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Utskriftsdato (23.9.2020)

Soft tissue sarcoma in the abdomen and pelvis

Soft tissue sarcomas of the abdomen and pelvis include a wide spectrum of histological subtypes with both low and high-grade tumors.

Sarcomas in the abdominal region are often grouped according to localization:

  • Retroperitoneal
  • Intra-abdominal
  • Gynecological
  • Abdominal wall  

Retroperitoneal sarcomas

A retroperitoneal tumor is localized behind the dorsal layer of the peritoneum from the diaphragm and down to the pelvic floor.

The most common sarcomas in this region comprise the histological subtypes liposarcoma and leiomyosarcoma. Other histological subtypes include pleomorphic sarcoma, malignant fibrous histiocytoma (MFH), fibrosarcoma, solitary fibrous tumor, malignant peripheral nerve sheath tumor, and others.

Intra-abdominal sarcomas

Intra-abdominal sarcomas are also referred to as visceral sarcomas and may involve any of the visceral organs within the abdominal cavity, the most common of which is the gastrointestinal tract. The most common histological subtypes include gastrointestinal stromal tumor (GIST) and leiomyosarcoma.

GIST may occur anywhere in the gastrointestinal tract, from the esophagus to the anus. In rare cases, they can occur outside the gastrointestinal tract, for example the greater omentum or retroperitoneum.

Gynecological sarcomas

The most common gynecological sarcomas occur in the uterus and comprise the histological subtypes leiomyosarcoma and endometrial stromal sarcoma. Other types of soft tissue sarcomas, in combination with adenomatous (adenosarcoma) or carcinomatous components (carsinosarcoma), can occur.

Abdominal wall sarcomas

Soft tissue sarcomas of the anterior abdominal wall include such histological subtypes as liposarcoma, synovial sarcoma, fibrosarcoma, dermatofibrosarcoma protuberans (DFSP) and others.

Incidence

In 2015, two persons were diagnosed with soft tissue sarcomas in the abdomen and pelvis, both were men. Soft tissue sarcomas in the abdomen and pelvis constitute 25-30% of all soft tissue sarcomas.

Retroperitoneal sarcomas amount to about 15% of all soft tissue sarcomas, while intra-abdominal sarcomas account for 10-15%. They occur in all age groups and involve men and women equally.

Gynecological sarcomas may occur in women of all ages and comprise about 5% of all uterine cancer. Among these, leiomyosarcoma amounts to about 60%, while endometrial stromal sarcoma and adenosarcoma, comprise 20% and 6%, respectively. 

Etiology of soft tissue sarcoma of the abdomen and pelvis

In most cases, the cause is unknown. Several risk factors have been identified that increase the likelihood of developing a soft tissue sarcoma.

Risk factors

  • External radiation therapy is the most well-established risk factor. Patients treated with radiation therapy for cancers of the breast, cervix, ovary, testes, retina, or lymphatic system have a much higher chance of developing a soft tissue sarcoma than the general population.

    The risk appears to be related to the dose of radiation. To limit this risk, radiation treatment for cancer is planned to ensure that the greatest amount of radiation is delivered to diseased tissue while surrounding healthy tissue is protected as much as possible.

  • Another risk factor for soft tissue sarcomas is exposure to certain chemicals in the workplace, including:
    • vinyl chloride
    • arsenic
    • herbicides such as phenoxyacetic acids
    • wood preservatives that contain chlorophenols
  • A genetic disposition for the development of soft tissue sarcoma has been shown for several inherited diseases:
    • Li-Fraumeni syndrome (associated with alterations in the p53 tumor suppressor gene)
    • von Recklinghausen disease (also called neurofibromatosis type 1 and associated with alterations in the NF1 gene)
    • hereditary leiomyomatosis and renal cell cancer syndrome (with alterations in the FH gene)
    • hereditary retinoblastoma (with alterations in the RB1 gene)

    Patients with these disorders are all at risk of developing soft tissue sarcomas.

  • Chronic lymphedema following radiation to, or surgical removal of lymph nodes, is also a risk factor.

Histology of soft tissue sarcoma of the abdomen and pelvis

There are many different histological types of soft tissue sarcoma. The most common are:

  • Liposarcoma
  • Gastrointestinal stromal tumor (GIST)
  • Leiomyosarcoma

Liposarcoma

Liposarcoma is one of the most frequently appearing sarcomas. There are many different subtypes of liposarcoma important to recognize because of varying biology.

Operation specimen with a well differentiated liposarcoma. Click to enlarge. Photomicrograph of a well differentiated liposarcoma. Click to enlarge.  Photomicrograph of a dedifferentiated liposarcoma. Click to enlarge

Well differentiated liposarcoma

Operation specimen from the posterior abdominal wall demonstrating a liposarcoma growing around the kidney. Click to enlarge.

Well differentiated liposarcoma is a tumor looking almost like a lipoma. The diagnosis is based on the finding of relatively mature fat cells with marked variation in cytoplasmic size. There are often atypical multivacuolated lipoblasts or atypical spindle cells in fibrous areas. The tumor can be lipoma-like, sclerosing, inflammatory or spindle celled. Differential diagnosis is lipoma, although lipoma  is very seldom located in the posterior abdominal wall in contrast to in the extremities.

Cytogenetic investigation is useful in the differential diagnosis of these tumors. Ring- or giant cell marker chromosomes derived from chromosome 12 q indicate well differentiated liposarcoma. MDM2 or CDK4 in chromosome 12 is amplified in these tumors. The majority of the well differentiated liposarcoma do not metastasize, although larger tumor more frequently recur.

Dedifferentiated liposarcoma

Dedifferentiated  liposarcoma include two distinct growth patterns, one partly well differentiated liposarcoma and the other looking more like a malignant fibrous histiosarcoma or fibrosarcoma. The dedifferentitated component is usually high grade malignant. Dedifferentiation can either be detected in the primary tumor or in a later occurring recurrences. These tumor types are more frequent in the posterior abdominal wall compared to the extremities. Cytogenetically they demonstrate the same findings as in well differentiated liposarcoma.

Gastrointestinal stromal tumor (GIST)

GIST is a cellular tumor in the gastro-intestinal tract  with spindle, epitheloid or pleomorphic  tumor cells that express KIT (CD117). This tumor originate from the mesenchymal stem cells that produce interstitial Cajal-cells (pacemaker cells). This is the most common mesenchymal tumor in the GI-tract, but comprise only 2,2% of all GI-tumors or 13,9% of small intestinal tumors. GANT (GI autonom nerve tumor) is considered to be a variant of GIST.

The most frequent location for GIST is the stomach (55-65%), small intestine (20-30%), Colon/rectum (5-8%), esophagus and other locations (2-3%). 

Before GIST was well recognized  it was diagnosed as leiomyoma, leiomyoblastoma or leiomyosarcoma.

Since  histological appearance do not correlate well to biological behavior malignancy grading is not used with GIST, instead a risk evaluation according the following table is performed.

Risk evaluation in GIST
Risk Size

Mitotic count (in 50 lf.)

Very low < 2 cm < 5   
Low 2–5 cm < 5
Intermediate < 5 cm 6–10
5–10 < 5
High > 10 cm Any mitotic count
All size > 10
> 5 > 5

Immunohistochemical investigation in GIST tumor usually demonstrate positive reaction for KIT (CD117) (95%), CD34 (70-80%), smooth muscle actin (SMA) 20-40% or Caldesmon (80%). Desmine and protein S-100 is usually negative in GIST. It is recommended to include an immunhistochemical panel with CD117, vimentin, desmine, actin, SMA, CD34, protein S-100, and AE1/AE3 when investigating spindle cell tumor in the abdomen.  

Operation specimen from the stomach with GIST. Click to enlarge.  Operations specimen from the rectum with a GIST. Click to enlarge.
Photomicrograph of GIST. Click to enlarge.

Mutations in GIST 

Majority of GIST has activating mutations in KIT, that codes for a tyrosinkinase receptor. Mutation produce a ligand

Photomicrograph demonstrating immunohistochemical positively for KIT (CD117) in a GIST. Click to enlarge.

independent  activation of tyrosinkinase that induce uncontrolled cell growth. In about 5% of all GIST there is a mutation in the related tyrosinkinase PDGFRA. Mutation in  KIT and PDGFRA genes can rather well predict the response to treatment with tyrosinsinhibitor imatinib.

Primary mutations in KIT is seen in exon 9,11,13 or 17. The most frequent is seen in exon 11(about 70%), while about 10-20% is in exon 9. Exson 9 mutations is more frequent in small intestine and seldom seen in stomach GIST. It has been shown that GIST with mutations in exon 11 respond better to imatinib than those with mutations in exon 9. 

About  5% of GIST is immunohistochemically negative for KIT (CD117). A majority of these have mutations in PDGFRA in exon 12,14 or 18.  PDGFRA mutations are strongly related to GIST located in the stomach and with epitheloid morphology.  GIST with exon 18 mutations is most frequent in these cases (80%) and point mutations that produce D842V is known to be associated with resistance to imatinib.

In some GIST no mutations can be detected (wild type). These respond poorly to imatinib treatment.

Patients with GIST that initially respond to imatinib treatment might subsequently over time develop resistance. the resistance is associated with new mutations in the tumor cells (secondary mutations).

Mutation analysis can be performed on frozen, fixed or paraffin-embedded material. The result of such analysis can of importance for deciding type of therapy.

