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Utskriftsdato (17.11.2017)

Anal cancer

Anal cancer develops from squamous epithelial cells similar to cancer in the upper part of the gastrointestinal tract. Treatment of anal cancer differs from colorectal cancer.

Anal cancer also includes:

  • perianal cancer or anal margin – develops from basal epithelial cells in the skin approximately 5 cm around the anal verge
  • giant condyloma acuminatum (Buschke Löwenstein tumor) – occurs as large tumors in the perineum  

The anal canal is 3-4  cm long and approximately 1 cm shorter in women than in men. It stretches from the anal verge to about 1 cm above the dentate line, which is the transition from cylindrical epithelial cells in the rectum to squamous epithelial cells in the anal canal.

Incidence

Compared to other cancers, anal cancer is rare and represents only 0.5% of all new cancer cases in the United States. Anal cancer is slightly more common in women than men and is most frequently diagnosed among people aged 55-64.

The number of cases of anal cancer diagnosed each year has been increasing over the last 10 years. In 2017, it is estimated to be 8,200 new cases of anal cancer in the United States (2).

Giant condyloma acuminatum is very rare; there are less than 100 cases reported in the literature. This type of tumor occurs most commonly around the age of 40 and is two to three times more common in men than in women.

 

Age-specific incidence of cancer in the anal canal, 2010–2014.

Source: National Cancer Institute. Bethesda, MD, USA

 

 

Incidence of cancer in the anal canal, 1975–2014.

Source: National Cancer Institute. Bethesda, MD, USA

Etiology of anal cancer

Infections with the Human Papilloma Virus (HPV), which is a very common infection in women, is an important risk factor. Most of the infections are temporary, but can be chronic and possibly cause cancer.

Infection with HPV is confirmed in about 90% of anal cancer and its pre-stages (dysplasia). Among the almost 100 HPV subtypes, there are very different tendencies to cause cancer. HPV 16 is the most important carcinogenic subtype and is confirmed the most frequently (about 80%). HPV 18 is detected more rarely (about 10%). HPV can also be found in genital warts. Mechanisms are unknown.

Risk factors

Patients who have had cervical cancer due to HPV have 4-5 times higher risk for developing anal cancer. 

  • Men and women who practice anal sex have a considerably increased risk for anal cancer, probably through the HPV infection.
  • HIV-positive patients who now live longer due to effective treatment and live long enough to develop cancer have a much higher risk.
  • Immunosuppressed patients, due to organ transplantation for example, have a 10 fold increased risk compared to the rest of the population. 
  • High use of tobacco appears to increase the risk for developing anal cancer, but the mechanism is unknown.

A large percentage of the population is infected with HPV. Most cases of anal and perianal cancer occur in heterosexual HIV negative and non-immunosuppressed patients.

Histology of anal cancer

The anal canal has short zones covered with different types of epithelium from proximal to distal end.

  • Rectal zone with colonic type of mucosa
  • Transitional zone varying with colonic mucosa and squamous epithelium
  • Squamous epithelium zone with non-keratinizing squamous epithelium
  • Perianal skin with keratinizing squamous cell epithelium

Carcinoma in the anal canal generally originate from the squamous epithelium in the distal part of the canal, but can also originate from cylindrical epithelium in the colonic mucosa or perianal glands in the transitional zone. Most adenocarcinoma in the proximal zone will be designated as distal carcinomas primary in the rectum.

Carcinoma precursor lesions

  • Anal Intraepithelial Neoplasia (AIN) (Bowen`s Disease)
  • Paget's disease
  • Adenomas (tubular, tubulo-villous, villous) in distal rectum/proximal anal canal

Carcinoma percursor lesions in the anal canal (AIN) are classified in the same way as cervical intraepithelial lesions (CIN).

AIN is divided into:

  • mild (grade 1)
  • moderate (grade 2)
  • severe dysplasia/carcinoma in situ (grade 3)

or into:

  • low-grade
  • high-grade intraepithelial neoplasia

High-grade intraepithelial neoplasia includes moderate and severe dysplasia. These lesions can appear as condylomas or flat lesions. The majority of in situ lesions and infiltrating squamous cell carcinomas are associated with HPV.

An uncommon (infrequent) intraepithelial lesion is the ”extramammary Paget's disease”. This lesion appears as skin eczema and histologically atypical mucosa, containing cells seen in the squamous epithelium. In about half of these cases, the patient also demonstrates a simultaneous rectal or colonic adenocarcinoma. In the other half, this lesion is believed to originate from apocrine glands. These have a strong recurrence tendency and can infiltrate.

Adenomas in the proximal anal canal will, in most cases, be considered rectal adenomas.

