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Utskriftsdato (25.9.2017)

Cancer in the esophagus

Oncolex is an online reference tool where health professionals can retrieve updated information about diagnostics, treatment and follow-up care of cancer.

The content is written by our editorial staff, in collaboration with medical professionals, specialised in the various types of cancer.

The information about cancer in the esophagus is currently under professional evaluation and will be available again as soon as the work has been completed.

Etiology of esophageal cancer

In most cases, the causes are unknown. However, the development of esophageal cancer is observed in connection with different risk factors.

Spinocellular cancer is related to:

  • alcoholism
  • smoking
  • corrosion damage (exposure to solvents and corrosive chemicals)

Adenocarcinomas are related to:

  • Obesity, with increasing frequency of reflux esophagitis 
  • Intestinal metaplasia (Barrett’s esophagus), which is a result of esophagitis.  

Histology of esophageal cancer

The esophagus is covered with squamous cell epithelium and contains as the rest of the gastro-intestinal tract three layers. In addition to the mucosa, the wall consists of the sub-mucosa separated from the mucosa by a thin layer of muscle (muscularis mucosa) and the outermost muscularis propria with circular and longitudinal muscle fibers.

Precursor lesions

  • Squamous cell dysplasia/Carcinoma in situ (low-grade or high-grade intraepithelial neoplasia)
  • Barrett’s esophagus with or without dysplasia/Carcinoma in situ in glandular epithelium (low-grade/high-grade dysplasia)

Precursor lesions are classified as squamous cell dysplasia (intraepithelial neoplasia) of low-grade or high-grade type. These lesions can precede squamous cell carcinomas or occur synchronous close to the invasive carcinoma.

Barrett`s esophagus represents as gastric or intestinal metaplasia (transformation of normal type of epithelium). These changes can appear due to reflux of gastric fluid in the distal (lower) part of the esophagus. Dysplasia preferably appears in the intestinal metaplasia of Barrett’s esophagus. The epithelial grading is as follows; negative for dysplasia, indefinite for dysplasia, low-grade or high-grade dysplasia.

Dysplasia in Barrett’s esophagus can develop into adenocarcinoma.

Classification and grading

The predominant carcinomas of the esophagus are squamous cell carcinomas and adenocarcinomas. The TNM system is used in the classification of these tumors. These carcinomas are graded as well, moderately and low differentiated dependent on the similarity to corresponding normal epithelium.

Within the squamous cell carcinomas and adenocarcinomas there are some variants/subtypes. Verrucous, spindle cell and basaloid are rare subtypes of squamous cell carcinoma. Mucoepidermoid or adenoidcystic carcinomas are variants of adenocarcinoma.

Other rare tumors are small cell carcinoma, malignant melanoma and undifferentiated carcinoma. These carcinomas can be very difficult to separate from metastasis to esophagus.

Mesenchymal tumors are rare in esophagus, but when they appear, leiomyomas are more common than GIST (gastrointestinal stromal tumor), in contrary to other parts of G-I tract. Malignant lymphomas and endocrine tumors are quite rare in this location.

Pathology reports

An operation specimen, including resection of the esophagus with tumor, should include the following information:

  • Classification
  • Grading
  • Infiltration depth
  • Circumferential margin
  • Number of lymph nodes with and without metastasis 
  • Tumor relation to resection borders
  • Vessel infiltration 
  • Perineural infiltration
  • pTNM

Metastatic patterns of esophageal cancer

Direct infiltration

The tumor can grow into the mediastinum, possibly to the trachea, to the right bronchus, or heart.

When infiltrating the pleura, the tumor can spread on the surface of the pleura.

Hematogenic spreading

The tumor cells spread first to the liver and lungs, but skin and other organs can also be affected.

Lymphatic spreading

The tumor cells can spread to lymph nodes in the upper abdomen, mediastinum, and cervically.

Staging of esophageal cancer

The TNM system, which is recommended by WHO, is used to classify cancer in the esophagus. The system is based on the extensiveness of the local tumor (T), degree of lymph node spreading (N), and metastases (M).