Leiomyosarcoma

Leiomyosarcoma in the posterior abdominal wall (retroperitoneum) or in the abdominal cavity are often well circumscribed tumors. Microscopically they demonstrate spindle or epitheloid cells with  atypia and partly cigar-formed nuclei. Immunohistochemical investigation demonstrate positivity for smooth muscle actin (SMA), actin, or desmine, but negative for CD117 and CD34. 
 
Operation specimen from the posterior abdominal wall with a leiomyosarcoma probably originating from a large vein. Click to enlarge. Photomicrograph of leiomyosarcoma. Click to enlarge.

Gynecologic sarcomas

The most common gynecologic sarcoma is leiomyosarcoma and endometriestroma sarcoma in the uterus. Other types of sarcoma can also appear and be located in all gynecological organs.
The criteria for malignancy grading of uterine sarcomas differ from soft tissue sarcomas and gastro-intestinal sarcoma.

Evaluation of operation specimens

When a soft tissue sarcoma is diagnosed the following information should be included in the pathology report:

  • Histological diagnosis
  • Malignancy grade /mitoc count
  • Tumor size (three dimensions or largest diameter)  
  • Vessel invasion
  • Necrosis (percentage area with necrosis)
  • Growth pattern (infiltrative growth or not)
  • Tumor localization and infiltration of surrounding tissue'
  • Resection borders
  • Result of additional special investigations (immunohistochemical or molecular, genetical.

Metastatic patterns of soft tissue sarcoma of the abdomen and pelvis

Abdominal and pelvic soft tissue sarcomas metastasize primarily hematogenously. The main organs at risk are liver and lungs. In a much lesser degree, abdominal and pelvic sarcomas metastasize to other soft tissues like muscle and subcutaneous fat or bone. Unlike carcinomas, soft tissue sarcomas rarely spread to lymph nodes.

A particular form of metastasizing seen especially in visceral and gynecological soft tissue sarcomas, and in a lesser degree in retroperitoneal or abdominal wall sarcomas infiltrating the peritoneum, is tranperitoneally. Trans- or intraperitoneal spreading poses a risk for relapse or metastases in the entire abdominal region. Transperitoneal metastases are like other metastases most often the result of advanced disease but these can also be iatrogenic after incomplete resections.

Staging of soft tissue sarcoma of the abdomen and pelvis

It is recommended that classification of soft tissue sarcoma in the abdomen and pelvis is done according to WHO guidelines. The American Joint Committee on Cancer (AJCC)/International Union Against Cancer (UICC) staging classification system is based on several factors. Its use in routine clinical practice is limited.

TNM Classification

The TNM system describes the extension of the disease at presentation.

  • (T) size of the tumor
  • (N) whether or not the sarcoma cells have spread to the lymph nodes, which in most soft tissue sarcoma patients is very rare
  • (M) whether or not the sarcoma cells have spread or metastasized to other parts of the body

The AJCC/UICC system also stresses the histopathological or malignancy grading. This component assesses how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. It is also often called tumor grade.

A four-point scale has been commonly used until recently:

  • Grade I and II are low-grade malignant (constitute about 30% of all tumors)
  • Grade III and IV are high-grade malignant (constitute about 70% of all tumors)

It is becoming more common to use a three-point scale (French system) where grade 3 is the most aggressive.

Other histopathological factors that are not part of the staging system but may be important for prognosis of soft tissue sarcomas include growth pattern, necrosis and vessel invasion.

The staging system used for gynecological sarcomas is the same as for endometrial cancer (FIGO). Specific staging of gynecological sarcomas is under development.

Symptoms of soft tissue sarcoma of the abdomen and pelvis

Retroperitoneal soft tissue sarcomas usually cause symptoms late and these are often due to the size of the tumor.

In up to 80% of cases, the tumor is discovered by palpation, either by the patient himself or as a coincidental finding during physical examination. A large tumor may lead to compression of surrounding organs leading to nonspecific gastrointestinal symptoms in about 50% of patients.

Most common symptoms for both retroperitoneal and intra-abdominal sarcomas include: 

  • Anorexia
  • Asthenia
  • Weight loss 
  • Discomfort in the abdomen

Intra-abdominal sarcomas can also cause more specific symptoms mostly due to tumor localization, ulceration or obstruction:

  • Bleeding
    • Hematemesis
    • Melena
    • Anemia
  • Stenosis/obstruction
    • Nausea
    • Dysphagia
    • Gastroesophageal reflux
    • Constipation
    • Ileus/subileus
    • Pain 

The majority of patients with uterine sarcomas present with abnormal uterine bleeding, regardless of histology. Bleeding may vary from spotting to severe menorrhagia and is reported in up to 95% of patients.

Differential diagnoses of soft tissue sarcoma of the abdomen and pelvis

Retroperitoneal

  • Carcinoma of the kidney
  • Adrenal tumor
  • Schwannoma
  • Metastases from germ cell tumor
  • Retroperitoneal fibromatosis
  • Reactive and inflammatory tumors

Intra-abdominal

  • Carcinoma
  • Lymphoma
  • Leiomyoma 
  • Fibromatosis
  • Reactive and inflammatory tumors

The unusual presentation of a tumor in the gastrointestinal tract or kidney and/or adrenal should always alert suspicion of a soft tissue sarcoma.

Gynecological

  • Leiomyoma
  • Carcinoma in the uterus or cervix

Abdominal wall

  • Lipoma
  • Fibromatosis

Prognosis of soft tissue sarcoma of the abdomen and pelvis

Retroperitoneal

The prognosis of patients with retroperitoneal sarcomas depends on the disease extent. For patients presenting without metastatic disease, complete surgical resection and histologic grade have been the main determinants of survival.

Complete surgical resection is one of the most important factors for cure or extended survival, as incomplete resection of the tumor or spill of tumor cells during the operative procedure greatly increases the chance for recurrence, and drastically reduces the prognosis.

Other prognostic factors in decreasing order include tumor size, histological subtype, growth pattern, necrosis, vascular and nerve invasion.

Intra-abdominal

The prognosis for localized GIST depends on the size of the tumor and number of mitoses, localization, and the quality of the operative procedure. The prognosis for metastatic GIST has significantly improved after the introduction of imatinib treatment in 2001.

Gynecological

As with other abdominal and pelvic soft tissue sarcomas, the prognosis of gynecological sarcomas is also dependant on presentation and on treatment. Size, histological type and malignancy grade all have prognostic significance.

Prognosis is better for endometrial sarcoma than for uterine leiomyosarcoma.

In localized tumors the quality of the operative treatment is of great prognostic significance.

Abdominal wall

Prognosis of primary localized soft tissue sarcomas of the anterior abdominal wall is dependent, as in other localizations, on malignancy grade, histologic subtype, size and quality of the operative resection.

References on soft tissue sarcoma of the abdomen and pelvis

  1. Anaya DA, Lev DC, Pollock RE. The Role of Surgical Margin Status in Retroperitoneal Sarcoma. J Surg Oncol 2008; 98:607-610.
  2. Bevilaqua R, Rogatko A, Hajdu S, et al. Prognostic Factors in Primary Retroperitoneal Sof-Tissue Sarcoma. Arch Surg 1991; 126: 328-334.
  3. Casali PG, Jost L, Sleijfer S, et al. Soft Tissue Sarcoma: ESMO Clinical Recommendations for the diagnosis, treatment and follow-up. Ann Oncol 2009; 20 (4): 132-136
  4. Dalton RR, Donohue JH, Mucha P, et al. Management of Retroperitoneal Sarcomas. Surgery 1999; 106: 725-733.
  5. DeMatteo RP, Heinrich MC, El-Rifai WM, et al. Clinical Management of Gastrointestinal Stromal Tumors: Before and After STI-571. Hum Pathol 2002, 33 (5) 466-477
  6. Fletcher CD, Berman JJ, Corless C, et al. Diagnosis of gastrointestinal stromal tumors: A consensus approach. Hum Pathol 2002 459–465
  7. Hohenberger P, Ronellenfitsch U, Oladeji O, et al. Pattern of Recurrence in Pateints with Ruptured Primary Gastrointestinal Stromal Tumour. Br J Surg 2010; 97: 1854-1859.
  8. Joensuu H, DeMatteo RP. The Management of Gastrointestinal Stromal Tumors: A Modell for Targeted and Multidisciplinary Therapy of Malignancy. Annu Rev Med 2012. 63:10.1-10.12
  9. Joensuu H, Fletcher C, Dimitrijevic S, et al. Management of Malignant Gastrointestinal Stromal Tumors. The Lancet Oncol 2002, Vol 3 (11) 655-664.
  10. Lahat G, Anaya DA, Wang X, et al. Resectable Well-Differentiated versus Dedifferentiated Liposarcomas: Two Different Diseases Possibly Requiring Different Treatment Approaches. Ann Surg Oncol 2008; 15 (6): 1585-1593
  11. Lewis JJ, Brennan MF. Soft Tissue Sarcomas. Curr Prob Surg, 1996; 33 (10): 817-880.
  12. Lewis JJ, Leung D, Woodruff JM, et al. Retroperitoneal Soft Tissue Sarcoma. Analysis of 500 patients treated and followed at a single institution. Annals of Surg 1998; 228 (3): 355-365.
  13. Livi L, Andreopoulou E, Shah N, et al. Treatment of Uterine Sarcoma at The Royal Marsden Hospital from 1974-1998. Clin Oncol 2004; 16 (4): 261-268.
  14. SSG XVII Recommendations for the Diagnosis and Treatment of Intraabdominal, Retroperitoneal, and Uterine Sarcoma.(Scandinavian Sarcoma group) 2008 [Online]; Available from: URL: http://www.ssg-org.net/
  15. Sæther G, Helgerud P, Talle K, et al. Retroperitoneal Soft Tissue Sarcoma. The Norwegian Radium Hospital (NRH) Experience. Abstract. SSG 20th Anniversary Meeting. Oslo 1999.
  16. Yeh JJ, Singer S, Brennan MF, et al. Effectiveness of Palliative Procedures for Intra-Abdominal Sarcomas. Ann Surg Oncol 2005; Vol 12 (12): 1084-1089.
  17. Nasjonal handlingsprogram med retningslinjer for diagnostikk, behandling og oppfølging av pasienter med sarkom (2015), Helsedirektoratet (National guidelines for diagnostic, treatment and follow-up care of  sarcoma, Norwegian Directorate of Health)

Diagnostics of soft tissue sarcoma of the abdomen and pelvis

Clinical examination

Specific or nonspecific symptoms in addition to a thorough clinical examination may alert the physician to the possible diagnosis of a soft tissue sarcoma. The physician may use one or more radiological modalities in order to help establish the correct diagnosis.