Classification and differentiation

The vast majority of anal canal carcinomas are squamous cell carcinomas. They can be keratinizing or non-keratinizing. Basaloid squamous cell carcinomas demonstrate significant basal cell appearance. This type should not be misdiagnosed as basal cell carcinomas in perianal skin, since they have much better prognoses. Squamous cell carcinomas in perianal skin have better prognoses than squamous cell carcinoma in the anal canal. In extensively growing squamous cell carcinomas it may be difficult to determine the correct origin and thus prognosis.

Photomicrograph demonstrating carcinoma in situ in the anal canal. Click to magnify. Photomicrograph demonstrating (Mb Bowen) carcinoma in situ in the skin of the anal canal. Click to magnify. Photomicrograph demonstrating squamous cell carcinoma in the anal canal. Click to magnify.

Verrucous carcinomas also designated as ”giant condyloma” (Buschke-Löwenstein tumor), are macroscopically cauliflower in shape. This tumor can grow in the perineum, perianally, and up in the anus, isolated in the rectum or on the penis. This tumor can also infiltrate vagina, rectum, and the urinary tract. This tumor is diagnosed when the size is up to 30 cm in diameter.

Histologically, the verrucous carcinomas show acanthosis and papillomatosis, and lack cellular atypia and definite stromal infiltration.

Adenocarcinomas in the anal canal can represent downgrowth from rectal carcinomas or originate from the rectal zone of the anal canal. Adenocarcinomas originating from the transitional zone appear like the above mentioned adenocarcinomas and do not seem to represent a special histological type. Although, adenocarcinomas can appear in the extramucosal part of the anal canal and originate from anorectal fistulas (Crohn's disease) or from anal glands. Both of these types of adenocarcinomas can appear as mucinous cysts and be highly differentiated adenocarcinomas. Anal adenocarcinomas can be very aggressive tumors.

Other tumor types:

  • Small cell carcinoma
  • Undifferentiated carcinoma
  • Endocrine tumors and carcinomas (carcinoid)
  • Malignant melanoma
  • GIST and other mesenchymal tumors
  • Malignant lymphomas

Fixation of the operation specimens

The specimen is cut open and cleaned before fixation in formalin. It is advantagous if the specimen is fixed by needle to a cork plate. This facilitates the evaluation of resection borders.

Pathology report

The pathology report on an operation specimen should include the following:

  • Localization (over/under ”pectinated line,” perianal skin)
  • Size
  • Classification
  • Grading
  • Infiltration depth
  • Number of lymph nodes with and without metastases
  • Tumor relation to resection borders
  • Blood vessel invasion
  • Perineural invasion
  • pTNM

Staging of anal cancer

The TNM-classification is used to divide anal cancer into stages. TNM assesses the tumor (T), lymph nodes (N), and metastases (M), at the time of diagnosis.

Tumor infiltration (T)

  • Tis  carcinoma in situ
  • T1  Tumor ≤ 2 cm in diameter
  • T2  Tumor > 2 cm, but < 5 cm in diameter
  • T3  Tumor ≥ 5 cm in diameter

 /upload/anal/stadier/anal_stadier_pt1_pt3.gif

  • T4  Tumor infiltration into neighboring organs (vagina, urethra, bladder, prostate) irrespective of size. Infiltration of sphincter muscle alone is not classified as T4.

 /upload/anal/stadier/anal_stadie_pt4.gif

Lymph node status (N)

  • N0  No regional lymph nodes
  • N1  Metastases in peri- or mesorectal lymph nodes

 

  • N2  Metastases in unilateral internal iliac and/or inguinal lymph nodes

 

  • N3  Metastases in peri- or mesorectal and inguinal lymph nodes and/or bilateral internal iliac and/or inguinal lymph nodes

 

  • NX  Regional lymph nodes cannot be assessed

Metastases (M)

  • M0  No metastases
  • M1  Metastases

Metastatic patterns of anal cancer

Local infiltration into neighboring tissue

  • Anal cancer develops from basal epithelial cells in the anal canal and often grows as an ulcerating tumor.
  • It can spread circularly in the anal canal, grow up into the rectum, or out through the anus. When there is infiltration through the anal musculature, the tumor can grow in the vagina. In men, it can in rare cases grow into the urethra or prostate.
  • In some cases, the tumor grows in the lower rectum, without any distinct connection to the anal canal.
  • Perianal cancer grows as a perianal ulcer or as hyperkeratotic tissue.

Spreading to regional lymph nodes (N-stage)

Lymph node metastasis occurs in up to 30% of the patients with anal cancer.