Tumor Infiltration (T)

 

  • T1: Infiltration in the lamina propria or submucosa
  • T2: Infiltration in the mucularis propria
  • T3: Infiltration through the adventitia, but not into other organs/structures

 

  • T4: Infiltration into adjacent structures

Lymph Node Status (N)

  • N0: No regional lymph node metastases
  • N1: Regional lymph node metastases 

Metastases (M)

  • M0: No metastases
  • M1: Metastases

For cervical esophageal cancer, mediastinal lymph node metastases are classified as M1.

For upper thoracic esophageal cancer, metastasis to cervical and supraclavicular lymph nodes is classified as M1a. Metastasis to coeliac lymph nodes is classified as M1b.  

For mid thoracic esophageal cancer, metastasis to supraclavicular lymph nodes is classified as M1b and coeliac as M1b.

For lower thoracic esophagus cancer, metastasis to supraclavicular lymph nodes is classified as M1b and coeliac as M1a.

Symptoms of esophageal cancer

  • Dysphagia is the most common primary symptom. It usually occurs when 1/2 to 2/3 of the circumference of the esophagus is infiltrated with tumor tissue. This symptom is therefore present later in the disease course. In the beginning, dysphagia is often temporary. Some patients have such difficulty swallowing that they are only able to take liquid food.
  • Reflux dyspepsia
  • Pain in the esophagus occurs frequently. 
  • Fistulas in the respiratory tract and to the chest cavity can occur in advanced stages.
  • Spreading to the pleura can cause pleural effusion and dyspnea.

Traditionally, patients with squamous esophageal cancer were underweight. As the diagnosis is made earlier in the disease course, and patients with intestinal dysplasia develop esophageal cancer, many of the patients today are overweight. 

About 50% of all patients diagnosed with cancer based on these symptoms are inoperable. In order for the disease to be operable, the diagnosis must be made when dyspepsia is the only symptom. 

Differential diagnoses of esophageal cancer

Benign conditions

  • Dysphagia and retention are due to acid reflux with ulcer or fibrosis in the wall of the esophagus.
  • Retention may also be due to esophageal achalasia and scleroderma.
  • Pain in the mediastinum may be due to heart disease.

Malignant conditions

  • Retention may be due to cancer in the stomach. 

  • Exhaustion/lethargy may be due to stomach cancer or other advanced cancer disease.
  • Fistula between the esophagus/respiratory passages may be due to cancer in the respiratory passages.

Prognosis of esophageal cancer

The earlier esophageal cancer is caught, the better chance a person has of surviving five years after being diagnosed. 19.6% are diagnosed at the local stage and the 5-year survival for localized esophageal cancer is 42.9%. The number of esophageal cancer deaths is highest among people aged 65-74. Death rates have been falling on average 0.9% each year over 2005-2014

In the United States, the 5-year relative survival rate for patients with esophageal cancer, during the period 2007-2013, is was 18.8%.

In 2014, there were an estimated 45,547 people living with esophageal cancer in the United States. (23)

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References on esophageal cancer

  1. Nasjonalt handlingsprogram med retningslinjer for diagnostikk, behandling og oppfølging av pasienter med spiserørskreft (2008), Helsedirektoratet (National guidelines for diagnostic, treatment and follow-up care of esophageal cancer, Norwegian Directorate of Health)
  2. Lin CC, Papadopoulos KP. Novel targeted therapies for advanced esophageal cancer. Dis Esophagus 2007; 20(5):365-71.
  3. Macdonald JS, Smalley SR, Benedetti J et al. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med 2001; 345(10):725-30.
  4. Mariette C, Piessen G, Triboulet JP. Therapeutic strategies in oesophageal carcinoma: role of surgery and other modalities. Lancet Oncol 2007; 8(6):545-53.
  5. Muller JM, Erasmi H, Stelzner M, Zieren U, Pichlmaier H. Surgical therapy of oesophageal carcinoma. Br J Surg 1990; 77(8):845-57.
  6. Pech O, May A, Rabenstein T, Ell C. Endoscopic resection of early oesophageal cancer. Gut 2007; 56(11):1625-34.
  7. Raja SG, Salhiyyah K, Nagarajan K. Does neoadjuvant chemotherapy improve survival in patients with resectable thoracic oesophageal cancer? