmenopausal women, with single cysts 8-10 cm or smaller in diameter, without septa or excrescences and with normal CA125 value, observation is acceptable. 

When a lesion is clinically suspect (complex cysts with solid areas, thick septa orexcrescences on ultrasound), the patient should undergo surgery with exploratory laparotomy. 

Ovarian cancer

Non-epithelial ovarian cancer 

Raised s-AFP suggests yolk sac tumor (endodermal sinus tumor), while raised s-HCG suggests an HCG-producing tumor, unless the woman is pregnant. Juvenile granulosa cell tumor is suspect in the case of premature menarche. With spontaneous onset of hirsutism, a Sertoli-Leydig tumor (androblastoma) is suspect.

If it is possible the patient has sarcoma, it is important to uphold the surgical principles for sarcoma surgery. 

In metastatic disease, the possibility of metastasis from another cancer type should be considered, primarily gastrointestinal cancer. Measurement of s-CEA may be useful. An ultrasound-guided biopsy for histological investigation may be done.

At The Norwegian Radium Hospital, it is not recommended to do a preoperative biopsy from a single, well-defined tumor since this may lead to spreading of an otherwise localized tumor.

Borderline ovarian cancer

This is the predominant tumor type in younger women with cystic tumors where the differential diagnosis is between a benign cyst, borderline tumor, or invasive epithelial tumor. In a significant number of women with borderline ovarian tumors, the disease is first diagnosed by histological examination of a presumed benign cyst.  

Borderline tumors are usually unilocular, cystic, possibly with internal excrescences in the capsule. An RMI score can not be expected to identify a borderline tumor. With multiocular cysts or larger solid areas, one should suspect an invasive epithelial tumor.

Fallopian tube cancer

Early stage fallopian tube cancer may present as hydrosalpinx and will appear as a cystic tumor on ultrasound. In some cases, cancer cells from fallopian tubes can be found in cervical cytology specimens. If adenocarcinoma cells are found in a cervical cell specimen where cancer cannot be found in the cervix or uterus, one should suspect fallopian tube or ovarian cancer. Fallopian tube cancer often metastasizes early to lymph nodes. In some patients, inguinal, mediastinal, or supraclavicular lymph node metastases are the first and only findings. 

Metastatic disease

In metastatic disease, the possibility of metastasis from another cancer type must be considered, primarily gastrointestinal cancer. Measurement of s-CEA may be useful. Raised s-CA125 is not specific for ovarian or fallopian tube cancer. A mild to moderate rise can be seen with benign conditions, as well as in peritoneal metastases from other cancer types. With raised CEA, it is recommended to calculate the relationship between CA125 and CEA. If this is lower than 25, it is recommended to perform upper endoscopy, colonoscopy, and mammography. An ultrasound-guided biopsy for histological examination is clearly recommended.

Oslo University Hospital (The Norwegian Radium Hospital) does not recommend taking a preoperative biopsy from a single, well-defined tumor as this can lead to spreading of an otherwise localized tumor.

Examination of suspect recurrence

If there is clinical suspicion of recurrence or increasing s-CA 125 without a clinically confirmed tumor, the following is recommended:

  • CT of the chest, abdomen and pelvis.
  • In the case of ascites, a diagnostic puncture for cytological examination.
  • Consider verifying recurrence by cytology or histology before new treatment is initiated. 

s-CA 125

Measurement of s-CA125 is commonly used in the follow-up. 

Spontaneous variations of +/- 70% may be accidental and without significance. Gynecologic Cancer Intergroup GCIG has agreed that there must be an increase of at least 100% to define progression. From a normal value, an increase to 70 IU or more must occur before the increase is diagnostic for progression. 

It has not been shown that early treatment of recurrence improves prognosis compared to waiting until occurrence of symptoms.

PROSEDYRER

DNA Ploidy Investigation Aided by Image Cytometry

General

DNA ploidy investigation is defined here as the sequence of operations originating from paraffin embedded tumor blocks consisting of selection of tumor area, sectioning for preparation, preparation, Feulgen staining, measurement, editing, and classifying. 

DNA ploidy is a cytogenetic term describing the number of chromosome sets (n) or deviations from the normal number of chromosomes in a cell.  In cytometry, the expression is used either to describe the DNA content in a cell (c) or the total DNA distribution in a cell population.

Image cytometry is based on the Feulgen technique which is a widely used staining procedure within biology. The Schiff or Schiff-related reagent is used to bind to aldehydes created after the DNA is hydrolyzed with acid. This allows for staining of DNA in situ. The staining intensity is proportional to the DNA concentration and the amount of DNA in the nucleus is expressed by light absorbed by the Feulgen stain in the whole nucleus.

The Feulgen reaction is used to quantify the amount of DNA in a tumor nucleus. A digital camera captures images of individual nuclei in the specimen. The images are divided into image elements (picture elements - pixels). The gray tone value for each pixel represents the intensity of DNA specific staining. The value is saved in the computer which numerates between 0 (black) and 1023 (white).  The relative amount of DNA in each nucleus (DNA ploidy) is yielded by summing the optical density of all the pixels in the nucleus. DNA-ploidy measured in this way has shown to be a good prognostic and predictive method. Optical Density (OD) and Integrated Optical Density (IOD) are defined as:

During ploidy measurement, the IOD values of all of the nuclei in the specimen are registered and can be graphically developed into a histogram (x-axis: IOD value, y-axis: number of nuclei).

Clinical DNA ploidy investigations are routinely performed mainly on material from different gynecological cancers, prostate cancer, and oral cancer.

Goal

The goal of the investigation is to estimate a prognosis for the patient's cancer type. The treatment is customized depending on the ploidy result.

Equipment

Use protective gloves for sectioning, preparation, and staining. Preparation up to rinsing and Feulgen staining should occur under a fume hood.

Standard equipment for sectioning and staining of sections:

Preparation

  • Centrifuge tube with cap, 10 ml, 2 per specimen
  • Glass pipettes for xylene and plastic pipettes for other solutions 
  • Specimen glasses with lids, 10 ml, 1 per specimen
  • Centrifuge
  • Water bath with thermostat
  • Cytospin centrifuge with equipment
  • 60 µm nylon filter
  • Polysinä slide

Measuring and Editing

Measuring must occur in a dedicated room with dimmed lighting and minimal interruptions.

  • PC with minimum 512 Mb RAM, 1,2 Gb hard disk, 3 com-ports
  • Minimum 17"-screen with good resolution 
  • Software from Fairfield Imaging Ltd., GB
  • Digital camera (Hamamatsu)
  • Microscope (Zeiss Axioplan 2, with 40 x lens, stage with controller (Prior))
  • Focusing unit with controller (LVPZT – amplifier, PI) 

Chemicals 

  • Aluminum potassium sulfate (AlK(SO4)2•12H2O)
  • Basic Fuchsin
  • Glacial acetic acid
  • Eosin
  • Absolute ethanol (96%)
  • Eukitt®
  • Hematoxylin
  • Potassium disulfite (K2S2O5)
  • Activated charcoal
  • Sodium disulfite (Na2S2O5)
  • Sodium iodate (NaIO3)
  • PBS (phosphate buffer)
  • Protease (type XXIV, bacterial)
  • HCl
  • Xylene

Solutions

The following solutions are standard solutions used for different procedures. Prepare well before the start of the procedure.

Eosin

  • 1.25 g eosin is dissolved in 1 L of 80% ethanol
  • Add 2.5 ml glacial acetic acid
  • Mix

Schiff reagent

  • Dissolve 5 g of basic fuchsin into 150 ml of 1 M HCl.
  • Add sodium disulfite (5 g dissolved into 850 ml distilled water). The solution should be red.
  • Let it stand overnight in the absence of light.
  • Add 3 g active charcoal
  • Shake for 2 minutes.
  • Filter multiple times until the solution is clear. Use a mask and gloves. Prepare the solution in a fume hood.

5 M HCl

  • 292 ml distilled water
  • 208 ml concentrated HCl (37 %)

Hematoxylin (Mayers)

  • 100 aluminum potassium sulfate is dissolved in 2 L distilled water
  • Add 4 g hematoxylin
  • Add 0.4 g sodium iodate for culturing
  • The solution should be stirred until the next morning.
  • Filter 200 ml and add 4 drops of glacial acetic acid 
  • Empty solution into a staining dish
  • Filter the solution each time before use
  • Add more glacial acetic acid as more solution is added

The following solutions should be fresh and mixed before use.

Protease solution (0,05 %)

  • 10 mg protease dissolved in 20 ml PBS.

Sulfite solution

  • 1 gram sodium disulfite in 190 ml distilled water.
  • Add 10 ml 1 M HCl.

This is enough for one staining jar.

 

 

 

Procedure

Image cytometry, specimen collection, and registration

Tissue specimens for ploidy investigations are summoned from an external or the present hospital. The examinations are ordered by a doctor. A pathologist examines the HE sections from the actual operation biopsy and chooses one or more blocks which contain the suspicious tissue. The tumor areas are marked on the HE sections. The blocks and corresponding HE sections are retrieved. The documents for the specimens are created.

Section protocol

  • From each chosen block, 1-10 sections of 50 µm thickness are taken. The number of sections prepared depends on the size of the tumor area.
  • At the end, a thin section is prepared and marked HE2 and stained with HE. All of the slides should be labeled with at least two different identifications.

The HE2 section is delivered to the doctor for examination for tumor tissue. The Feulgen-stained monolayer is delivered in the absence of light (for example under aluminum foil) for measurement.

Monolayer preparation of 50 µm thick paraffin sections

Preparation should be performed under a fume hood. The xylene waste should be in a dedicated container. Observe the slide/specimen precisely and be careful with removal of all fluid.

  • Remove paraffin by adding 4 ml xylene to the specimen container.  Let it stand for 30 minutes. Remove xylene and repeat.
  • Remove the xylene by adding 4 ml absolute ethanol. Let stand it for 5 minutes. Remove the ethanol and repeat. Avoid cross-contamination!
  • Rehydration occurs by adding 4 ml of 96% ethanol to each specimen. Let it stand for 10 minutes. In 10 minute intervals, add 1 ml, 1 ml, and 2 ml of distilled water (concentration of ethanol after each addition will be 85%, 74%, and 50%).
  • Rinsing: Remove the ethanol and add 4 ml of PBS. Centrifuge for 5 minutes at 1000 rpm (150 G) and remove supernatant. Repeat. Use new pipette for each specimen. This applies for the rest of the procedure.
  • During enzyme treatment, the nuclei are liberated. Preheat the protease solution in a water bath (37ºC and 200 rpm). Incubation time is determined by trial and can vary for tissue type.
  • To stop the enzyme activity: place the specimens on ice and add 4 ml of cooled PBS. Let the specimens stay in ice until the spinning is finished. Observe the suspensions to obtain an impression of the density of cells while pipetting multiple times. Filter the suspension through a 60 µm nylon filter into a new tube. Centrifuge at 1000 rpm (150 G) for 10 minutes. Remove the supernatant. Add 4 ml PBS, resuspend and centrifuge again. Remove the supernatant, but let approximately 1 ml remain (assess based on pellet).
  • Spin: Pipette the right amount of nuclei suspension in the test chambers. This is based on experience. The fist specimen spin is assessed unstained under the microscope. With a 40x objective, there should be at least 30-40 nuclei in the field of vision. Centrifuge at 600 rpm (40 G) for 5 minutes. Slowing should occur gradually. Make at least 2 spins for each specimen. Finished monolayers are post-fixed with 4% buffered formalin overnight at minimum, but tolerate standing over a weekend.   
  • Stain the spins with the Feulgen stain.

Feulgen staining of monolayer

  • Post fixation: 4 % formalin over night. Rinse carefully in water (dip the slides in distilled water).
  • Hydrolysis: 5 M HCl for 60 minutes. The time may vary for different specimens, and a hydrolysis curve for different tissue types should be prepared to ensure correct hydrolysis time. Dispose of HCl in the proper container. Fill and empty the glass with distilled water x 3.
  • Sulfite rinse: Rinse 3 x 10 minutes in sulfite solution. Rinse one more time for 5 minutes in running water.
  • Dehydration: Place the slides into a metal slide holder and rinse in distilled water, 70 % ethanol, 96 % etanol, 2 x absolute ethanol. Rinse in xylene x 2.

Mount cover glass with Eukitt® from xylene.

Automatic measurement of monolayer

  • Find the best monolayer (dense with nuclei, but without many overlapping nuclei) and place in position in the microscope.
  • Start the measurement program, choose storage location, and enter detail of case.
  • Click Accept. A window appears with image field and menu – the program is in Capture-mode.
  • Check the monolayer position with the help of Image Position and autofocusing.
  • Click Blank Shade Image Position, check that the screen area is totally blank, set the value to 800 ±2 and click Capture.
  • Go to Automatic mode and set the maximum limit for number of fields to be scanned and total number of nuclei to be measured - remember to adjust the total amount if suspicious of a large number of non-tumor nuclei in the specimen.
  • Start Auto Capture and the measurement with automatically start until one of the following occurs:
    • The limit for the number of nuclei is reached.
    • The limit for the number of fields is reached.
    • The machine does not find more nuclei and automatically stops.
  • Record the number of fields and gallery distribution in the measurement form.
  • Click Exit and save the measurement.
  • Make necessary file transfers for later editing and back-up.

Editing of automatic measurement

  • Open "Histogram Draftsman" and the actual case for editing.
  • It is recommended that the galleries are sorted by area before assessment and editing. Browse through all galleries to get an impression of the quality of the specimen (for example poor segmenting, cytoplasm disturbances etc. are more the rule than the exception, in certain specimens).
  • The dynamic for editing is subjective, however here is a method:
    • First edit gallery 4, followed by gallery 3, 2 and lastly gallery 1.
    • Editing of each gallery occurs in the series:
      • Excluding (to gallery 6)
      • Moving (to other galleries)
      • Browse through each gallery at least twice, with and without masking lines and in different modes. Some properties are more visible in certain modes.
  • Goal for editing:
    • Gallery 1: tumor nuclei (main gallery)
    • Gallery 2: lymphocytes (reference gallery)
    • Gallery 3: large immune nuclei (partly reference gallery)
    • Gallery 4: fibroblasts partly reference gallery)
    • Gallery 5: nuclei with uncertain properties
    • Gallery 6: excluded nuclei
  • The following nuclei are excluded:
    • Sliced nuclei (mikrotom)
    • Nuclei, for other reasons, without intact membrane
    • Overlapping nuclei
    • Necrotic and apoptotic nuclei
    • Nuclei with foreign bodies
    • Heavily over-segmented or under-segmented nuclei

The edited file must be saved before closing "Histogram Draftsman".

Classification of DNA-histogram

Classification of DNA histogram is based on edited galleries in Histogram Draftsman. The classification is based on a visual assessment of all galleries (quality of editing and nuclei composition of the specimen).

 When editing has been verified, the histogram is retrieved. Assess the composition/placement of the different nuclei types and place the 2c peak (diploid G1 top).  Place "tags" for each potential G1 peak in the tumor nuclei area. These tags give information about the peaks':

  • Mean IOD-value (Integrated Optical Density).
  • CV (coefficient of variation)
  • DI (DNA-Index) 
  • percent share of total histogram
  • 5c ER (Exceeding Rate)
  • 9c ER

The histogram is classified into one of four possible categories:

  • Diploidy: There is a normal amount (23 chromosome pairs = duplicate set) of DNA in the cell nucleus. This is the normal situation for the resting phase of the cell cycle.
  • Tetraploidy: DNA-content in the cell nucleus is double. This is normal in liver cell nuclei and in the G2 phase before mitosis. 
  • Polyploidy: A further doubling of DNA content in the cell nucleus without cell division (eight copies of each chromosome). In general, polyploid is used to name nuclei where there are multiple copies of cell DNA.
  • Aneuploidy: The DNA content in the cell nuclei has not been equally represented under cell division. The chromosomes might be missing partly or completely, or whole or parts of chromosomes might be added.

Due to constant improvements in technical quality, classification criteria is steadily developing and international consensus conferences are held at regular intervals (1). The following should be regarded as the present criteria for DNA ploidy classification: 

  • DIPLOIDY  
    • Only one G0/G1-peak
    • G2-peak is under 10 % or less than SFF (S-phase fraction)
    • 5c ER is less than 1 %
  • TETRAPLOIDY
    • Peak at 4c, 8c and DI 1,9-2,1 (if DI is 1,8-1,9 or 2,1-2,2  the rule is used for ± 2xCV).
    • 4c is over 10 % (and larger than SFF) or visibly SFF/G2 for one 4c-peak over 1 %.
  • POLYPLOIDY
    • Peak at 8c, 16c and DI 3,8-4,2 (if 4c has high CV then DI-limit is 3,6-4,4).  
    • 8c is over 10 % or visibly SFF/G2 for one 8c-peak over 1 %.
  • ANEUPLOIDY    
    • Non-euploid G1-peak (euploid: 2c, 4c, 8c, etc.)
    • 5c/9c ER is larger than 1 % and does not represent euploid populations

REFERENCE

Haroske G, Baak JP, Danielsen H, Giroud F, Gschwendtner A, Oberholzer M, Reith A, Spieler P, Bocking A. Fourth updated ESACP consensus report on diagnostic DNA image cytometry. Anal Cell Pathol. 2001 23(2):89-95.

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Pelvic paraaortal lymph node dissection/sampling

General

In a pelvic/paraaortal lymph node dissection, the lymph nodes in the pelvis and along the aorta and vena cava are completely removed. This is done to diagnose microscopic spreading of tumor cells. 

In pelvic/paraaortal lymph node sampling, the pelvic lymph nodes and paraaortal lymph nodes are examined for microscopic spreading. Visible lymph nodes are removed, but not all the lymphatic tissue. 

Dissection/staging of pelvic/paraaortal lymph nodes is performed as a separate surgical procedure, or combined with a larger procedure (for example radical ovarian surgery). When the procedure is carried out separately, it is performed as conventional laparascopic or robot-assisted surgery. A pelvic lymph node dissection is always performed for cervical cancer, for ovarian and uterine cancer. 

Indications

  • Cervical cancer
  • Uterine cancer 
  • Ovarian cancer 
  • Fallopian tube cancer

Goal

  • Diagnose microscopic tumor spreading

Preparation

  • Large bowel emptying
  • Thrombosis prophylaxis

Implementation

  • Open the space between the ureter and the pelvic wall.
  • Hold the ureter on the medial side and dissect down on the lateral side.
  • Open the paravesical space.
  • Split the tissue over the external iliac artery.
  • Use forceps and start on the medial side. Hold the nodes while the assisting surgeon carefully releases them.
  • Spare femoral genital nerve to avoid paralysis.
  • Localize the obturator nerve in the obturator fossa.
  • Locate the lymph nodes above this and remove them.
  • Remove the lymph nodes by the common iliac artery.
  • Use clamps to secure lymphatic vessels if needed.
  • Extirpate the same amount of lymph nodes from both sides.
  • Put the lymph nodes in formalin for evaluation by a pathologist.

Follow-up

  • Standard observation for postoperative complications

Positron Emission Tomography (PET)

General

Positron Emission Tomography (PET) is a nuclear medical examination method. PET is a well-documented, well-established and very useful tool in oncological imaging.

Indications

Oncological imaging for:

  • Staging the primary diagnosis and recurrence
  • Evaluating the effect of aggressive chemotherapy treatment
  • Evaluating the effect of completed treatment, including differentiating scar tissue from viable residue tissue
  • Suspicion of recurrence (for example, increased level of tumor marker in the blood)

Goal

  • To provide concrete diagnostic information that will provide a basis for the choice of the best possible treatment.

Definitions

PET has a very high sensitivity and can register absorption of radiopharmaceutical agents in extremely low concentrations. Since the central atoms in biochemical compounds (carbon, oxygen, nitrogen) all have positron-emitting isotopes that can be produced in small hospital cyclotrons, it is possible to mark a number of central molecules such as oxygen, water, amino acids, various metabolites, hormones, and neurotransmitters.

For clinical PET, dextrose is usually used where a hydroxide group is replaced by 18F (18-flourine), a compound that is called 18F-FDG (flourine-18 labeled deoxyglucose). 18F-FDG has a high affinity for cells with increased metabolism, for example cancer cells. The substance is transported into the cells and phosphorylates glucose to 18F-FDG-phosphate, but no further break-down occurs. Because cell membranes are impermeable to phosphorylated deoxyglucose, an intracellular accumulation of the substance occurs.

Limitations

  • Small tumors ( < 0,5 cm) and tumors with low to moderate absorption can escape detection.
  • Inflammatory conditions will produce increased absorption.
  • For patients with diabetes (especially those requiring insulin) and non-fasting patients, high muscular absorption will reduce the sensitivity for tumor detection.
  • Some tumor types have low FDG absorption (for example, prostate and bronchoalveolar carcinoma).