Spreading to lymph nodes can develop in two different ways:  

  • Anterior spreading in the groin via subcutaneous lymph pathways in the pelvic floor. This is more frequent in anal cancer than rectal cancer. Lymph node metastases in the groin can grow and attach to the underlying pelvic floor and to the femoral veins. These lymph nodes sit characteristically medial to the symphysis.   
  • Spreading upward to the perirectal lymph nodes (outside the mesorectum) and mesorectal lymph nodes (situated in mesorectal fat tissue around the rectum) and to lymph nodes along the internal iliac veins on the pelvic wall and to the presacral lymph nodes. This is especially the case with large tumors. 

Metastases

Hematogenic spreading occurs in less than 10% of the patients at the time of diagnosis, and most frequently for large primary tumors.

Metastasis to the:

  • liver – most commonly affected organ
  • lungs – second most commonly affected organ
  • bone
  • brain

Symptoms of anal cancer

  • Bleeding from the anal opening, pain, discomfort or itching around the anal opening are common symptoms .
  • In some cases, a lump or sore is felt, especially in perianal cancer. Some tumors have a central ulcer, while other tumors can spread under an intact mucous membrane.
  • Stool incontinence may occur.
  • Rectovaginal fistulas can occur when tumors are large and infiltrate the vagina.
  • Anocutaneous fistulas and abcesses can develop around the anus.
  • For large tumors with development of abscesses, induration around the abscess can make it difficult to assess the actual border of the tumor.

Differential diagnoses of anal cancer

In early phases, the symptoms resemble common and benign illnesses.

Symptoms related to benign differential diagnoses

  • Bleeding from hemorrhoids is the most common differential diagnosis. Many patients are bothered by hemorrhoids, but anal cancer is rare. Therefore, bleeding due to anal cancer is often misinterpreted as hemorrhoids in the beginning and is first discovered during rectal exploration.  
  • Anal fissure is a relatively common differential diagnosis.
  • Unspecific anal itching/discomfort may be mistaken for anal cancer.

Possible differential diagnoses

  • Rectal cancer can be mistaken for anal cancer and vice versa when the rectum tumor grows down into the anal canal, or when the anal tumor grows from the dentate line and up into the rectum. Therefore, review of the pathology is essential as the treatment of adenocarcinoma of the rectum and squamous cell carcinoma of the anal canal is different.
  • Cervical cancer can be a possible differential diagnosis for large anterior tumors which grow both in the cervix/vagina and anus.
  • Benign polyps can be mistaken for an early polypoid tumor.
  • Perianal eczema can be mistaken for perianal cancer.
  • Large tumors presenting with an abscess can be mistaken for benign perianal abscesses.
  • Paget’s disease is easily mistaken for malignant melanoma in situ.

Prognosis of anal cancer

The prognosis depends on whether the anal cancer is localized, regional, or metastatic at the time of diagnosis. 48.2% are diagnosed at the local stage and the 5-year survival for localized anal cancer is 81.3%. The overall 5-year survival rate for anal cancer patients during the period 2007-2013 was 66.9%.

Death rates have been rising on average 2.9% each year over 2005-2014. The percent of anal cancer deaths is highest among people aged 55-64. The number of deaths was 0.2 per 100,000 men and women per year based on 2010-2014 deaths and in 2017 there are an estimated 1,100 people will die of this disease (2).