Computed Tomography (CT)

CT is the preferred general screening tool for abdominal and retroperitoneal tumors. It has as the main advantages short scan times, limited motion artifacts and reproducible results. The introduction of helical CT and especially multi-slice technique has improved anatomical detail and the quality of multi-planar reconstructions. CT of the abdomen and pelvis can be complemented with a CT of the chest in order to fully evaluate the possibility of metastatic disease.

Magnetic resonance imaging (MRI)

Though CT is the preferred imaging tool for the abdomen and pelvis, MRI scan is a superb adjunct to the evaluation of tumors in the pelvis. While motion artifacts significantly reduce image quality of the abdomen and to certain extent of the retroperitoneum, MRI of the pelvis can greatly aid in defining the extent of disease and in the establishment of the correct diagnosis in the pelvis.

Ultrasound (US)

Abdominal ultrasounds are often performed for initial screening and can lead to the detection of a tumor and the decision of further work-up with CT. Their quality is highly dependent on the examiners experience and they are not reproducible.

X-rays

A chest x-ray is often used as the initial screening test for possible disease extention in the chest.

Endoscopy

Gastroscopy is usually performed to evaluate tumors in the upper gastrointestinal tract, including esophagus, stomach and duodenum. It can be supplemented with endoscopic US and possibly endoscopic fine-needle biopsy.

Referral to a Sarcoma Center

Clinical and radiological findings suspect for a soft tissue sarcoma (CT) form the background for further referral to a sarcoma center. The patient with a tumor suspicious of a sarcoma should be referred to a sarcoma center without previous biopsy or operation. The attempt at biopsy or tumor removal can lead to spreading of tumor cells and drastically reduce the possibility for successful curative treatment.

At a sarcoma center, clinical information and images are assessed by a multidisciplinary team, and further work-up, the necessity of a biopsy and treatment are determined.

Typical image diagnostic findings

CT of retroperitoneal sarcoma. Click to enlarge image. CT of GIST in stomach. Click to enlarge image. MRI of leiomyosarcoma in the uterus. Click to enlarge image.

Biopsy

Cytology by fine-needle aspiration or biopsi-guided by ultrasound or CT scan is the method of choice for obtaining tissue and establishing the correct histological diagnosis. 

A fine-needle aspiration or biopsy is deemed necessary in the following cases:

  • For a tumor with uncertain nature where the diagnosis is decisive to determine whether the patient will be operated or whether the patient will be treated with chemotherapy or radiotherapy.
  • For a tumor with uncertain nature where the operative treatment extend is dependant on the benign or malignant nature of the tumor.

Retroperitoneal, intra-abdominal, gynecological or abdominal wall tumors are often removed without previous biopsy in order to avoid spreading of tumor cells.

PROSEDYRER

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.

Ultrasound-guided needle biopsy in the abdomen

General

CT and other radiological examinations are often used for assessment of possible spreading of different cancer types. For these examinations, it is possible to find enlarged lymph nodes or unspecific lesions where it is necessary to confirm or exclude metastases. If the lesion is visible on ultrasound, ultrasound-guided biopsy is the optimal method for clarification. The exception is for suspicion of sarcoma which should be adequately reported with pictures before sample collection. The indication assessment is done by a sarcoma specialist.

Ultrasound-guided biopsy is a quick method for diagnosing possible pathology of suspect lesions/changes deep in the abdomen. We always use fine-needle aspiration initially. The cell sample is stained immediately and assessed by a cytologist. In many cases, the diagnosis for metastasis or reactive lymph node is certain after rapid staining and microscopy. When relevant, a pistol biopsy is performed as well. In these cases, it is necessary to wait 4-6 days to initiate treatment while awaiting the result.

Indication

  • Lesions of unknown type in the abdomen evident by radiological examinations.

Goal

  • Confirm or exclude metastases of suspect lesions in the abdomen evident by radiological examinations.

Equipment

  • Ultrasound apparatus with (transducer) for the procedure.
  • Local anesthetic (5 ml Xylocain 10 mg/ml). (Not always for cytological biopsies - always for histological biopsies.)
  • Syringe (5 ml) and needle for anesthesia. (22 G B&D spinal needle)
  • Needle for cytology material. (22 G B and D spinal needle)
  • 4 specimen slides for the material 

For a histological biopsy with biopsy pistol, the following is used additionally:

  • separate 18 G or 16 G needle + pistol, possibly disposable  
  • glass slides for storage of histological material (formalin, Ringer solution, McCoy, dry glass slides for freezing etc. – depending on tentative diagnosis).

For sterile bandaging (used for local anesthesia)

  • Sterile cover
  • Sterile disposable tweezers
  • Sterile compresses 5 x 5 cm
  • Chlorhexidine colored 1 mg/ml
  • Sterile gloves
  • Sterile condom for UL-head
  • Sterile gel
  • Mepore bandage 6 x 7 cm

Preparation

  • For ultrasound-guided puncture in the abdomen, the patient should fast the last 4 hours before the exam for best possible access.
  • Depending on the localization and localization of the lesion, normal blood tests should be done beforehand for bleeding parameters (hemoglobin, thrombocytes, possibly INR).
  • The patient is informed about what will happen.
  • The patient should lie comfortably on the examination table.
  • Inform the patient during the procedure.   

Implementation

Ultrasound-guided biopsy is taken with or without local anesthesia depending on depth, localization, and patient cooperability.

  • Localize the lesion with the ultrasound probe.
  • Determine the best puncture point and direction.
  • Wash the point of puncture with colored chlorhexidine 1 mg/ml.
  • Allow the skin to dry.
  • Inject the local anethesia with the help of ultrasound in the entire puncture canal, especially the skin, muscle fascia, peritoneum, and organ surfaces. It is important the patient does not experience any pain when the biopsies are taken. If the puncture is painful, it is easy to lose control of the needle, and small lesions are difficult to reach.
  • Puncture the spinal needle quickly through the skin.
  • Insert the the needle with the help of ultrasound through the peritoneum and into the lesion.
  • Retrieve the mandrin.
  • Move the needle back and forth 2-3 times per second. Due to capillary action, the cells will be collected in the needle.  
  • When the material is evident in the upper part of the needle, it is retrieved.
  • Deposit the material onto a specimen slide.

Spread for cytology

  • Spread the material out with a specimen slide.
  • Dry the material under a fan or similar.
  • Staining: fixation fluid with methanol + haemacolour + rinsing in water:
    • 5 dips in fixator: allow the solution to drip off the paper.
    • 3 dips in color solution 1.
    • 6 dips in color solution 2. Allow the solution to drip off the paper.
    • Rinse in 2 baths of clean water.
    • Examine the specimen under a microscope with 10x or 20x objective.

    Microscopic assessment of cell material is done by a cytologist to determine if supplementary tests are necessary.

    Histological biopsy (pistol biopsy)

    • Place local anesthesia in the entire puncture canal down to the lesion. This is done with the help of ultrasound.
    • Make a small incision in the skin.
    • Insert the biopsy needle up to the lesion, preferably a little ways in, depending on the size of the lesion and type of tissue in front and behind the lesion.
    • Pull the trigger to take the sample.
    • Retrieve the needle and open it.
    • Place the piece of tissue in a holder 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 the localization of the lesion and nature, bleeding may occur after the biopsy procedure.
    • For intense pain or bleeding, the patient must be observed at the post or intensive unit, depending on severity, while necessary measures are taken.
    Ultrasound-guided needle biopsy in abdomenUltrasound-guided needle biopsy in the abdomenUltrasound-guided needle biopsy from abdomen
    Ultrasound-guided needle biopsy from the abdomenUltrasound-guided needle biopsy in the abdomenUltrasound-guided needle biopsy from abdomenUltrasound-guided needle biopsy in the abdomen

    Treatment of soft tissue sarcoma of the abdomen and pelvis

    Treatment for soft tissue sarcomas of the abdomen is determined mainly by the stage of the disease. Treatment options include surgery, radiation therapy, chemotherapy and pharmacological treatment. A multidisciplinary team of sarcoma specialists can help plan the best treatment for the patient.

    Treatment of localized disease

    Surgical resection is the standard primary treatment for all patients with localized abdominal and pelvic sarcomas, including retroperitoneal, intra-abdominal, abdominal wall and gynecological sarcomas.

    The requisite for cure is complete surgical resection with microscopic tumor-free margins in the first attempt. This predisposes that the tumor is removed without contamination of surrounding tissue and the abdominal cavity from inadvertent tumor rupture.