Sources of error

  • Infections and inflammatory conditions (including post-operative changes) will result in increased absorption.
  • Normally, the intestine can have a high absorption.
  • Myocardium often displays high absorption, also in fasting patients.
  • 18 F-FDG is excreted through the kidneys and FDG in the urinary tract can be misinterpreted.
  •  Absorption in brown fat tissue can be misinterpreted as a tumor if PET is not compared with CT. PET/CT combined in the same apparatus gives better specificity than PET alone.

Equipment

  • PET/CT-scanner  
  • Radio-pharmaceutical agent: 18F-FDG is formed by radiating a heavier natural variant of oxygen with protons. This occurs in a cyclotron. Fluorine-18 (18F) is produced at the hospital cyclotron located at Rikshospitalet .

Preparation

Patient preparation depends on the clinical diagnosis.

  • Fast for at least 6 hours before the examination in order to increase the absorption of 18F-FDG. But the patient should drink plenty (2-4 glasses per hour. Water, tea, or coffee without sugar or cream/milk added can be substituted for water.
  • Measurement of s-glucose is performed before injection of 18F-FDG.
  • After intravenous injection of 18F-FDG, it is very important that the patient lies relaxed in a quiet room without talking and avoiding all forms of stimuli, in order to avoid non-specific absorption of 18F-FDG in the muscles.
  • Tranquilizers and painkillers are often administered prior to the injection.
  • The patient should be warm and comfortable prior to the injection in order to prevent absorption in the brown fat, which may affect the interpretation.

There will be other precautions for neurological and cardiological diagnoses.

Implementation

  • The patient must lie completely still while the images are being taken.
  • A whole-body examination takes approximately 25 minutes.
  • For PET, tissue absorption is displayed by positron-emitting, radiopharmaceutical preparations.

Registration of emission

  • The positron is considered a positively charged electron.
  • When the positron leaves the radioactive core, it will travel up to a few millimeters before it collides and fuses with an electron and is transformed into energy; this is called annihilation.
  • The mass of the positron and the electron is transformed into energy in the form of two photons, each of 511 keV, which are emitted in diametrically opposing directions (180°).
  • A ring detector around the patient will catch the photons.
  • The two photons will encounter the ring detector at the same time (coincident detection), and because they have moved in exactly opposite directions, the detection will precisely localize the radiation focus (for example, a lymph node with tumor tissue).
  • A modern PET-camera with ring detector can map the entire body in 20 minutes.
  • The PET-scanners have integrated CT, so that the information from PET is accurately localized anatomically.

Examples of findings

  • Anal cancer: Anal tumor and metastasis in lymph node
  • Hodgkin's lymphoma (HL): HL with involvement of: soft tissue in the larynx , vertebra L4 ,  os pubis L  and femur
  • Cancer of the rectum: Adenocarsinom in rektosigmoideum liver metastases
  • Intracranial tumors: Astrocytoma grade II/III, left parietal lobe  high-grade glioblastoma, right frontal lobe 
  • Lung cancer: Lung tumor  lung cancer with lymph node spread
  • Sarcoma: Soft tissue sarcoma in the left thorax
  • Cancer in the esophagus: Tumor in the distal esophagus
  • Colon cancer: Metastasis-suspect lesion in adrenal gland

Follow-Up

  • At the end of the examination, the radioactivity is small, but the patient should keep a distance (about 3 meters) from children and pregnant ladies the day of the scan.
  • The result will normally be available the following day.
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Postitron emission (PET) with <sup>18</sup>F-FDGPositron emissions tomografi (PET) with <sup>18</sup>F-FDGPositron emission tomography (PET) with <sup>18</sup>F-FDGPositron emission tomography (PET) <sup>18</sup>F-FDG
Positron emission tomography (PET) with <sup>18</sup>F-FDGPositron emission tomography (PET) <sup>18</sup>F-FDGPositron emission tomography (PET) with <sup>18</sup>F-FDGPostitron emission (PET) with <sup>18</sup>F-FDG
Postitron emission (PET) with <sup>18</sup>F-FDGPostitron emission (PET) with <sup>18</sup>F-FDGPostitron emission (PET) with <sup>18</sup>F-FDGPostitron emission (PET) with <sup>18</sup>F-FDG
Positron emmissions tomography (PET) with<sup>18</sup>F-FDGPositron emission tomography (PET) with <sup>18</sup>F-FDGPositron emission tomografi (PET) with <sup>18</sup>F-FDG

Ultrasound-guided fine-needle aspiration and biopsy from the pelvis

General

MRI or CT is often used to assess possible spreading of different cancer types. A cytological or histological assessment of a tumor is often needed. If the lesion can be seen by vaginal ultrasound, ultrasound-guided biopsy is the optimal method for this. For localized tumor, for example a well-limited ovarian tumor without sign of spreading, the risk for spread in connection with the biopsy procedure must be taken into consideration. For probable stage I ovarian cancer, biopsy is generally contraindicated due to the risk of spread. For suspicion of sarcoma, the indication must be done by a sarcoma treatment specialist. For cytological examination, it is possible to obtain the result already the same or the following day while a histological examination requires a few days.

Indication 

  • Unknown type of lesion in the pelvis

Goal

  • To confirm or exclude metastases from suspect lesions in the pelvis.

Equipment

  • Ultrasound specimen with transducer for the procedure
  • Syringe (20 ml and syringe holder)
  • Needle for cytology material. (22 G B&D spinal needle)
  • 4 slides for the specimen

For histological biopsy (pistol biopsy) this is used in addition:

  • Separate 18 G or 16 G needle + gun
  • Slide for fixing histology material (formalin, Ringer solution, McCoy, dry glass for freezing etc. - depending on tentative diagnosis)
  • Sterile condom for ultrasound probe
  • Gel

Preparation

Depending on the localization of the lesion and availability, routine blood tests must be ordered regarding bleeding parameters (hemoglobin, thrombocytes, possibly INR).

  • Make sure the patient is well situated on the examination table.
  • Inform the patient during the procedure.

Implementation

Ultrasound-guided biopsy from the pelvis is taken usually under general anesthesia, but fine-needle aspiration for cytology examination can be taken without anesthesia.

Cytology sample (fine-needle aspiration)

  • Wash the vagina with chlorhexidine 1 mg/ml
  • Localize the lesion with the ultrasound probe
  • Determine the best point of puncture and direction. Use a puncture line.
  • Puncture the spinal needle quickly through mucous membrane.
  • Insert the needle into the lesion using ultrasound.
  • Pull out the mandrin.
  • Insert the needle into the lesion.
  • Aspirate while the needle moves back and forth 2-3 times per second until the material is visible in the upper part of the needle.
  • Retract the suction and pull the needle out.
  • Deposite the specimen onto the slide

Spread for cytology

  • Spread the specimen onto the slide.
  • Dry the specimen under a fan or hairdryer.
  • Alternative 1: send the specimen unfixed to the cytologist.
  • Alternative 2: Immediate staining and assessment.
    • Fixation solution with methanol + haemacolor + rinse in water
    • 5 dips in fixer. Allow the solution to drip off onto paper.
    • 3 dips in stain solution 1.
    • 6 dips in stain solution 2. Allow the solution to drip onto paper.
    • Rinse in 2 baths of clean water.
  • Examine the specimen under the microscope with 10x or 20x objective.
  • Microscopic assessment of the cell material should be done by a cytologist to determine if supplementary samples are needed. 

Histological biopsy (pistol biopsy)

  • For pistol biopsy, general anesthesia is used.
  • Insert the biopsy needle up to the lesion and insert slightly, depending on the size and type of the tissue in front and behind the lesion.
  • The needle moves 2.5 cm forward when released.
  • Retract the pistol such that the sample is taken.
  • Retrieve the needle out and open it.
  • Place the piece of tissue on a slide with transfer medium, for example formalin.  

Follow-up

  • After uncomplicated biopsies, outpatients must remain at the hospital for 1 hour before going home.
  • Depending on localization of the lesion and nature, bleeding may occur after biopsy procedure.
  • For intense pain or bleeding, the patient must be observed at the post or intensive unit dending on severity while necessary measures are taken.
Ultrasound-guided fine-needle aspiration and biopsy from the pelvis.Ultrasound-guided fine-needle aspiration and biopsy from the pelvis.Ultrasound-guided fine-needle aspiration and biopsy from pelvisUltrasound-guided fine-needle aspiration and biopsy from the pelvis.
Ultrasound-guided fine-needle aspiration and biopsy from pelvisUltrasound-guided fine-needle aspiration and biopsy from the pelvis.Ultrasound-guided fine-needle aspiration and biopsy from the pelvis.Ultrasound-guided fine-needle aspiration and biopsy from the pelvis
Ultrasound guided fine-needle aspiration and biopsy from the pelvisUltrasound-guided fine-needle aspiration and biopsy from the pelvis.Ultrasound-guided fine-neelde aspiration and biopsy from the pelvis.Ultrasound-guided fine-needle aspiration and biopsy from the pelvis.

Treatment of ovarian and fallopian tube cancer

The primary treatment for ovarian and fallopian tube cancer is surgery and chemotherapy. The goal is to remove all of the tumor tissue and achieve a correct stage determination.

Patients with ovarian cancer in stage I in the low-risk group do not need chemotherapy. All other patients needs postoperative chemotherapy. Early stage fallopian tube cancer (£ stage II) may have a different biology from ovarian cancer. Many patients have lymph node metastases, therefore, a pelvic and paraaortal lymph node dissection is recommended during the primary operation. Stage I with infiltration of serosal tissue or tumor rupture increases the frequency of recurrence. Adjuvant chemotherapy may be considered.

Patients with poor general health condition, or high probability that the tumor cannot be completely resected, may be candidates for neoadjuvant chemotherapy, postponing the operation until after three cycles. 

  • Borderline ovarian cancer can usually be treated with surgery alone, even in advanced cases. This type of tumor is slow-growing and does not respond well to chemotherapy.
  • Non-epithelial ovarian cancer is generally sensitive to chemotherapy and radiation therapy, but due to side effects, radiation therapy is not widely used.
  • Germ cell tumors are high-grade malignant tumors which respond well to treatment with chemotherapy and radiation therapy. These tumors are often unilateral. Due to the sensitivity to chemotherapy, conservative  surgery may be carried out and the patient will most often preserve her fertility.   

Radiation therapy is not often used, except in specific palliative situations.

Recurrence

For recurrence of ovarian or fallopian tube cancer, where recurrence is twelve months or more after primary treatment, it is recommended to operate before starting chemotherapy, in some cases. For most patients, immediate chemotherapy is started.  

Surgery of ovarian and fallopian tube cancer

The treatment goal is to achieve the correct stage determination and to remove all tumor tissue. Surgical treatment for this cancer is often technically demanding and should be carried out at a center with expertise in this type of surgery.  

Patients with unexpected malignant/borderline histology after operation for a presumed benign tumor, must be submitted to evaluation for reoperation at a gynecologic oncology department.

Epithelial ovarian and fallopian tube cancer

In stage I ovarian and fallopian tube cancer, a hysterectomy and removal of the ovaries is performed. BSO (bilateral salpingo-oophorectomy), omentectomy and extirpation of lymph nodes in the pelvis and paraaortally are standard operations. 

For stage II–IV, surgery is the standard initial treatment. The goal is to remove all tumor tissue. BSO, hysterectomy, omentectomy, resection of peritoneal implants and extirpation of suspicious lymph nodes in the pelvis and paraaortal region are usual procedures.

For a patient with a significantly reduced health condition or unresectable tumor, it may be recommended to give start treatment with chemotherapy and evaluate surgery after 3 courses of chemotherapy (neoadjuvant chemotherapy).

In cases where optimal debulking was not achieved by the primary operation, it may be recommended to perform interval debulking, which is optimally performed after three cycles, but not later than after 4 cycles. This is most appropriate when the primary surgery was performed by a non-specialized gynecological oncologist, while an effect on survival was not found after the primary surgery was carried out by a specialized gynecological oncologist.

Secondary debulking after completing six cycles of chemotherapy has not been shown to improve survival.

Borderline ovarian cancer occurs usually in younger women still wishing to become pregnant. Since these tumors seldom are bilateral, a unilateral extirpation of the adnexa may be adequate. It is recommended to perform an omentectomy for full stage determination. If the contralateral ovary appears normal, it is recommended to avoid taking a biopsy from this ovary. Lymph node staging is not recommended. In case of peritoneal implants, it is recommended to perform as complete a surgical resection as possible. With aneuploid tumors, there is a significant increase in risk for recurrence. Bilateral salpingo-oophorectomy and omentectomy should be considered. A hysterectomy is not necessary unless there are implants on the uterus. 

Non-epithelial ovarian cancer

Women wishing to preserve fertility:

  • For younger women wishing to preserve their fertility, it is recommended to refer primary surgery to a regional center with a gynecological oncology department. A unilateral oophorectomy is performed. With tumor involvement of the contralateral ovary, a tumor resection is recommended with preservation of the ovary. Remaining tumor in an ovary is allowed if necessary to preserve fertility because these tumors are extremely sensitive to chemotherapy.
  • For intraabdominal spread, a maximal tumor reduction is performed. 
  • Pelvic and paraaortal lymph node staging is recommended. For a unilateral tumor, it is recommended to perform lymph node staging on the same side. At minimum, palpation with biopsy is done on the enlarged lymph nodes. 

Women not wishing to preserve fertility:

  • Hysterectomy, BSO and omentectomy is recommended.
  • Pelvic and para-aortal lymph node staging is recommended.
  • For advanced disease, debulking surgery is performed including removal of both ovaries.

Women with Y-chromosome:

  • With granulosa cell tumors where the uterus is not removed, curettage is performed to exclude uterine cancer. 
  • Second-look laparotomy is not recommended.

Treatment of recurrence

Data from recent studies on recurrence indicates that surgery can extend survival in cases where all tumor tissue can be removed by operation. A long interval (>12 months), after primary surgery, is a good prognostic sign. 

Surgery may be beneficial for late-occurring localized recurrences, but should be performed at a regional center. Most studies recommend secondary cytoreduction only if single site of disease (vs. carcinomatosis) and long disease-free interval.

The most common form of recurrence in borderline tumors is in the remaining ovary. Surgical treatment with resection or extirpation of the ovary can be performed. For other forms of intraperitoneal recurrence, a resection is performed where possible.

For recurrence of non-epithelial ovarian cancer, removal of all tumor tissue is recommended if possible.

Palliative surgery

Many patients are bothered by subileus/ileus. Intestinal surgery to relieve symptoms should be considered if expected survival is > 1 month and the patient's general health condition allows. Ascites and pleural taps are performed as needed.

PROSEDYRER

Hysterectomy with bilateral salpingo-oophorectomy for early stage ovarian cancer

General

When ovarian cancer is confirmed, radical surgery is usually performed by removal of both ovaries (bilateral salpingo-oophorectomy – BSO) and the uterus (hysterectomy), as well as extirpation of pelvic and paraaortal lymph nodes. It is very important to thoroughly inspect the peritoneum in the upper abdomen including the diaphragm.  Random biopsies are taken of the peritoneum lateral to the ascending and descending colon. This type of surgery can also be performed by conventional laparascopy or robot-assisted surgery.

For ovarian cancer in younger women wishing to preserve their fertility, it may be possible to leave the healthy ovary and uterus. This is possible if the tumor is localized to one ovary and the patient is at low risk for recurrence. 

The risk assessment is based on the histological type, grade of differentiation, and ploidy. The result of these examinations will not be available until some time after the operation. If the examinations indicate a high risk for recurrence, it may be necessary to remove the remaining ovary in a subsequent laparoscopic procedure. 

Borderline ovarian cancer usually occurs in younger women still wishing to become pregnant. Since these tumors are rarely bilateral, it may be adequate to perform a unilateral adnexal extirpation. It is recommended to do an omentectomy for a full stage evaluation. If the contralateral ovary is normal in appearance, it is recommended to avoid taking a biopsy from this ovary. There are no reasons for lymph node staging.

With spreading of borderline tumors, it is recommended to resect as much as possible. For aneuploid tumors, there is a significant risk for recurrence. This is the cause for immediate surgery with a bilateral salpingo-oophorectomy and omentectomy. A hysterectomy is not necessary unless there are implantations on the uterus.

The appendix is removed in the case of mucinous tumors.

Because of the danger of spreading of ovarian cancer to the peritoneum, the omentum is also often removed (omentectomy).

The ovary can also be removed if there is suspicion of cancer to establish a histological diagnosis. During the operation, the ovary is examined using frozen sections to obtain a histological diagnosis. The diagnosis is normally available after 30 minutes. Based on the histological diagnosis, further course of action for the operation is planned.  

Indication

  • Suspect or confirmed ovarian cancer

Goal

  • Curative treatment and stage determination

Equipment

Gynecological surgery tray

Preparation

  • Large bowel emptying
  • Thrombosis prophylaxis
  • Antibiotic prophylaxis

Implementation

 

  • The patient lies in the supine position.
  • For cancer of the adnexa, a mid-line incision is made.
  • Make an incision from the top of the symphysis to the navel extending into the epigastrium as needed. Make the incision long enough allowing for sufficient space to prevent rupturing of  the ovaries during mobilization.
  • If present, aspirate ascites into a syringe with a catheter.  
  • If there are no ascites, rinse the abdomen with 50 ml NaCl 9 mg/ml and aspirate in the same syringe. Deliver the aspirate for a cytological examination. 
  • Arrange the Bookwalters retractor to obtain optimal working space and overview.
  • Inspect and palpate the entire abdomen for possible metastasis.  Inspect the adnexa and abdominal cavity. Check the liver, spleen, lymph nodes, diaphragm, stomach, intestines, and omentum.
  • Pack away the intestines with compresses saturated with NaCl 9 mg/ml. Keep them in out of the operation field with disharp and the retractors.  
  • Check that the individual retractors are not pressing on the psoas muscles and femoral nerve to avoid compression injuries, neuropathy, and paralysis in the femoral area.
  • Lower the cranial end of the opration table (Trendelenburg’s position).
  • Clamp with Kochers forceps on each corner of the uterus. The assisting surgeon should hold the uterus.
  • Clamp the round ligament on both sides.
  • Split the peritoneum over the bladder. 
  • If the tumor is localized to the adnexa without adherances to the peritoneum, a simple removal of the adnexa is carried out. The specimen is sent for frozen sectioning. If there is infiltration of the peritoneum, the infiltrated part is removed along with the adnexa. 
  • Split the peritoneum along the pelvic wall.
  • Open the extraperitoneal space along the pelvic wall.
  • Identify the ureter and avoid it.
  • Divide the suspensory ligament containing the blood supply to the adnex.
  • Dissect the peritoneum off the ureter and its accompanying structures, and push the ureter down before the peritoneum is divided.
  • Dissect along the peritoneal to the uterus.
  • Separate the adnex from the uterus.
  • Send the adnexa for examination by frozen microscopy.
  • Push the bladder peritoneum down to below the cervix.
  • Clamp the parametrium close to the uterus using Leibingers forceps.
  • Place the Leibinger forceps closely and obliquely towards the vagina and cut with scissors.
  • Place Kocher forceps on the vagina immediately under the cervix to lift the vagina.
  • Use diathermy to remove the uterus and cervix immediately distal to the cervix.
  • Close the top of the vagina with surures.
  • Carry out  lymph node staging.  
  • Perform an omentectomy.  
  • Close the abdominal wall. 

Follow-up

Observe for normal postoperative complications.

Hysterectomy and bilateral salpingo-oophorectomy for fallopian tube cancer

General

For confirmed cancer, radical surgery is ordinarily performed by removal of both adnexa (bilateral salpingo-oophorectomy – BSO) and the uterus (hysterectomy). Staging of the pelvic and paraaortal lymph nodes is also performed, as well as checking for spreading to the rest of the abdomen and lymph nodes. The omentum is also removed due to the threat of spreading to the omentum (omentectomy).  

During the operation, the adnexa is sent for frozen microscopic examination to obtain a histological diagnosis. The diagnosis is usually available after 30 minutes.  The further course of the operation is planned based on the histological examination.

Fertility-conserving surgery is not recommended for fallopian tube cancer.

Indications

  • Suspect or confirmed fallopian tube cancer.

Goal

  • Stage determination and curative treatment.

