oncolex logo
Utskriftsdato (24.9.2020)

Uterine cancer

/upload/corpus uteri/corpus.gifUterine cancer includes cancer occurring in the body of the uterus.

These cancer types are:

  • endometrial cancer
  • carcinosarcoma
  • adenosarcoma
  • leiomyosarcoma
  • endometrial stromal sarcoma
  • other types of sarcoma

Endometrial cancer originates from the mucosa of the uterus. Mixed epithelial and mesenchymal tumors (carcinosarcomas) consist of an epithelial and sarcomatous component. In carcinosarcomas, both components are malignant.

Carcinosarcomas are monoclonal and originate from endometrial carcinoma. The sarcoma component has developed separate from the carcinoma, and is often seen in postmenopausal women. This type behaves biologically as aggressive carcinomas with a high frequency of metastasis, especially to lymph nodes. 

The most common types of sarcomas are leiomyosarcomas and endometrial stromal sarcomas, but all soft-component sarcomas can occur in the uterus. Sarcomas have a biology completely different from carcinomas. The largest difference is that sarcomas almost never metastasize to lymph nodes, but metastasize via blood. They have a great tendency to implantation in the peritoneum if spilled. This is a critical point during surgery. 

Leiomyosarcoma, endometrial stromal sarcoma and adenosarkoma are described in the sarcoma chapter.  

Incidence 

Approximately 2.8 % of women will be diagnosed with endometrial cancer at some point during their lifetime and this cancer type represents 3.6% of all new cancer cases in the United States. Endometrial cancer is most frequently diagnosed among women aged 55-64.

In 2017, it is estimated to be 61,380 new cases of endometrial cancer in the United States (24).

 

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

Source: National Cancer Institute

 

 

Incidence of uterine cancer, 1975–2014.

Source: National Cancer Institute. Bethesda, MD, USA

Etiology of uterine cancer

Risk factors

  • Long-term separate estrogen stimulation increases the incidence of endometrial hyperplasia and cancer (1-2). This is observed with long-term unopposed estrogen replacement, estrogen-producing tumors, and obesity leading to increased peripheral production of estrogen from steroid hormones and disturbances of ovulation (3).
  • Tamoxifen treatment for breast cancer increases the risk for endometrial cancer due to its stimulating effect on the endometrium (4).
  • Women with the inherited mutation for DNA repair genes in families with HNPCC (Hereditary non-polyposis colorerectal cancer or Lynch syndrome) have an increased risk for developing endometrial cancer (5). 
  • Use of combination birth control pills reduces the risk significantly for development of endometrial cancer (6).
  • Carcinosarcomas have similar risk factors including obesity, nulliparity, and exogenous estrogen therapy (7).
  • Radiation treatment slightly increases the risk for later development of sarcoma in the treated area (8).

Histology of uterine cancer

The most frequent type of cancer originating in the uterine mucosa is endometrioid adenocarcinoma, designated as type 1 endometrial cancer.

 

Uterine specimen with endometrioid carcinoma. Click to enlarge.
Photomicrograph demonstrating deeply infiltrating endometrioid adenocarcinoma in the left picture. Click to enlarge.

 

Type 1 endometrial cancer appears in perimenopausal women. These tumors are related to increased and long-standing estrogen stimulation. In general, endometrioid adenocarcinomas have a good prognosis, but poorly differentiated (grade 3) tumors have a less favorable outcome, comparable to that for type 2 tumors.

Type 2 endometrial cancer is usually seen in older postmenopausal women (usually > 60 years of age) without any sign of long-standing estrogen stimulation, and mainly consists of serous papillary adenocarcinoma and clear cell carcinoma.

Correct subtyping of endometrial carcinoma requires well-trained pathologists with adequate experience in the field.

Additional methods are sometimes necessary to correctly diagnose these tumors, such as immunohistochemistry using antibodies against p53, estrogen receptors and others.

The histopathological classification (WHO)

  • Endometrioid adenocarcinoma (75%–80%)        
  • Adenocarcinoma with squamous cell differentiation
  • Adenoacanthoma
  • Adenosquamous carcinoma
  • Serous papillary carcinoma (< 10%)  
  • Mucinous carcinoma (1%)
  • Clear cell carcinoma (4%)       
  • Squamous cell carcinoma (< 1%)
  • Mixed carcinoma (10%)
  • Undifferentiated carcinoma

Mixed epithelial and mesenchymal tumor

These tumors include carcinosarcomas, which contain both malignant epithelial and a mesenchymal components. Adenosarcoma consists of a benign epithelial and malignant mesenchymal (sarcomatous) component.

Carcinosarcomas are classified as mixed, but are today considered as a variant of endometrial carcinoma. These tumors usually appear in older women and have a very poor outcome.

Adenosarcomas are now considered as a variant of sarcomas.

Staging of uterine cancer

According to FIGO (The International Federation of Gynecology and Obstetrics), surgical staging should be performed. Patients not treated with primary surgery are staged according to the clinical examination limited to the following methods: inspection, colposcopy, palpation under general anesthesia, biopsies, fractionated abrasion, conization, cystoscopy, rigid sigmoidoscopy, chest X-ray, bone X-ray, and urography. 

If there is uncertainty in staging, the lowest alternative should be chosen.

Findings on MRI, CT, and ultrasound may influence the choice of therapy, but should not change the stage.

Staging according to FIGO  (revised September 2009)

The tumor should be graded histologically as G1 (highly differentiated), G2 (moderately differentiated) or G3 (low or undifferentiated).

Stage I

Stage I: Tumor is confined to the uterus.

  • Stage Ia: None or less than half myometrial infiltration.
  • Stage Ib: Infiltration in half or more than half of the myometrium.

Stage II

Stage II: Cervical stromal invasion, but not extending beyond uterus. (Endocervical glandular involvement should only be considered as stage I and not as stage II.)  

Stage III

Stage III: Local and/or regional spreading of tumor.

  • Stage IIIa: Infiltration of the serosa and/or adnexa
  • Stage IIIb: Metastasis to vagina and/or parametrial infiltration
  • Stage IIIc: Metastasis to retroperitoneal lymph nodes in the pelvis and/or paraaortally

Positive cytology should be reported separately without changing the stage.

/upload/corpus uteri/stadier/corpus_stadium3.gif 

Stage IV

Stage IV: Tumor infiltrates the bladder and/or intestinal mucosa and/or distant metastasis 

  • Stage IVa: Infiltration of the bladder or intestinal mucosa
  • Stage IVb: Distant metastasis including intraabdominal metastases and/or inguinal node metastases.

 /upload/corpus uteri/stadier/corpus_stadium4.gif

Metastatic patterns of uterine cancer

When endometrial cancer is diagnosed, it is usually confined to the uterus with 80% in stage I.

Metastasis occurs primarily by direct invasion of the uterine wall and down to the cervix and further to the parametria or the abdominal cavity. Vaginal spreading also occurs, and tumor cells can spread to the abdominal cavity via the fallopian tubes. Further metastasis can occur lymphogen to lymph nodes on the pelvic wall and/or paraaortic, as well as via blood to the lungs and liver. 

Serous-papillary and clear cell tumors have a great tendency to spread to the abdominal cavity in the same way as ovarian cancer, as well as a great tendency for spread to lymph nodes. 