References on anal cancer

  1. Nasjonalt handlingsprogram med retningslinjer for diagnostikk, behandling og oppfølging av anal cancer (2017), Helsedirektoratet (National guidelines for diagnostic, treatment and follow-up care of anal cancer, Norwegian Directorate of Health)
  2. 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
  3. Tanum G. Treatment of relapsing anal carcinoma. Acta Oncol 1993; 32(1): 33–35.
  4. Glynne-Jones R, Nilsson PJ, Aschele C et al. Anal cancer: ESMO-ESSO-ESTRO clinical practice guidelines for diagnosis, treatment and follow-up. Radiotherapy and Oncology 111 (2014) 330-339.
  5. James RD, Glynne-Jones R, Meadows HM, Maughan T et al. Mitomycin or cisplatin chemoradiation with or without maintenance chemotherapy for treatment of squamous-cell carcinoma of the anus (ACT II): a randomised, phase 3, open-label, 2 × 2 factorial trial. 2013 May;14(6):516-24.
  6. Ajani JA, Winter KA, Gunderson LL et al. Fluorouracil, mitomycin, and radiotherapy vs fluorouracil, cisplatin, and radiotherapy for carcinoma of the anal canal: a randomized controlled trial. JAMA Apr 23;299(16):1914-21
  7. Guren MG, Dueland S, Skovlund E, Fosså SD, Poulsen JP, Tveit KM. Quality of life during radiotherapy for rectal cancer. Eur J Cancer 2003 Mar; 39(5):587-94.
  8. Bentzen AG, Guren MG, Wanderås EH, Frykholm G, Tveit KM, Wilsgaard T, Dahl O, Balteskard L. Chemotherapy of anal carcinoma: survival and recurrence in an unselected national cohort. Int J Radiat Oncol Biol Phys. 2012 jun 1;83(2):e173-80.
  9. Bentzen AG, Balteskard L, Wanderås EH, Frykholm G, Wilsgaard T, Dahl O, Guren MG. Impaired health related quality of life after chemoradiotherapy for anal cancer: late effects in a national cohort of 128 survivors. Acta Oncol. 2013 May; 52 (4):736-44.
  10. Bentzen AG, Guren MG, Vonen B, Wanderås EH, Frykholm G, Wilsgaard T, Dahl O, Balteskard L. Faecal incontinence after chemoradiotherapy in anal cancer survivors: long-term results of a national cohort. Radiother Oncol. 2013 Jul;108(1):55-60.
  11. Nilsson PJ, Svensson C, Goldman S, Glimelius B. Salvage abdominoperineal resection in anal epidermoid cancer. Br J Surg 2002; 89(11): 1425–9.
  12. Bai YK, Cao WL, Gao JD, Liang J, Shao YF. Surgical salvage therapy of anal cancer. World J Gastroenterol 2004; 10(3): 424-6.
  13. Barbaro G, Barbarini G. HIV infection and cancer in the era of highly active antiretroviral therapy (Review). Oncol Rep 2007; 17(5): 1121-6.
  14. Bell SW, Dehni N, Chaouat M, Lifante JC, Parc R, Tiret E. Primary rectus abdominis myocutaneous flap for repair of perineal and vaginal defects after extended abdominoperineal resection. Br J Surg 2005; 92(4): 482–486.
  15. Dev VR, Gupta A. Plastic and reconstructive surgery approaches in the management of anal cancer. Surg Oncol Clin N Am 2004; 13(2): 339-53.
  16. Tei TM, Stolzenburg T, Buntzen S, Laurberg S, Kjeldsen H. Use of transpelvic rectus abdominis musculocutaneous flap for anal cancer salvage surgery. Br J Surg 2003; 90(5): 575-80

Diagnostics of anal cancer

The purpose of diagnostic tests is to:

  • Assess whether or not cancer is present
  • Assess local and/or general extension

Clinical examination

  • Inspection of the anal region and groin
  • Rectal/vaginal examination and palpation of groin

Laboratory tests

  • No specific blood tests, but routine blood tests should be taken.

Endoscopy with biopsy

  • Ano/proctoscopy – The anal canal is examined with an anoscope. The rectum should be simultaneously examined by proctoscopy because of differential diagnoses.
  • Biopsy – Especially for perianal cancer, there may be relatively large areas with dysplasia and smaller areas with cancer. Multiple biopsies may therefore be necessary. The areas biopsied in the tumor should therefore be marked on a drawing.
  • Fine-needle biopsy/cytology is performed on suspect lymph nodes in the groin and possibly using ultrasound.

Image diagnostics

  • MRI of the pelvic area with groin provides the best way of assessing the extention of the tumor locally in the anal canal and in surrounding organs.
  • An ultrasound examination of the anal canal may help evaluating early stage cancer.
  • CT abdomen/thorax provides the best assessment for metastases.
  • PET CT should be performed for accurate N and M staging. PET is not significant for T status. In a study of 61 patients, it was found that PET/PET-CT changed the stage in 23 % (15 % higher stage, 8 % lower stage) compared to CT and anorectal ultrasound. The indication for curative to palliative treatment changed in only 3 %, but in 13%, there were consequences for the size and shaping of the radiation field. PET is recommended with anal cancer greater than 2 cm.
  • The TNM classification should be included in the patient journal at the conclusion of the evaluation.
  • With stricturing tumors and incontinence or fistulas, a stoma may be considered to relieve symptoms before starting radiation therapy.

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Rectoscopy with fine needle biopsy

General

Rectoscopy is the most simple diagnostic examination for suspicion of rectal cancer or cancer in the anal canal. The examination is always combined with rectal exploration and possibly needle biopsy.

The examination is performed with a rectoscope, which is a stiff tube with a light source. With this, the rectum is inspected as well as the surrounding mucous membrane - usually about 15 cm up from the anal opening. Behind the rectum ampule, right inside the anal canal, there is a large angle in which it is difficult to see small changes. This must be assessed carefully by exploration.

During the examinations, biopsies can be taken.