Equipment

Gynecological surgery tray

Preparation

  • Large bowel emptying
  • Thrombosis prophylaxis
  • Antibiotic prophylaxis

Implementation

  • The patient lies in the supine position.
  • For cancer of the adnexa, a mid-line incision is made.
  • Make an incision from the top of the symphysis to the navel extending into the epigastrium as needed. Make the incision long enough allowing for sufficient space to prevent rupturing of  the ovaries during mobilization.
  • If present, aspirate ascites into a syringe with a catheter.  
  • If there are no ascites, rinse the abdomen with 50 ml NaCl 9 mg/ml and aspirate in the same syringe. Deliver the aspirate for a cytological examination. 
  • Arrange the Bookwalters retractor to obtain optimal working space and overview.
  • Inspect and palpate the entire abdomen for possible metastasis.  Inspect the adnexa and abdominal cavity. Check the liver, spleen, lymph nodes, diaphragm, stomach, intestines, and omentum.
  • Pack away the intestines with compresses saturated with NaCl 9 mg/ml. Keep them in out of the operation field with disharp and the retractors. 
  • Check that the individual retractors are not pressing on the psoas muscles and femoral nerve to avoid compression injuries, neuropathy, and paralysis in the femoral area.
  • Lower the cranial end of the opration table (Trendelenburg’s position).
  • Clamp with Kochers forceps on each corner of the uterus. The assisting surgeon should hold the uterus.
  • Clamp the round ligament on both sides.
  • Split the peritoneum over the bladder. 
  • If the tumor is localized to the adnexa without adherences to the peritoneum, a simple removal of the adnexa is carried out. The specimen is sent for frozen sectioning. If there is infiltration of the peritoneum, the infiltrated part is removed along with the adnexa. 
  • Split the peritoneum along the pelvic wall.
  • Open the extraperitoneal space along the pelvic wall.
  • Identify the ureter and avoid it.
  • Divide the suspensory ligament containing the blood supply to the adnex.
  • Dissect the peritoneum off the ureter and its accompanying structures, and push the ureter down before the peritoneum is divided.
  • Dissect along the peritoneal to the uterus.
  • Separate the adnex from the uterus.
  • Send the adnexes for examination by frozen microscopy.
  • Push the bladder peritoneum down to below the cervix.
  • Clamp the parametrium close to the uterus using Leibingers forceps.
  • Place the Leibinger forceps closely and obliquely towards the vagina and cut with scissors.
  • Place Kocher forceps on the vagina immediately under the cervix to lift the vagina.
  • Use diathermy to remove the uterus and cervix immediately distal to the cervix.
  • Close the top of the vagina with surures.
  • Carry out  lymph node staging.  
  • Perform an omentectomy.
  • Close the abdominal wall. 

 

Follow-up

Observe for normal postoperative complications.

Removal of extensive pelvic and abdominal tumors

General

This operation is performed either as primary treatment before chemotherapy or after the patient has been given 3 to 4 cycles of chemotherapy (interval debulking).

The extensiveness of the operation can vary greatly, all depending on the extent of the tumor masses. 

With an extensive tumor in the pelvis, it is often necessary to remove the uterus and adnexa and resect part of the recto-sigmoid en bloc. A recto-sigmoid anastomosis can then be performed (low anterior resection). It may be necessary to resect parts of the intestinal system. If the spleen in infiltrated, this can be removed, as well as in extirpation of a single liver metastasis. Extensive resections or removal of the spleen will normally not be performed if there will be remaining macroscopic tumor after the operation. The patient should be prepared for a possible intestinal operation, and antibiotic prophylaxis should be given. The appendix should be removed in the case of mucinous tumors (only ovarian cancer) and when it is infiltrated by tumor or traumatized.   

A mid-line incision should always be used with suspicion of extensive pelvic and abdominal tumors. The operation is started by aspirating ascites for cytological examination. If there are no ascites, the cavity should be rinsed with 50 ml sterile water, which is sent for cytological examination. A thorough inspection of the pelvis and upper abdomen, including the diaphragm with description of size and localization of tumor changes, is done. Any adherences should be described as well as any possible rupture of tumor pre- or intraoperatively. 

If all intraabdominal and pelvic tumor tissue is successfully removed, the pelvic and paraaortal lymph nodes are removed. It is sometimes necessary to perform a partial or complete peritonectomy and/or diaphragm resection to remove all tumor tissue.

Indications

  • Advanced ovarian cancer
  • Fallopian tube cancer

Goal

  • As much of the tumor should be removed as possible.
  • The operation is also intended to map the extent of the tumor and to remove a specimen of tumor for histological examination.  

Preparation

Adequate preoperative examination of patients with pelvic tumors is very important. Calculation of the malignancy index score (RMI) should be included. The possibility of another cancer form should also be evaluated before the operation. 

  • Large bowel emptying
  • Thrombosis prophylaxis
  • Antibiotic prophylaxis

Implementation

  • A midline incision in made. It may be necessary to extend this into the epigastrium.
  • If ascites is present, a sample is taken and sent for a cytological examination. 

Survey the extent of the tumor tissue

  • Inspect the pelvic organs and peritoneal surfaces in the entire abdominal cavity including the diaphragm. 
  • Inspect the intestines and the entire length from the ligament of Treitz to the rectum.
  • Palpate organs for tumors. 
  • Palpate lymph node stations along the pelvic wall and paraaortally.
  • If there is no macroscopic tumor in the abdominal cavity, biopsies should be taken from the peritoneum, and an omentectomy should be performed to diagnose possible metastasis. 
  • Describe the size, localization, and number of remaining tumor changes after the operation. 

Prepare a plan for the operation

  • Try to remove all tumor tissue.
  • If this is not possible, try to reduce the amount of tumor tissue so the size of remaining elements is as small as possible, or under 1 cm regardless.
  • If it is not possible to adequately remove the tumor tissue, there will be no benefit of removing organs. The operative procedure then cannot be expected to improve the patient's prognosis. 

Pelvis:

  • If there is spreading of tumor tissue to the peritoneum, this is removed along with the tumor. An extraperitoneal technique is then recommended. 
  • If the recto-sigmoideum is infiltrated, it may be necessary to perform a recto-sigmoid resection (low anterior resection).  
  • The urinary tracts are usually spared since the bladder is rarely infiltrated.

Abdomen:

  • The greatest limitation for removal of all tumor tissue is the presence of extensive carcinomatosis on the small intestine, as well as tumor in the hepatic port, or metastasis to the liver.
  • Omentum infiltrated with tumor is often removed without damaging the colon. 
  • If necessary, the colon can be resected to remove tumor tissue.
  • If tumor infiltrates the peritoneum, the area can be removed.
  • If the spleen in infiltrated, it can be removed.
  • A partial or total diaphragmatic resection is performed if the diaphragm is infiltrated. 

Retroperitoneum:    

  • Enlarged lymph nodes are removed, if possible, and of benefit to the patient's prognosis.
  • If all visible tumor is removed, thoroughly check the lymph nodes stations in the pelvis and paraaortally, and take representative biopsies.

Removal of extensive tumor in the pelvis

  • The bladder is dissected off the anterior of the uterus.
  • The peritoneum is divided on the pelvic walls. 
  • Cut down to the retroperitoneal space of the pelvic walls.
  • Identify the ureters and dissect them down to the inlet of the bladder.

For a simultaneous en bloc low anterior resection of the recto-sigmoideum (to remove all tumor tissue in the pelvis where tumor is infiltrating the colon/sigmoideum/rectum):

  • Divide the sigmoid colon with GIA® proximal to the tumor tissue.
  • Divide and ligate the ovarian arteries. 
  • Divide the peritoneum across to the pelvic inlet.
  • Divide and ligate the arteries to the intestines.
  • Then, divide extraperitoneally and free the ureter from the peritoneum. The autonomous nerves following the ureter should be preserved. The dissection should be carried on down behind the sigmoideum and rectum.
  • Divide and ligate the uterine arteries. This must be done at the level of the ureter or on the pelvic wall.
  • Divide and suture ligate the parametria.
  • Open the anterior vagina and divide it.
  • Dissect retrograde up between the rectum and uterus until reaching tumor tissue. 
  • Divide and suture ligate the sacrouterine ligaments.
  • Isolate the rectum at the level of division.  
  • Clamp the rectum with TA® and divide it.
  • Remove the specimen consisting of the uterus, adnexa, and part of the recto-sigmoideum and tumor tissue.
  • Anastomosize the remaining sigmoid colon/descending colon with rectal stump with CEEA®. To accomplish this, the left colon flexure and the descending colon is mobilized. This part of the operation is usually left until the end.

Omentectomy  

  • See procedure for omentectomy.
  • In some cases, the transverse colon must be resected to remove tumor.

Ileocoecal resection

  • It may be necessary to resect parts of the small intestine if there is tumor infiltration. In the case of tumor on the ileocoecal transition, it may be necessary to perform an ileocoecal resection. 
  • Divide the mesenterium.
  • Cut and ligate/suture the arteries.
  • Divide the intestine with GIA®.
  • Anastomosize the ends with GIA®.
  • Suture the openings with GIA® in the intestine in two layers.
  • Suture the opening in the intestinal mesenterium.

To finish, place a vacuum drain to the Douglasi pouch and then close the abdominal wall. 

Follow-up

Observe for normal postoperative complications.

Removal of extensive pelvic and abdominal tumorsRemoval of extensive pelvic and abdominal tumorsRemoval of extensive pelvic and abdominal tumorsRemoval of extensive pelvic and abdominal tumors
Removal of extensive pelvic and abdominal tumorsRemoval of extensive pelvic and abdominal tumorsRemoval of extensive pelvic and abdominal tumorsRemoval of extensive pelvic and abdominal tumors
Removal of extensive pelvic and abdominal tumors

Omentectomy

General

The omentum is removed for ovarian cancer, fallopian tube cancer, and cancer in the peritoneum, as well as serous papillary and clear-cell endometrial cancer because there is often macro and/or microscopic spreading. The omentum is removed to diagnose spreading. 

The omentectomy is part of the stage determination.

Indications

  • Ovarian cancer 
  • Fallopian tube cancer 
  • Cancer in the peritoneum
  • Serous papillary and clear-cell endometrial cancer

Goal

  • Remove visible tumors and to check for possible micrometastases.

Equipment

Gynecological surgery tray

Preparation

  • Large bowel emptying
  • Thrombosis prophylaxis

Implementation

  • Lift the omentum to obtain good visualization of the blood vessels. 
  • The blood vessels are divided and ligated immediately distal to the colon. 
  • The middle layer of thin tissue consisting of two peritoneal sheets with loose connective tissue in between is divided with diathermy.
  • The omentum may be adherent to the spleen and pulling may cause the spleen to rupture and bleed.
  • In cases where the tumor tissue is close to the colon, the tissue will often open when carefully splitting the peritoneum with diathermy.  
  • All blood vessels are ligated.

At Oslo University Hospital, the tissue specimens are sent dry to the pathology lab for processing and fixing.

Follow-up

Observe for normal postoperative complications.

Stoma

General

Intestinal stoma is often required during treatment of rectal cancer and sometimes for colon cancer. The stoma is either permanent or temporary. Stoma is also constructed for temporary relief of distal anastomosis or ileus.

Permanent stoma is prepared when the rectum is removed or when there is an inoperable tumor or ileus due to extreme adherences. Preferably, it is placed as close to the anus as possible to provide the best possible reabsorption of nutrition and fluid.

The procedure may be performed by laparoscopy.

A stoma can have with one or two openings. The type of stoma depends on the purpose of the stoma and anatomical conditions in the abdomen.

End stoma 

The colon is divided and the oral end is brought out. The end stoma is easier to handle and is better looking than a loop stoma. The end stoma is usually performed for permanent stomas and for relief of fistulas.

Loop stoma 

The colon is not divided but is pulled out like a loop through the abdominal wall. An opening is made in the top of the loop. The stoma has two openings: one oral and one aboral. The stoma can be prepared in two ways:

  • symmetrical—an opening is made on the top of the extracted "backwards U." The ingoing and outgoing openings of the bowel looks similar. Symmetric loop stoma are usually performed for colostomy  .
  • asymmetrical—the oral part of the bowel is brought forward and empties easier into the bag while the aboral part of the bowel is at the skin level and the opening is small. Asymmetric loop stoma is usually created for an ileostomy .

Sigmoid colostomy 

Sigmoid colostomy is the most common form of colostomy. The stoma is installed if it is not technically possible or sensible to anastomose the colon to the rectum/anal canal. It is then constructed as a permanent end stoma. This is done in 15-30% of patients with rectal cancer.

Indications

Permanent:

  • for rectal amputation
  • to avoid permanent incontinence of poor anal sphincter function (Hartmann's operation)
  • to relieve an inoperable fistula anally from the stoma

Temporary:

  • for preoperative radiation
  • relief of rectal ileus

Sigmoid colostomies are easy to maintain. The stools usually has a normal consistency and causes little irritation to the skin.

Transverse colostomy 

The transverse colon is brought out in the right rectus muscle. This is a loop stoma and is often temporary. It is often difficult to maintain because the stoma is voluminous and the feces is thin and foul-smelling. This type of stoma is associated with more complications than a sigmoidostomy. As a temporary stoma it has similar frequency of complications as ileostomas.

There is a risk that the bowel content may pass into the distal opening with an incomplete relief of stools.

Indications

  • relieve stenosis in the left colon
  • relieve low anastomosis or rectum resection
  • allow rinsing of the left colon through the stoma in limited anastomosis leakage

Ileostomy

The ileum is brought out  20-30 cm from the cecum and preferably in the right rectus muscle as an asymmetrical loop stoma. It is relatively simple to construct but can be difficult to maintain due to thin fecal content. The longer nipple will help avoiding damage to the skin.

Indications

  • protect anastomoses after rectosigmoid resection
  • relieve bowel obstruction
  • relieve preoperative radiation of stenosis due to colorectal cancer
  • relieve fistula

Indications for stomas

  • Cancer in the rectum (rectum amputation, Hartmann)
  • Cancer in the colon

Goals

  • Facilitate output of bowel contents
  • Relieve the bowel/stenosis/fistula

Equipment

  • Laparotomy tray and possibly laparoscopy equipment.
  • A device to place under the loop.

Preparation

The patient should be prepared for:
  • anatomical and physiological changes following the operation
  • what a stoma involves
  • stoma equipment and how it functions
  • the stoma is edematous the first weeks after the operation and that it will normalize

Stoma marking

The patient is informed of the purpose of the stoma marking. The goal is to find appropriate placement in order for the patient to maintain the stoma.

It is important to see the patient, lying, sitting, standing, and during movement. By seeing the abdomen in different positions, the abdomen's shape is emphasized such that individual considerations are taken during marking. The patient should be able to address their own wishes and desires.

Factors influencing the location

  • the stoma should be visible to the patient.
  • the stoma should be placed within the rectus muscle
  • the stoma disc and stoma should not come in conflict with skin folds, groin, hollow areas, iliac crest, scars, hernias, the navel, or straps for prosthesis or binder
  • the stoma should not hamper the clothing
  • choice of stoma type

Marking:

  • The rectus muscle is identified on the side where the stoma will be placed
  • The appropriate stoma location is adjusted by using a piece of tape which is moved about on the abdomen when the patient lies down, sits, and stands.
  • The patient must be offered to walk with the disc and bag to check that the stoma marking is optimal.
  • Final marking for placement is done with a waterproof marker.

Implementation

  • When the stoma is not brought out through the abdominal inscision but through a separate hole in the abdominal wall it will be easier to handle. For transversostomy: an incision is made in the right rectus muscle and the omentum is dissected off the attachment to the relevant part of the colon. It may be difficult to obtain sufficient length of the bowel without damaging the vessel supply if the abdominal wall is thick. For an ileostomy, this is more simple.
  • The least amount of skin is removed if the stoma is not brought out through the abdominal inscision.
  • The bowel is pulled out as a backwards "U" and is not divided.
  • The bowel is sutured to the peritoneum.
  • The bowel is sutured to the anterior fascia.
  • A tube or skin bridge is placed under the loop at the skin level to prevent the bowel from retracting.
  • The bowel lumen is opened at the top and the bowel wall is everted and sutured to the skin.
  • For a section in the right rectus chain, the stoma is placed out through a separate incision to facilitate stoma hygiene.
  • Colostomy should preferably be pulled 1-2 cm out over the skin level. Ileostomy: 2-3 cm.

End sigmoid colostomy:

  • A mid-line incision to the right of the navel is made.
  • The bowel is divided with a closing-dividing stapler.
  • The bowel is mobilized by adequate division of the vessels without damaging the vessel archade to permit the bowel to be pulled out through the skin without tightening.
  • In the abdominal wall, the peritoneum and posterior fascia leaf are split.
  • The musculature is split length-wise and as much as necessary transversally.
  • The anterior fascia leaf is split in a cross.
  • A skin cylinder with underlying fatty tissue is removed up to the fascia.
  • The extracted bowel opening is sutured to the fascia and everted with sutures  in the bowel tube, mucosa  and skin.

Follow-up

The very first stoma changes after an operation should be performed on the third postoperative day. If the stoma bandage leaks, this must be changed earlier. The change should be carried out by a stoma nurse/nurse while the patient is in the supine position. The stoma is observed for possible infection, necrotizing mucosa or abdominal wall, loosening of sutures, and for leakage of air and bowel content. Bag inflation is a signs of bowel activity. It is appropriate to use a colorless, drainable bag in the first period since the bowel content is thinner in the beginning. If a bag with a filter is used, the filter should be covered.

As soon as the patient is ready for it, the patient is trained for stoma changing/cleaning. Training should occur daily until the patient has mastered it.

Transverse colostomies and ileostomies can be closed after about six weeks. For closing of ileostomy, there is a higher chance of postoperative ileus and possibly also for bowel leakage than with colostomy.

For Hartmann's operation, the goal in some instances is to perform a re-anastomosis of the bowels and to avoid permanent stoma.

Complications of stoma

Early

  • Infection in the subcutaneous tissues occurs relatively often and more commonly with obesity.
  • Necrotizing of mucosa or the entire abdominal wall occurs more frequently in patients with a thick subcutaneous fat layer.
  • Loosening of eversion sutures along the edge occurs relatively frequently.
  • Retraction of stoma to the skin level or under occurs relatively rarely, but more frequently for loop colostomy. Retraction can cause overflow to the disconnected bowel. This is especially unfortunate in fistula relief.
  • Colo-cutaneous/ileo-cutaneous fistulas occur rarely.

Delayed

  • Peristomal hernia is a complication where the stoma bulges out like lump on the skin. This can make attachment of the stoma bag more difficult and the stoma may have to be moved.
  • Stenosis in the stoma opening occurs relatively rarely. It occurs if the bowel opening is not adequately inverted or if the tip of the stoma necrotizes down to or under the skin level.
  • Retraction of the stoma down to or under the skin level occurs relatively rarely.
  • Prolapse of stoma is a relatively rare complication where the bowel turns itself 10 cm or more out through the stoma opening. This happens most often in transverse colostomy stomas. The herniation can cause increased pressure to the bowel vessels through the abdominal wall and possible cause bowel necrosis. This complication can be treated conservatively but may relapse.
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Drug therapy of ovarian and fallopian tube cancer

The goal of chemotherapy is to treat macroscopic and microscopic metastasis. 

Ovarian cancer

Epithelial ovarian cancer

For epithelial ovarian cancer in stage I, randomized studies have shown that postoperative chemotherapy can reduce the risk for recurrence and improve survival in patients having a significant risk for recurrence. Clear-cell tumors and moderately differentiated tumors have a high risk for recurrence. Aneuploid tumors also have a significantly higher risk for recurrence. The difference in frequency of recurrence related to stage Ia, Ib, and Ic is modest, however, especially compared to ploidy analysis.

The patient is evaluated according to a low/high risk group:

  • Low risk: Stage 1a–c, grade 1–2, non clear-cell type and diploid
  • High risk: All grade 3, all clear-cell, all aneuploid

Low risk patients are not given postoperative chemotherapy if they are staged correctly and operated radically. All patients in the high risk group are offered adjuvant chemotherapy. Standard treatment is currently carboplatin and paclitaxel combination therapy, and is given over 3–6 cycles. In a randomized study where the effect of 3 versus 6 cycles was assessed, no difference in survival was found between 3 and 6 cycles.

Patients with stage II-IV ovarian cancer are offered chemotherapy. Standard treatment is carboplatin and paclitaxel given over 6 cycles. No data are available supporting more than 6 cycles, dose escalation, or addition of a third drug. Patients with reduced general health condition and/or elderly may be offered treatment with carboplatin alone. Patients with significantly reduced kidney function may be offered paclitaxel or liposomal doxorubicin (Caelyx®) alone.

A phase III study of neoadjuvant chemotherapy of patients in stage IV or stage III with uncertain resectability of the tumor was recently published. This study  set up by EORTC concluded that neoadjuvant chemotherapy followed by interval debulking was no worse than primary debulking surgery followed by chemotherapy treatment in "bulky" in stage IIIc and IV patients. Complete resection of all macroscopic tumor disease was, regardless of neoadjuvant chemotherapy or primary surgery, the most important prognostic factor. Patients in stage IIIa, IIIb, IIIc and IV that are considered to be radically operable should undergo primary surgery. For patients with reduced general health condition, neoadjuvant chemotherapy can be offered.