Carcinosarcomas have great tendency to spread to lymph nodes.

Symptoms of uterine cancer

  • Postmenopausal bleeding
  • Perimenopausal abnormal bleeding
  • Premenopausal bleeding changes in women with anamnestic amenorrhea
  • Postmenopausal pyometra

Symptoms of local recurrence

  • Vaginal bleeding or discharge
  • Pain in the pelvis or lower abdomen
  • Back pain
  • Swelling in the legs/edema
  • Weight loss
  • Chronic cough

Differential diagnoses of uterine cancer

  • Endometrial hyperplasia with atypia
  • Primary ovarian or fallopian tube cancer with spreading to the endometrium
  • Primary cervical or endocervical cancer with infiltration of the endometrium
  • Two primary cancer types of the internal genitals simultaneously
  • Inflammatory changes of the endometrium. This diagnosis may be difficult.

Prognosis of uterine cancer

The prognosis depends on whether the endometrial cancer is localized, regional, or metastatic at the time of diagnosis. 66.9 % are diagnosed at the local stage and the 5-year survival for localized endometrial cancer is 95.3%. The overall 5-year survival rate for endometrial cancer patients during the period 2007-2013 was 81.3%.

Most deaths from endometrial cancer occur in women who are middle-aged or older. The number of deaths is highest among women aged 65-74. Death rates have been rising on average 1.4% each year over 2005-2014.

In 2014, there were an estimated 710,228 women living with endometrial cancer in the United States and in 2017 there are an estimated 10,920 women will die of this disease (24).

 

Title is not translated!

Chapter does not contain text!!

References on uterine cancer

  1. Weiderpass E, Baron JA, Adami HO, Magnusson C, Lindgren A, Bergstrom R et al. Low-potency oestrogen and risk of endometrial cancer: a case-control study. Lancet 1999; 353: 1824-8.
  2. Pike MC, Peters RK, Cozen W, Probst-Hensch NM , Felix JC, Wan PC et al. Estrogen-progestin replacement therapy and endometrial cancer. J Natl Cancer Inst 1997; 89: 1110-6.
  3. Weiderpass E , Adami HO , Baron JA , Magnusson C , Bergstrom R , Lindgren A , Correia N , Persson I . Risk of endometrial cancer following estrogen replacement with and without progestins. J Natl Cancer Inst. 1999 Jul 7;91(13):1131-7
  4. Bergman L , Beelen ML , Gallee MP , Hollema H , Benraadt J , van Leeuwen FE. Risk and prognosis of endometrial cancer after tamoxifen for breast cancer. Comprehensive Cancer Centres' ALERT Group. Assessment of Liver and Endometrial cancer Risk following Tamoxifen. Lancet. 2000 Sep 9;356(9233):881-7 
  5. Hendriks YM, Wagner A, Morreau H, Menko F, Stormorken A, Quehenberger F, Sandkuijl L, Moller P, Genuardi M, Van Houwelingen H, Tops C, Van Puijenbroek M, Verkuijlen P, Kenter G, Van Mil A, Meijers-Heijboer H, Tan GB, Breuning MH, Fodde R, Wijnen JT, Brocker-Vriends AH, Vasen H. Cancer risk in hereditary nonpolyposis colorectal cancer due to MSH6 mutations: impact on counseling and surveillance. Gastroenterology. 2004 Jul;127(1):17-25
  6. Weiderpass E, Adami HO, Baron JA, Magnusson C, Lindgren A, Persson I. Use of oral contraceptives and endometrial cancer risk (Sweden). Cancer Causes Control. 1999 Aug;10(4):277-84.
  7. Zelmanowicz A, Hildesheim A, Sherman ME, Sturgeon SR, Kurman RJ, Barrett RJ, Berman ML, Mortel R, Twiggs LB, Wilbanks GD, Brinton LA. Evidence for a common etiology for endometrial carcinomas and malignant mixed mullerian tumors. Gynecol Oncol. 1998 Jun;69(3):253-7
  8. Mark RJ, Poen J, Tran LM, Fu YS, Heaps J, Parker RG. Postirradiation sarcoma of the gynecologic tract. A report of 13 cases and a discussion of the risk of radiation-induced gynecologic malignancies. Am J Clin Oncol. 1996 Feb;19(1):59-64. 
  9. Abeler VM, Vergote IB, Kjørstad KE et al.: Clear cell carcinoma of the endometrium. Prognosis and metastatic pattern. Cancer 1996, 78:1740-1747
  10. Dijkhuizen FP, Mol BW, Brolmann HA, Heintz AP. The accuracy of endometrial sampling in the diagnosis of patients with endometrial carcinoma and hyperplasia: a meta-analysis. Cancer. 2000 Oct 15;89(8):1765-72.
  11. Kinkel K, Kaji Y, Yu KK, Segal MR, Lu Y, Powell CB, Hricak H. Radiologic staging in patients with endometrial cancer: a meta-analysis. Radiology. 1999 Sep;212(3):711-8.
  12. Frei KA, Kinkel K. Staging endometrial cancer: role of magnetic resonance imaging. J Magn Reson Imaging. 2001 Jun;13(6):850-5
  13. Creasman WT, Morrow CP, Bundy BN, Homesley HD, Graham JE, Heller PB. Surgical pathologic spread patterns of endometrial cancer. A Gynecologic Oncology Group Study. Cancer 1987; 60: 2035-41. 
  14. Creutzberg CL, van Putten WL, Warlam-Rodenhuis CC, van den Bergh AC, de Winter KA, Koper PC, Lybeert ML, Slot A, Lutgens LC, Stenfert Kroese MC, Beerman H, van Lent M; postoperative Radiation Therapy in Endometrial Carcinoma Trial. Outcome of high-risk stage IC, grade 3, compared with stage I endometrial carcinoma patients: the Postoperative Radiation Therapy in Endometrial Carcinoma Trial. J Clin Oncol. 2004 Apr 1;22(7):1234-41
  15. Creutzberg CL, van Putten WL, Koper PC, Lybeert ML, Jobsen JJ, Warlam-Rodenhuis CC, De Winter KA, Lutgens LC, van den Bergh AC, van der Steen-Banasik E, Beerman H, van Lent M; PORTEC Study Group. Survival after relapse in patients with endometrial cancer: results from a randomized trial. Gynecol Oncol. 2003 May;89(2):201-9
  16. Creutzberg CL, van Putten WL, Koper PC, Lybeert ML, Jobsen JJ, Warlam-Rodenhuis CC, De Winter KA, Lutgens LC, van den Bergh AC, van de Steen-Banasik E, Beerman H, van Lent M. Surgery and postoperative radiotherapy versus surgery alone for patients with stage-1 endometrial carcinoma: multicentre randomised trial. PORTEC Study Group. Post Operative Radiation Therapy in Endometrial Carcinoma. Lancet. 2000 Apr 22;355(9213):1404-11
  17. Aalders J, Abeler V, Kolstad P, Onsrud M. Postoperative external irradiation and prognostic parameters in stage I endometrial carcinoma: clinical and histopathologic study of 540 patients. Obstet Gynecol. 1980 Oct;56(4):419-27.
  18. Kristensen G, Trope C. Endometrial Cancer: The Management of High-risk Disease. Curr Oncol Rep. 2004 Nov;6(6):471-5
  19. Randall ME, Filiaci VL, Muss H, Spirtos NM, Mannel RS, Fowler J, Thigpen JT, Benda JA; Gynecologic Oncology Group Study. Randomized phase III trial of whole-abdominal irradiation versus doxorubicin and cisplatin chemotherapy in advanced endometrial carcinoma: a Gynecologic Oncology Group Study. J Clin Oncol. 2006 Jan 1;24(1):36-44
  20. Fleming GF, Brunetto VL, Cella D, Look KY, Reid GC, Munkarah AR, Kline R, Burger RA, Goodman A, Burks RT. Phase III trial of doxorubicin plus cisplatin with or without paclitaxel plus filgrastim in advanced endometrial carcinoma: a Gynecologic Oncology Group Study. J Clin Oncol. 2004 Jun 1;22(11):2159-66
  21. Abeler VM, Kjorstad KE. Endometrial adenocarcinoma in Norway. A study of a total population. Cancer. 1991 Jun 15;67(12):3093-103.
  22. Annual report on the results of treatment in gynaecological cancer. J Epid Biostat 2001; 6: 45-86.
  23. Cancer in Norway 2013, Cancer Registry of Norway, Institute of Population-based Research. Oslo, Norway
  24. Howlader N, Noone AM, Krapcho M, Miller D, Bishop K, Kosary CL, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER Cancer Statistics Review, 1975-2014, National Cancer Institute. Bethesda, MD