    Treatment of metastastatic disease 

    The disease is not considered to be curable if the tumor is locally advanced and deemed unresectable. Even if it is not possible to achieve curative surgery, the possibility for palliative surgery should be assessed to reduce symptoms. Palliative surgery may also prolong survival in selected cases.

    Patients with liver or lung metastases should be assessed for liver or lung resection and/or other appropriate treatment.

    Chemotherapy and radiation are given in certain cases depending on histology, grade of malignancy and extent of disease. The principles for systemic treatment of soft tissue sarcomas localized in extremities are used as a guide.

    Treatment of recurrent disease

    Many recurrences occur in the same site as the primary tumor. In other cases, the recurrence is limited to one or a few well-defined lesions retroperitoneally or in the abdominal cavity.

    The standard treatment for patients with recurrence is to repeat the surgical resection according to the same principles as for primary resection. The aim remains a curative operation with complete resection and tumor-free margins.

    The ability to achieve this declines as the number of local recurrences increases. The optimal time for surgical treatment of recurrence depends on size, location and symptoms.

    Treatment of GIST

    Treatment of localized GIST follows the same surgical principles as for other soft tissue sarcomas of the abdomen. The goal of surgery is to resect the tumor with microscopic free margins in the organ of origin and without violating the pseudocapsule of the tumor.

    Large primary and localized GIST can be treated with neoadjuvant pharmacological therapy with imatinib in order to attempt size reduction and organ preservation. Neoadjuvant treatment is usually given until peak response at about 6-12 months.

    Resected high risk GIST is most often treated with adjuvant pharmacological therapy for 36 months.

    For an inoperable tumor, local relapse, or metastases, pharmacological treatment with imatinib is the first-line of therapy.

    Surgery of soft tissue sarcoma of the abdomen and pelvis

    Surgical resection with negative margins remains the standard treatment for patients with localized abdominal sarcomas, including retroperitoneal, intra-abdominal, abdominal wall and gynecological sarcomas.

    The goal and requisite for cure is complete surgical resection with microscopic tumor-free margins in the first attempt. This procedure predisposes that the tumor is removed without contamination of surrounding tissue and the abdominal cavity from inadvertent dissection into the tumor pseudocapsule or overt tumor rupture.

    The size of the tumor, pattern of growth, and location close to vital organs and structures at the time of diagnosis often renders the surgical resection a complicated procedure. Good preoperative planning is crucial. 

    All radiological images must be assessed carefully to plan the extent of the surgery. As complete resection is the goal, adequate margins around the tumor must be defined. Compression of the tissue around the lesion versus direct tumor infiltration into structures is not always evident radiologically. When necessary, surrounding organs must be assessed for en bloc resection.

    In retroperitoneal soft tissue sarcomas especially, en bloc resection of organs surrounding the tumor is often necessary in order to achieve the goal of a complete resection. This is performed in up to 80% of cases. This principle also applies to sarcomas in other abdominal and pelvic localizations.

     

    PROSEDYRER

    Excision of retroperitoneal sarcoma

    General

    Surgery is the only curative treatment of retroperitoneal sarcoma and the prerequisite is complete resection with negative microscopic margins. A successful procedure is dependent on good planning.

    Retroperitoneal sarcomas are often diagnosed late and are therefore often large at the time of diagnosis. Because of this, tumors often have a close relation to a number of neighboring organs and structures. In order to achieve the goal of resecting the tumor with negative margins, tumors must often be resected with neighboring organs.

    Retroperitoneal sarcomas can occasionally have close relations to, and originate from vital vascular structures such as the vena cava and the descending aorta. The possibility of resection of vital structures and/or organs defines operability.

    Indication

    • Sarcoma in the retroperitoneum

    Goal

    • Cure the disease
    • Palliation

    Equipment

    • Laparotomy tray
    • Helgerud's retractor
    • Self-retaining retractor, Bookwalter or similar
    • Depending on the localization of the tumor: Ligasure, staple instruments (GIA, TA) 

    Preparation

    • Preoperative colon emptying
    • Antiobiotic prophylaxis
    • Thrombosis prophylaxis
    • Epidural catheter is inserted for pain treatment
    • A bladder catheter is installed unless the procedure is of very short duration.
    • The patient is operated under general anesthesia.
    • Positioning of the patient depends on where the incision is made.

    Implementation

    • A generous midline incision is the preferred surgical approach. Occasionally, this incision is extended to either groin or as a thoracotomy for optimal exposure.
    • The tumor must be excised with an intact pseudo-capsule in order to attain negative margins and avoid tumor spillage. This can only be achieved by careful dissection within normal tissue around all planes of the tumor.
    • If necessary, involved and/or contiguous fixed organs must be removed en-bloc with the tumor. Violation of the tumor capsule undoubtedly leads to tumor cell spillage and this in turn translates to a high risk for relapse and reduced prognosis.
    • Tumors localized in the right retroperitoneal space are often resected en-bloc with the right kidney, right adrenal gland, and right hemicolon. When in the left retroperitoneal space, tumors are often removed together with the left kidney, left adrenal gland, tail of the pancreas, spleen, and left hemicolon.
    • In some cases, muscular structures that delimit the retroperitoneal space like the diafragm, psoas, iliacus, or transversus abdominis must be partially resected together with the tumor. In other cases, small bowel is fixed to the tumor and must also be partially removed.

    Follow-up

    Complications that can occur:

    • Bleeding
    • Infection
    • Cardiopulmonary complications
    • Anastomosis failure
    Most patients are ready for discharge after 5-10 days.

    When the histology result is available and the treatment is considered finished, the patient is followed up:

    • Biannually the first 5 years with clinical examinations supplied with CT abdomen/pelvis and thoracic X-ray
    • The next five years, annually

    Excision of GIST

    General

    For localized intraabdominal or visceral sarcomas including GIST, operative treatment with complete resection of the tumor is the only curative modality and is indicated in all patients that seem medically fit to undergo the procedure.

    Only in selected cases of localized GIST, especially in the rectum, where downstaging of the tumor is desirable in order to limit the extent of an operation, will neoadjuvant treatment with thyrosinase kinase inhibitors be instituted for a period ranging from 6-12 months.

    Intraabdominal sarcomas can present with an intact serosal covering toward the peritoneal cavity, but in many instances this margin is nonexistent and the tumor has a naked intraperitoneal surface that greatly increases the risk of transperitoneal metastasis.

    Tumor rupture, if not already present before operation, should be avoided by meticulous handling of these tumors. All peritoneal surfaces should be examined for potential metastasis.

    The extent of resection of the gastrointestinal organ of origin is dependent on the size of the tumor base, its location and other anatomical and physiological aspects. Partial resections are most often sufficient to achieve negative tumor margins.

    When surrounding organs have tight adherances to the tumor, an en bloc resection of these organs with the tumor should be performed. Only in selected cases should these patients be treated by laparoscopic procedures.

    Indication

    • GIST

    Goal

    • The patient is free of macroscopic tumor tissue.

     

    Equipment

    • Common laparotomy tray
    • Self-retaining abdominal retractor, Bookwalter or similar
    • Depending on the localization of the tumor: Ligasure, staple instruments (GIA, TA)

    Preparation

    • Depending on the localization of the tumor in the GI-tract, preoperative colon emptying may be necessary.
    • Antibiotic and thrombosis prophylaxes are given.
    • Epidural catheter is inserted for pain treatment.
    • A bladder catheter is installed unless the procedure is of very short duration.
    • The patient is operated under sedation.
    • The positioning of the patient depends on location of the incision.

    Implementation

    The same oncological principles described in the resection of retroperitoneal sarcomas are applied.
    • A generous midline incision is the preferred surgical approach.
    • Occasionally, this incision is extended to either groin or as a thoracotomy for optimal exposure.
    • The tumor must be excised with an intact pseudo-capsule in order to attain negative margins and avoid tumor spillage. This can only be achieved by careful dissection within normal tissue around all planes of the tumor.
    • If necessary, involved and/or contiguous fixed organs must be removed en-bloc with the tumor. Violation of the tumor capsule undoubtedly leads to tumor cell spillage and this in turn translates to a high risk for relapse and reduced prognosis.
    • Tumors localized in the right retroperitoneal space are often resected en-bloc with the right kidney, right adrenal gland, and right hemicolon. When in the left retroperitoneal space, tumors are often removed together with the left kidney, left adrenal gland, tail of the pancreas, spleen, and left hemicolon.
    • In some cases, muscular structures that delimit the retroperitoneal space like the diafragm, psoas, iliacus, or transversus abdominis must be partially resected together with the tumor. In other cases, small bowel is fixed to the tumor and must also be partially removed.

    A detailed operative description, including status of peritoneal surfaces, inadvertent intralesional dissection and tumor rupture must be reported in order to aid in risk-classification and indication for postoperative systemic treatment.

    Follow-up

    Complications that can occur:

    • Bleeding
    • Infection
    • Anastomosis failure
    • Stenosis development
    • Cardiopulmonary complications
    Most patients are ready for discharge after 5-6 days.

    When the histology result is available, it is determined whether the patient requires chemotherapy.

    If the treatment is considered finished, the following outpatient follow-ups are standard:

    • Biannually for the first 5 years with clinical examinations supplemented with CT of abdomen/pelvis and thoracic X-ray
    • Annually for the next 5 years

    Removal of uterine sarcoma

    General

    Patients suspect of harbouring a soft tissue sarcoma of the uterus or other internal gynecological organs by clinical examination and/or radiological studies should promptly be referred to a specialized sarcoma center. This should be done without previous biopsy.

    Prognosis of patients with localized gynecological sarcomas is as with other abdominal sarcomas greatly dependent on the correct initial treatment.