Indications

  • Suspicion of cancer or inflammation in the rectum
  • Suspicion of cancer or inflammation of the anal canal

Goal

  • Diagnose changes in the rectum
  • Diagnose changes in the anal canal
  • Biopsy taking

Equipment

  • Rectoscope
  • Double balloon for inflating air into the colon
  • Light source for rectoscope
  • Gel for exploration
  • Rectal suction
  • Biopsy forceps
  • Specimen glass with formalin
  • Needle for fine needle biopsy and fine needle cytology

Preparation

  • The colon is emptied the day of the examination with enema 1-2 hours prior.
  • The patient must fast for the last 6 hours before the exam but may drink fluids up to 2 hours prior in case short term sedation is necessary.
  • The patient lies in the lithotomy position.

Implementation

  • Before endoscopy, a thorough exploration is performed.
  • The rectoscope is lubricated and inserted into the rectum.
  • The stick in the rectoscope used to ease insertion is removed.
  • The scope is inserted further into the bowel.  
  • Air is inflated into the bowel to improve overview.
  • If needed, surface or fine needle biopsies are taken. 
  • The biopsy needle is inserted into the lesion along the finger
  • When the biopsy needle is released, the mandrin is first released followed by the needle 2.5 cm forward.
  • The biopsy remains in a notch in the mandrin.
  • The scope is retrieved with circular movements such that the entire bowel is inpected. Be aware of the "blind zone" behind.
  • The exam takes about 5 minutes.

Follow-up

The patient is observed for:

  • bleeding if a biopsy is taken
  • pain (gas pains can be expected)

At the outpatient clinic, the patient may go home the same day. Test results are usually available after 1-4 weeks.

An appointment for possible further follow-up and treatment is made.

RectoscopyRectoscopyRectoscopyRectoscopy

Positron Emission Tomography (PET)

General

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

Indications

Oncological imaging for:

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

Goal

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

Definitions

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

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

Limitations

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

Sources of error

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

Equipment

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

Preparation

Patient preparation depends on the clinical diagnosis.

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

There will be other precautions for neurological and cardiological diagnoses.

Implementation

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

Registration of emission

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

Examples of findings

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

Follow-Up

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

Treatment of anal cancer

Up until 20 years ago, treatment for anal cancer was resection by radical surgery which led to a permanent colostomy. However, anal cancer is a cancer type that is sensitive to radiation. With radiation therapy, the sphincter muscle can be preserved, and colostomy can be avoided in up to 80 % of patients. Radiation therapy with or without chemotherapy has given better survival results, and therefore replaced surgery as primary treatment in the 1980s.

Radiation therapy combined with chemotherapy (5-fluorouracil and mitomycin C) is the primary choice of treatment providing better response, better local control and better colostomy-free survival than radiation therapy alone. However, hematologic toxicity can be significant. The treatment is also given for palliative purposes to patients with advanced disease to reduce local side effects in the pelvis. 

Surgery as primary treatment is performed today for limited indications such as resection of small (< 1 cm) perianal, high and moderately differentiated tumors that can be removed without involvement of the sphincter muscle. For a marginal resection (< 5 mm), a reexcision should be performed. More extensive surgery is indicated if, after chemoradiation as primary treatment, there is still remaining tumor, or remaining tumor does not disappear after 2-3 months observation time. A rectum amputation is then often necessary and may cure the disease. Rectal amputation is reserved for persistent disease after chemoradiation or for local recurrence.

Metastases are treated with chemotherapy, possibly followed by surgery.

The treatment of giant condyloma is primarily surgery in contrast to perianal cancer as chemoradiation does not appear to have any substantial effect. Radiochemotherapy is given in some advanced cases. Experience is based on reported case statistics. Local podophyllin treatment may be effective treatment for condyloma acuminatum, but has no effect on giant cell condyloma.

Surgery of anal cancer

Primary surgery may be relevant for small perianal cancers (< 1 cm). Sigmoidostomy may have to be performed before start of radiation treatment for defecation problems, obstruction, incontinence or fistula.

Local treatment failure (remaining cancer or local recurrence)

Local treatment failure includes both cancer remaining after chemoradiotherapy, progression of tumor in spite of chemoradiotherapy, or later local recurrence. There is no reason for differentiating the various malignant conditions with regard to surgical intervention.

A local ulceration remaining after radiotherapy leaves suspicion of persistent cancer and must be biopsied. There is much evidence suggesting that active follow up will increase the percentage of early diagnoses of local treatment failure, thereby increasing the frequency of radical salvage operations. Local treatment failure is usually given as 20-25% within a three year period.

Patients with local treatment failure shall be considered for salvage surgery with abdomino perineal resection (rectal amputation). The tumor should be biopsied and the patient evaluated for operability and resectability. MRI of the pelvis should be performed and distant metastases must be excluded by CT and PET scan. For operable metastases in the groins salvage surgery may be an option. For other distant metastases surgery may be considered in special cases, but the effect of this is not documented.

Local surgery

A few patients may be treated by local resection of the recurrence, especially if the tumor is located in the soft tissue and is mobile. This, however, is rarely the case. Recurrence of small perianal cancers that previously have been locally resected may be re-resected with wide margins.

Radical salvage surgery

Radical or extended rectal amputation (APR) is indicated if the cancer is not confined within the intestinal tube or anal verge. The tumor tends to grow circularly into the surrounding tissues leaving the margins towards the surrounding organs or structures threatened or invaded. Such extended operations should be performed as en-bloc resection where free margins of all cancer tissue is the goal. Tissue with post-irradiation scarring and fibrotic tissue should be resected. Wide resections of the perineum and often the muscles of the pelvic floor as well as resections of the posterior vaginal wall will often have to be performed. The perianal skin must also be widely resected. The perineal resection must often be more extensive than in operations for rectal cancer. For posteriorly growing tumors the coccygus or distal sacrum may have to be removed as part of the en-bloc resection. It has been shown to be advantageous to stop the abdominal resection earlier and continue in a plan outside the pelvic floor from the perineal side. An extended symmetrical specimen may then be obtained. Such extended operations should always be performed in large lowlying tumors (T3/T4). Delayed healing of the perineum is commonly seen when primary closure is performed. (40-70%).

Reconstruction by plastic surgery

Salvage surgery leaves a large defect in the perineum, pelvic floor and cavity. To cover the defect, improve the healing and reduce the danger of pelvic abscesses, reconstruction by plastic surgery is often part of the surgical procedure. Application of flaps may reduce the healing problems down to 15%. Mobilization of the omentum into the pelvis may be advantageous.

Dissection of inguinal lymph nodes

For simultaneous inguinal lymph node metastases a formal lymph node dissection should be performed in combination with the pelvic surgery. This should also be done for isolated inguinal lymph node manifestations.

Prognosis after salvage surgery

Salvage surgery can give patient with local treatment failure a chance of freedom for cancer. Positive resection margin is the strongest negative predictor for survival after the salvage surgery. It is customary to estimate a local cancer control of 50-60% and a 5-year survival of 40-46% after salvage surgery.

Centralisation

Local recurrence of cancer in the anal canal is a rare condition. The combination of surgical challenges with extensive surgery and the required cooperation with other surgical specialties (urology, plastic surgery) suggests that salvage surgery for local treatment failure of anal cancer should be centralized in Norway.

Surgery for metastases

There are no large studies on the effect of surgery for distant metastases from anal cancer. Surgery for metastases in inguinal lymph nodes may be relevant when local chemoradiotherapy has failed. For few or single metastases in the follow up period surgery may be considered. Advanced liver- and lung- surgery has not been evaluated with regard to survival.
Symptomatic tumors, as for instance from the vertebral column, other parts of the skeleton and CNS, may be considered for palliative surgery. Sigmoidostomy may be appropriate for locally inoperable tumor or recurrence.

Drug therapy of anal cancer

MiFu (mitomycin C and 5-fluorouracil) was standard chemotherapy treatment until 2000. Cisplatin had shown a certain effect on recurrence and metastasizing anal cancer. Because of this and existing phase I and phase II studies, cisplatin combined with 5-FU neoadjuvant and adjuvant was introduced as primary treatment to improve survival times.

However on the basis of international randomized studies and international practice, which showed no better effect for CiFu, one chose to go back to MiFu. MiFu has less side effects and is easier to manage. In advanced stages (T3-4 and all N +) the treatment increased from one to two cycles concomitant.

Well to moderately differentiated T1 tumors < 1 cm N0

Chemotherapy is not standard.

Poorly differentiated T1 tumors, T1 > 1 cm and T2 tumors N0

A MiFu cycle concomitantly with radiation therapy starting the first or second day of radiation is recommended.

Advanced primary tumors (T3-T4, N0 and all N+)

Two MiFu cycles concomitantly with radiation therapy. The first cycle starts day 1 and second cycle on day 29 (5th radiation week).

Limited metastatic desease to lungs and liver

Limited metastatic desease to lungs and liver should be considered for curative surgery combined with preoperative chemotherapy. Two cycles of MiFu or two cycles of CiFu are given depending on previous chemotherapy given as primary treatment and response. 

Metastatic desease which is not suitable for primary surgery should be considered for cisplatin/5-FU or possibly other types of chemotherapy. Subsequent surgery or radiation therapy should be considered if the response to chemotherapy is good. 

PROSEDYRER

Sun Exposure under Drug Therapy

General

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

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

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

Indication

Sun exposure in connection with drug cancer treatment.