Diagnostics of uterine cancer

The patient is examined by vaginal ultrasound, and in case of symptoms, a specimen is taken for histological evaluation.

For confirmed uterine cancer, information on the histological type, grade of differentiation, and possible infiltration of the cervix should be collected. It must also be determined if there is metastasis outside the uterus. A pipelle specimen is often suffisient to confirm the histology and degree of differentiation. If this information is not present, dilatation and curettage (D&C) must be performed. 

MRI gives a good impression of how deeply the tumor infiltrates the uterine wall and the cervix, as well as the involvement of the lymph nodes in the pelvis and paraaortic areas. (11-12). Preoperative evaluation of tumor infiltration into the cervix is best confirmed by MRI. D&C does not always provide reliable information regarding this.

Examinations 

  • Gynecological examination under general anesthesia with D&C for evaluation of histological type and grade of differentiation. This is done if this information is not available from the endometrial biopsy. 
  • MRI of the abdomen and pelvis for assessment of the extension of the tumor, as well as possible metastases
  • Chest X-ray

The goal of the MRI examination for endometrial cancer is to assess the tumor's size, depth of invasion into the myometrium, invasion of the cervix, and spread outside the uterus, primarily to the pelvic and paraaortic lymph nodes. 

The evaluation should identify the patients to be offered more comprehensive surgery than a hysterectomy. The treatment schedule must be determined and also if a referral to a gynecological oncology department is necessary. Patients needing only hysterectomy and bilateral salpingo-oophorectomy can have the surgery performed at their local hospital, while patients requiring more comprehensive surgery are referred to gynecologic oncology centers for treatment.

 

Endometrial tumor in the uterine fundus and a small myoma.
Tumor showing less contrast absorption than the surrounding normal myometrium.
In part cystic and in part solid/recurrent tumor from uterine cancer.
Corresponding recurrent tumor posterior in the pelvis with close relation to the rectum.
Filling of lung artery from the right lower lobe causing a contrast defect in the vessel. This finding is consistent with a lung embolism as a complication of uterine cancer.
Large, mucinous tumor distending into the uterine cavity, filling the vaginal lumen and protruding from the vaginal opening.

Recurrence

About 70% of recurrences occur within 3 years after primary treatment. 

Examinations

  • Chest X-ray
  • CT abdomen/pelvis
  • Bone scintigraphy, if necessary 
  • PET-CT, if necessary

The most common localizations of recurrence are:

  • pelvis
  • upper abdomen
  • lungs
  • liver
  • bone
  • brain (rare)

PROSEDYRER

DNA Ploidy Investigation Aided by Image Cytometry

General

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

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

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

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

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

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

Goal

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

Equipment

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

Standard equipment for sectioning and staining of sections:

Preparation

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

Measuring and Editing

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

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

Chemicals 

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

Solutions

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

Eosin

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

Schiff reagent

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

5 M HCl

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

Hematoxylin (Mayers)

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

The following solutions should be fresh and mixed before use.

Protease solution (0,05 %)

  • 10 mg protease dissolved in 20 ml PBS.

Sulfite solution

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

This is enough for one staining jar.

 

 

 

Procedure

Image cytometry, specimen collection, and registration

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

Section protocol

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

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

Monolayer preparation of 50 µm thick paraffin sections

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

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

Feulgen staining of monolayer

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

Mount cover glass with Eukitt® from xylene.

Automatic measurement of monolayer

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

Editing of automatic measurement

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

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

Classification of DNA-histogram

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

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

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

The histogram is classified into one of four possible categories:

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

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

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

REFERENCE

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

DNA Ploidy Investigation Aided by Image CytometryDNA Ploidy Investigation Aided by Image CytometryDNA Ploidy Investigation Aided by Image CytometryDNA Ploidy Investigation Aided by Image Cytometry
DNA Ploidy Investigation Aided by Image CytometryDNA Ploidy Investigation Aided by Image CytometryDNA Ploidy Investigation Aided by Image CytometryDNA Ploidy Investigation Aided by Image Cytometry
DNA Ploidy Investigation Aided by Image CytometryDNA Ploidy Investigation Aided by Image CytometryDNA Ploidy Investigation Aided by Image CytometryDNA Ploidy Investigation Aided by Image Cytometry
DNA Ploidy Investigation Aided by Image CytometryDNA Ploidy Investigation Aided by Image CytometryDNA Ploidy Investigation Aided by Image CytometryDNA Ploidy Investigation Aided by Image Cytometry
DNA Ploidy Investigation Aided by Image CytometryDNA Ploidy Investigation Aided by Image CytometryDNA Ploidy Investigation Aided by Image Cytometry

Histological sampling with pipelle or similar instrument

General

Cancer is always suspected when a woman has postmenopausal bleeding, even if benign conditions are most common. When postmenopausal bleeding occurs, ultrasound is always performed as well as endometrial sampling for histological evaluation. The tissue sample can be taken with either a pipelle or equivalent instrument, or by fractionated abrasion. The endometrial sampling can be done as an outpatient procedure without anesthesia, however, fractionated abrasion requires anesthesia.  

A meta-analysis (10) has shown a 97–99% sensitivity and 98–100% specificity of pipelle or vabra methods in diagnosing endometrial cancer. The amount of material obtained by pipelle is sometimes minimal to determine the histological type and grade. In such cases, we choose to do fractionated abrasion under general anesthesia.

Indication

  • Postmenopausal bleeding

Goal

  • To obtain a representative endometrial sample for histological evaluation.

Equipment

  • Pipelle
  • Broad-spectrum antiseptic such as chlorhexidine 0.5 mg/ml
  • Specimen container with formalin

Preparation

  • Inform the patient about the sampling procedure.
  • Sampling may cause some discomfort, but little pain.
  • The sampling is done at an outpatient clinic without general anesthesia.
  • The patient lies in a gynecological position during the sampling.