Two prospective randomized studies, GOG-218 and ICON7, also recently published, investigated whether the angiogenesis inhibitor Avastin® combined with standard treatment with carboplatin and paclitaxel, improved progression-free survival. PFS was one of the endpoints. Addition of Avastin® gave a significantly better median PFS of 3.8 months and 1.8 months respectively. However, it is still too early to evaluate the effect on long-term survival. The side effects of Avastin® combined with carboplatin and paclitaxel were tolerable. At present, it cannot be predicted whether the combination of carboplatin, paclitaxel, and Avastin® will be the new standard treatment for advanced ovarian cancer. A decision will not be made until long-term surival and cost-benefit analyses are published.

Intraperitoneal chemotherapy (IP) may be appropriate for patients with no macroscopic tumor or only minimal changes remaining after surgery. A Cochran review concluded that with IP, a significantly prolonged long-term survival and progression-free survival was achieved in patients with optimal tumor-reducing surgery in stage I. Toxicity, especially neurotoxicity, and the risk for complications are significant. 

Chemotherapy generally has little effect on borderline tumors and adjuvant chemotherapy is not offered. In selected cases, it may be appropriate to try treatment with carboplatin and paclitaxel. 

The following chemotherapies are recommended by Oslo University Hospital for advanced ovarian cancer:

  • Combination regimen of carboplatin and paclitaxel in 6 cycles. The recommended dose for carboplatin AUC = 5-6 and paclitaxel 175mg/m² body surface area given over 3 hours every 3 weeks.
  • In cases where the patient does not tolerate this combination, carboplatin alone is given (AUC=5-6)
  • Patients hypersensitive to paclitaxel can alternatively be given docetaxel (Taxotere®), gemcitabine or liposomal doxorubicin (Caelyx®)  
  • Fit patients, adequately operated in stage III may be considered for IP with cisplatin or paclitaxel. 

We strive to include as many patients as possible in clinical studies.

Non-epithelial ovarian cancer

Types:

  • Rare germ cell tumors (endodermal sinus tumor, embryonal carcinoma, polyembryoma, choriocarcinoma, immature teratoma grade 3, mixed types, dysgerminomas, and immature teratoma grade 1-2)
  • Sex cord thecomas/fibromas (granulosa cell tumors, Sertoli-Leydig cell tumor and thecoma)

Non-epithelial ovarian cancer is generally more sensitive to chemotherapy than epithelial ovarian cancer, with the exception of granulosa cell tumors. 

For non-epithelial stage 1a, the preferred treatment is adjuvant chemotherapy with BEP (bleomycin, etoposide, cisplatin) appropriate for:

  • endodermal sinus tumor
  • embryonal carcinoma
  • polyembryoma
  • choriocarcinoma
  • immature teratoma grade 3 
  • mixed types

Adjuvant treatment is usually not given for:

  • dysgerminoma
  • immature teratoma grade 1–2 ,
  • granulosa cell tumor
  • Sertoli-Leydig cell tumor 
  • thecoma 

In advanced stages with remaining tumor after surgery, 3 cycles of BEP are given (cisplatin, etoposide, bleomycin), followed by 1 to 3 cycles of EP.

Fallopian tube cancer

Fallopian tube cancer is treated the same way as epithelial ovarian cancer.

Treatment of recurrence

Recurrence of epithelial ovarian cancer is separated into early and late recurrence.

Early recurrence occurs within the first 6 months after finished primary treatment and is considered resistant to platinum based chemotherapy. Further treatment of these patients will be palliative. Treatment with other types of chemotherapy than those used for primary treatment may be appropriate. 

Liposomal doxorubicin (Caelyx®) and topotecan are the two best documented chemotherapy drugs for this type of situation. In phase II studies, gemcitabine has shown response rates and progression-free survival equivalent to liposomal doxorubicin (Caelyx®) and topotecan. Weekly paclitaxel has also shown an equivalent effect in phase II studies, and has a favorable side effect profile. Hormonal treatment with tamoxifen appears to have a certain stabilizing effect.  

Late recurrence occurs after 6 months subsequent to finished primary treatment and is considered platinol-sensitive. There is a high likelihood for response to re-treatment with carboplatin combination treatment.

The best treatment is liposomal doxorubicin and carboplatin (CD). A prospective randomized study compared CD to carboplatin and paclitaxel (CP) and showed an improved median PFS of 11.3 months compared to 9.4 months (p = 0.005). It is still too early to draw conclusions regarding long-term survival. The most significant side effects for CD were hand and foot syndrome, nausea, and mucositis, while for CP, side effects were alopecia and neuropathy.

The second alternative to CD and CP is carboplatin with gemcitabin and liposomal doxorubicin with trabectedin.

If combination treatment is not tolerable, carboplatin alone is given.

Patients with non-epithelial ovarian cancer who have not been given chemotherapy as primary treatment are treated with BEP. In the case of BEP resistance, the patient can be offered treatment with POMB-ACE. High-dose treatment may be appropriate in some cases. 

Recurrence of fallopian tube cancer is treated the same way as recurrence of epthelial ovarian cancer.

PROSEDYRER

Gyn_BEP

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Sun Exposure under Drug Therapy

General

Correct information about the possibility of sunbathing may affect patients health and quality of life.

Precautions in connection with sunbathing should be followed under medical cancer treatment and for 2-3 weeks after end of treatment.

Drug cancer treatment includes chemotherapy, antibodies and other drugs used in cancer treatment.

Indication

Sun exposure in connection with drug cancer treatment.

Goal

Prevent sun damage of the skin during and after cancer drug treatment.

Definitions

Photosensitivity

Increased sensitivity to ultraviolet light have been associated with certain drugs used in cancer treatment. Photosensitivity reactions can be expressed in various ways. They can be phototoxic, which is by far the most common, or photoallergic (8,14). Druginduced photosensitivity is mainly caused by wavelengths in the UVA range, but UVB rays may also be involved (8).

Phototoxicity

A phototoxic reaction is reminiscent of a reinforced sunburn, with redness, edema, pain and increased sensitivity in sun-exposed areas of the skin. This is caused by a photochemical reaction of a photosensitive drug and irradiation of sunlight on the skin, which leads to skin cell death. In severe cases, blistering can occur (14). Symptoms may appear immediately or as a delayed inflammatory reaction (3). Higher doses of medication will give an increased risk of skin reaction (14). Healing of skin area will often lead to a hyperpigmentation that can last from weeks to months before they might disappear (8). Although the incidence of drug-induced photosensitivity is unknown, phototoxic reactions is possibly more common than is diagnosed or reported.

Photoallergy

An immunological reaction usually occurring 24-72 hours after sun exposure. The reaction degenerates as an itchy, eczema-like eruptions. In acute cases, one can see rash liquids. The prevalence of eczema is usually limited to sun-exposed skin, but can in severe cases spread to larger areas of the body. Unlike a phototoxic reaction, photoallergy is less dependent on the dose of the causative drug (8).

Photoinstability

Some drugs can be degraded when exposed to light. This can happen both before administration and when the drug is circulating in the body. This degradation can cause redness/rash and edema of the skin. This applies especially for dacarbazine (9). It is unknown whether the effect of the drug is affected and it is therefore recommended that one avoids direct sunlight as long as the drug is active in the body.

PPE ( palmoplantar erythrodysesthesia = Acral erythema )

PPE is also called hand-foot syndrom. The condition starts with altered skin sensation that develops into burning pain, swelling and redness of palm of the hands and soles of the feet. The symptoms can also occur in other parts of the body that is subjected to pressure, for example under tight clothing. In severe cases large blisters and ulceration can develop. The pain can be so severe that daily activities is limited.

PPE is often seen with liposomal doxorubicin (Caelyx®) and high dose cytarabine, but may in principle occur with any anthracyclines, taxanes and fluorouracil (5- FU® ) (9,14) .

Acne-like rash

Pimple-like eruptions in skin areas with a lot of sebaceous glands such as the face, scalp, chest and neck. In contrast to common acne, the liquid-filled blisters does not contain any bacteria (9,10,15).

Hyperpigmentation

Hyperpigmentation is a common side effect in patients receiving chemotherapy, especially alkylating drugs and antibiotics with cytostatic effect. The area that has increased pigmentation may be localized or diffusely distributed. It can occur in the skin, mucous membranes, hair and nails. Pigment changes can be normalized upon discontinuation of the drug, but it may also persist.

Fluorouracil is one of the most common drugs which can provide hyperpigmentation. Others are; metotrexate, busulfan, doxorubicin liposomal, Hydroksyurea®, procarbazine, bleomycin, cyclophosphamide, doxorubicin , ifosfamide, tegafur, mitoxantrone, daunorubicin, fluorouracil, cisplatin, carmustine, thiotepa, docetaxel, vinorelbine, vincristine, imatinib and combination regimens (14).

An increased pigmentation in sun-exposed areas with the use of methotrexate, fluorouracil and capecitabine is described (16,17,18). Beyond that there is little evidence in the literature  that hyperpigmentation aggravates by sun exposure.

Radiation Recall Dermatitis (RRD)/Photo Toxic recall reaction

Flares of an inflammatory skin reaction in an area of ​​previous radiation damaged skin resulting from sunburn or external radiation. RRD can occur from months to years after the initial radiation damage.

Drugs that can provide RRD are; bleomycin, capecitabine, cyclophosphamide, dactinomycin, cytarabine, daunorubicin, docetaxel, doxorubicin liposomal, doxorubicin, etoposide, fluorouracil, gemcitabine, Hydroksyurea® , idarubicin, lomustine, melphalan, methotrexate, paclitaxel, tamoxifen and vinblastine (14). EGFR inhibitors (cetuximab , gefitinib and erlotinib) may also cause other skin reactions that may be exacerbated by sun exposure (9,10,19).

Preparation

The patient is given written and verbal information by the medical responsible doctor and nurse at the start of the drug cancer treatment, and it is repeated as necessary.

Implementation

General Precautions

Prevention and protection:
  • Limit sun exposure during the first days after the cure.
  • Observe skin daily to detect any skin reactions early.
  • Avoid getting sunburned.
  • View extra care between 12.00-15.00 (2).
  • Wear protective clothing and headgear (2,3,4,5,6).
  • Wide-brimmed hats protect better than caps (2.4).
  • Please note that the window glass does not protect against UVA rays (7).
  • Use sunscreen; to protect against UVA and UVB rays, a minimum SPF 15 (3,4,6,8) is applied several times daily.
  • Use mild skin care products without perfumes.

In case of an eruption, sun exposure (including solarium) should be avoided until the skin is healed. Adverse skin reactions can be alleviated with moist and cooling compresses. Mild cortisone salves can also be highly effective. For very severe cases, systemic cortisone might be necessary (3,6,7,9).

When a photosensitive reaction occurs, it is important to consider what other medications the patient is receiving which can also trigger such reactions. For example, steroids, some antibiotics, diuretics and NSAIDs.

Medicaments that most commonly cause skin reactions

Medicament Common reactions Remedial action
Dakarbazin (DTIC)


Phototoxic/photoinstability
See general precautions
Redness in skin, tingling of the scalp and general unwellness
Avoid sunlight completely the day of the treatment (9)
Methotrexate
Phototoxic

See general precautions
Acne-like rash
Avoid direct sun exposure, heat and humidity (9,10). Avoid soap, alcohol based skin products (9). Use moisturizing products and oil bath (4,9,10).
Palmoplantar erythrodysesthesia = Acral erythema (PPE)

Preventive: Pyridoxin (vitamine B6) (2,6,9)

Avoid sunlight, heat, pressure against the skin and tight clothing can according to some studies have an effect (11,12,13). Use moisturizer.

Treatment/relief: Cortisone salves, cortisone tablets, cold compress, cold baths

(2, 9)

Fluorouracil (5-FU®)

 

Phototoxic See general precautions
Palmoplantar erythrodysesthesia = Acral erythema (PPE) Preventive: Pyridoxin (vitamin B6) (2,6,9)

Avoid sunlight, heat, pressure against the skin and tight clothing can according to some studies have an effect (11,12,13). Use moisturizer.

Treatment/relief: Cortisone salves, cortisone tablets, cold compress, cold baths   (2, 9)

Radiation recall
Treatment as with phototoxic

Kapecitabin (Xeloda®)

 

Phototoxic See general precautions
Palmoplantar erythrodysesthesia = Acral erythema (PPE)

Preventive: Pyridoxin (vitamin B6) (2, 6, 9). Preventive: Pyridoxin (vitamin B6) (2, 6, 9)

Avoidance of sunlight, heat, pressure against the skin and tight clothing can according to some studies have an effect (11,12,13). Use moisturizer.

Treatment/relief: Cortisone salves, cortisone tablets, cold compress, cold baths (2, 9)

Vinblastin

 

Phototoxic
See general precautions
Radiation recall Treatment as with phototoxic
Doxorubicin liposomal (Caelyx®)
Palmoplantar erythrodysesthesia = Acral erythema (PPE) Preventive: Pyridoxin (vitamin B6) (2, 6, 9)

Avoidance of sunlight, heat, pressure against the skin and tight clothing can according to some studies have an effect (11,12,13). Use moisturizer.

Treatment/relief: Cortisone salves, cortisone tablets, cold compress, cold baths (2, 9)

Tegafur

 

Phototoxic
See general precautions
Palmoplantar erythrodysesthesia = Acral erythema (PPE) Preventive: Pyridoxin (vitamin B6) (2, 6, 9)

Avoidance of sunlight, heat, pressure against the skin and tight clothing can according to some studies have an effect (11,12,13). Use moisturizer.

Treatment/relief: Cortisone salves, cortisone tablets, cold compress, cold baths    (2, 9)

EGFR-hemmere

(Cetuximab, panitumab, erlotinib, gefitinib, lapatinib, vandetanib)

Phototoxic
See general precautions
Acne-like rash
Avoid direct sun exposure, heat and humidity (9,10). Avoid soap, alcohol based skin products (9). Use moisturizing products and oil bath(4, 9, 10).

Beyond the medications listed in the table the literature gives som evidence that these substances may cause phototoxic skin reactions :

  • paclitaxel (Taxol®)
  • docetaxel (Taxotere®)
  • hydroxycarbamide ( Hydroksyurea® )
  • imatinib ( Glivec® ) and Dapson® and that paclitaxel can provide radiation recall .

References


  1. LOV-1999-07-02-63 Pasientrettighetsloven - pasrl. Lov om pasientrettigheter.
  2. Polovich M, White JM, Kelleher LO. Chemotherapy and biotherapy guidelines: recommendations for practice. Pittsburgh, PA: Oncology Nursing Society; 2005.
  3. González E, González S. Drug photosensitivity, idiopathic photodermatoses,and sunscreens. J Am Acad Dermatol 1996;35:871-85;quiz 886-7.
  4. Liffrig, JR. Phototrauma prevention. Wilderness Environ Med 2001;12:195-200.
  5. Tan E. Skin toxicity of chemotherapy drugs [created 2007, last updated  2010 Mar 5]. Hentet 1. desember 2010 fra: http://dermnetnz.org/reactions/chemotherapy-toxicity.html
  6. Gould JW, Mercurio MG, Elmets CA. Cutaneous photosensitivity diseases induced by exogenous agents. J Am Acad Dermatol 1995;33:551-73.
  7. Payne, AS & Bernandin, RM. Sunburn [topic last updated 2010 Oct 06]. I: BMJ Best Practice. Hentet 23. november 2010 fra http://bestpractice.bmj.com
  8. Zhang AY, Elmets CA. Drug-induced photosensitivity [updated 2010 Jan 15]. Hentet 1. desember 2010 fra: http://emedicine.medscape.com/article/1049648-overview
  9. Ulrich J, Hartmann JT, Dörr W, Ugurel S. Skin toxicity of anti-cancer therapy. J Dtsch Dermatol Ges 2008;6:959-77.
  10. Agero AL, Dusza SW, Benvenuto-Andrade C, Busam KJ, Myskowski P, Halpern AC.Dermatologic side effects associated with the epidermal growth factor receptor inhibitors. J Am Acad Dermatol 2006;55:657-70
  11. Alley E, Green R, Schuchter L. Cutaneous toxicities of cancer therapy. Curr Opin Oncol 2002;14:212-6.
  12. Mangili G, Petrone M, Gentile C, De Marzi P, Viganò R, Rabaiotti E. Prevention strategies in palmar-plantar erythrodysesthesia onset: the role of regional cooling. Gynecol Oncol 2008;108:332-5.
  13. Tanyi JL, Smith JA, Ramos L, Parker CL, Munsell MF, Wolf JK. Predisposingrisk factors for palmar-plantar erythrodysesthesia when using liposomal doxorubicin to treat recurrent ovarian cancer. Gynecol Oncol 2009;114:219-24.
  14. Payne AS, Savarese DMF. Cutaneous complications of conventional chemotherapy agents. I: UpToDate [version 18.2 2010]. Hentet 1. desember 2010 fra: http://www.uptodate.com
  15. Heidary N, Naik H, Burgin S. Chemotherapeutic agents and the skin: an update. J Am Acad Dermatol 2008;58:545-70.
  16. RELIS Sør. Hyperpigmentering av cytostatika og forverring av sollys. I: RELIS database 2010, Spm.nr 4736. Hentet 1. desember fra: http://relis.arnett.no/Utredning_Ekstern.aspx?Relis=2&S=4736
  17. Hendrix JD Jr, Greer KE. Cutaneous hyperpigmentation caused by systemic drugs. Int J Dermatol 1992;31:458-66.
  18. Schmid-Wendtner MH, Wendtner CM, Volkenandt M, Heinemann V. Clinical picture: leopard-like vitiligo with capecitabine. Lancet 2001;358(9293):1575.
  19. Segaert S, Tabernero J, Chosidow O, Dirschka T, Elsner J, Mancini L, et al. The management of skin reactions in cancer patients receiving epidermal growth factor receptor targeted therapies. J Dtsch Dermatol Ges 2005;3:599-606.

Preparation of Chemotherapy, Spills, and Cleaning a LAF Bench

General

Preparation of chemotherapy outside of a pharmacy

At Oslo University Hospital, the pharmacy primarily prepares chemotherapy for each patient. If it is necessary to dilute/mix the medicine at the department, then this should occur in a designated room with a LAF bench (laminar airflow bench). Many chemotherapy drugs are carcinogenic and teratogenic, and it is extremely important for health personnel to follow directions for preparation of of these medications. At Oslo University Hospital, all chemotherapy should be prepared and administered by a nurse who has completed a cytostatic treatment course at Oslo University Hospital, or by nurses who are certified cancer nurses from Oslo University College.

Pregnant women and employees under physician orders not to temporarily or permanently work with chemotherapy drugs, should not handle or be exposed to these chemicals. Nursing mothers may handle chemotherapy drugs as long as they follow the general guidelines for chemotherapy handling. For each work place, there should be written guidelines for handling of chemotherapy drugs and for first aid for spills and maintenance of fume hoods etc..

Designated room with LAF-bench to dilute/mix chemotherapy

  • The ventilation should be separate from the main ventilation and fumes should be vented to the outside and if necessary, filtered.
  • The room should be well illuminated for visual control of the fluid.
  • The LAF bench should be a workbench having sterile, filtered air from the ceiling with defined speed and an approved fume hood. The bench should be routinely tested and approved.

Goal

  • To protect nurses and surroundings from exposure to cytotoxic chemicals and to preserve the sterility of the drug.

Handling of chemotherapy spills

Chemotherapy drugs are a heterogeneous group of drugs in which many are known mutagens, teratogens and/or carcinogens. Allergic reactions have also been reported. Studies show that there is a health risk during exposure of chemotherapy drugs and there are guidelines for minimizing exposure of health personnel to these chemicals. Workers in daily contact with these drugs will be more at risk due to the increasing use of chemotherapy. Chemotherapy spills refers to spills during preparation and leakage from infusion bags.

Goal

  • To ensure that spills of chemotherapy drugs or waste materials that contain these chemicals are handled in a safe way to protect health and safety.

Cleaning of LAF-bench

The Norwegian Work Authority recommends that each workplace should have written guidelines for handling chemotherapy drugs, first aid for spills, and maintenance of fume hoods etc. A LAF-bench (laminar airflow bench) is a bench protecting workers from the drug being prepared and also protects from microbiological organisms. Those who carry out cleaning should have training and knowledge of the risk for exposure to chemotherapy drugs.