Goal

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

Definitions

Photosensitivity

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

Phototoxicity

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

Photoallergy

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

Photoinstability

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

PPE ( palmoplantar erythrodysesthesia = Acral erythema )

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

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

Acne-like rash

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

Hyperpigmentation

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

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

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

Radiation Recall Dermatitis (RRD)/Photo Toxic recall reaction

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

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

Preparation

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

Implementation

General Precautions

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

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

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

Medicaments that most commonly cause skin reactions

Medicament Common reactions Remedial action
Dakarbazin (DTIC)


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

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

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

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

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

(2, 9)

Fluorouracil (5-FU®)

 

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

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

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

Radiation recall
Treatment as with phototoxic

Kapecitabin (Xeloda®)

 

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

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

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

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

Vinblastin

 

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

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

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

Tegafur

 

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

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

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

EGFR-hemmere

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

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

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

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

References


  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 anal cancer

Well to moderately differentiated T1 tumors < 1 cm N0

Regional lymph nodes are not included in the radiation field as the risk for subclinical disease is small. A tumor with margin is treated with 2 Gy fractionations to 54 Gy.

Poorly differentiated T1 tumors, T1 > 1 cm, and T2 tumors without evidence of lymph node metastases

Recommended radiation dose is:

  • 54 Gy to primary tumors and lymph node metastases with margin 
  • 46 Gy to areas at risk for involvement

Advanced primary tumors (T3-T4, N0 and all N+)

Recommended radiation dose is:

  • 58 Gy to primary tumor and lymph node metastases with margin
  • 46 Gy to areas at risk for involvement 

Cranially, the radiation field should reach the promontory level (splitting point for the common iliac artery) for tumors which grow into the rectum and N+ tumors. For T1-2N0 tumors localized distally to the dentate line, the upper field limit should be equivalent to the lower part of the ileosacral joints. The inguinal glands should be irradiated if the tumor in the anal canal stretches caudal to the dentate line, which is often the case.

For Paget's disease, local radiation treatment may be a good alternative to surgery. These rare cases should be evaluated by an oncologist and a surgeon.

Side effects that may occur during treatment

Acute side effects, (0-3 months from the start of radiation therapy), primarily affect cells that divide rapidly.

In combined (concomitant) treatment for anal cancer, radiation therapy causes the most acute side effects. Chemotherapy is responsible for a mild to moderate bone marrow suppression and leukopenia occurs often.

The acute radiation injury to the pelvis particularly affects the mucosa of the small intestine, germinal cells and skin. Further, the mucosa of the colon/rectum, the urothelium in the urinary tract and the vagina may also be affected.

All patients develop radiation dermatitis with varying extent during radiation therapy. The area around the anus, external genitalia, rima dormitory and groins are most affected.The skin becomes red and sore, and erosions may occur.

Many patients experience radiation enteritis with diarrhea, frequent bowel movements, urge and abdominal pain.This depends on the amount of intestine (especially the small intestine) located in the pelvis and thereby included in the radiation field. The mucous membranes of the vagina become sore. Fatigue and loss of appetite are common.

Most acute side effects disappear within six weeks after treatment.

However, the germinal cells are very sensitive to radiation therapy. In women the damage is irreversible and leads to infertility, since the ovaries usually are included in the radiation field.

Men may also become sterile. The testes may be difficult to shield from the radiation field.

If appropriate, the patient is offered sperm banking before the radiation therapy. 

 

PROSEDYRER

Sperm Banking

General

Sperm banking services may apply to patients having a disease or undergoing treatment which reduces or eradicates the patient's fertility. The decision for storage is made by the doctor in charge of the patient in cooperation with the chief physician at the andrology laboratory.

Stored sperm can only be used for assisted fertilization by the patient's spouse or partner in a stable relationship (duration more than 2 years).

The offer for freezing and storing sperm does not guarantee treatment with assisted fertilization. The decision for this is made by the treating doctor according to guidelines and laws for assisted fertilization.

The patient may store up to three samples. The samples should be taken with a few days in between and the patient should not have ejaculated for two days prior to sample collection.

Indications

  • Cancer treatment rendering a man infertile.

Goal

  • The possibility of having children after treatment is concluded.

Equipment

  • A urine sample container.
  • A room for the patient to be undisturbed.

Preparation

  • Inform the patient verbally and in writing.
  • Conform to rules and guidelines.
  • A blood test for HIV and hepatitis to rule out infectious sperm.

Imlementation

  • The sperm sample is collected via masturbation and is collected directly into a urine sample container. A condom should not be used as this contains spermicide.
  • The sample should be allowed to cool and should be delivered to the andrology laboratory in less than one hour after ejaculation.

Follow-Up

  • The sperm sample is held in under quarantine until HIV and hepatitis results are available.
  • The sperm can be stored for 10 years and possibly longer if the patient desires.
  • After filling 55 years or death the sperm is destroyed.

Complication treatment of anal cancer

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

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

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

PROSEDYRER

Smoking cessation in connection with cancer treatment

General

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

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

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

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

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

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

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

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


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

 

Indication

Weaning of nicotine in connection to cancer treatment. 

Goal

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

Preparation

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

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

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

Implementation

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

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

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

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

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

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

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

Treatment with nicotine replacement therapy

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

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

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

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

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

Side effects

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

Precautions

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

Treatment with non-nicotine medications

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

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

Side effects

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

Precautions

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

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

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

Side effects

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

Precations

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

Follow-up

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

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

References

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Intravenous Extravasation of Cytotoxic Drugs

General

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

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

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

Risk factors for intravenous extravasation:

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

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

  • Non-cytotoxic/irritating
  • Tissue irritant
  • Cytotoxic

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

Indication

  • Intravenous extravasation of cytotoxic drugs. 

Goal

  • Limit damage of tissue from intravenous extravasation.

Definitions

Non-cytotoxic drugs or non-irritants

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

Irritants

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

Cytotoxic drugs

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

DNA-binding

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

  • Anthracycline
  • Alkylating drugs
  • Other

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

Non DNA-binding

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

  • Vinca alkaloids
  • Taxanes

 

Chemotherapy cytotoxicity (1)
Cytotoxic, necrosis

Irritant, can cause flaking or inflammation

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

 * = Anthracycline

** = Alkylating agents

*** = Vinca alkaloids

**** = Taxanes

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

All chemotherapy drugs can damage tissue in high concentrations.

References

 

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

Preparation

Identification of an extravasal injection

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

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

 

Implementation

Flow chart for treatment of intravenous extravasation of cytotoxic drugs:

Emergency response:

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

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

Conservative treatment

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

Localize and neutralize:

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

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

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

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

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

Treatment 

Dexrazoxan (Savene®)

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

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

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

Cost

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

Dimethylsulfoxide (DMSO)

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

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

Hyaluronidase

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

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

Surgical treatment

"Wash-out"

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

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

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

References

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

Follow-Up

For conservative treatment 

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

For emergency surgical treatment

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

 

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

Follow-up care after treatment of anal cancer

Four to six weeks after chemotherapy and radiation are finished, the patient should be examined for assessment of local response. This is because the degree of actual tumor regression may be difficult to determine, and it may be necessary to take new biopsies. Immediatley after treatment, the patient should be followed up every month until the tumor has completely disappeard. If the tumor does not show complete response after a maximum of 3 months, the tumor should be considered therapy-resistant and a rectal amputation should be considered.

An oncologist has the primary responsibility for the follow-up, however anorectoscopy can be carried out by a surgeon.

Most recurrences appear within 2-3 år.

Further recommended follow-up

  • Every 3 months for the first 2 years.
  • Every 6 months for 5 follow-up years. 
  • Later follow-up annually by a general practitioner.

Examinations at follow-up check

  • General health status, especially anorectal symptoms, from pelvis and abdomen
  • Clinical examination of the anal area and perineum, palpation of the abdomen/groin, rectal exploration
  • Blood tests (hematology, liver and kidney function). 
  • CT of the thorax/liver (thoracic X-ray, ultrasound liver after 3, 6, 12, 18 and 24 months. Then annually the next three years.
  • PET/CT, at three months follow-up, if taken before treatment start
  • MRI pelvis at 3, 6 and 12 months follow-up. Then, only if clinically indicated.
  • Anorectoscopy at follow-ups the first year, possibly longer.
  • Evaluation of local anal function, supplementary examinations for documentation of reduced function.

Complications after chemotherapy/radiation treatment

  • Stool urgency occurs in some patients. Frequent bowel movements and continued loose stool may occur, especially after high doses of radiation.
  • Chemotherapy and radiation can in some cases, cause varying degrees of anal incontinence, partly due treatment and partly due to necrosis of large tumor involving the sphincter. This may require sigmoideostomy. 
  • Anal stenosis may occur, which is a condition requiring a sigmoideostomy.
  • Sterility in women. Germinal cells in the ovaries are very senstive to radiation. The ovaries are often located in the radiation field causing the patient to enter menopause and become sterile. 
  • Sterility in men. Germinal cells in the testicles are also very sensitive to radiation. If the testicles are included or close to the radiation field, the risk for sterility is great. In some cases, it is possible to shield the testicles, sparing the germinal cells from radiation.  
  • Dry and atrophic vaginal mucosa.
  • Cystitis may occur and possibly reduction in size of the bladder (rare) causing frequent urination.

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