Implementation

  • The vagina and cervix are washed with broad-spectrum antiseptic (chlorhexidine) 0.5 mg/ml).
  • The gynecologist inserts the pipelle into the cervical canal and up into the uterine cavity until it reaches the top of the uterine cavity.
  • Vacuum is created by aspiration and maintaining this.
  • Scrape the material from the uterine wall all the way around by moving the pipelle back and forth under rotation.
  • Remove the pipelle.
  • Empty the pipelle of collected material and put it into a specimen container with formalin.

Follow-up

A follow-up meeting with the gynecologist will take place when the result is available.

Histological sampling with pipelle.Histological sampling with pipelleHistological sampling with a pipelle

Histological sampling by D&C

General

Cancer should always be considered when a woman has postmenopausal bleeding, even if benign conditions are most common. When postmenopausal bleeding occurs, ultrasound is always performed as well as sampling for histological evaluation. The sample can be taken by pipelle or D&C. The pipelle sampling can be performed on outpatient basis without general anesthesia. D&C requires anesthesia.

Comparative studies have shown a high sensitivity for diagnosing endometrial cancer. Endometrial biopsy is accurate in making the diagnosis in most cases. However, if the endometrial biopsy is negative and a cause of the bleeding has not been determined, a D&C is required. The amount of material collected by the pipelle technique is, however, not always enough to determine the histological type and grade. If the pipelle sampling is too scarce, subsequent fractionated abrasion must be performed under general anesthesia.

Indication

  • Postmenopausal bleeding

Goal

  • Obtain a representative endometrial sample for hostological evaluation

Equipment

  • Abrasion tray:
  • Broad-spectrum antiseptic (chlorhexidine) 0.5 mg/ml
  • Specimen containter with formalin

Preparation

  • Inform the patient about the sampling procedure.
  • The sampling is done under general anesthesia.
  • The patient lies in a gynecological position during the sampling.

Implementation

  • The vagina and cervix are washed with broad-spectrum antiseptic (chlorhexidine).
  • The cervical canal is dilated to Hegar dilator number 9.
  • First, scrape the cervical canal with a curette.
  • Place the specimen into a specimen container.
  • Scrape the uterine cavity with a curette. Thoroughly scrape the entire cavity all around, as well as from the fundus.
  • The material is put in a specimen container.

Hysteroscopy may be performed in conjunction with D&C.

Observations

  • There is a risk for perforation of the uterine wall during this procedure. If this should happen, the patient will be observed at the hospital until the next day due to the risk for bleeding or intestinal perforation. 
  • Infections can occur.
  • Light bleeding can also occur about two weeks after sampling.
Histological sample by fractionated curettageHistological sampling by fractionated abrasion.

Treatment of uterine cancer

The choice of treatment depends on the stage of the disease. Different treatment methods are used.

Surgery of uterine cancer

Stage I

Surgery is the primary treatment for uterine cancer. At the beginning of the operation, a thorough inspection of the abdomen is done, and abdominal rinse fluid is collected for cytological evaluation, possibly after abdominal lavage. 

  • With a tumor confined to the uterus, a total abdominal hysterectomy and bilateral salpingo-oophorectomy are performed. If there is invasion of the cervix (stage II), a radical hysterectomy is performed. An alternative for stage II uterine cancer is a regular hysterectomy followed by radiation treatment. 
  • In cases of serous-papillary and clear-cell tumors, an omentectomy and lymph node extirpation is always performed.
  • LND is performed in many cases of endometrial cancer and is determined by histology, grade, pre-operative factors, frozen section results and patient comorbidities.

Postoperative treatment 

  • Endometrioid tumors in stage I grade 1–2 are categorized in the low-risk group. The frequency of recurrence is 5–7% (21). Recurrences are most commonly localized to the vagina or pelvis, and can be treated with radiation with good results (15). At Oslo University Hospital, it is recommended not to give adjuvant treatment to this patient group.
  • Endometrioid tumors in stage Ib grade 1–2 as well as stage Ia grade 3 are categorized as moderate risk group. The frequency of recurrence is about 10%. Recurrences are most commonly localized to the vagina or pelvis and are treated with radiation therapy achieving good results (15). An effect has not been found on survival by adjuvant radiation therapy of these two groups of patients (16). At Oslo University Hospital, it is not recommended to give adjuvant radiation therapy to this patient group.
  • Endometrioid tumors in stage Ib grade 3 are considered high risk with a recurrence rate of about 25%. Recurrences are partly localized to the pelvis and partly outside the pelvis. Adjuvant radiation to the pelvis reduces the frequency of local recurrences, but do not increase survival. A recent Cochrane analysis showed marginally improved survival by adjuvant chemotherapy.  
  • Serous papillary as well as clear cell tumors have a high risk for recurrence in both stage Ia and Ib. Adjuvant radiation to the pelvis reduces the frequency of local recurrences, but do not increase survival.
  • Adjuvant treatment with progestagens has no documented effect.

Postoperative chemotherapy with 6 courses of carboplatin and paclitaxel is offered to:

  • Patients with tumors of grade 3 and invasion of the myometrium of 50% or more
  • All patients with type 2 tumors
  • All patients with carcinosarcoma

Lymph node staging

The risk for lymph node metastasis is about 5% in the low risk group, about 10% in the moderate risk group, and 25% or higher in the high risk group (13).

Lymph node staging in endometrial cancer is controversial and has not been shown to increase survival in 2 randomized studies. At the Norwegian Radium hospital, pelvic and paraaortal lymph node staging is performed in all patients in the high risk group and in patients with stage Ib, grade 2 or 3 as well as in patients with carcinosarcoma.

Stage II

In the case of visible macroscopic tumor tissue on the cervix, the possibility of cervical cancer must be considered. MRI is usually helpful for differential diagnoses. For stage II confirmed preoperatively, we recommend a radical hysterectomy with bilateral salpingo-oophorectomy and pelvic and paraaortic lymph node staging.

Postoperative treatment

External radiation treatment to the pelvis is recommended for stage II in case a simple hysterectomy is performed.

All patients with stage II are offered postoperative chemotherapy with 6 courses of carboplatin and paclitaxel.

Stage III–IV

This is a heterogenous group of tumors where the primary examinations have confirmed metastasis outside the uterus in some cases, while for others, this is first confirmed by the histological evaluation after surgery for assumed stage I cancer. 

If there is spreading to the pelvis, it was previously recommended to give radiation before surgery. Recent studies (19) show, however, that chemotherapy is more effective than radiation for advanced endometrial cancer. It is therefore recommended to remove the tumor by surgery followed by chemotherapy. An alternative is neoadjuvant chemotherapy followed by surgery.

If the tumor can be completely removed by surgery based on a thorough preoperative evaluation, we choose primary surgery first, otherwise, we consider to give neoadjuvant chemotherapy.

Aftercare

  • Stage IIIa: Chemotherapy after surgery
  • Stage IIIb with parametrial infiltration: Neoadjuvant chemotherapy followed by surgery will usually be given. Supplemental radiation will be considered. Treatment often consists of surgery. The extent of chemotherapy combined with radiation therapy is evaluated individually.
  • Stage IIIb with vaginal metastasis: Individualized treatment. Surgery with full resection if possible followed by chemo. Radiation is an option in case of unresectable tumor.
  • Stage IIIc: If the lymph nodes are considered removable by surgery, the treatment is initiated by surgery and followed by chemotherapy.
  • Stage IV: If there is invasion of the bladder or rectum as well as confirmed distant metastases (liver, lungs, or bone) treatment is assessed individually. Treatment often begins with chemotherapy if the patient's general health condition is acceptable. Further treatment in the form of surgery or radiation will depend on the effect of the chemotherapy on the tumor and the disease profile. For hormone receptor-positive tumors, hormone treatment may also be considered.