Goal

  • Maintain a clean LAF bench
  • Avoid contamination and preserve the sterility of the drug 
  • Protect people and surroundings from exposure

Source

Applicable directives and guidelines (www.lovdata.no)

  • Warn against exposure to chemicals at the workplace (Kjemikalieforskriften §24), mandated by The Norwegian Labour Inspection Agency from 5 May 2001, last edition from 26 April 2005.
  • Guidance for chemical directives attachment VII Cytostatica from September 2003 (www.arbeidstilsynet.no).

Equipment

  Preparation of chemotherapy in a hospital

  • 2 pairs of gloves: vinyl gloves inside and sterile, powder-free latex gloves outside
  • Protective coat with long arms/plastic apron
  • Arm protectors
  • LAF bench
  • Dilution fluid
  • Syringes and cannulas
  • Sterile compresses
  • Disposable cloths
  • 70% ethanol
  • Absorbent benchcoat with plastic underside for the work bench
  • If a LAF bench is not used, use a protective mask with aerosol filter and protective goggles.

Handling of chemotherapy spills

Spill kit includes:

  • 2 pairs of nitrile gloves, long
  • 2 pairs of latex gloves, long
  • 2 pairs of shoe covers
  • Plastic coat\apron
  • 1 mask
  • 2 diapers
  • 1 bed absorbent bed sheet
  • 2 plastic bags with zippers (30 x 40 cm)
  • 4 thin, white plastic bags (60 x 90 cm)
  • Absorbant material   
  • 8 disposable wash cloths

Washing of LAF-bench

  • Plastic apron
  • Arm protectors
  • Gloves: either double vinyl gloves or special gloves
  • Disposable cloths
  • 70% ethanol
  • Bucket and soapy water
  • Waste container with plastic bag for chemotherapy waste (biohazardous waste)

 

 

Preparation

Preparation of chemotherapy outside of the pharmacy

For preparation of chemotherapy drugs, use gloves and a protective lab coat with long arms or tight-fitting cuffs.   Use two pairs of gloves where the inner pair is vinyl or other latex-free material. The outer glove should be sterile and of latex or other material which is impenetrable.  The gloves are recommended to be changed every half hour for preparation of chemotherapy drugs, and right away with spills.

  • Start the LAF-bench a minimum of 30 minutes before use.
  • Wash hands
  • Put on the inner gloves
  • Disinfect the work surface with 70% ethanol
  • Cover the work surface with a benchcoat. This should not cover the vent; otherwise, the bench will not function properly.
  • Read the dilution directions and find the necessary equipment and medications as described.
  • Choice of dilution system/fluids
    • A transfer cannula should be used in preference to a syringe where possible to maintain a closed system as much as possible.
    • If a syringe is used: use a syringe with Luer lock connection. These have a better connection between the syringe and the cannula.
  • Check the expiration on the drug packaging and infusion fluid.
  • Check that the drug in liquid form does not contain particles or visible solids.
  • Check that the packaging does not have any cracks or leakages.
  • Perform necessary calculations, date, and sign the work form.
  • Obtain another nurse to double check: right patient, work form, drug, dosage, fluid type and volume, as well as calculations.  All checks should be against the original ordination. The person doing the check should sign and date it.
  • Set out necessary equipment on the LAF-bench or where the work will take place. The equipment should be placed in the corner within the ventilation of the LAF-bench.  Remove the outer packaging of the sterile gloves and lay the gloves on the bench.
  • Put on the protective clothing (coat/apron and arm protectors)
  • Put on the sterile gloves in the bench
  • Disinfect the rubber membrane on the infusion bag and hood windows as well as the ampules.
  • Make sure the protective glass on the LAF-bench is pulled down to the correct work level as recommended by the manufacturer of the bench.

Handling of chemotherapy spills

All, except the workers who clean the spill, should leave the room.  Preferably, two people should help each other to remove the spill.  This way, one can ensure that proper precautions are taken.

At Oslo University Hospital, a packet is available from the pharmacy for chemotherapy spills.

Washing of LAF-bench

  • The LAF-bench should be operating under cleaning.
  • The sash should be down, as under normal working conditions.
  • Use a plastic apron, arm protectors, and gloves.

 

 

Implementation

Preparation of chemotherapy drugs outside of a pharmacy

Aseptic procedure

  •   To avoid turbulence of the sterile, laminar air stream:
    • Work at least 15 cm inside the perforation with steady movements
    • Avoid hands or other objects from coming between the airflow and the medicine.
  • Make only one medicine at a time.
  • A full syringe or finished bag should be labeled for the next preparation.  The label should be labeled with the patients name, birthdate, drug and dosage, preparation date, expiration, and the name of the person who prepared and checked the medicine.
  • Avoid spills and aerosol formation
    • Use a dry, sterile compress around neck of the ampule when it is broken.
    • When the cannula is removed from the syringe, hold a sterile compress around the barrel neck to catch any spills.
    • Hold the syringe/ampule such that the opening is directed away from the face.
    • For solid substances, solvent should be added along the glass wall to avoid whirling of particles.
    • With positive/negative pressure in the hood glass: apply a filter cannula first to reduce pressure.
    • With use of adapter: place adapter first in the infusion bag and connect to the hood glass with medicine.
    • When the air is removed from the syringe, place the cannula cap on the cannula again while the syringe is held vertically with the cannula upright. A sterile compress should be held around the opening between the cannula and the syringe to collect spillage.
    • Clean up spills at once
  • After each addition, the contents of the infusion container should be mixed well by inverting and repeating 5-6 times.
  • Infusion fluid which has been added to should be marked satisfactorily.
  • The finished solution should be scrutinized for solid or foreign particles. All solid should be dissolved.
  • If visible changes occur under the mixing procedure, the physician should be contacted and the fluid should not be used. Store the infusion fluid and packaging of the added drug and contact the pharmacy (chemist) for further clarification.
  • All used equipment should be rolled up in the benchcoat (alternatively, all used equipment can be placed in a plastic bag which can be tied or closed with zipper) and disposed of in box with plastic bag for chemotherapy waste/biohazardous waste.
  • LAF-bench should be stopped at least 30 minutes after use.

Multiple additions

  • Addition of multiple drugs for chemotherapy solutions should be avoided. If it is still appropriate, there should be clear documentation of the mixture.
  • Different chemotherapies can mix if their mixing properties are documented (and checked with pharmacist).

Handling of chemotherapy spills

  • Use two pairs of disposable latex\nitrile gloves, plastic coat, mask, shoe covers (used with floor spills) and protective goggles.
  • Lay the smallest diaper in the middle of the spilled fluid. Then, place the absorbent bed sheet over the diaper and the rest of the fluid. Use more diapers and absorbent material if necessary.
  • Dispose of used diapers, absorbent material, bed sheets, and gloves is appropriate waste container, which can be closed.
  • Use new gloves and wash thereafter with soapy water and disposable wash cloths a minimum of three times. Use a new cloth before each wash. Used cloths should not be put back in the wash solution.  Used cloths and gloves should be disposed in the appropriate waste containers (in plastic bags which can be closed).
  • The plastic bags with used equipment should be disposed of in the appropriate containers which are properly labeled.

Washing of LAF-bench

  • Other than a cannula bucket, nothing should be stored in the bench after the last preparation.
  • Washing with 70% ethanol is sufficient if there are no visible spills.
  • For visible spills, wash the bench with soapy water and spray afterwards with 70% ethanol (see procedure under). Soapy water is the most effective for removing chemotherapy spills.

Routine washing

  • Washing should be done every 1-4 weeks depending on frequency of use.
  • Spills and dust pose risks for washing.
  • It is important that any remaining solution of chemotherapy is not spread under washing.
  • Use disposable cloths.
  • To avoid contamination of washing water, the washing hand should not be dipped in the water.
  • Wash with slow movements and use a new cloth as needed.
  • Cloths that have been in contact with the bench should not be put back in the washing water and should be discarded in proper waste container.
  • Wash first the walls from top to bottom with soapy water (the cleanest to the most contaminated) – place the cloth on a squeegee for hard-to-reach areas.
  • The filter in the ceiling of the bench should not be washed.
  • Wash the work surface in the bench – wash from back to forward (from the cleanest to the most contaminated).
  • Raise the work surface.
  • Wash the work surface on the underside, especially the closest, perforated part.
  • Then wash the underside bottom of the work surface.
  • Wash thereafter all surfaces (not the ceiling) with 70% ethanol.
  • Remove protective clothing.
  • Discard all protective clothing for one-time use and washcloths in the appropriate waste container.
  • Wash hands.
  • Replace the cannula bucket.
  • There should be a record for bench washing; the employee who washes should sign and date the record.

Follow-up

Aerosol formation with spraying or squirting can occur:
  • when a syringe is used and cannula is retracted for transfer
  • when an ampule is broken
  • when air is removed to measure volume
  • with a leak in a syringe or IV catheter
  • with waste handling

First aid if contact with chemotherapy drugs

  • Skin: Rinse well with water for 15 minutes. Wash contacted area with regular soap.
  • Eyes: Rinse well with water, or use spray bottle with NaCl 9 mg/ml (at least 20-30 minutes of continual rinsing).
  • Contact a doctor.

Radiation therapy of ovarian and fallopian tube cancer

Radiation therapy is seldom indicated for epithelial ovarian cancer and fallopian tube cancer. In some cases, it may be appropriate to give palliative radiation treatment. This applies to tumors that have ruptured the vagina and cause bleeding. Radiation therapy is also given in cases of brain metastases.

Non-epithelial ovarian cancer is generally sensitive to radiation therapy, but is only used in rare cases. Radiation therapy may be considered for treating recurrence, since these tumors are radiosensitive.

Complication treatment of ovarian and fallopian tube cancer

Surgery, chemotherapy, and radiation therapy cause side effects to varying degrees.

It is usually necessary to provide supportive care in order for the patient to complete the planned treatment and obtain its full effect.

Supportive care can also be provided to reduce side effects and improve the patient's quality of life during and after treatment.

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Nutrition during Cancer Treatment

General

Monitoring the patient's nutritional status is an important part of cancer treatment. The goal is to identify malnutrition as early as possible in order to initiate treatment as quickly as possible.

Measures include diet according to symptoms and the nutritional condition. The patient should be offered nutrition-rich food, snacks, nutritional drinks, tube feeding and intravenous nutrition.

Because cancer treatment breaks down both cancer cells and normal cells, the body requires an adequate supply of nourishment to increase growth of new cells. 

In cancer patients, the sensation of hunger is not always present to the necessary degree. In these cases, it is important to take actions to improve the nutritional status of the patient. The nutritional condition is easiest followed by monitoring body weight over time.

Indication

  • Cancer treatment (chemotherapy, radiation, surgery).

Goal

  • Maintain nutritional status in order for the patient to have the best possible conditions for implementing treatment.

Definitions

Subjective Global Assessment (SGA)

Subjective Global Assessment (SGA) is a scheme for classifying the patient's nutritional status.

Other tables that are frequently used are Malnutrition Universal Screening Tool (MUST), Mini Nutritional Assessment (MNA) and Nutrition Risk Score (NRS). In principle, these schemes are prepared in the same way as SGA, but they are not validated for patients with cancer.

Weight loss is one of the most important signs of change in nutritional status. A weight loss of more than 15% over the past 6 months or more than 5% over the last month is a significant and serious weight loss. If the weight loss occurs in combination with low BMI (body mass index) (< 20 kg/m2 for adults) and/or a food intake of less than 60% of the calculated requirement over the past 10 days, the patient will be malnourished or be at nutritional risk.

Calculation of nutrition and fluid requirements

  • Ambulatory patients:  30-35 kcal/kg/day
  • Bed-ridden patients:  25-30 kcal/kg/day
  • Elderly above 70 years:  Recommended amount is reduced by 10%
  • Fluid requirement:  30-35 ml/kg/day

Nutritionally enriched diet / enrichment of food and beverages

Nutritional beverages may be used as a meal in itself or between meals. Nutritional drinks can be a more valuable snack than "normal" food, because it is often easier for the patient to drink than to eat. It has been shown that if nutritional drinks are introduced as snacks, it does not affect the energy intake during the main meals.

There are a number of ready-made nutritional drinks on the market. Some of the products are of nutritionally complete. They contain carbohydrates, protein and fat and are supplemented with all the necessary vitamins, minerals and trace minerals and possibly fiber. Some of these products can be used as the sole source of nutrition. The energy content varies from 85-200 kcal/100 ml and some products have a high protein content. Other nutritional drinks are supplement drinks adjusted to individual needs such as allergies, intolerance and special conditions associated with illnesses.

The products are also adapted to age, and the dose is determined individually by a clinical dietician/doctor.

Many patients prefer homemade nutritional drinks based on full fat milk, cream, ice cream, fruit and possibly flavor supplements. These are free of additives and have a fresher taste. The energy and protein content is close to the commercial products and at the same time they are more sensibly priced.

Tube feeding

Tube feeding is preferable to total parenteral nutrition (TPN) when the digestive system is working. Nutrition supply to the intestine is more physiological. It protects against bacterial growth, maintains the intestine's mucous membrane structure and function, and promotes motility. Tube feeding involves less risk of metabolic complications.

Tube feeding is used in the event of

  • insufficient food intake (less than 60% of energy requirements) over the past 5-7 days despite oral intake
  • weight loss >2 % over the past week, >5 % over the past month or >10% over the past 6 months
  • danger of weight loss due to planned treatment
  • low albumin values (under 35 g/l, lower limit for normal area)
  • stenosis with feeding obstacles in pharynx/gullet

Tube feeding must not be used for the following conditions.

  • Paralysis or ileus of the alimentary tract
  • Short bowel syndrome
  • Serious diarrhea
  • Serious acute pancreatitis
  • Obstruction of the intestine
  • Serious fluid problems

Tube feeding solutions

The tube feeding solution must be nutritionally complete because they shall be used as the sole source of nourishment. The most frequently used are standard (1 kcal/ml), fiber-containing (1 kcal/ml) or energy-rich (1.5 kcal/ml). There are also tube feeding solutions which are adapted to patients with digestion and absorption problems, patients with diabetes or lactose allergy, and intensive care patients.

Tube feeding solutions, which are adapted to cancer patients are energy-rich (1.5 kcal/ml). They contain extra omega-3 fatty acids, rich in MCT acid and enriched with extra vitamins and minerals. Recommended dosage is 500 ml/day.

Parenteral nutrition

Parenteral nutrition should only be used if food by mouth or tube feeding cannot be maintained. Parenteral nutrition can also be used as a supplement to tube feeding or ordinary food. 

Precautions must be taken for kidney failure, heart failure, lung failure, large fluid and electrolyte loss, diabetes mellitus and liver failure.

Preparation

The patient is classified as well-nourished, somewhat malnourished or seriously malnourished on the basis of information about weight development, food intake, symptoms and physical functioning. This classification has been shown to correlate well with more objective measurements of nutritional status and morbidity, mortality and quality of life.

Actions include individual adjustment of diet according to symptoms and nutritional status.

Tube feeding

The end of the tube is often inserted into the stomach. In the event of poor gastric function, total gastrectomy or pancreatic resection, the feeding tube should be inserted in the duodenum or jejunum. The position of the feeding tube is vital for the choice of feeding-tube solution and mode of administration.

The most common solution is to insert the tube nasogastrically, but it can also be done through the abdominal wall (PEG).

Parenteral nutrition

It is preferable to use intravenous or parenteral nutrition as a supplement to oral/tube feeding instead of only TPN (total parenteral nutrition).

  • Central veins must be used for TPN with high osmolality.
  • Peripheral veins can be used for short-term parenteral nutrition. In this case, a large vein on the forearm is used and a small needle. Nutrition is then given as more diluted solutions.

Implementation

All patients are weighed regularly (1–2 times each week). This is a prerequisite to being able to register changes in the nutritional status.

Varied and healthy food contributes to the growth of new cells and enhances the immune system.

  • Fruit, berries and vegetables are rich in vitamins, minerals, antioxidants and fiber, which contribute to enhances the immune system and contributes to keeping the digestive system working.
  • Fish, shellfish, poultry, meat, eggs, cheese, milk, beans and nuts are rich in proteins, which are the building blocks of new cells.
  • Bread, rice, pasta, porridge and breakfast cereals supplement the diet with proteins, carbohydrates, fiber, vitamins and minerals.
  • Oil, margarine, butter, mayonnaise products, nuts, cream, heavy cream, desserts etc. are fat and energy rich products, which are important to maintain the energy intake at a satisfactory level.
  • Cancer patients also have a requirement for plenty of fluid, especially during treatment, to discharge waste.

Often, the patients must have an individually adjusted diet. In the event of lack of appetite, it is generally more important that you eat (enough food) than what you eat (the right food). It is beneficial to have small portions and for the food to be as abundant in energy as possible. These patients will often have a need for 6–8 small meals everyday to obtain their energy requirements.

Enrichment of food and drink is done in order to increase the energy content of the food product without increasing the volume. Full-fat products such as full-fat milk, cream, butter, heavy cream, mayonnaise, sugar, honey, eggs and cheese etc. are primarily used. Enrichment powders from pharmacies may also be used. Some powders are nutritionally complete, i.e. they contain everything the body requires in terms of energy and nutrients, while others only contain pure energy (carbohydrates, fat and/or protein). 

Tube feeding

Tube feeding is given continuously with a low drop rate or by interval/bolus administration (individually adapted meals with high drop rate).

When the patient's energy and fluid requirements are fulfilled, it will be decided whether the patient will be given bolus or continuous supply at night, in order to increase mobilization during the day. However, this requires that the patient does not have diarrhea, nausea or other complaints associated with the supply of nutrition.

For a running feeding tube:

  • Every 4-8 hours, it should be aspirated in order to monitor the gastric emptying. This applies especially to immobile and weak patients.
  • Weekly or more often, the nutrition program/fluid balance, evaluation, edema control, blood tests (albumin, K, Mg, P, blood glucose) should be monitored weekly or more often.
  • Every 4-6 weeks, the tube should be changed. Alternate the uses of nostrils avoid irritation in the nose through prolonged feeding.

Experience shows that the use of infusion pumps causes fewer side effects and ensures correct volume and rate.

Bolus supply

Initiation of tube feeding with bolus supply is only recommended

  • if the patient been taking any food until the last 24 hours
  • if the patient is taking some food and requires tube feeding for additional nourishment

It is recommended to use pumps for bolus supply for the first 1–2 days.

Continuous supply

If the patient cannot tolerate bolus supply (vomiting, abdominal discomfort, nausea, diarrhea), reverting to continuous supply should be considered.

Tube feeding should always be administered continuously to very malnourished patients or if the tube end is located distally to the pylorus.

Parenteral nutrition

If the patient has a satisfactory nourishment status, begin with 100% of the requirement. If the patient is seriously malnourished, start with 80 % of the requirement and increase slowly to 100% over the course of three days.

The patient must be monitored closely in relation to

  • electrolytes (potassium, phosphate and magnesium).
  • infusion rate.
  • twenty-four hour urine sample and fluid balance should be calculated daily.
  • glucose in the blood and urine, and electrolyte in the blood should be examined daily at the start.
  • liver tests, kidney function tests and triglycerides should be taken examined at least once every week.

For TPN treatment longer than 1 month, vitamins and trace elements should be examined.

Follow-up

The patient's nutrition status should be monitored at follow-up visits after the end of treatment.

Transfusions

General

Transfusions of blood components are often necessary for the patient to complete the planned cancer treatment.

Blood transfusions are appropriate for low hemoglobin (Hb) and thrombocyte transfusions for low thrombocytes (trc) which also poses a risk for serious bleeding.

Normal values

  • Hemoglobin 13.4–17 g/dl
  • Platelets 145–348 109/l

Indications

Blood transfusion

Assessment for a blood transfusion based on:

  • Hb/hct
  • symptoms/sign/function level
  • underlying disease (heart/lung, serious infection)
  • expected development of anemia (marrow function, current bleeding)
  • acute blood loss > 15% of total blood volume
  • Hb < 8.0 g/dl and symptom causing chronic anemia
  • Hb < 8.0 g/dl and reduced bone marrow production without sign of regeneration
  • Hb < 8.0 g/dl in perioperative period
  • Hb < 7.0 g/dl in patients without symptoms of other disease
  • Hb < 10.0 and receiving radiation therapy

Platelet transfusion

The patient is assessed for thrombocyte transfusion based on:

  • clinical status (bleeding, bleeding tendency, or fever/infection)
  • ongoing bleeding and thrombocytopenia < 50x19/l
  • degree of thrombocytopenia and cause of thrombocytopenia (reduced production or increased consumption)

Prophylactic platelet transfusion

  • For values < 10x109/l secondary to previous chemotherapy
  • Before invasive procedures
  • For spinal puncture and installation of central vein catheter, thrombocytes should be 30x109/l and 
  • Puncture biopsies (liver/kidney/tumor) > 40x109/l
  • For major surgeries, thrombocytes should be > 50x109/l. After surgery, thrombocytes should be monitored and transfusion repeated, if necessary.