    At the specialized sarcoma center, the patient will be evaluated by a multidisciplinary team which will determine the need for biopsi and the treatment plan.

    Total hysterectomy and bilateral salpingo-oophorectomi is the standard treatment for localized sarcomas of the uterus not infiltrating through the serosal surfaces.

    An extended resection is indicated for all tumors extending beyond the uterus serosa and multiorgan resection must be carried out for tumors densely adhered to or infiltrating neighbouring organs. Since especially endometrial stromal sarcomas, but also other gynecological sarcomas are hormone sensitive, bilateral ooporectomy is always indicated.

    Utmost care must be taken to achieve negative tumor margins over all surfaces and including in the vagina. The limited pelvic space renders resection of large gynecological sarcomas especially challenging. Laparoscopic resections for uterine sarcomas should not be attempted.

     

    Goal

    • Curative treatment where the avoidance of spreading of tumor cells is considered.

    Indication

    • Uterine sarcoma

    Equipment

    • Gynecological laparotomy tray
    • Bookwalters retractor
    • Surgical stapler (f.ex. TA®)

    Preparation

    • Bowel emptying
    • Thrombosis prophylaxis
    • Antibiotic prophylaxis

    Implementation

    For the operative treatment of gynecological sarcomas, the same oncological principles described in the resection of retroperitoneal sarcomas are applied.

    • Make a mid-line incision.
    • Use a Bookwalters retractor.
    • Check the entire abdomen for possible spreading:
      • Liver, spleen, lymph nodes, diaphragm, stomach, bowels, pelvis, top of uterus.
      • Palpate the ovaries and fallopian tubes for adherances or infiltration into uterus (from either the disease, previous endometriosis, or previous infection)
    • Lower the patient's head to to remove the bowels away from the operation field (Trendelenburg).
    • Pack away the bowels in a compress soaked with NaCl 9 mg/ml. Hold in place with decharp og spekler.
    • Stitch the peritoneum to the symphysus to remove the bladder from the operation field.
    • Hold the uterus by salpinger with two Kocher forcepses.
    • Open to the retroperitoneum on the pelvic side-wall.
    • Incise the bladder peritoneum to separate the bladder from the anterior uterus.
    • Separate the bladder from the anterior uterus and cervix.
    • Identify the superior vesical artery and follow it to the origin from the internal iliacal artery.
    • The uterine artery is ligated close to the vesical artery.
    • Identify both ureters and follow them to the confluence with the bladder.
    • Remove the supportive tissue on the ureter (go through ”roof of the tunnel") and release ureter.
    • Retract the ureter to include resection of the parametria which lies adjacent to the uterus as well as to achieve space for instruments for removal of uterus.
    • Make sure the ureter is not separated from the pelvic wall to maintain the blood supply to the ureter.
    • Avoid damage of nerves.
    • Check that the ureter is retracted from the area to be resected.
    • Remove the uterine adjacent part of the parametrium (approx. 2 cm) as there may be cancer there. This is not done for a routine hysterectomy.
    • Conserve the parametrium as much as possible in order to avoid nerve damage causing for urinating.
    • Do not remove lymph nodes for sarcoma operations since there is very little chance of metastases in them.
    • Repeat the procedure on the other side of the uterus.
    • Open the peritoneum from behind to retract the colon (the rectum is attached to the posterior vaginal wall)
    • Divide the sacral-uterine ligament and make a suture ligate. Go gradually forward.
    • Push the rectum down to create more room to separate the top of the vagina.
    • Divide the cardinal ligament down along the vaginal wall and cut with the tip of the scissors all the way down to the wall.
    • Use a surgical stapling instrument (for example TA®) to close the top of the vagina (due to sarcoma)
    • Rinse the remainder of the vagina with sterile water (hypotonic solution to destroy possible tumor cells)
    • Put a new row of staples below the previous row with a surgical stapler. Make sure the ureter is not clamped in the instrument.
    • Divide between the two rows of staples. Be certain of cutting below the first row (to avoid contamination of tumor cells in the abdomen - spill of tumor cells is crucial for the patient's prognosis)
    • The unfixed specimen should be delivered dry and immediately to the laboratory.
    • Secure hemostasis. 
    • Count gauze pads and instruments.
    • Rinse the abdomen with 2 L sterile water to remove possible tumor cells.
    • Suture the fascia.
    • The skin may be closed with a skin stapler.
      • A detailed operative description, including status of peritoneal surfaces, inadvertent intralesional dissection and tumor rupture must be reported in order to aid in risk-classification and prognosis.

       

        Follow-up

        Complications that can occur:

        • Bleeding
        • Infections
        • Pain
        • Urination problems: the patient should have a catheter for 3-5 days. Monitor bladder emptying after removal of Foley catheter.

        Drug therapy of soft tissue sarcoma of the abdomen and pelvis

        Chemotherapy is administered to a  limited degree for abdominal sarcomas, but the benefit has not been clearly documented yet. Pre- and postoperative chemotherapy is administered for small round cell sarcoma (Ewing's sarcoma, rhabdomyosarcoma, desmoplastic small round-cell tumors, and mesenchymal chondrosarcoma.

        The tyrosine kinase inhibitor imatinib (Glivec®), has shown a dramatic effect on inoperable and/or metastasizing GISTs (gastrointestinal stromal tumor). Objective responses are observed in approximately 60% and the disease stabilizes in approximately 20%. Approximately 50% of patients with advanced GIST live after 5 years of imatinib use.

        Imatinib

        All medical treatment of Gists should take place in close collaboration with Regional Sarcoma Centers. Proper diagnosis and treatment require cooperation between surgeon, oncologist, radiologist and pathologist. The Sarcoma Centers are mainly responsible for the treatment plan.

        The majority of GISTs (>80%) have active mutations in KIT, which code for the tyrosine kinase enzyme. The mutation status for KIT is important to predict the response of treatment with the tyrosine kinase inhibitor, imatinib. Primary mutations occur in exon 9, 11, 13, or 17. Most mutations (approximately 70%) occur in exon 11, but 10-20% of the mutations are found in exon 9. Exon 9 mutations are seen most frequently in the small intestine and rarely in the stomach.

        The recommended start dosage of imatinib is 400 mg daily. The dosage may be increased to 800 mg daily at progression or in case of a KIT mutation in exon 9. It is recommended to follow international guidelines for treatment of GIST when treating this patient group. 

        The benefit of imatinib after removal of the primary tumor (adjuvant) is examined in multiple studies in both Europe and the US. Norway has participated in a study through the Scandinavian Sarcoma Group and the German Sarcoma Group where the effect of 1 and 3-year treatment with imatinib 400 mg was compared. The results from this study show better effect with 3 years of treatment. Therefore, 3 years of adjuvant treatment, with 400 mg imatinib daily, is recommended for patiens with certain tumor risk factors.  

        The side effects of imatinib are usually moderate: edema, nausea, diarrhea, dermatitis, and fatigue. Tumor bleeding is shown in approximately 5% and can be fatal. Interactions with medications which metabolize in the liver via CYP3A4 are known, and simultaneous use of paracetamol (acetominophen) and warfarin should be avoided.

        Patients where a positive effect of imatinib is not observed (primary or secondary resistance) or who experience unacceptable side effects, may be offered a next-generation tyrosine kinase inhibitor, sunitinib. This drug was registered in Norway in 2007. The effect is a combination of tyrosine kinase and angiogenesis inhibition. In 98 GIST patients with progression on imatinib, objective response/stable illness was reported for more than 6 months in 54% of the patients.

        Patients with mutation in exon 9 usually respond better to sunitinib than to imatinib primarly. 

        Sunitinib is available in capsules and the dosage is 50 mg/daily for 28 days followed by a two week break. Some patients tolerate 37,5 g daily better, without break.

        One should be aware of the most serious side effects: hypothyroidism, palmar or plantar erythema, hypertension and heart failure. Less serious side effects are fatigue and symptoms from the gastrointestinal tract, from skin and mucous membranes.

        In the Sarcoma Centers in Norway other tyrosine kinase inhibitors are under testing for GISTs, which has progressed during treatment with imatinib and sunitinib.

        Preoperative imatinib treatment is an option to mutilating surgery or when there is a risk of tumor rupture. A mutation analysis of the tumor tissue should be performed in advance. These patiens should be treated at a Regional Sarcoma Center. 

        PROSEDYRER

        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


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        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 soft tissue sarcoma of the abdomen and pelvis

        Radiation treatment is not usually administered, however if the surgical margin is minimal/intralesional in a small, well-defined area, the patient is assessed for 2 Gy x 25 postoperative radiation treatment.

        Intra-operative radiation therapy (IORT) may lead to delayed relapse of the disease, but a prolongation of survival has not been shown.

        Complication treatment of soft tissue sarcoma of the abdomen and pelvis

        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 beneficial effect.

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

        PROSEDYRER

        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.

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        Treatment of Nausea Induced by Chemotherapy

        General

        The majorities of chemotherapy drugs are emetic to varying degrees and may cause nausea and vomiting. Today, there are efficient antiemetic drugs that can significantly reduce the side effects.

        Other factors that can aggravate or prolong the presence of nausea and vomiting are: pain, anxiety, electrolyte disturbances, constipation, dyspepsia, and ulcers.

        There is a distinction between acute nausea, which occurs within the first 24 hours, and late nausea, which occurs later than 24 hours after the treatment.

        Acute nausea can be effectively treated with 5HT3-antagonists (ondansetron, tropisetron, palonosetron), and possibly combined with steroids. Dopamine antagonists (metoklopramid, metopimazine) also have some effect on acute nausea. If this treatment is not effective, it may be improved with aprepitant.