PROSEDYRER

Hysterectomy and bilateral salpingo-oophorectomy for endometrial cancer

General

For confirmed endometrial cancer, the standard procedure is removal of the uterus (hysterectomy) and both ovaries (bilateral salpingo-oophorectomy, or BSO). The surgeon also checks for metastasis to other parts of the adomen and lymph nodes.

Due to the possibility of metastasis to the peritoneum and lymph nodes from serous papillary and clear cell tumors, the omentum (omentectomy) and lymph nodes are also removed. 

In tumors of low differentiation, serous papillary carcinoma, clear cell carcinomas, and carcinosarcomas, there is a high risk for metastases to lymph nodes. Lymph node staging in the pelvis and paraaortic is therefore always performed for these tumors. 

For high and moderately differentiated endometrioid tumors, the decision for lymph node staging depends on depth of invasion into the myometrium evaluated from MRI. Metastases to the adnexae or synchronous primary tumors of the adnexae are confirmed in about 20% of patients, therefore it is recommended to remove these by surgery.

This operation is preferably performed by endoscopy if the situation allows.

 

Indication

  • Suspect or confirmed endometrial cancer

Goal

  • Curative treatment and staging

Equipment

Gynecological surgery tray

Preparation

  • Enema 
  • Thrombosis prophylaxis
  • Antibiotic prophylaxis

Implementation

  • The patient lies in the supine position.
  • An incision is made in the midline from above the symphysus to the navel, extending upward as needed. The incision should be long enough to provide adequate space to avoid rupturing of the ovaries when mobilized. 
  • Any ascites are aspirated into a syringe.
  • If there are no ascites, the abdomen is rinsed with 50 ml NaCl 9 mg/ml and aspirated into the same syringe. The aspirate is sent for cytological examination. 
  • Bookwalter's retractor should be mounted with adequate distance from the patient to allow enough space and overview. 
  • Check that the retractors are not pressing on the psoa muscle or femoral nerve to avoid compression damage, neuropathy, and paralysis in the femoral area.
  • Tip the patient by lowering the caudal end (Trendelenburg).
  • Inspect and palpate the entire abdomen for possible metastasis.
  • The ovaries and abdomen are inspected. Inspect the liver, spleen, lymph nodes, diaphragm, stomach, intestines, and omentum. 
  • Pack away the intestines with compresses moistened with NaCl 9 mg/ml. Keep these in place with retractors. 
  • Fasten a Kocher forcep on each corner of the uterus. The assisting surgeon holds the uterus.
  • Clamp and divide the round ligament on both sides.
  • Divide the bladder peritoneum.
  • Divide the peritoneum along the pelvic wall.
  • Open the extraperitoneal space along the pelvic wall.
  • Indentify the ureter and avoid it.
  • Clamp the infundibulopelvic artery which is the blood supply to the adnexa.
  • The ureter is separated from the peritoneal surface so the ureter can be pushed down before the surface is divided.
  • Dissect along the peritoneal surface to the uterus. 
  • Divide the adnexa from the uterus.
  • Push the bladder peritoneum well down to reach below the cervix.
  • Clamp the parametria closely to the cervix.
  • Place clamp diagonally and close to the vagina on the sides and cut.
  • Place Kocher forceps on the vagina immediately under the cervix to lift the vagina.
  • Use diathermy to remove the uterus and cervix immediately distal to the cervix.
  • Sew the top of the vagina.
  • Perform node staging.
  • Perform the omentectomy
  • Close the abdomen.

Follow-up

Regular postoperative observations

Radical hysterectomy for endometrial cancer

General

Endometrial cancer in stage II can either be treated with a radical hysterectomy or a hysterectomy followed by radiation therapy. As per January 2006, there are no studies comparing the effect and morbidity of the two treatment alternatives. At Oslo University Hospital, a radical hysterectomy is performed when MRI shows involvement of cervical stroma. 

Difficulty emptying the bladder is a serious side effect after a radical hysterectomy due to damage to the autonomous nerves of the bladder during the operation. It is therefore very important to avoid these nerves during the operation.

During the operation, the sacrouterine and cardinal ligaments are divided 2-3 cm from the cervix. This is to remove possible micrometastases near the cervix.  

Pelvic and paraaortal lymph node staging is always performed for these patients. 

 

Indication

  • MRI indicates cervical involvement

Goal

  • Cure the disease

Equipment

Gynecological surgery tray

Preparation

  • Enema
  • Thrombosis prophylaxis
  • Antibiotic prophylaxis

Implementation

  • Make a midline incision in the abdomen.
  • Inspect the pelvis and upper abdomen for possible pathological findings.
  • Dissect the pararectal and paravesical spaces. 
  • Dissect and push the bladder away from the cervix.
  • Ligate the uterine artery bilaterally.
  • Dissect the ureter.
  • Autonomous nerve pathways to the bladder follow the ureter. The dissection of the ureters must be close to the peritoneum to preserve these nerve pathways. 
  • The ureters are dissected from the parametria by opening the roof of the ureteral tunnel.
  • Avoid dissecting the plexus area.
  • Cut and ligate the adnexae and attach them to the pelvic or abdominal wall. Mark with metal clips. Usually, the ovaries are attached to the abdominal walls in the iliac fossa.
  • Dissect and divide the cardinal and sacrouterine ligaments on both sides at a distance of 2-3 cm from the cervix. 
  • Extirpate the uterus using diathermy 2–3 cm distal to the cervix so that the specimen has a 2-3 cm vaginal cuff.
  • Suture the vagina using the Benedetti Panizi method. Start from behind and suture towards the front. This will create a rounded vaginal top without deep hollows in the vaginal corners. 
  • Perform hemostasis in the pelvis and continue with the para-aortic and pelvic lymph node dissection.
  • Perform hemostasis again and close the abdomen.

Follow-up

Observations

  • The patient normally has a bladder catheter for 3 to 5 days after the operation. 
  • After removal of the catheter, residual urine must be checked. The patient may have problems emptying her bladder.
  • The volume of residual urine should be less than 100 ml before the patient is discharged.

Complications

  • Urinary tract infection due to insufficient bladder emptying
  • Lymph edema of the lower extremities

Follow-up

The patient should have an outpatient follow-up visit every 3 months with a gynecological examination in the first 2 years, 6 month intervals the next 5 years, and then annually.

Omentectomy

General

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

The omentectomy is part of the stage determination.

Indications

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

Goal

  • Remove visible tumors and to check for possible micrometastases.

Equipment

Gynecological surgery tray

Preparation

  • Large bowel emptying
  • Thrombosis prophylaxis

Implementation

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

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

Follow-up

Observe for normal postoperative complications.