Remember clinical evaluations: possible bleeding, other risk factors for bleeding, diagnosis, treatment, prognosis.

Goal

  • Complete the planned treatment
  • Ensure hemostasis 
  • Ensure adequate oxygen transport to peripheral tissue.
  • Maintain intravascular fluid volume for adequate circulations of vital organs

Definitions

Blood

For a blood transfusion for anemia, SAGMAN erythrocytes are used. One unit is obtained from 450 ml blood. Most of the plasma is removed and replaced with 100 ml SAGMAN solution (Saltwater-Adenine-Glucose-Mannitol). Hematocrit is about 0.60%.

Platelets

One unit contains 240-300 x 109 platelets and is prepared from blood donors with type O and A. In acute situations, the receiver's blood group is of minor importance.
Two kinds of platelet products are available:
  • Apheresis platelets produced from thrombophereses from one donor
  • Buffcoat platelets produced from buffy coat from 4 donors

All cellular blood products should be leukocyte filtered. Leukocyte filtration is done to remove antigen-presenting and virus-bearing cells. 99.99% of leukocytes in the unit are removed.

Radiation

Blood and thrombocytes are irradiated to a minimum of 25 Gy in the blood bank to eliminate T-lymphocytes.

This is done for:

  • Bone marrow transplant or stem cell transplant (1 month before or 3 months after HMAS until 1 year after allogeneic stem cell transplant)
  • For use of HLA-compatible platelet concentrations
  • For all transfusions from relatives
  • For use of fresh blood
  • For use of fludarabine

Preparation

Blood tests

Before the first blood transfusion, the following blood tests are performed:
  • Virus antigens
    • HCV
    • HBV
    • HIV
Every three days, and as needed, pre-transfusion tests are taken.

Compatibility

Erythrocyte concentration—Rh(D) negative products can usually be given to everyone while Rh(D) positive can only be given to Rh(D) positive receivers.

Thrombocyte concentration—Rh(D) negative girls and women in fertile ages who obtain Rh(D) positive thrombocyte products should be given a prophylaxis for Rh immunization. Boys/men and women who are over the fertile age may obtain thrombocytes regardless of Rh(D) type.

Implementation

Blood components should never be given together with other medications.
  • Premedication if the patient has reacted to previous transfusions.
  • Secure venous access
  • The blood product is checked to ensure the correct unit is given to the correct patient.
  • Use blood set with filter
  • Give SAGMAN over 1 hour and thrombocytes 20-30 minutes per unit.
  • Rinse the set with NaCl 9 mg/ml at the end of the infusion
  • Store the blood product bag for one day before discarding

Observations

The patient should be observed during the transfusion with emphasis on reactions. Most serious transfusion reactions occur within the first 20 minutes.

Symptoms of transfusion reaction:
  • chills
  • fever
  • feeling of heat in the face
  • breathing difficulty
  • itching
  • nervousness
  • fall in blood pressure
  • shock
Suspect/manifest blood transfusion reaction:
  • Stop transfusion immediately
  • Start treatment if necessary (intravenous fluid, adrenalin, steroids, oxygen, respirator)
  • Check blood bag and compatibility form. The residue should be sent to the blood bank.

Follow-up

Hemoglobin and thrombocytes are checked.

If poor effect of platelet transfusion, platelet value should be checked after approximately one hour. The value should have increased by approximately 30x109/l or more after a standard dose.

If the increase is drastically less, the cause may be:
  • Abnormally high consumption. This is an indication for more frequent transfusions.
  • Antigens against HLA or platelet-specific antigens. The patient must be examined in cooperation with the blood bank to find compatible donors.

Bone Marrow Stimulation with G-CSF

General

Bone marrow stimulation with G-CSF (Neupogen®, Granocyte®) is only recommended for febrile neutropenia which does not respond to antibiotic treatment, severe neutropenia (granulocytes < 0.5 x 109 /L for more than 1 week), and in cases where it is necessary to administer curative treatment with sufficient dosage intensity.

Indications 

  • To maintain dosage intensity for curative treatment; when a reduction in dosage will significantly reduce the chance of cure.
  • As prophylaxis for treatments associated with a high risk for febrile neutropenia (> 40 %)
  • Febrile neutropenia that does not respond quickly to antibiotic treatment
  • Long-lasting neutropenia

Goal

  • Maintain treatment intensity

Preparation

The patient should be adequately informed about the treatment.

Implementation

  • The dosage of Neupogen® is 5 µg/kg daily. The treatment is initiated, at the earliest, 48 hours after the treatment is completed. The treatment continues for 10 days.
  • The dosage of Neulasta® is 6 mg subcutaneously administered 24 hours after chemotherapy is completed. The neutrophil cells are counted on day 15.
  • The subsequent course is started on day 21, if the neutrophil count is 0.5 or higher, and the patient has not had febrile neutropenia.
  • It is important not to postpone the treatment if the neutrophil count is 0.5 or higher. The neutrophil count will compulsory decline after ending Neupogen® stimulation. Low values at the start of treatment should not be alarming if the values during hospitalization have been high enough to avoid febrile neutropenia.
  • Stimulation late in the cycle should only be performed for long-lasting, severe neutropenia. At least 48 hours should pass after completed stimulation treatment before the next chemotherapy course  is started. In these cases, it is always important to check that the doses are correct and to recalculate GFR etc. Continuation of chemotherapy will either require a drastic dosage reduction or secondary prophylaxis with G-CSF.

 

Follow-up Care

It is of utmost importance that the patient is informed of the risk of infections associated with a low neutrophil count.

Patients at risk for developing  very low values, must be  informed to take their temperature if they feel unwell or  febrile. In case of  a temperature above 38 °C they should contact their doctor immediately.

Erythropoitin (EPO) for anemia

General

Anemia with hemoglobin < 11.0 mg/l is normal during chemotherapy. This will often lead to prominent fatigue. Anemia can be treated symptomatically with transfusion of erythrocytes, or bone marrow can be stimulated with erythropoitin (EPO).

Patients with chemotherapy-induced anemia will usually have sufficient iron storage, but some may need iron supplementation. 

Anemia should normally not cause postponement of treatment. It is quickly corrected by an erythrocyte transfusion – and treatment may then be started.

Indication

  • Patients with chemotherapy-induced anemia

Contraindications

  • Hypersensitivity to darbepoetin alfa, r-HuEPO or any of the additional ingredients.
  • Poorly-controlled hypertension
  • Reduced liver function (raised s-bilirubin). EPO is most likely eliminated via the liver. There is presently no toxicity data on patients with reduced liver function.
  • Some studies indicate a detrimental effect on patient survival by the use of EPO in cancer patients, and this treatment should be avoided for anemia in cancer patient for whom there is a curative goal with the treatment.

 

Goal

  • Reach hemoglobin level of 12–13 g/l

Preparation

  • Survey blood status
  • Evaluate iron status

Implementation

  • EPO is given in a dosage of 40,000 IE subcutaneously once daily
  • With use of Aranesp®, one dose of 500 μg subcutaneously is given every third week
  • For hemoglobin of 12 g/l, the dose is reduced by 25–50%, for example 300 μg every third week
  • For hemoglobin of 14 g/l, treatment is stopped until it has fallen to under 12 g/l where treatment is resumed with a 50% dose (for example, 300 μg or lower every third week). Repeated dosage reductions may be necessary. 
  • If the increase in hemoglobin rises above 2 g/dl (1.3 mmol/l) within 4 weeks, the dose should be reduced by 25–50%.

Assurance of efficient erythropoesis

  • Low s-iron and high ferritin implies iron deficiency. It is then recommended to give iron supplementation, for example slow-release iron tablets 100 mg x 2 daily for the first 4 weeks then once daily. If still no effect from this treatment, immediate action should be taken to find the cause.
  • Lack of iron, folic acid, or vitamin B12 reduces the effect of erythropoietin-stimulating drugs and should therefore be treated.
  • In the case of functional iron deficiency, iron storage is not released as needed and iron must be taken parenterally. Functional iron deficiency is characterized by normal or raised ferritin and normal serum iron/TIBC. 
  • Simultaneous infections, inflammatory or traumatic episodes, hidden blood loss, severe aluminum toxicity, or underlying hematological disease or bone marrow fibrosis can also impair erythropoietin response.
  • Reticulocyte count should be monitored as part of the evaluation.
  • If typical causes for no response have been excluded and the patient has reticulocytopenia, a bone marrow examination should be considered. If bone marrow assessment implies erythroaplasia (Pure Red Cell Aplasia – PRCA), testing with anti-erythropoietin antibodies should be done.

Follow-up

Follow-up of hemoglobin under EPO treatment is necessary because overstimulation can lead to polycytemia.

Scalp Cooling Treatment

General

Scalp cooling has long been a well-known technique to prevent hair loss. In 1996 in Great Britain, a machine was developed for the technique, which has a thermostat cooling system of glycol and water. The fluid circulates in a silicon cap placed on the head of the patient. Today there about 450 cooling cap machines in use, most of which are in Europe. Of these, about 60 are in the Nordic countries, 30-35 of which are in Norway. At Oslo University Hospital, 2-3 patients receive this treatment daily. A cooling machine reduces the temperature in the scalp to about  10 ºC using a cooling cap and is effective at preventing hair loss caused by chemotherapy of moderate intensity.

The mechanism of action appears to be partly vasoconstriction, but more importantly, temperature-dependent reduction of cellular uptake of chemotherapy drugs. Successful results are achieved with taxane.

The effect of cooling cap treatment is individual, but experience shows that most patients using this technique are able to avoid using a wig.

In order for the patient to gain the optimal effect of cooling treatment, it must be applied from the first to the last treatment. Since not all patients receive chemotherapy at Oslo University Hospital, it must be determined whether the patient can receive scalp cooling treatment during all chemotherapy courses before starting. Some patients apply for treatment at a hospital where they know scalp cooling treatment is available.

Indications

To what degree scalp cooling affects the temperature conditions in the bone marrow of the cranium does not appear to be sufficiently documented. In the literature, concern has been expressed that cooling may conserve micrometastases in the scalp; however, documentation of this is scarce. Due to this lack of documentation, Oslo University Hospital has decided that scalp cooling treatment is not recommended during chemotherapy with curative intention for cancers where micrometastases in the scalp or bone marrow is a problem (breast cancer, malignant lymphoma, leukemia). 

For palliative chemotherapy however, it appears the method is acceptable as well as for chemotherapy with curative intention for cancer where metastasis to the skin, subcutis or bone marrow is uncommon.

For gynecological cancers, bone metastases are very rare. Scalp cooling is therefore not contraindicated during chemotherapy for such cancers. For many women, hair loss is significant for their self image. We recommend offering gynecological cancer patients the option of scalp cooling to prevent hair loss during chemotherapy. 

Goal

  • Prevent chemotherapy-induced hair loss (alopecia).

 

Equipment

  • Scalp cooling machine
  • Scalp cap with coupling  
  • Paper cap
  • 5 unsterile compresses 10 x 10 cm
  • Towel
  • Chair or bed for the patient
  • Blanket or warm water bottle   

Preparation

Preparation for use of scalp cooling machine

Before the machine is turned on

  • Check that the plug is in the outlet and is connected.
  • Check the level of the fluid in the window on the back of the apparatus and fill if necessary.
  • Check that the tubes to the fluid are not twisted or broken.
  • Check that there is no visible leakage of cooling fluid.

When the machine is turned on

  • When the power is on, the light should be green.
  • Make sure that both tubes for the cooling fluid are connected to the recirculation ports.
  • Press PUMP ”on” when the left display shows a temperature of -4 °C to -5 °C.
  • Listen for the motor.
  • The temperature of the cooling fluid is shown on a designated thermometer.
  • When the right display shows HI and a sound alarm starts, push the MUTE button on the control panel. When only one arm is used, the available arm is connected to the machine.

After 15 minutes

  • The display will show a slow decreasing temperature.
  • When the left display shows -4 °C to -5 °C, and the right display shows lower than 5 °C, the system is ready for use. This may take from 1 hour to 90 minutes after PUMP "on" is pressed, depending on the temperature of the room.

Preparation of the patient

Choose the correct size of the cap (small, medium, large).

Recommended cooling times for common chemotherapy drugs
  Before After
FEC/EC
30 minutes 1–1 ½ hour
Paclitaxel weekly 90 mg/m2 30 minutes 1 hour
Paclitaxel triweekly 175 mg/m2 30–45 minutes 1 ½ hour

Implementation

  • The patient sits in a chair or lies in a bed 45 minutes before the chemotherapy infusion starts. 
  • The strap from the cap should be fastened under the chin - the patient may do this to make sure it is comfortably tight.
  • Make sure the cap fit snugly to the scalp, especially on the upper part of the head.
  • Tighten the straps on the cap - this is critical for maximal effect.
  • Place compresses between the chin and chin strap.
  • Protect the patient's ears and forehead with compresses if the patient feels that they become too cold. A towel can be placed around the neck.
  • Turn off the pump on the machine and connect the cap. 
  • Turn on the pump again and check that the cooling fluid is circulating and the cap becomes cold.
  • Ensure the patient is as comfortable as possible.
  • The patient usually experiences the first 10-15 minutes as the coldest but adapts to the temperature.
  • The patient sits/lies with the cap on for 30-45 minutes before the chemotherapy infusion starts depending on the type of chemotherapy. 
  • The chemotherapy infusion is connected to the patient.
  • The patient sits with the cap on during the entire infusion. If the patient needs to visit the toilet, the pump is turned off and the cap is disconnected. The patient must keep the cap on while using the toilet.
  • The patient sits with the cap for 1-2 hours after the infusion is completed depending on the type of chemotherapy. 
  • When the treatment is finished, the pump is turned off.
  • Remove the cap, compresses, and paper cap.
  • The machine is turned off and the cap is disconnected from the machine.
  • The cap should be washed in warm soap water and dried.

Follow-up

Recommended hair care for optimal results  

Certain chemotherapy drugs and dosages cause hair loss after treatment is finished. Losing hair is a very sensitive issue for most, even if a wig is an option. 

Scalp cooling treatment can contribute to preventing or reducing hair loss to avoid use of a wig.

Experience with scalp cooling treatment shows that 70-90% of patients do not need to use a wig, provided that recommended cooling times both before and after the infusion are followed (see preparation).

The result can be maximized by following these recommendations:

  • Use a neutral pH shampoo and conditioner.
  • Do not wash your hair less than 24 hours before treatment.
  • Limit hair washing and always use a conditioner.
  • Wash your hair in cool water with light finger motions.
  • Allow your hair to dry naturally without rubbing with a towel and do not use a hair dryer.
  • Use a soft, satin-like pillowcase for sleeping.
  • Use a wide-toothed comb instead of a brush.
  • Allow your hair to hang naturally instead of pulling it up/back.
  • Do not use hairspray or other products.
  • If you wish to color your hair, environmentally friendly products should be used.
  • Show this information when you visit the hair dresser.
  • Follow these recommendations for 6-8 weeks after the last treatment.  

For successful results, do not use harsh methods which will weaken your hair.

If you lose hair despite treatment and optimal care, continued cooling can further hasten growth.

Scalp Cooling TreatmentScalp Cooling TreatmentScalp Cooling TreatmentScalp Cooling Treatment
Scalp Cooling TreatmentScalp Cooling Treatment

Febrile Neutropenia

General

Febrile neutropenia occurs in compromised immune systems due to a low number of leukocytes, especially granulocytes. Patients with a declining number of granulocytes after chemotherapy, can during bacterial sepsis, quickly develop extensive neutropenia and become critically ill. Febrile neutropenia can be a life-threatening condition.

A patient with neutropenia and simultaneous fever or clinical suspicion of systemic infection should be treated as quickly as possible with broad spectrum antibiotics including gram-negative and gram-positive coverage as soon as the required microbiological samples are taken.

The clinical situation is most critical in patients who have not yet started antibiotic treatment. When broad-spectrum antibiotic treatment is started, monitoring the fever may be permitted.

Fever is often the only symptom. Some have septicemia without fever. One should therefore also be aware of other symptoms such as lethargia, diarrhea, or visible sign of infection. The local clinical symptoms and signs (redness, pain, temperature increase, swelling (boil), and reduced organ function) are most often very much reduced or completely absent during neutropenia.

Indications

  • A patient with neutropenia and simultaneously fever or clinical suspicion of systemic infection

Goals

  • Avoid septicemia.
  • The patient is able follow the planned scheme of treatment.

Definitions

Fever is defined as:

  • a single (rectal) temperature ≥ 38.5 °C or
  • temperature ≥ 38 °C for more than 2 hours or
  • temperature ≥ 38 °C measured three times during 24 hours

There is a known increase of infections when neutrophil < 1.0 x 109/l.  The infection risk increases with degree and duration of neutropenia. The neutropenia is considered severe when granulocytes are ≤ 0.5 x 109/l.

Preparation

The following diagnostic tests should be performed:

  • Adequate microbiologic tests: blood culture x 2-3, throat/nasopharynx, urine, catheter opening any surgical incisions. All blood cultures should be taken simultaneously to avoid losing valuable time.
  • Blood culture and other microbiological samples should be taken before antibiotic treatment is started
  • Blood tests with differential count of leukocytes, thrombocytes, Hb, CRP, SR, creatinine
  • X-ray of chest

Information

Before initiation of chemotherapy, the patient should be extensively informed, both verbally and in writing, of febrile neutropenia and  its consequences.

A patient who can develop febrile neutropenia should obtain a written statement of the condition to present to other treatment providers.

Use of an isolated or private room

Patients with neutrophil granulocytes ≤ 0.3 x 109/l should have a private room if possible. Guidelines for protective isolation should be followed. Thorough washing of hands is especially important.

 

Implementation

  • Treatment is started as soon as possible.  Treatment may be postponed a maximum of 30 minutes to complete microbiological testing.
  • Start septicemia treatment for fever if neutropenia is expected, regardless of granulocyte value.

Antibiotic regimen

  • Benzylpenicillin sodium 5 mg IE x 4 tobramycin or gentamicin 5-10 mg/kg x1
  • Tazocin® 4 g x 3
  • Cefotaxime® 1 g x 4 if aminoglycoside should be avoided
  • Ceftazidim® 1 g x 4  with suspicion of pseudomonas infection
  • Meronem ® 0.5 g x 4 usually 2nd or 3rd choice

When using aminoglycoside, the first dose should be high. Keep in mind the following:

  • age
  • sex
  • kidney function
  • fat index   

Otherwise, the dose should be decided from concentration of aminoglycoside determined after the second day and thereafter monitored 2x per week. 

Serum concentration of tobramycin and gentamycin

For single dose in 24 hours

  • Trough concentration (0-test = 24 hour test) < 0.5 mg/l
  • Top concentration (30 minute after infusion is completed) > 12 mg/l

For multiple doses in 24 hours

  • Trough concentration < 2 mg/l, top concentration (30 minutes after the infusion is completed) preferably > 8-10 mg/l 
  • Avoid aminoglycoside :
    • If kidney function is reduced. Avoid aminoglycoside if cisplatin is used. If cisplatin has been previously used, many patients will have subclinically reduced kidney function. If necessary, use aminoglycoside for a short period and monitor kidney function closely.
    • If carboplatin is used, determine glomerulus filtration rate (GFR) for each new treatment. Penicillin/aminoglycoside can be used if GFR is stable (has not declined more than 15% if initial value is in the normal range)
    • With sarcoma: Protocols with very high doses methotrexate and ifosfamid (> 5 g/m2) should be used in sarcoma treatment. It is not abnormal for these patients to have an increase in creatinine.
    • with massive ascites
    • with suspicion of or documented myeloma kidney (myelomatosis)
    • If aminoglycoside has been used in the past two weeks
  • Suspicion of staphylococcus aureus as a cause of infection (relatively rare)
    • Give penicillinase-stable penicillin, cloxacillin, or dicloxacillin, possibly clindamycin instead of ordinary penicillin. Yellow staphylococci are also killed by cefotaxime and by merop
  • Gram-positive cocci in multiple blood cultures and if the patient has clinical signs of infection
    • Use vancomycin 500 mg x 4 until resistance determination is available
  • Poor patient condition and suspicion of gram-negative septicaemia
    • Use “double gram-negative” with for example ceftazidim or tobramycin
    • Other preparations with good effects against most gram-negative bacteria are meropenem and ciprofloxacin
  • Suspicion of anaerobic infection
    • Use an anaerobic drug: Metronidazol 500 mg x 3, clindamycin 600 mg x 4, piperacillin/tazobactam 2g x 4 or meronem 500 mg x 4.  This especially applies if there is suspicion of anaerobic infection under the diaphragm such as gallbladder, intestines, perforation, abscess.
    • penicillin is often adequate for anaerobic infections above the diaphragm.