        If standard prophylaxis and treatment of nausea is not satisfactory, other nausea regimens should be tried.

        Indication

        • Nausea induced by chemotherapy drugs.

        Goal

        • Prevention and treatment of nausea and vomiting.

        Definitions

        Chemotherapies according to emetic potential

        High emetogenicity   

        Group 1

        Moderate emetogenicity   

         Group 2

        Low/minimal emetogenicity

        Group 3

        All cisplatin-containing regimens (CiFu, GemCis, BEP, TIP, VIP, PV, AP, EDP, DHAP, ECX, weekly dose cisplatin, and others) BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosfamide, vincristine, prokarbazine, prednisolone)
        Doxorubicin/epirubicine weekly dose
        Doxorubicin/ifosfamide Bendamustine
        Docetaxel
        FEC-60 og FEC-100
        (fluorouracil, epirubicin, cyklophosfamide)
        Carboplatin
        ENAP (etoposide, mitoxsantrone, cytarabine, prednisolone)
        ABVD (doxorubicin, bleomycin, vinblastine, dakarbazine Carboplatin/pemetrexed
        FLv (fluorouracil)
        FOLFIRINOX
        Carboplatin/vinorelbine
        FuMi (fluorouracil, mitomycin)

        CHOP (cyclophosfamide, doxorubicin, vincristine, prednisolone)
        Gemcitabine

        CHOEP (cyclophosfamide, doxorubicin, vincristine, etoposide, prednisolone)
        Methotrexate weekly dose
           Dakarbazine
        Navelbine
              ECO/ACO (epirubicin/doxorubicin, cyclophosfamide, vincristine)
        Paclitaxel
               EOX (epirubicin, oxaliplatin, capecitabine)
        Pemetrexed
              EPOCH-F (etoposide, prednisolone, vincristine, cyclofosfamide, doxorubicin, fludarabine)

            EPOCH-F (etoposide, prednisolone, vincristine, cyclophosfamide, doxorubicin, fludarabine)
         
            FLIRI (fluorouracil, irinotecan)
         
            FLOX (fluorouracil, oxaliplatin)    
           Gemcitabine/carboplatin      
           HD-Cytarabine
           
            HD-Methotrexate    
          IGEV (ifosfamide, gemcitabine, vinorelbine)
          
           IME (ifosfamide, methotreksate, etoposide)  
           Irinotecan  
           Streptozocin  
           Vorphase (cyclophosfamide)
         

        References

        1. Lehne G, Melien Ø, Bjordal K, Aas N, Mella O. Kvalme og oppkast ved cytostatikabehandling i: Dahl O, Christoffersen T, Kvaløy S, Baksaas. Cytostatic Medication cancer treatment. 7. edition. Oslo. Department of Pharmacotherapeutics and The Norwegian Cancer Society, 2009, p 119-130.

        Preparation

        Nausea regimens are selected according to the emetogenicity of the relevant drugs.

        • Inform about the risk for and treatment of nausea. 
        • In the event of anxiety or conditional nausea, give tranquilizers if necessary.

        Implementation

        • Start with an optimal antiemetic regimen starting with the first cycle of chemotherapy in order to counteract the amplification of the nausea that often occurs with a new treatment.
        • Start the oral antiemetic regimen 1-2 hours before chemotherapy and approx. 15-30 minutes before an intravenous injection.
        • If the patient is already nauseous, the medication should be administered parenterally or rectally.

        Antiemetic regimens

        Mildly emetic chemotherapy

        • Metoclopramide 10 mg is given intravenously before treatment with cytostatic agents.
        • Metoclopramide 10 mg is given orally uptil 3 times.

        Moderately emetic chemotherapy

        Ondansetron 8 mg orally 2 x daily. In the event of nausea before treatment, give ondansetron intravenously. If this has little effect, try ondansetron 8 mg x 3 or change to a 5HT3-antagonist, for example, tropisetron 5 mg orally/intravenously or palonosetron 250 µg intravenously.

        Highly emetic chemotherapy, or if other treatment does not help

        For highly emetic chemotherapy drugs, or if other treatment is not adequate, a 5HT3-antagonist can be given orally or intravenously. It should be combined with dexamethasone 8-16 mg intravenously ½-1 hour before treatment, and further, 8 mg x 2 intravenously or orally on the first day.

        In addition, dopamine antagonists may be given, for example, metoclopramide 10 mg x 3.

        In some cases, traditional nausea treatment is not sufficient. In this case, the patient can be treated with aprepitant. Aprepitant is used for highly emetic regimens and for patients where the usual antiemetic treatment has failed during moderate emetogenic treatment. Aprepitant is given orally 1 hour before chemotherapy and is combined with dexamethasone and 5HT3-antagonists:  125 mg capsules orally on day 1, then 80 mg orally on days 2-5, depending on the duration of the treatment. Aprepitant can enhance the effect of taxane and etoposide, as well as vinorelbine, and can reduce the effect of warfarin.

        The regimen is repeated daily if highly emetic treatment is given over a number of days.

        Delayed nausea

        Aprepitant in combination with dexamethasone and 5HT3-antagonists is preferable if there is a high risk of delayed nausea and vomiting. This is offered especially to patients who have previously experienced delayed nausea.

        Conditional nausea

        In the event of conditional nausea, diazepam or other tranquilizers may be considered. Diversion or desensitization can be tried in more serious cases.

        Follow-up

        Ondansetron can have a constipating effect. Use of a laxative for several days should be considered.

        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.

        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.

        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.

        Movement and strict bed rest for threatening spinal cord lesion

        General

        Approximately 5% of the patients with advanced malignancies develop symptoms of threatening spinal cord lesion. The condition is most frequently in patients with cancer originating from lungs, prostate or breast, but is also seen in other types of cancer where bone metastases may occur.

        Symptoms

        • Pain in the back, possibly in the neck
        • Changes in existing pain (increased intensity, changed character, radiance of pain)
        • Pain that worsens with exertion (for example cough, sneeze or going to the toilet)
        • Walking difficulties and inability to control the extremities
        • Paralysis of the legs and-/or arms
        • Loss of sensation
        • Urinary problems and/or defecation problems

        The stability in columna

        • Ambulatory patients without neurological deficits do not need strict bed rest.
        • For other patients, it may be appropriate to have strict bed rest until the stability of columna is assessed. The need of strict bed rest is assessed by a physician based on the risk of increased neurological deficits and the degree of pain. When columna is considered stable enough (usually clarified 2 to 4 days after the initiation of radiotherapy), gradually mobilization until pain threshold should quickly get started. Increasing pain or neurological deficits should be observed during mobilization.
        • For strict bed rest, the head end of the bed can be elevated up to 30 ° C.
        • If flat bed rest causes increased pain, the head end of the bed should be raised until pain reduction.

        Indication

        • Threatening spinal cord lesion caused by tumor/metastases.

        Goal

        • Limit spinal cord damage so that  functions may be maintained.

        Preparation

        The patient and their family should receive proper information and guidance regarding to disease, treatment and restrictions. For advanced disease, small chance of getting better and short life expectancy, quality of life rather than strict restrictions should be emphasized.

        The patient should, if he/she wishes, be involved in decisions regarding to treatment and further training.

        Implementation

        Use of cervical collar and corset

        • Lack of documentation of the effect of using cervical collar and corset, require the patient's wishes to be taken into account in assessing whether this should be used.
        • Cervical collar may be relevant for spinal cord lesions in the cervical level of the spinal cord. Some patients find this pain relieving. A neurologist/neurosurgeon will decide whether there is a need for cervical collar.
        • A corset are generally not used preoperatively, but if prescribed by a surgeon, it may be used postoperatively.
        • The corset must be adjusted by a prosthetist or physiotherapist.
        • The corset is put on in either supine position, sitting position or in standing position, initially by competent personnel. The patient is instructed to put on the corset unassisted.

        Bed rest and positioning

        • The patient should be referred for physical therapy at an early stage. To avoid accumulation of mucus in the lungs, the physiotherapist should give instructions in appropriate breathing exercises, consider use of mini-pep and need for chest physiotherapy.
        • Patients who need strict bed rest must have electrically controlled bed with a pressure relieving mattress.

        Movement in bed

        • The patients must be instructed in how to move to lateral position in bed using logrolling. Logrolling involves moving to lateral position without rotation or flexion/extension in columna. The healthcare staff are performing the movement to lateral position by rolling the patient while their hands are securely placed over the patient's hips and back/shoulder.
        • If the patient has mobility in the legs, he/she may, using bent knees and hips and feet down in the mattress as well as arms straight up in the air as levers, roll over to lateral position.
        • When the patient needs to be moved higher up in bed, the bed should be tilted a bit backward, the patient is lifted calmly with the sheet close to the body by means of the draw sheet and two persons.
        • Slingbar is not recommended for cervical or thoracic lesions.

        Activity during bed rest

        • By instructions from a physiotherapist, nurses can assist the patient to do appropriate activity and exercises. Passive exercises when paresis or paralysis is present, otherwise active exercises.
        • Activity that causes pain must be interrupted.
        • Individually customized movements of upper and lower extremities, passive or active, are carried out in a supine position with a low strain on columna.
        • A footboard made of compact foam at the end of the bed is an aid to prevent the patient from sliding down in the bed and provides a resistant surface against which the patient can push for a good venous-/muscle pump.
        • Strength training of arms by static resistance to the mattress and without movement of the columna, is recommended. Light hand weights for arm exercises are only considered when the affection is in the lumbar level.
        • The need for contracture prophylaxis is considered, and if there is a drop foot a footboard should be customized.
        • Instructions in self-training will be given, preferably also as a written program as well.

        Thrombosis prophylaxis

        • Bedridden patients should have compression stockings in thigh/- possibly knee length, unless contraindicated.
        • Patients at high risk of venous thrombosis should also have subcutaneous thrombosis prophylaxis with low molecular weight heparin.
        • The duration of thrombosis prophylactic treatment is considered individually based on current risk factors, general health condition and mobilization of the patient.

        Pressure relief and prevention of pressure ulcers

        • Patients who must have strict bed rest is particularly prone to pressure ulcers.
        • Prevention of pressure ulcers must be followed in relation to risk assessment, assessment of the patient's skin, skin care, nutrition, pressure relieving underlay, change of position in bed/chair and mobilization.
        • For patients with/having strict bed rest, change of positions in bed must be in accordance with the restrictions.

        Bladder function

        • An assessment of  the bladder function is done at arrival. An accuracate anamnesis is obtained: Last urination, episodes of incontinence, frequency, painful urination and abdominal pain.
        • Evaluate the  bladder function at least once a day for any changes.
        • If incontinence, insert a permanent catheter.
        • If it turns out to be permanent muscle tone, evaluate eventually intermittent catheterization or insertion of suprapubis catheter.
        • Bedpan/urinal bottle should be easily accessible at strict bed rest. When using bed pan, loggrolling is required.

        Gastrointestinal function

        • An assessment of  the gastrointestinal function is done at arrival.
        • An accuracate anamnesis is obtained: Last bowel movements, frequency, consistency, nausea/vomiting, abdominal pain and previous ailments.
        • Evaluate the gastrointestinal function evaluated at least once a day.

        Pain relief

        • Spinal cord compression can cause severe pain that may be difficult to treat. If so, contact the pain -/palliative team.

        Mobilization

        • The patient and the healthcare staff collaborate to find the right level of activity.
        • Go gradually from an increased angle on the bed`s back rest to sitting position, to sitting position on the bedside and then to standing position. The back rest is gradually raised to about 45 ° and the bed´s leg-rest is angled and the patient can try this sitting position, further to 60 °. By worsening of pain and/or neurological outcomes, the patient is returned to the previous position for reconsideration. If the increase of the back-rest is unproblematic, the patient can further be mobilized to the bedside.
        • The first time the patient is moved to sitting position on the bedside, this is preferably done by a physiotherapist together with a nurse by rolling over to lateral position (logrolling). The patient sits up assisted by two persons, one at the upper body and one supporting the legs over the edge of the bed.
        • When affection in the cervical region only, the patient can be mobilized up to a sitting position by raising the head of the bed and bring the legs over the bedside. The patient is allowed to sit for a little while, blood pressure and pain are evaluated.
        • Exercises to increase circulation and good breathing exercises are recommended. Balance in a sitting position is considered.
        • When the patient is moved to standing position, custom walking aids must be used (pulpit walker or forearm walker). To ensure safe mobilization the first time, assistance of two persons are recommanded.
        • For lasting paresis, a high-back reclining wheelchair with leg rests should be customized.
        • The need of other aids, like transfer slide board, drop foot brace, grasping forceps and similar equipment, should be considered.
        • Instruction in self-training should be given, preferably after a written program in standing exercise and walking exercice with support.
        • Gradually, the patient can sit  for short periods of time, using a good armchair with a high seat and good backrest.

        Follow-up Care

        • Patients with a long life expectancy should be considered for further training at a suitable institution.
        • Patients with a short expected life expectancy are usually not recommended for stay at rehabilitation institutions.

        The website www.physiotherapyexercises.com is recommended for obtaining exercises.

        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

        Follow-up care after treatment of soft tissue sarcoma of the abdomen and pelvis

        Despite adequate surgery, local relapse or intraperitoneal metastases occur in > 50% of patients with a high-grade malignant tumor, and >30% of patients with low-grade malignant tumors. In most cases of high-grade malignant sarcomas, relapse is diagnosed within 2 years. For low-grade malignancy, relapse can occur many years later and not uncommonly 5-10 years after primary treatment.

        Patients are followed up at a sarcoma center for 10 years with and examined every 6 months for the first 5 years and annually for the last 5 years.

        Examinations performed are:

        • Clinical examination
        • CT of abdomen and pelvis
        • Chest X-ray

        Surgery, radiation, and chemotherapy can cause delayed reactions of different character. The seriousness depends on the type of treatment and individual tolerance.

        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

        Lymphedema

        General

        According to etiology, there are two general classifications of lymphedema primary and secondary lymphedema. Primary lymphedema is caused by deficient or faulty development of the lymph system. Secondary lymphedema occur as a complication from trauma or diseases which damage the lymphatic vessels or lymph nodes. The primary cause of lymphedema in the western world, is impaired or disrupted flow of lymph fluid caused by cancer or cancer treatment (secondary lymphedema).

        Lymphedema occurs when the transport capacity of the lymph system is reduced significantly.
        The swelling is caused by an accumulation of fluid (rich in protein) in the tissue, due to reduced drainage of lymph fluid (1,2). The swelling is often chronic. A lymphedema can lead to pain/discomfort and changes in the soft tissues in the affected area (fibrosis) (3,4). Lymphedema occurs most often during the first 2-3 years after cancer treatment (5 6). Without treatment, lymphedema can lead to progressive swelling.

        In some cancer treatment the lymph nodes and fatty tissue are removed, most often in the axilla, pelvis and the groin. This treatment causes damage to the lymphatic wessels and reduces the number of lymph nodes. The subsequent reduced capacity for drainage of lymph fluid in the arm and leg may result in lymphedema.

        Radiation therapy may cause tissue scarring and fibrosis. The combination of surgery and radiation therapy to the axilla additionally increases the risk of developing lymphedema.

        Cancer related lymphedema can also occur due to metastasis in areas where blocking the central lymph vessels in advanced disease.

        Factors which may increase the risk for developing lymphedema are:

        • obesity
        • infection in the area where lymphedema occurs
        • overheating/sunburn
        • trauma of the arm/leg on the operated side

        Indications for treatment

        Lymphedema in the arm/hand, breast, leg, groin, face and neck after treatment of:

        • breast cancer where axillary dissection is performed
        • gynecologic cancer where the lymph nodes in the pelvis or the groin are removed
        • melanoma where the lymph nodes in the axilla or the groin are removed
        • lymphoma and cancer of the head and neck region where lymph nodes in the neck region are removed
        • prostate cancer where the lymph nodes in the pelvis or the groin are removed
        • sarcoma where lymph nodes are removed

        Without treatment the lymphedema can increase in size. This may cause skin changes (fibrosis), increased swelling and therefore more discomfort in the area (3).

        Contraindications

        Absolute
        • acute infections, local or general (erysipelas)
        • arterial insufficiency with risk of necrosis
        • thrombosis and embolism
        Relative

        Untreated cancer disease, heart failure, or kidney failure

        Goal

        • reduce lymphedema
        • relieve tormenting side effects
        • improve function 
        • prevent complications such as skin changes and inflammation in the area (erysipelas)

        References

        1. Rockson SG. Diagnosis and management of lymphatic vascular disease. J Am Coll Cardiol 2008;52:799-806.
        2. Lawenda BD, Mondry TE, Johnstone PAS. Lymphedema: (Review) A primer on the identification and management of a chronic condition in oncologic treatment. CA Cancer J Clin 2009;59:8-24.
        3. Mortimer PC. The patophysiology of lymphedema. Cancer 1998;83(12 Suppl American): 2798-802.
        4. Erickson VS, Pearson ML, Ganz PA, Adams J, Kahn KL. Review: Arm edema in breast cancer patients. J Natl Cancer Inst 2001;93:96-111.
        5. Nesvold IL, Dahl AA, Løkkevik E, Mengshoel AM, Fosså SD. Arm and shoulder morbidity in breast cancer patients after breast-conserving therapy versus mastectomy. Acta Oncol 2008;47:835-842.
        6. Norman SA, Russel Locario A, Potashnik SL, et al (2009) Lymphedema in breast cancer survivors: incidence, degree, time course, treatment, and symptoms. J Clin Oncol 2009;27:390-397.
        7. Johansen J, Overgaard J, Blichert Toft M, Overgaard M. Treatment morbidity associated with the management of the axilla in breast-conserving therapy. Acta Oncol 2000;39:349-54

        Definitions

        Complete psysical therapy treatment of lymphedema

        Consists of manual lymph drainage, compression therapy, skin care and instruction in exercises and self-treatment (1). The treatment is performed by physical therapists with special expertise.
        The treatment may be extensive at the start. In cases of severe swelling one usually start with manual lymph drainage followed by bandaging of the arm/leg (1).

        Manual Lymph Drainage

        This is a kind of massage which requires guided training to perform optimally. The goal is to encourage the drainage of lymph fluid and thereby reduce the swelling of the tissue (2). It is quite different from other kinds of massage applied within physiotherapy. The anatomical conditions of the lymph system is the basis for manual lymph drainage. These are: the course of the large lymph veins, the borders of different lymphatic functional regions (watershed), natural anastomoses crossing these lines, and the lack of valves in the lymphatic vessels .

        Bandaging

        Bandaging is used mostly at the start of a treatment to reduce swelling. When the swelling is reduced a compression stocking is adjusted.