Pelvic paraaortal lymph node dissection/sampling

General

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

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

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

Indications

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

Goal

  • Diagnose microscopic tumor spreading

Preparation

  • Large bowel emptying
  • Thrombosis prophylaxis

Implementation

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

Follow-up

  • Standard observation for postoperative complications

Drug therapy of uterine cancer

For advanced disease with spreading outside the uterus, newer studies (19) have shown that chemotherapy is more effective than radiation therapy. A recent Cochran analysis showed clear evidence for improvement of survival by postoperative chemotherapy.

The combination of cisplatin and doxorubicin was considered standard treatment (18). A more recent study has shown that the addition of paclitaxel extends survival time (20). However, these regimens have relatively severe side effects, and many patients are in poor physical condition. At Oslo University Hospital, the combination of carboplatin and paclitaxel is used. This combination is under testing in a phase III study where it is compared with the cisplatin, doxorubicin, and paclitaxel regimen (GOG#0209).

Hormonal treatment

For hormone receptor-positive tumors (ER/PR), about the same response rate can be achieved with hormonal treatment as chemotherapy. Therefore, it is recommended in most cases to start hormonal treatment and reserve chemotherapy for cases where hormonal treatment does not achieve the desired effect. In patients with hormone receptor-negative tumors, hormone treatment cannot be expected to have an effect. Serous papillary tumors do not have hormone receptors, and tumors of low differentiation rarely have hormone receptors. 

Treatment with progestins has shown a response rate of 15–30%. The treatment response is related to the detection of the hormone receptor. Oral treatment is as effective as parenteral treatment. Actual drugs are Farlutal® and Megace® daily. Blocking of estrogen production in postmenopausal women using aromatase inhibitors is an experimental treatment currently under evaluation.  

Treatment for recurrence  

  • Patients with localized recurrence in the pelvis who have not previously had radiation treatment are given irradiation to the pelvic tumor. 
  • For localized pelvic recurrence, previously irradiated, chemotherapy or hormonal therapy is given. In rare cases, surgery may be appropriate. 
  • For recurrence in the upper abdomen, chemotherapy or hormonal treatment is given. 
  • For recurrence in the lungs, chemotherapy or hormonal treatment is given. For localized recurrence, surgery may be appropriate if systemic treatment does not provide complete remission. 
  • For brain metastases, surgery may be appropriate for a solitary metastasis, otherwise radiation treatment is given. 
  • For bone metastases, radiation may be given to prevent fractures. Additional systemic treatment may also be appropriate such as chemotherapy or hormonal treatment.  

PROSEDYRER

Gyn_cisplatin

Gyn_Cisplatin ukentlig

Kapitteloverskrift mangler!

Kapittelet mangler tekst!

Kapitteloverskrift mangler!

Kapittelet mangler tekst!

Kapitteloverskrift mangler!

Kapittelet mangler tekst!

Kapitteloverskrift mangler!

Kapittelet mangler tekst!

Gyn_Doksorubicin

Kapitteloverskrift mangler!

Kapittelet mangler tekst!

Kapitteloverskrift mangler!

Kapittelet mangler tekst!

Kapitteloverskrift mangler!

Kapittelet mangler tekst!

Kapitteloverskrift mangler!

Kapittelet mangler tekst!

Gyn_Karboplatin

Kapitteloverskrift mangler!

Kapittelet mangler tekst!

Kapitteloverskrift mangler!

Kapittelet mangler tekst!

Kapitteloverskrift mangler!

Kapittelet mangler tekst!

Kapitteloverskrift mangler!

Kapittelet mangler tekst!

Gyn_Karboplatin Epirubicin

Kapitteloverskrift mangler!

Kapittelet mangler tekst!

Kapitteloverskrift mangler!

Kapittelet mangler tekst!

Kapitteloverskrift mangler!

Kapittelet mangler tekst!

Kapitteloverskrift mangler!

Kapittelet mangler tekst!

Gyn_Karboplatin Paklitaxel

Kapitteloverskrift mangler!

Kapittelet mangler tekst!

Kapitteloverskrift mangler!

Kapittelet mangler tekst!

Kapitteloverskrift mangler!

Kapittelet mangler tekst!

Kapitteloverskrift mangler!

Kapittelet mangler tekst!

Gyn_Paklitaxelukentlig

Kapitteloverskrift mangler!

Kapittelet mangler tekst!

Kapitteloverskrift mangler!

Kapittelet mangler tekst!

Kapitteloverskrift mangler!

Kapittelet mangler tekst!

Kapitteloverskrift mangler!

Kapittelet mangler tekst!

Gyn_Paklitaxel_hver_3_uke

Sun Exposure under Drug Therapy

General

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

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

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

Indication

Sun exposure in connection with drug cancer treatment.

Goal

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

Definitions

Photosensitivity

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

Phototoxicity

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

Photoallergy

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

Photoinstability

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

PPE ( palmoplantar erythrodysesthesia = Acral erythema )

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

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

Acne-like rash

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

Hyperpigmentation

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

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

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

Radiation Recall Dermatitis (RRD)/Photo Toxic recall reaction

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

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

Preparation

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

Implementation

General Precautions

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

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

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

Medicaments that most commonly cause skin reactions

Medicament Common reactions Remedial action
Dakarbazin (DTIC)


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

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

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

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

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

(2, 9)

Fluorouracil (5-FU®)

 

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

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

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

Radiation recall
Treatment as with phototoxic

Kapecitabin (Xeloda®)

 

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

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

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

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

Vinblastin

 

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

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

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

Tegafur

 

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

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

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

EGFR-hemmere

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

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

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

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

References


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

Preparation of Chemotherapy, Spills, and Cleaning a LAF Bench

General

Preparation of chemotherapy outside of a pharmacy

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

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

Designated room with LAF-bench to dilute/mix chemotherapy

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

Goal

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

Handling of chemotherapy spills

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

Goal

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

Cleaning of LAF-bench

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

Goal

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

Source

Applicable directives and guidelines (www.lovdata.no)

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

Equipment

  Preparation of chemotherapy in a hospital

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

Handling of chemotherapy spills

Spill kit includes:

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

Washing of LAF-bench

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

 

 

Preparation

Preparation of chemotherapy outside of the pharmacy

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

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

Handling of chemotherapy spills

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

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

Washing of LAF-bench

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

 

 

Implementation

Preparation of chemotherapy drugs outside of a pharmacy

Aseptic procedure

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

Multiple additions

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

Handling of chemotherapy spills

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

Washing of LAF-bench

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

Routine washing

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

Follow-up

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

First aid if contact with chemotherapy drugs

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

Radiation therapy of uterine cancer

Primary treatment

Primary radiation therapy is rarely given for endometrial cancer, but may be appropriate for patients with inoperable tumors. In such a case, external radiation therapy is given with 46–50 Gy towards the uterus and iliacal lymph nodes. This is supplemented with brachytherapy to the uterine tumor.

Recurrence

For localized pelvic recurrence which has not previously been treated with radiation, the pelvic tumor is irradiated. 

For brain metastases, stereotactic radiation is appropriate for 1 to 3 (max) metastases that are not too large.

For solitary brain metastases, surgery may be appropriate.

Multiple or large brain metastases are treated with total brain irradiation.

For bone metastases, radiation therapy is sometimes given.

Complication treatment of uterine cancer

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

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

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

PROSEDYRER

Antiemetisk behandling gyn

Kapitteloverskrift mangler!

Kapittelet mangler tekst!

Kapitteloverskrift mangler!

Kapittelet mangler tekst!

Kapitteloverskrift mangler!