With continuing clinical signs of infection, adjust the antibiotic treatment according to resistance determination in blood culture. Maintain gram-negative coverage.

Systemic fungal treatment

By persistent fever after multiple days with broad spectrum antibiotic treatment, one should consider empirical treatment of possible candida-sepsis, for example with fluconazole 600 mg the first 24 hours, and thereafter 400 mg x 1.

If candida is documented without adequate response to fluconazole, a fungicide drug should be used, for example amphotericin B.

If suspected infection with Aspergillus apply voriconazole, amphotericin B or caspofungin.

Follow-up

Observe for symptoms of a new infection.

Cold Gloves and Socks

General

Clinical studies (Journal of Clinical Oncology – July 1, 2005 from Southwest Technologies) have shown that use of cold gloves and socks reduces nail loss and skin damage in patients receiving docetaxel and pegylated liposomal doxorubicin.

Indications

  • Docetaxel treatment for prostate and breast cancer
  • Pegylated liposomal doxorubicin treatment for ovarian cancer

Contraindications

  • Should not be used in patients with curative treatment (adjuvant/neoadjuvant treatment of breast cancer)
  • Raynaud's disease
  • Distal metastases
  • Distal arterial insufficiency
  • Cold intolerance

Goal

  • To avoid loosening/loss of nails or skin damage
  • Preventing neuropathy

Equipment

The gloves and socks are made of a glycerine gel which maintains its elasticity also when frozen. The outer fabric is water-proof and elastic. The Velcro holds the products securely in place.

  • Elasto-Gel cold gloves and/or socks
  • Disposable gloves/socks for use inside

Preparation

  • The products should be stored in the plastic bag in a freezer which maintains a temperature of -25 to -35°C for at least 12 hours before use. The elasticity is maintained in temperatures down to -30 °C.
  • Gloves/socks should be used at each treatment to maintain the effect.

Implementation

  • Wear disposable gloves/socks inside for hygienic reasons.
  • Put on gloves/socks 15 minutes before treatment and remove at the earliest 15 minutes after the end of treatment.
  • If the treatment lasts 1-1 ½ hours, the gloves/socks should be changed. This should take place after 45 minutes (or more often) if the patient feels they become too warm.
  • Change the gloves/socks as quickly as possible to avoid reflexes caused by dilatation of blood vessels.

Follow-up

  • Allow the gloves/socks to dry after use before they are put in the freezer again.
  • As needed, clean the surfaces in contact with skin with soapy water and dry thereafter. Never immerse the gloves/socks in water.
Hypothermia gloves and socksHypothermia gloves and socksHypothermia gloves and socksHypothermia gloves and socks
Hypothermia gloves and socks

Intravenous Extravasation of Cytotoxic Drugs

General

Intravenous extravasation occurs when there is an accidental leak of intravenous cytotoxic fluid (chemotherapy drug) from the vein to surrounding tissue.  

If chemotherapy is given in a peripheral vein, a large vein should be used, which is preferably in the underarm. Before the infusion begins, the vein should be checked for leaks by injecting NaCl 9 mg/ml or glucose 50 mg/ml. Backflow should also be checked. The patient must be informed that pain or burning in the area is not normal and they must inform the doctor.

Cytotoxic chemotherapy drugs should always be given through a central vein catheter to reduce the risk of intravenous extravasation.

Risk factors for intravenous extravasation:

  • Small veins (infants and children)
  • Brittle veins (elderly patients)
  • Reduced physical health (cancer patients)
  • Sclerosizing veins
  • Rolling veins
  • Poor circulation (if the needle is placed in an arm with edema)
  • Obstructed vena cava (raised venous pressure may cause leakage)
  • Conditions such as diabetes and radiation damage
  • Obesity

Chemotherapeutic drugs are separated into three groups according to the degree of toxicity:

  • Non-cytotoxic/irritating
  • Tissue irritant
  • Cytotoxic

Cytotoxic drugs can cause blisters or ulcerations leading to skin necrosis if extravasation occurs. If intravenous extravasation is left untreated, it can lead to permanent tissue damage, necrosis, scar formation around ligaments, nerves and joints, infections, abscesses, contractures, and in the worst case, amputation.

Indication

  • Intravenous extravasation of cytotoxic drugs. 

Goal

  • Limit damage of tissue from intravenous extravasation.

Definitions

Non-cytotoxic drugs or non-irritants

Non-cytotoxic/non-irritant drugs normally do not cause skin necrosis.

Irritants

Drugs that are tissue irritants can cause pain in and around the injection site and along the vein. They can also cause inflammation. Some tissue irritating drugs cause ulceration if a large amount leak extravasally.

Cytotoxic drugs

Cytotoxic drugs are categorized into subgroups according to the mode of damage. This categorization is important for the choice of treatment.

DNA-binding

DNA binders absorb locally into the cells, bind to DNA, and cause cell death. After cell death, the drug molecule can be liberated from the dead cell and start killing healthy cells. This group is divided into these subgroups:  

  • Anthracycline
  • Alkylating drugs
  • Other

For doxorubicin and mitomycin, progrediating tissue damage has been reported over weeks, and in some cases, months after intravenous extravasal injection.

Non DNA-binding

This group of medications can lead to cell death through other mechanisms than DNA binding drugs. This group is divided into:

  • Vinca alkaloids
  • Taxanes

 

Chemotherapy cytotoxicity (1)
Cytotoxic, necrosis

Irritant, can cause flaking or inflammation

Non-cytotoxic or non-irritant
Amsacrine Cisplatin Aldesleukin
Decarbazine Doxorubicin liposomal Alemtuzumab
Dactinomycin Estramustine** Asparaginase
Docetaxel**** Etoposide Bleomycin
Doxorubicin* Floxuridine Bevacizumab
Epirubicin* Florouracil Bortezomib
Daunorubicin* Irinotecan Cetuximab
Idarubicin* Carboplatin Cyclophosphamide**
Irinotecan Carmustin** Cytarabine
Kloremtin** Oxaliplatin Fludarabine
Mitoguazon Pemetrexed Gemcitabine
Mitomycin-C Ralitrexed Ibritumomab tiuxetan
Mitoxanthrone Temoporfin Ifosfamide**
Paclitaxel**** Teniposide Interferon
Plicamycin Topotecan Cladribine
Streptozocin Methylene blue***** Clofarabine
Verteporphin   Melfalan**
Vinblastine***   Methotrexate
Vindesine***   Rituximab 
Vincristine***   Tiotepa**
Vinorelbine***   Trastuzumab

 * = Anthracycline

** = Alkylating agents

*** = Vinca alkaloids

**** = Taxanes

*****= Methylene blue is not a chemotherapy drug, but is used for ifosfamide-induced encephalopathy, and is therefore included on the list.  

All chemotherapy drugs can damage tissue in high concentrations.

References

 

  1. Allwood M, Stanley A WP. The Cytotoxics Handbook. Ed. 4th ed. 2002. 2001
  2. Ekstravasation Guidelines Implementeringsværktøj [Online] 2007 [hentet 10. mars 2009]; Tilgjengelig fra URL: http://www.cancerworld.org/CancerWorld/getStaticModFile.aspx?id=2726

Preparation

Identification of an extravasal injection

  • A burning, stinging pain or other acute change of the puncture site.
  • Local redness or inflammation of the skin around the puncture site.
  • The infusion rate slows/stops.
  • Swelling of the puncture site.

Extravasation has probably also occurred if blood cannot be aspirated, resistance is felt on the plunger when a syringe is used, and/or there is no current if the drug is infused. 

 

Implementation

Flow chart for treatment of intravenous extravasation of cytotoxic drugs:

Emergency response:

  • Stop the infusion immediately.
  • Allow the needle to remain and aspirate with as much water as possible. Avoid applying direct pressure on the area of extravasation.  
  • The volume, type, and time of extravasation should be recorded.
  • A doctor/plastic surgeon should be called for to examine the patient.
  • The damaged area and skin manifestations should be marked/photographed.
  • The affected area should be kept elevated.
  • The remaining chemotherapy should not be discarded.
  • The patient should be informed about what is happening and what must be done. 
  • The needle is removed while aspirating.
  • Pain medication is administered if necessary.

Based on which medication has leaked extravasally, the doctor or plastic surgeon will decide whether conservative treatment or primary surgery is necessary.

Conservative treatment

Conservative treatment consists of two different treatment strategies to limit the damage by extravasation: localize/neutralize and spread/dilute (2).

Localize and neutralize:

  • Place an ice pack on the area for 15-20 minutes, at least 4 times daily for multiple days. A coldpack is used to limit spreading of the drug. Studies have indicated that there is reduced cellular uptake of drugs at lower temperatures (2).
  • The drug that has leaked extravasally is neutralized by a specific drug if the instructions are followed.
  • The affected area of the body should be kept elevated.

Spread and dilute (applies to vincristine, vinorelbine, vindesine, and vinblastine):

  • Warm compresses are placed on the area for 15–20 minutes, at least 4 times daily, for multiple days.
  • To dilute the drug that has leaked extravasally, many subcutaneous injections are given with hyaluronidase diluted with sterile water.

If the patient has lasting pain or blisters, surgical treatment should be considered by excising the area with direct sutures, skin transplant, or flap reconstruction.

Another type of reconstruction may be necessary at a later time. 

Treatment 

Dexrazoxan (Savene®)

Dexrazoxan is an EDTA analong used to treat extravasation of anthracycline (doxorubicin, daunorubicin, epirubicin, idarubicin). The mechanism of action is not fully understood, but it is believed that it may work through two mechanisms. By chelating iron, the formation of the iron-doxorubicin complex and  iron-mediated hydroxy radicals are hindered, which cause oxidative damage to cell membranes and proteins. Another possible mechanism is inhibition of topoisomerase II (3).

Treatment lasts for 3 days. In all cases of extravasation of anthracycline, this treatment should be assessed by an oncologist and surgeon/plastic surgeon.

  • The first infusion should start as soon as possible and within 6 hours after extravasation. 
  • On the following two days, the infusions should occur at the same time as the previous infusion (+/- 3 hours).
  • If possible, the infusion should be placed in a vein where there is no extravasation.
  • An ice pack or cooling element used on the area must be removed at least 15 minutes before the infusion starts to ensure sufficient blood circulation.

Cost

A package costs about NOK 100,000.-. If the expiration date runs out, the drug is replaced by the pharmaceutical company free of cost.

Dimethylsulfoxide (DMSO)

DMSO (70–90% solution) quenches free radicals and prevents formation of sores. The solution can be used after extravasation of cytotoxic drugs (anthracycline, mitomycin C, doxorubicin, idarubicin, epirubicin andactinomycin D) together with cooling of the area when other treatment methods cannot be used (5, 6). DMSO cannot be used in combination with dexrazoxan (3, 4).

  • An area twice as big as the affixed area is treated with the solution every 8 hours for one week.(6)

Hyaluronidase

Hyaluronidase is an enzyme that breaks down hyaluronic acid found in connective tissue. This leads to permeability and increased diffusion of the drug that is leaking extravasally, and is used only to spread the drug out into the tissue (spread and dilute).  

  • Hyaluronidase is administered subcutaneously or intradermally in 5-10 locations on the border of the area where the drug has leaked extravasally (7).

Surgical treatment

"Wash-out"

The washing out technique can be used with chemotherapy drugs when tissue damage is likely. When used with anthracycline, it is important that this is performed before the chemotherapy drug goes intracellularly.

In most cases, this is a very successful method if it is performed within 6 hours after the extravasation.

  • The patient receives regional anesthesia.
  • Multiple small incisions must be made to ensure sifficient access to the damaged subcutaneous tissue.
  • With an infiltration needle, which is usually used for liposuction, isotonic NaCl is flushed through the tissue and drains through the incisions.
  • The infiltrated fluid is then carefully removed by suction through a small needle used for liposuction.
  • The procedure is repeated until 300-500 ml fluid is used.

References

  1. Ekstravasation Guidelines Implementeringsværktøj [Online] 2007 [hentet 10. mars 2009]; Tilgjengelig fra URL: http://www.cancerworld.org/CancerWorld/getStaticModFile.aspx?id=2726
  2. Hasinoff BB. Dexrazoxane use in the prevention of anthracycline extravasation injury. Future Oncol 2008; 2006: 1–15.
  3. Statens legemiddelverk. Preparatomtale. 2008
  4. Langstein HN, Duman H, Seeling D, Butler CF, Evens GR. Retrospective study of the management of chemotherapeutic extravasation injury. Ann Plastic Surg 2002; 49: 369–74. 
  5. Bertelli G, Gozza A, Forno GB, Vidili MG, Silvestro S, Venturini M et al. Topical dimethylsulfoxide for the prevention of soft tissue injury after extravasation of vesicant cytotoxic drugs: A prospective clinical study. J Clin Oncol 1995; 13: 2851–5.
  6. Clinical Pharmacology© 2008 database. Hyaluronidase. 2008.

Follow-Up

For conservative treatment 

The damaged tissue should be observed for multiple weeks (with mitomycin at least 13 weeks) since necrosis can occur after months.

For emergency surgical treatment

Patients treated by a plastic surgeon should receive follow-up care by the surgeon until the wound has healed.

 

Intravenous extravasation of cytotoxic drugs.Intravenous extravasation of cytotoxic drugs.Extravasation of tissue toxic chemotherapy

Smoking cessation in connection with cancer treatment

General

In patients treated with surgery, radiation and/or chemotherapy, the treatment efficacy may be affected by smoking. Smoking has an impact on both metabolism and pharmacokinetics.

Smoking may inhibit wound healing after surgery and increase the probability of surgical site infections. Because smokers generally have more mucus in the airways and are less able to remove it, they also may have a increased risk of serious lung complications during anesthesia. However, it is disputed whether or not it is beneficial to quit smoking directly prior to surgery and this should be considered in each case individually. (28,30-33). Smokers are more prone to stagnation of bronchial secretion than non-smokers and rapid postoperative extubation is important. 

Patients who continue smoking during radiation therapy have a lower risk of complete respons, development of secondary cancer, increased toxicity and several other side effects compared to non-smokers and smokers that quit before treatment. Continued smoking during radiation therapy is also associated with oral mucositis, impaired ability to taste, dry mouth, reduced voice quality, weight loss, cachexia, fatigue, pneumonia, bone-and soft tissue necrosis.

Tobacco may have an effect the metabolism and the mechanisms of chemotherapy and in this way may make the treatment less effective. Smokers undergoing chemotherapy may also experience a weakened immune system, increased rates of infection, exacerbation of common side effects, weight loss, cachexia, fatigue and cardiac or pulmonary toxicity. Some findings suggest that it may also apply to monoclonal antibodies.

Cancer patients who quit smoking before chemo- and radiation therapy get a total symptom burden equal to that of non-smokers, but those who continue to smoke state a higher symptom burden. Targeted measures in smoking cessation may increase quality of life and lead to less treatment interruptions.

A lot of patients wonder if there is any point to quit smoking after receiving a cancer diagnosis. tudies show that continued smoking is associated with increased treatment-related toxicity, increased risk of second primary cancers, reduced quality of life, reduced treatment effect and reduced survival in patients with cancer. This applies to both cancer diagnoses where smoking is a known causal factor, as with lung- and head and neck cancers and in cases where smoking has no known correlation with the diagnosis. Studies conducted on smoking and cancer diagnoses such as breast cancer, prostate cancer, colorectal cancer, esophageal cancer, cervical and ovarian cancer as well as leukemia and lymphoma cancers show that to continuation of smoking after a proven cancer diagnosis is associated with increased risk of mortality.

Studies support that quitting smoking improves cancer, and emphasizing the potential importance of targeted smoking cessation in cancerpatients during and after treatment. The link between tobacco and impact on cancer and cancer treatment is a complex matter.

Regarding the significance of the various components much is still unkown. When it comes to tobacco use in cancer treatment research is primarily done on the link between cigarette smoking and efficacy of cancer treatment. Nevertheless, it cannot be excluded that using other smokeless tobacco products such as snuff and chewing tobacco, may also impact the cancer treatment. According to international guidelines all tobacco use should be stopped during cancer treatment.


Benefits of smoking cessation and risks of continued smoking in patients with cancer
Quitting smoking results in the following benefits: Continued smoking results in a risk of :
  • improved treatment results.
  • less side effects
  • fewer infections
  • improved respiration and circulation
  • increased survival
  • reduced efficacy of treatment.
  • postoperative complications and longer recovery.
  • cardiovascular and respiratory complications.
  • recurrence of cancer, and secondary cancer.
  • shortened life expectancy.

 

Indication

Weaning of nicotine in connection to cancer treatment. 

Goal

Healthcare providers should convey evidence-based information to patients about how smoking affects cancer treatment, the risk of side effects and prognosis and also provide guidance and relevant treatment for smoking cessation.

Preparation

Patients require clear, formalized and fact-based guidance and continuous follow-up. Many patients want encouragement for smoking cessation early in the disease. Being hospitalized is a good opportunity because patients have access to support and help to reduce nicotine withdrawal symptoms and discomfort.

A patient recently diagnosed with cancer is often motivated to quit smoking and also receptive to conversations about how to do this. Motivation or willingness to quit often changes during the treatment, and use of tobacco and motivation should therefore be discussed at every consultation.

Clarifying the patient´s smoking habit is important. The time of day the patient lights their first cigarette says something about the degree of addiction. Making the patient aware of the situations in which he or she smokes most; at work, at home or in social settings, can help break unwanted patterns of behavior.

Implementation

The best and most direct approach to motivate the patient is telling that tobacco use will decrease the effectiveness of treatment and the most important thing the patient can do himself is to stop using tobacco.

  • Speak directly to the patient about how tobacco use may decrease the effectiveness of treatment.
  • Discuss smoking cessation with the patient at each visit.
  • Clarify any misunderstandings about the risks of tobacco use. Point out the importance of quitting.

Sometimes there may be misunderstandings about what kind of health risk smoking during and after cancer treatment may entail.

Advice to those who are not ready for smoking cessation
The smokers statement The response of health care professionals
Justifications
The damage from smoking is already done.
Some damage is done, but continued smoking will still damage your health and reduce the effects of treatment. Quitting smoking is more important now than ever.
This response tells the patient that it is not too late to quit smoking, and the effect of treatment will be positive.

I have reduced smoking.
That is great, and now you need to focus on quitting completely. What do you think keeps you from quitting altogether?
This response tells the patient the importance of quitting completely, as the benefits of quitting at baseline are documented.
This is not a good time to quit smoking.
The benefits of quitting are greatest now, before treatment begins. What is needed to make you feel ready to quit smoking?
 
This response make the patient aware of the fact that quitting smoking optimizes the cancer treatment.

Health professionals must assist the patient identifying realistic expectations and goals for smoking cessation. For some, it may feel easier to scale down the number of cigarettes than to quit completely. The patient should know that every puff affects their health, and that the total health benefits can only be achieved through smoking cessation. For patients unable to stop completely, a gradual reduction may be a step in the right direction.

The probability of success for smoking cessation significantly increases for those who receive professional help in combination with nicotine replacement therapy (NRT) or non-nicotine based products. For the best possible effect of NRT the patient needs professional guidance to find the right product and dosage. For some patients combining two products or receiving a higher dosage than recommended will give the best effect. Sometimes the product must be replaced during the treatment.

Treatment with nicotine replacement therapy

Topical products are patches (Nicorette®, Nicotinell®), chewing gum (Nicorette®, Nicotinell®), lozenges (Nicorette®, Nicotinell®), inhalator (Nicorette®) or a combination of these. These products contain nicotine and therefore reduce the withdrawal symptoms experienced after smoking cessation.

  • Patch: Nicorette® 5 mg,10 mg and 15 mg/16 hours up to 6 months or Nicotinell® 7 mg,14 mg og 21 mg/24 hours up to 3 months.
  • Chewing gum: Nicorette®/Nicotinell® 2 mg and 4 mg, 8-12 pcs/day up to 12 months.
  • Lozenges: Nicorette® 2 mg and 4 mg, typically 8-12 pcs/day, maximum respectively 15 pcs/day up to 9 months or Nicotinell® 1 mg and 2 mg, typically 8-12 pcs/day, maximum is respectively
    25 and 15 pcs/day up to 12 months.
  • Inhalator: Nicorette® 10 mg/dosage container, 4-12 pcs/day up to 6 months.

Combination therapy means combining patches with chewing gum, lozenges or an inhalator.

  • Nicorette® patch15 mg/16h and Nicorette chewing gum 2 mg. 5-6 chewing gums daily. Maximum 24 pcs/day
  • Nicorette® patch 15 mg/16h and Nicorette® inhalator 10 mg: 4-5 dosage-container daily. Maximum 8 pcs/day

Nicotine replacement therapy increases the chance of smoking cessation by 50 to 70% after six months. Two products used in combination increase the chance of smoking cessation compared to the use of only one product.