        Compression stocking

        Clinical experience and research show that compression is the most important treatment. (3;4) Accordingly it is of great importance to adjust a compression stocking for the arm or leg. If there is swelling of the hand, a compression glove might help.
        A compression stocking is used to increase tissue tension. The pressure from the stocking increases absorption of tissue fluid. The stocking provides a graded pressure highest distally and lowest proximally. To adjust the stocking, the circumference of the arm or leg is measured at several defined points. There are several compression classes, but the most commonly used are class 1 and 2. The stocking should provide a constant pressure without causing discomfort. It may take some time to get used to the compression stocking. Some choose to use the stocking occasionally, while others wear it daily.
        A facemask at night is recommended to treat lymphedema in the neck and face region (5). Patiens with lymphedema in the groin can be helped by using a bike pant or a panty. Bandaging, tubigrip or bike pants may benefit if there is swelling of the penis and scrotum .

        Intermittent pressure massage with pulsation

        Treatment is carried out with an electronically powered apparatus which blows air in a double-walled cuff. The cuff, covering the whole arm or leg, has multiple channels and creates a peristaltic pressure wave in proximal direction. The treatment encourages the lymph drainage and thereby reduces the swelling (4).

        References

        1. The diagnosis and treatment of peripheral lymphedema. Consensus document of the International Society of Lymphology Executive Committee. Lymphology 2003;36:84-91.
        2. McNeely ML, Peddle CJ, Yurick JL, Dayes IS, Mackey JR. Conservative and dietary interventions for cancer-related lymphedema: A systematic review and meta-analysis. Cancer 2010.
        3. Badger C, Preston N, Seers K, Mortimer P. Physical therapies for reducing and controlling lymphedema of the limbs. Cochrane Database Syst Rev 2004;CD003141.
        4. Johansson K, Albertsson M, Ingvar C, Ekdahl C. Effects of compression bandaging with or without manual lymph draining treatment in patients with postoperative arm lymphedema. Lymphology 1999;32:103-110.
        5. Deng J, Ridner SH, Murphy BA. Lymphedema in patients with head and neck cancer. 2011;38:1-10.

                                                                                  

        Preparation

        Main points of information

        Information should be given to patients who have received surgery only or combined with radiotherapy with increased risk of getting lymphedema. The patient usually gets information about lymphedema after the surgery. Sufficient information and guidance is important and crucial for both avoiding getting lymphedema and being able to identify lymphedema at the very beginning.

        • The function and purpose of the lymphatic system
        • Causes of lymphedema
        • Symptoms of lymphedema
        • Different treatment options
        • Precaution
        • Complications/side effects caused by the disease and treatment
        • The importance of maintaining mobility in the arm or leg

        Symptoms of lymphedema

        • A feeling of uncomfortable change
        • A feeling of heaviness
        • Bursting pain
        • Changes of consistency (visible or palpable) in the soft tissues
        • Suspicion of increased circumference
        • Swelling may disappear overnight, but usually returns during daytime
        • Some have swelling sporadically

        The dominating symptom is lasting swelling in the involved area. Other symptoms will to a large extent depend on the amount, duration, and localization of the edema.

        Moderate swelling after cancer surgery, can be a reaction which often spontaneously disappears.

        Diagnostics

        Lymphedema is usually measured using a clinical method. There are multiple methods to measure the extent of lymphedema. The gold standard is the water displacement method, which measures and compares the volumes of both arms/legs. But a method of comparing volume by using several circumferential measurements of the arms/legs is often used in research and sometimes in the clinical setting. The most widely used method is measurement of circumference at multiple anatomic points on the arm/leg with comparison with the contralateral arm/leg. A difference in circumference of ≥2cm is often defined as lymphedema. Stemmer sign is also used.

        Implementation

        With development of lymphedema, it is important to take precautionary measures as soon as possible. Treatment with compression is the component which seems to be most effective in reducing the swelling. Manual lymph drainage is often used in combination with bandaging in the first 1-2 weeks of the treatment. This complete decongestive therapy is a composite treatment including multiple techniques which are performed by a specially trained physical therapist.

        The intensive phase

        • Compression treatment – possibly with bandaging and thereafter adjustment of an elastic stocking
        • Manual lymph drainage
        • Circulation and drainage inducing exercises
        • Skin care

        During the intensive phase, the patient is usually treated 5 days a week with continuously bandaging until the desired volume reduction is achieved. This usually takes one to two weeks.

        Bandaging

        After stimulating the lymphatic flow by manual lymph drainage, a compression stocking is used or the whole arm is bandaged for one to two weeks. The bandages should be worn as long as they are not too uncomfortable. Correct bandaging with short, elastic bandages provide the tissue with high pressure under activity and low pressure while resting.

        • An ointment with a low pH (5.5) should be applied to the skin.
        • A light tube gauze should be worn.
        • The padding is then applied.
        • The bandaging starts distally to the lymphedema.
        • The bandages are laid evenly, circularly, and in multiple layers.
        • The pressure should decrease gradually from distal to proximal.
        • The pressure is regulated partially with the bandaging technique and mainly by the number of layers of bandages.

        Compression stocking

        • The stocking may be removed at night.
        • At night an ointment is preferably applied to the skin.
        • With incipient  lymph edema, wear the stocking during activity.
        • In moderate and extensive lymph edema, the stocking is usually worn all day.
        • The stocking should be washed at least every third day.

        A poorly customized stocking may create faulty compression. The most frequent error is that the compression stocking is used after it has lost its elasticity (worn out) and therefore has less effect.

        Manual Lymph Drainage

        The massage strokes should be performed in the direction of the lymphatic drainage with light pressure and with slow motions. The treatment should not be painful.

        Manual lymph drainage has four main movements: standing circles, pumping grip, turning grip, and corkscrew grip.

        Pressure massage with pulsator

        Pulsation is never a first choice for treatment of lymphedema, but could be a measure over time when monitoring has shown that the treatment is effective. At the start, the patient should be informed about possibly complications. Sometimes, an increase in edema is seen proximal to the cuff. Further pulsation treatment should then be postponed until manual lymph drainage and exercises have improved the condition. If the pressure is too high, the lymphatic vessels may be damaged and the amount of interstitial fluid may increase.
        The pressure should be moderate and the patient should experience the treatment as comfortable. It is not the amount of pressure that is important, but uniform rhythmic pressure wave. Tuning of rate and pressure are adjusted for each patient.
        Usually, the treatment should last for twenty minutes at the start increasing gradually to thirty to forty minutes. Can be used daily or when needed. Pulsation treatment may also be performed by the patient at home.

        Skin Care

        Regardless of whether the patient has lymphedema or not, it is important to hinder the occurrence of scratches, sores, and unnecessary skin irritation. Use of gloves is appropriate in some situations. The patient should also be cautious of overheating and sunburn. The main goal of skin care is to prevent infections, because this can trigger an eruption of lymph edema.

        Regular use of bandages and compression stockings dries out the skin. Use of skin care products and cleansers with a low pH (5.5) are recommended. Good skin care keeps the skin soft and supple and maintains the skins natural ability to fight infection.

        Disinfecting ointment and adhesive tape should be used in the event of an ulcer or scratch or if there is danger of infection.

        Maintenance phase

        • Use of elastic stocking and/or glove as needed
        • Skin care
        • Regular exercises to facilitate the muscle-joint pump
        • Possible intermittent pressure massage with pulsator

        The patient obtains some treatment during the maintenance phase and may have treatment by a physical therapist if necessary. In the short term, the treatment is almost always satisfactory. In the long run, the result depends on the patient practicing the measures recommended. The pulsator may usually be borrowed from a health care center.

        Exercises to improve mobility and lymph flow of the shoulder/arm

        Dynamic exercises with a relaxation phase are optimal. "Throwing" movements may feel uncomfortable. Many experience that it is better to walk with poles, but it is important to maintain a loose grip of the pole.

        Correctly adjusted movement exercises:

        • induce circulation without straining the reduced lymphatic system
        • provide adequate joint movements
        • stimulate dynamic change between tension and relaxation, preferably in conjunction with respiration

        Movement therapy in a heated pool may be favorable for some lymphedema patients. Water pressure stimulates lymphatic drainage and simultaneously activates circulation and movement.

         

        Follow-Up

        If necessary, the patient may obtain a referral for physical therapy in their home area for further follow-up. Follow-up and guidance by a physical therapist with the necessary skills is important. Some with serious lymphedema will need frequent treatment for the rest of their life. But others will be able to manage the treatment themselves by adhering to the guidelines that they have learned. Compression with stockings and skincare are often sufficient treatment. So many patients do not need physical therapy as treatment, but rather information and functional guidance.

        Moderate physical activity improves joint movement, circulation, and well-being, as well as stimulation of lymph drainage. Blood pressure should not be measured and vaccinations should not be given in the treated arm. Gloves are recommended for gardening.

        Complications

        Fibrosis of the dermis and epidermis with affects some persons with lymphedema. The skin loses its elasticity and is more easily traumatized than normal skin.

        The immune system is weakened in the edematous area. This may be for multiple reasons, among others, weakened transport of dendritic cells, lymphocytes, and proteins. If the area’s regional lymph nodes are removed, this will also weaken the local immune system.

        In some edema patients, especially secondary lymphedema, a distinctive reaction (erysipelas) may occur in the skin of the affected area. This will usually start acutely with a strong feeling of malaise with high fever, hyperemia with flushing, and increased swelling of the skin. The area of skin involvement is often limited. The symptoms are usually improved after four to six days but it is not uncommon for the edema to deteriorate. The condition should be treated with antibiotics (penicilin) as quickly as possible.

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        Lymph edema in the arm.Lymph edema in the arm.