Kapittelet mangler tekst!

Kapitteloverskrift mangler!

Kapittelet mangler tekst!

Kapitteloverskrift mangler!

Kapittelet mangler tekst!

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.

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.

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.

Scalp Cooling Treatment

General

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

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

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

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

Indications

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

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

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

Goal

  • Prevent chemotherapy-induced hair loss (alopecia).

 

Equipment

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

Preparation

Preparation for use of scalp cooling machine

Before the machine is turned on

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

When the machine is turned on

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

After 15 minutes

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

Preparation of the patient

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

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

Implementation

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

Follow-up

Recommended hair care for optimal results  

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

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

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

The result can be maximized by following these recommendations:

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

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

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

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

Erythropoitin (EPO) for anemia

General

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

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

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

Indication

  • Patients with chemotherapy-induced anemia

Contraindications

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

 

Goal

  • Reach hemoglobin level of 12–13 g/l

Preparation

  • Survey blood status
  • Evaluate iron status

Implementation

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

Assurance of efficient erythropoesis

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

Follow-up

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

Smoking cessation in connection with cancer treatment

General

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

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

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

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

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

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

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

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


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

 

Indication

Weaning of nicotine in connection to cancer treatment. 

Goal

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

Preparation

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

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

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

Implementation

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

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

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

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

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

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

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

Treatment with nicotine replacement therapy

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

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

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

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

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

Side effects

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

Precautions

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

Treatment with non-nicotine medications

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

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

Side effects

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

Precautions

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

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

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

Side effects

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

Precations

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

Follow-up

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

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

References

  1. Gritz E, Fingeret M, Vidrine D. Tobacco control in the oncology setting. American Society of Clinical Oncology, eds Cancer Prevention An ASCO Curriculum Alexandria, VA: American Society of Clinical Oncology. 2007.
  2. ASCO ASoCO. Tobacco Cessation Guide for Oncology providers,. 2012 (02.12.2014).
  3. Zevallos JP, Mallen MJ, Lam CY, Karam-Hage M, Blalock J, Wetter DW, et al. Complications of radiotherapy in laryngopharyngeal cancer: Effects of a prospective smoking cessation program. Cancer. 2009;115(19):4636-44.
  4. Obedian E, Fischer DB, Haffty BG. Second malignancies after treatment of early-stage breast cancer: Lumpectomy and radiation therapy versus mastectomy. Journal of Clinical Oncology. 2000;18(12):2406-12.
  5. Park SM, Lim MK, Jung KW, Shin SA, Yoo K-Y, Yun YH, et al. Prediagnosis smoking, obesity, insulin resistance, and second primary cancer risk in male cancer survivors: National Health Insurance Corporation Study. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2007;25(30):4835.
  6. Van Den Belt-Dusebout AW, De Wit R, Gietema JA, Horenblas S, Louwman MWJ, Ribot JG, et al. Treatment-specific risks of second malignancies and cardiovascular disease in 5-year survivors of testicular cancer. Journal of Clinical Oncology. 2007;25(28):4370-8.
  7. Warren GW, Kasza KA, Reid ME, Cummings KM, Marshall JR. Smoking at diagnosis and survival in cancer patients. International Journal of Cancer. 2013;132(2):401-10.
  8. Hooning MJ, Botma A, Aleman BMP, Baaijens MHA, Bartelink H, Klijn JGM, et al. Long-term risk of cardiovascular disease in 10-year survivors of breast cancer. Journal of the National Cancer Institute. 2007;99(5):365-75.
  9. Li CI, Daling JR, Porter PL, Tang M-TC, Malone KE. Relationship between potentially modifiable lifestyle factors and risk of second primary contralateral breast cancer among women diagnosed with estrogen receptor–positive invasive breast cancer. Journal of Clinical Oncology. 2009;27(32):5312-8.
  10. Kenfield SA, Stampfer MJ, Chan JM, Giovannucci E. Smoking and prostate cancer survival and recurrence. JAMA - Journal of the American Medical Association. 2011;305(24):2548-55.
  11. Joshu CE, Mondul AM, Meinhold CL, Humphreys EB, Han M, Walsh PC, et al. Cigarette smoking and prostate cancer recurrence after prostatectomy. Journal of the National Cancer Institute. 2011;103(10):835-8.
  12. Phipps AI, Baron J, Newcomb PA. Prediagnostic smoking history, alcohol consumption, and colorectal cancer survival: The Seattle Colon Cancer Family Registry. Cancer. 2011;117(21):4948-57.
  13. Kountourakis P, Correa AM, Hofstetter WL, Lee JH, Bhutani MS, Rice DC, et al. Combined modality therapy of cT2N0M0 esophageal cancer. Cancer. 2011;117(5):925-30.
  14. Waggoner SE, Darcy KM, Fuhrman B, Parham G, Lucci J, Monk BJ, et al. Association between cigarette smoking and prognosis in locally advanced cervical carcinoma treated with chemoradiation: A Gynecologic Oncology Group study. Gynecol Oncol. 2006;103(3):853-8.
  15. Schlumbrecht MP, Sun CC, Wong KN, Broaddus RR, Gershenson DM, Bodurka DC. Clinicodemographic factors influencing outcomes in patients with low-grade serous ovarian carcinoma. 2011. p. 3741-9.