Side effects

  • Headache, dizziness, nausea, flatulence and hiccup.
  • Irritation in the mouth and esophagus using chewing gum/ lozenges/inhalator
  • Skin irritations while using patches.

Precautions

  • Precaution in acute cardiovascular disease, peripheral arterial disease, cerebrovascular disease, hyperthyroidism, diabetes mellitus, kidney- and liver failure and peptic ulcers.
  • Should not be used during pregnancy, unless the potential benefit outweighs the potential risk.
  • The products should not be used during breastfeeding.

Treatment with non-nicotine medications

Bupropion (Zyban®) is a selective reuptake inhibitor of dopamine and norepinephrine. The mechanism behind why the ability to refrain from smoking increases by using bupropin is unknown. A should be set for smoking cessation for the second week of treatment.

Bupropion increases the chance of smoking cessation after 6 months by nearly 70%.

Side effects

  • Dry mouth, nausea, insomnia, hypersensitivity reactions and seizures (convulsions)

Precautions

  • Contraindicated in people with disease that can cause convulsions,  people with substance abuse or other circumstances lowering the seizure threshold.
  • Depression, which in rare cases includes suicidal thoughts and – behavior including  suicide attempt.
  • Safety and efficacy have not been established for people under 18 years.
  • Should not be used during pregnancy.

Varenicline (Champix®) is a partial agonist by a subtype of nicotinic receptors. It has both agonistic activity with lower intrinsic efficacy than nicotine and antagonistic activity in the presence of nicotine.

A date for smoking cessation should be set. Treatment should start 1-2 weeks, or up to 35 days, before that date. The starting dose is 0,5 mg one time daily on days 1-3, then 0,5 mg two times daily on days 4-7, then 1 mg two times daily on day 8 and until the end of treatment. The treatment should last for 12 weeks.

Side effects

  • Nausea, sleep disturbances, headache, constipation, flatulence and vomiting

Precations

  • Links have been reported between the use of varenicline and an increased risk of cardiovascular events, suicidal thoughts, depression and aggressive and erratic behavior
  • Safety and efficacy have not been established for people under 18 years of age
  • Should not be used during pregnancy

Follow-up

If the patient experiences a relapse, it is important to inform them that this is completely normal, and encourage them to continue. If the most common measures do not work,
consideration should be given both to increase the NRP and to provide closer follow-up by health care providers.

Guidance in smoking cessation is described in the literature as brief and clear advice and then further follow-up with a telephone helpline offering treatment for addiction and behavior change/issues. It is not necessary for the patient to have decided to quit smoking in order to be referred to a quitline. If the patient agrees to receive a call from quitline, he or she will be followed up by a supervisor. Supervisors are bound by confidentiality, are up-to-date professionally and offer free follow-up counseling calls for up to a year.

References

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Follow-up care after treatment of ovarian and fallopian tube cancer

  • During the first two years, follow-up visits are every three months.
  • From the third until and including the fifth year, follow-up visits are every six months.
  • After five years, follow-up visits are annual.

Examinations:

  • Physical and clinical examinations. Routine testing of CA 125 and possibly other tumor markers is controversial.
  • Work-up with imaging or endoscopy is performed as needed.
  • Recurrence should be verified histologically or cytologically before new treatment is started. 

Follow-up of non-epithelial ovarian cancer

For non-epithelial ovarian cancer, most recurrences are diagnosed within 1-2 years, however granulosa cell tumors may recur later.

Examinations:

  • Gynecological examination and measurement of tumor markers (s-AFP, hCG, CA 125)
  • For virilizing tumor, s-testosterone is a tumor marker. 

s-CA 125

Measurement of s-CA125 is normally not used in follow-up. There may be incidental variations of +/- 70 %, without having any significance. Gynecologic Cancer Intergroup (GCIG) has agreed that an increase of at least 100% must be present to define progression. From a normal value there must be an increase of 70 IU or more before the increase is diagnostic.  

If there is a positive increase of s-CA 125, but the gynecological examination, chest X-ray, and CT of the abdomen/pelvis do not show sign of recurrence, an MRI or PET scan will confirm a tumor, if present. 

It has long been discussed whether treatment of early recurrence based on CA125 gives better survival than treatment started after clinical detection of recurrence. Results from a randomized prospective study (ICON5) have recently been published showing not difference between the groups, and these results may influence follow-up recommendations.

PROSEDYRER

Fatigue before, during, and after Cancer Treatment

General

There are many reasons why cancer patients feel fatigued. In many patients, the causes are synergistic. Cancer patients are often very sick during treatment periods and may experience extreme fatigue during intensive chemotherapy. It is also very important to be aware that fatigue is a symptom of many other medical conditions, both physical and psychological, which also affects cancer patients. Some known causes of fatigue associated with cancer and cancer treatment are: 

  • Cancer itself
  • An operation
  • Current or recently concluded chemotherapy
  • Current or recently finished radiation therapy
  • Severe anemia
  • Other symptoms such as pain and nausea 
  • Fever or infection
  • Too little fluid or food intake
  • Reduced lung function
  • Changes in sleep
  • Worries, anxiety, stress, or depression

For some of these conditions, such as infections, there is medical treatment available. Fatigue that occurs after an operation or during chemotherapy and radiation therapy will, for most, gradually disappear when strength is regained. If a patient was feeling healthy after treatment and all of the sudden experiences fatigue, they should contact their doctor. If a patient feels fatigue and at the same time feels stressed, worried, or down, they may be reluctant to speak to their doctor or health personnel about it. It is still recommended to talk about these problems. Talking about it may be therapeutic, and provides room for discussing measures with a qualified person with experience with patients that have the same problems. For cured patients experiencing chronic fatigue, it may be difficult to pinpoint a specific cause. Many of these patients experience improvement by changing their lifestyle to a lower tempo than before the diagnosis.

Definition

Everyone knows what it feels like to be tired, fatigued, or lethargic when sick. This feeling is the most common side effect of cancer and cancer treatment. A symptom is a condition or state that something is not right in the body. Other frequent symptoms associated with cancer and cancer treatment are reduced appetite and nausea. Most patients who experience fatigue associated with cancer say that the feeling does not improve with rest, and many describe a lack of energy or exhaustion.  

If fatigue arises during chemotherapy or radiation therapy, most patients experience that it will gradually go away when treatment is over and their strength is regained. This type of fatigue is considered acute. Improvement may take time depending on the intensity of treatment. Some patients experience that fatigue lasts for months, or even years. This is considered chronic fatigue. The ability to carry out daily activities, a lack of humor, health-related worries, a reduced capacity to carry out work functions, or less energy for family, can also accompany chronic fatigue. Most patients will find it difficult to be told by their doctor that they are considered healthy, while their friends and family expect them to be normal again, despite having a lack of energy and ability to perform activities they want to.  

For many, feeling fatigued is often accompanied by having difficulty concentrating, poor memory, and an increased need for sleep. Most patients will need more sleep than before they became sick. For many, sleep is not restful, and it may take time to "get going" in the morning. Many also experience that they quickly become drained of strength if they exert themselves, and that it takes a long time before regaining strength after exertion. Exertion in this context can mean both physically and mentally such as working on a task that requires concentration.

Preparation

Fatigue can occur in all phases of cancer illness. Some patients feel it before the diagnosis, and almost all patients experience fatigue during radiation therapy or chemotherapy. A minority of patients experience long term fatigue after cancer treatment is over and the disease is cured. Patients who cannot be cured will almost always feel tired, worn-out, and exhausted. The degree of fatigue in these patients varies depending on the cancer type, spreading, and other symptoms of the disease.

The patient should be given necessary information on both causes of fatigue and measures he/she can take.

Implementation

General measures that can reduce feeling tired and fatigued

Following suggestions are meant as general advice that may not necessarily apply to everyone in all situations. This advice is based on results from studies, experiences from cancer patients, and recommendations from experts. Each patient should assess what works for them. It is recommended to express concerns and seek advice for what measures you can take and what you should avoid.

General advice
  • Try to live as "normal" as possible.
  • Try to plan your day to include time to rest.
  • Take many small breaks during the day instead of a few long ones.
  • Rest after strenuous activity.
  • Plan your daily activities and do those that are most important for you.
  • Set realistic goals for yourself and try to be happy with those you accomplish.
  • Try to recognize activities that make you especially tired/fatigued and limit them, or spread them out over longer intervals. 
  • Try to accept that you do not have the energy to do the things you could previously.
  • Assess what is important for you to do yourself and what you can allow others to do.
  • Assume you will be tired after something strenuous even if you experience the activity as positive.

Physical activity and exercise

Exercise and physical activity that is appropriate for you will reduce the feeling of fatigue. Regular exercise is the most effective measure against chronic fatigue in cancer patients. Nevertheless, both too much and too little exercise can worsen fatigue, therefore, it is important to find a level (frequency and intensity) that suits you. You should never exercise so intensely that you must stop a session or exercise period because you are exhausted. Remember that daily form varies for everyone and adjust your exercise routine accordingly. Make long-term goals (months) and gradually increase activity, and carefully for a period. 

  • Activities such as walking, biking, swimming, dance, and aerobics are recommended.
  • Light exercise periods at regular intervals are better than intense, sporadic periods.
  • Always start with a slow tempo and increase gradually before finishing with a slow tempo again.
  • Always sit down and rest after exercise but try not to lay down and sleep.
  • Physical therapists and sport pedagogs can provide advice on exercises that are right for you. The principles are the same for all exercise, but it should be adjusted for your energy level.  

Sleep

Many cancer patients with chronic fatigue have sleep pattern disturbances. It is important to maintain a normal rhythm even if you feel like sleeping during the day.

  • Try to wake up at the same time every day and keep a regular bedtime.
  • Avoid too much activity right before bedtime.
  • Try not to sleep during the day because this will disturb your biological rhythm.
  • But, a short afternoon nap may be energizing!
  • Rest during the day by relaxing in a good chair, but try not to fall asleep.
  • Speak to your doctor about lasting sleep disturbances.

Nutrition

Having a reduced appetite or intake of food can also result in a lack of strength and energy. We recommend eating healthy food regularly, and to follow the national guidelines on nutrition. Special diets or supplements do not improve fatigue unless there is a deficiency.

Work situation

Some patients do not have the strength to continue working, or they must reduce their hours because of chronic fatigue. Consulting with a social worker may be beneficial for guidance regarding your work situation, your welfare rights, and financial situation. 

Some adjustments that you and your employer can make:

  • Discuss the possibility for more simple or easier tasks, especially if you have a physically demanding profession.
  • Assess the possibility of reducing your hours.
  • Remember to take regular breaks also at work, if possible.
  • Assess the possibility of flexi-time to work during the hours you have energy, as well as the possibility of working from home.

Care for children

Caring for children or adolescents may be very difficult when you are fatigued or lack energy and strength. There are, however, some measures you can take:

  • Explain to your children that you are tired and are not able to do as much as you used to.
  • Discuss what the children can help you with and allow them to take part in household chores.
  • Try to establish permanent household chores for all family members.
  • Try to do activities that suit you that do not require too much energy, and can be performed without too much exertion. 
  • Ask and accept help from others for driving to and from activities, school, etc. if this relieves you.

Drug therapy

In Norway, there is currently no specific drug therapy for chronic fatigue associated with cancer. If the fatigue is due to specific conditions, this is of course treated with medication, if possible. Sometimes, such treatments improve the fatigue, but other times they do not. Examples of treatment that often reduce fatigue are treatment for infections and depression. 

Treatment with medications that stimulate production of red blood cells is not recommended for cancer patients due the the danger of serious side effects.

Follow-up

Information about fatigue

Healthcare workers in cancer care will often have knowledge about fatigue and cancer. Most general care physicians have general experience with fatigue but meet relatively few cancer patients. There is a lot of information available on the internet of varying quality. Below is a list of web adresses and some literature. Be aware that you may find opposing advice because knowledge on treatment especially, is limited.

Some articles/books:

  • Armes J., m.fl. (2004). Fatigue in cancer. Oxford University Press.
  • Berger A.M., m.fl. (2009). NCCN Clinical Practice Guidelines in Oncology. Cancer-Related Fatigue. www.nccn.org
  • Patarca-Montero R. (2004). Handbook of cancer-related fatigue. Haworth Medical Press

Life with a stoma

General

A stoma changes lifestyle to different degrees as well as to body image, and practical and emotional questions will arise associated with this.

A stoma is seldom a hindrance to resuming social life, but requires time to become accustomed to the change in bodily functions. Most can continue with recreational activities and work as before.

The patient should obtain training in stoma maintenance and hygiene during the first days after the operation. The patient should quickly start maintenance of the stoma.

Indication

  • Sigmoideostomy
  • Transversostomy
  • Ileostomy

Goal

  • Live comfortably with a stoma

Equipment

  • Stoma disc and pouch  
  • Unsterile compresser
  • Water
  • Stoma template
  • Pen
  • Scissors
  • Barrier cream
  • Waste pouch

Remedies

Barrier cream is a special cream intended for the skin around the stoma.The cream increases moisture and strengthens the skin. It contains little oil in order for the stoma to attach to the skin. The cream should be spread in a thin layer and excess cream should be wiped away after a few minutes for optimal attachment of the stoma disc.

Barrier film is found as a spray or applicator and lies as a membrane on the skin as a protectant from bowel content.

Stoma powder is used when the skin is sore and moist. The powder is sprinkled on moist areas and absorbs the moisture in order for the disc to attach itself. Powder on dry skin is blown away as this will reduce the adherence of the disc.

Paste and gaskets allow for tighter bandaging where the skin around the stoma is uneven. Gasket paste contains alcohol and burns where the skin is sore. This can be avoided by sprinkling stoma powder on the skin first.

Crystal violet 0.5% is a dye with antibacterial and antifungal properties. It will also dry out moist skin. The substance is spread with a cotton ball and allowed to air dry before a new skin disc is applied.

Hydrocortisone cream 0.1% can also be applied to sore skin. The cream in an anti-inflammatory and should not be used more than 14 days in a row. The cream is massaged into the skin. Excess cream should be dried after a few minutes for optimal adherance of the stoma disc.

Preparation

When the patient is ready to carry out stoma changes, the situation should be as close to their home situation as possible. The patient can choose to sit or stand and it is recommended to carry out the change in front of a sink with running, temperate water. It is helpful to have extra room for equipment within reach.

A bag for waste is attached to the trouser waistband to catch bowel content when the disc and pouch are removed.

It may be appropriate to shave the area where the stoma disc will be attached for better adherence.

Challenges regarding odor are greatest immediately following surgery. It is therefore recommended to change the bag in a well-ventilated room and/or to use a fan.

Implementation

Stoma care

  • To avoid spillage on clothing and to collect used equipment, the waste bag is attached to the waistband.
  • The stoma disc is loosened with a moist compress and carefully removed.
  • The skin and stoma are carefully washed with a lukewarm compress before it is dried/air dried/blown dry. It is the normal for the the stoma to bleed when touched.
  • Red, dry skin can be moistened with barrier cream in a thin layer. The cream should absorb into the skin for a few minutes before excess cream is dried away such that the disc will adhere to the skin.
  • The stoma template is cut out of cardboard or colorless, stiff plastic to the size of the stoma . A caliper can be used for measurement .
  • The stoma template is placed on the back of the new adherence disc and traced before adherence disc is cut and threaded over the stoma. Check that it sits properly on the skin.
  • A one component bandage consists of a complete bag with adhesive surface . The one component closed back is changed after every bag change which is usually 2-3 times a day. A one component reusable bag is changed daily or every other day.
  • A two component bandage consists of s skin disc and bag in two parts . The bag is threaded over the stoma and attached to the disc. The disc is usually changed 2-3 times per week. The closed, reusable bag is changed like a one component bandage and changed as needed.

For a small intestine stoma, it is recommended to change the bag before breakfast because the bowel content comes almost immediately after the patient has eaten.

Irrigation

Irrigation is an alternative to a skin disc and back and is used in patients with a colostomy. The advantage of irrigating is that in between, there is little feces and bowel gases and the risk for odor and sound is less. Irrigation is time consuming (about one hour) which should be done every other day. Most patients therefore recommend using stoma bags.

  • A water holder with water regulation and an irrigation bag is required.
  • The colon is emptied by regular insertion of water enema.
  • The bowel is emptied every other day by using around 800-900 ml of body temperature spring water set via the stoma and in the bowel.
  • The stoma is bandaged in the end with a mini bag or Mini Cap with air filter with little/no space for bowel content.
  • At the Radium Hospital, stoma nurses are reponsible for training the patients in the technique.

Follow-up

Upon discharge from the hospital, the patient obtains stoma supplies for about 4 weeks. The patient should be checked regularly at a stoma clinic or by nurse or doctor in their home town.  Stoma patients need follow-up to assist with practical and emotional challenges.

Stoma supplies can be obtained from a surgical store or pharmacy as a "blue prescription" § 3.1 in one year intervals. The equipment is specified on a stoma bandage card which is attached to the prescription. It is common to obtain equipment for a 3 month period. The patient should pay a copayment until they have a "free-card."

Daily life

A stoma itself is not a hindrance in the workplace or in daily life. For air travel, stoma equipment should be stored in hand luggage. Stoma equipment cannot be purchased on a "blue prescription" outside Norway. A shower can be taken with or without the bag. Bathing can done with the bag if the filter is covered. Tight clothing and waistbands which might squeeze the bag such that it does not fill properly should be avoided.

Sexuality

A stoma itself is not a hindrance for a normal sexual relations. Lack of energy and changes in body image after surgery may require time before sexual desire resumes. This will happen more quickly if partners are open about their relationship where both are able to express feelings and needs and have consideration for each other. If sexual relations become more difficult to master, it might be beneficial to seek professional help.

Special conditions for females

For stoma operated females who have removed the colon or rectum, the uterus can lean to the back in the empty space. The vagina can also be bent where a pocket can form in which discharge collects. The pocket is emptied by changing body position. It is helpful to rinse the vagina regularly with water containing a small amount of yogurt or a tablespoon of vinegar to one liter of water. This can be added to a an ear rinsing balloon which is obtained at a pharmacy.

A bentover uterus may cause pain and during intercourse but can be avoided by choosing positions in which the female is not on her back. If the operation after cancer treatment has lead to nerve damage, reduced feeling and discomfort from vaginal dryness may occur. Lubrication jelly will help this.

A stoma is not a hindrance for pregnancy and birth. Before the stoma is installed, the woman should discuss prevention and sterilization with her doctor and whether she plans on having children. The doctor can then take the necessary precautions.

Special conditions for males

The nerves in the groin area may be damaged during cancer treatment and surgery. This can lead to impotence and ineffective ejaculation. There are measures for impotence which may also be psychological and resume after time. It is important the patient is informed about this before the operation.

Nutrition

It is usually not necessary to change eating habits. It may be appropriate to resume the eating habits the patient had prior to surgery. Food that is tolerated is very individual and it is also necessary to try different foods. It is recommended to eat 4 medium-size meals a day. If one does not prefer to eat enough at each mealtime then snacks are recommended. Irregular mealtimes can cause irregular bowel motions and gas.  General advice is to chew food well, take time for meals, and drink at least two liters of water per day.  Food should have a low fat content and moderate amounts of fiber. Regular exercise with relaxation after mealtimes is recommended.

Food which can cause constipation/ileus

Nuts, fibrous foods such as asparagus, oranges, celery, seeded grapes, prunes, mushrooms, popcorn and corn shells, and fruit skin can cause constipation.

Food which can cause gas

Carbonated beverages, cabbage, onions, beans, sorbitol (artificial sweetener), chewing gum, and spicy foods can cause gas. Tea, caraway, fennel seed, and blanching of cabbage vegetables before boiling as well as physical exercise at a moderate tempo can be preventative. The pharmacy has over-the-counter products to prevent gas from accumulating.

Foods which can cause thin stool

Dried fruit, orange juice, pears, cherries, plumbs, hermetic fruit, alcohol, sorbitol, aspartame, sugar in large quantities, and fatty foods can cause diarrhea. Ripe bananas, blueberries, boiled potatoes, carrot puree, apple sauce, apple juice, pasta, rice, boiled milk, and peanut butter have the opposite effect. The pharmacy has over-the-counter products which improve the absorbance function of the bowel and can be taken in prevention and regularly.

General advice for ileostomy operated patients

Food can be salted extra due to loss of electrolytes through bowel movements. Food with a high fiber content should be chewed well to ease digestion and hinder enteralgia. It is recommended to take vitamin B12 due a lack of nutrient absorption in the lower part of the small intestine. Electrolyte mixtures are available at the pharmacy. Sport drinks can be taken used an alternative.

 

 

 

 

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