  16. Nagle CM, Bain CJ, Webb PM. Cigarette smoking and survival after ovarian cancer diagnosis. Cancer Epidemiol Biomarkers Prev. 2006;15(12):2557-60.
  17. Ehlers SL, Gastineau DA, Patten CA, Decker PA, Rausch SM, Cerhan JR, et al. The impact of smoking on outcomes among patients undergoing hematopoietic SCT for the treatment of acute leukemia. Bone Marrow Transplant. 2011;46(2):285-90.
  18. Talamini R, Polesel J, Spina M, Chimienti E, Serraino D, Zucchetto A, et al. The impact of tobacco smoking and alcohol drinking on survival of patients with non-Hodgkin lymphoma. International Journal of Cancer. 2008;122(7):1624-9.
  19. Toll B, Brandon T, Gritz E, Warren G, Herbst R. AACR Subcommittee on Tobacco and Cancer. Assessing tobacco use by cancer patients and facilitating cessation: an American Association for Cancer Research policy statement. Clin Cancer Res. 2013;19:1941-8.
  20. Arntzen A, Sandvold B. Hvordan veilede om røykeslutt? Sykepleien Forskning. 2010;5(3):182-90.
  21. Dresler CM. Is it more important to quit smoking than which chemotherapy is used? 2003. p. 119-24.
  22. Hsu CCT, Kwan GNC, Chawla A, Mitina N, Christie D. Smoking habits of radiotherapy patients: Did the diagnosis of cancer make an impact and is there an opportunity to intervene? J Med Imag Radiat Oncol. 2011;55(5):526-31.
  23. Richards J. Words as Therapy: Smoking Cessation. The journal of family practice. 1992;34(6):687-92.
  24. Cooley ME, Lundin R, Murray L. Smoking cessation interventions in cancer care: opportunities for oncology nurses and nurse scientists. Annual review of nursing research. 2009;27:243.
  25. Mazza R, Lina M, Boffi R, Invernizzi G, De Marco C, Pierotti M. Taking care of smoker cancer patients: a review and some recommendations. Annals of Oncology. 2010;21(7):1404-9.
  26. Waller LL, Weaver KE, Petty WJ, Miller AA. Effects of continued tobacco use during treatment of lung cancer. 2010. p. 1569-75.
  27. Peppone LJ, Mustian KM, Morrow GR, Dozier AM, Ossip DJ, Janelsins MC, et al. The Effect of Cigarette Smoking on Cancer Treatment-Related Side Effects. Oncologist. 2011;16(12):1784-92.
  28. Kuri M, Nakagawa M, Tanaka H, Hasuo S, Kishi Y. Determination of the duration of preoperative smoking cessation to improve wound healing after head and neck surgery. Anesthesiology. 2005;102(5):892.
  29. Krueger JK, Rohrich RJ, Mustoe TA. Clearing the smoke: The scientific rationale for tobacco abstention with plastic surgery. 2001. p. 1074-5.
  30. Nakagawa M, Tanaka H, Tsukuma H, Kishi Y. Relationship between the duration of the preoperative smoke-free period and the incidence of postoperative pulmonary complications after pulmonary surgery. Chest. 2001;120(3):705-10.
  31. Barrera R, Shi W, Amar D, Thaler HT, Gabovich N, Bains MS, et al. Smoking and timing of cessation: Impact on pulmonary complications after thoracotomy. Chest. 2005;127(6):1977-83.
  32. Mason DP, Subramanian S, Nowicki ER, Grab JD, Murthy SC, Rice TW, et al. Impact of Smoking Cessation Before Resection of Lung Cancer: A Society of Thoracic Surgeons General Thoracic Surgery Database Study. Annals of Thoracic Surgery. 2009;88(2):362-71.
  33. Gajdos C, Hawn MT, Campagna EJ, Henderson WG, Singh JA, Houston T. Adverse Effects of Smoking on Postoperative Outcomes in Cancer Patients. Ann Surg Oncol. 2012;19(5):1430-8.
  34. Alsadius D, Hedelin M, Johansson KA, Pettersson N, Wilderang U, Lundstedt D, et al. Tobacco smoking and long-lasting symptoms from the bowel and the anal-sphincter region after radiotherapy for prostate cancer. Radiother Oncol. 2011;101(3):495-501.
  35. Chen AM, Chen LM, Vaughan A, Sreeraman R, Farwell DG, Luu Q, et al. Tobacco smoking during radiation therapy for head-and-neck cancer is associated with unfavorable outcome. International Journal of Radiation Oncology Biology Physics. 2011;79(2):414-9.
  36. Eifel PJ, Jhingran A, Bodurka DC, Levenback C, Thames H. Correlation of smoking history and other patient characteristics with major complications of pelvic radiation therapy for cervical cancer. Journal of Clinical Oncology. 2002;20(17):3651-7.
  37. Bjarnason GA, MacKenzie RG, Nabid A, Hodson ID, El-Sayed S, Grimard L, et al. Comparison of Toxicity Associated With Early Morning Versus Late Afternoon Radiotherapy in Patients With Head-and-Neck Cancer: A Prospective Randomized Trial of the National Cancer Institute of Canada Clinical Trials Group (HN3). International Journal of Radiation Oncology Biology Physics. 2009;73(1):166-72.
  38. Browman GP, Wong G, Hodson I, Sathya J, Russell R, McAlpine L, et al. Influence of Cigarette Smoking on the Efficacy of Radiation Therapy in Head and Neck Cancer. The New England Journal of Medicine. 1993;328(3):159-63.
  39. Browman GP, Mohide EA, Willan A, Hodson I, Wong G, Grimard L, et al. Association between smoking during radiotherapy and prognosis in head and neck cancer: A follow-up study. Head Neck-J Sci Spec Head Neck. 2002;24(12):1031-7.
  40. Travis LB, Gospodarowicz M, Curtis RE, Clarke EA, Andersson M, Glimelius B, et al. Lung cancer following chemotherapy and radiotherapy for Hodgkin's disease. Journal of the National Cancer Institute. 2002;94(3):182-92.
  41. Ford MB, Sigurdson AJ, Petrulis ES, Ng CS, Kemp B, Cooksley C, et al. Effects of smoking and radiotherapy on lung carcinoma in breast carcinoma survivors. Cancer. 2003;98(7):1457-64.
  42. Dresler CM, Gritz ER. Smoking, smoking cessation and the oncologist. 2001. p. 315-23.
  43. Balduyck B, Nia PS, Cogen A, Dockx Y, Lauwers P, Hendriks J, et al. The effect of smoking cessation on quality of life after lung cancer surgery. Eur J Cardiothorac Surg. 2011;40(6):1432-8.
  44. Hamilton M, Wolf JL, Rusk J, Beard SE, Clark GM, Witt K, et al. Effects of smoking on the pharmacokinetics of erlotinib. Clinical Cancer Research. 2006;12(7 I):2166-71.
  45. Helsedirektoratet. Forberedelse til røykeslutt 2011. Available from: http://helsedirektoratet.no/publikasjoner/forberedelser-til-roykeslutt/Publikasjoner/forberedelse-til-roeykeslutt.pdf   
  46. Brunnhuber K, Cummings KM, Feit S, Sherman S, Woodcock J. Putting evidence into practice: Smoking cessation: BMJ Publishing Group; 2007.
  47. Helsedirektoratet. Røyketelefonen 2013 [updated 12.12.201102.12.2014]. Available from: http://www.helsedirektoratet.no/folkehelse/tobakk/snus-og-roykeslutt/royketelefonen/Sider/default.aspx.
  48. Legemiddelverk S. Legemidler A-Å 2013 [02.12.2014]. Available from: http://www.legemiddelverket.no/Legemiddelsoek/Sider/Legemidler_A-AA.aspx.
  49. Hughes JR, Stead LF, Lancaster T, Rev CDS. Antidepressants for smoking cessation. Cochrane Database of Systematic Reviews: Reviews 2007. 2014 (1).
  50. Stead LF, Perera R, Bullen C, Mant D, Hartmann-Boyce J, Cahill K, et al. Nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev. 2012;11(11).
  51. Cahill K, Stead LF, Lancaster T, Polonio IB. Nicotine receptor partial agonists for smoking cessation. Sao Paulo Med J. 2012;130(5):346-7

Follow-up care after treatment of uterine cancer

The Norwegian Radium Hospital at Oslo University Hospital has chosen to abandon adjuvant radiation treatment for patients with tumors belonging to the low and moderate risk groups. It is important to diagnose recurrence in these patients, since treatment of recurrence can give good results. Recurrences are most often localized to the pelvis and can usually be diagnosed by a gynecological exam.

Intervals for follow-up

  • During the first 2 years, there is a follow-up visit every 3 months.
  • From the third to the fifth years, follow-up visits are every 6 months.
  • After 5 years, follow-up visits are annual.

Appropriate examinations depend on the disease and the primary treatment given. A lung X-ray is taken every year. Patients who have primarily received surgical treatment are examined generally by gynecological examination and cytological specimen for the vaginal top. Patients who have received radiation therapy are examined by gynecological exam. There is no value in doing a cytological evaluation on tissue previously treated with radiation. 

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.

Lymph edema in the armLymph edema in the arm.Lymph edema in the legLymph edema in the leg
Lymph edema in the arm.Lymph edema in the arm.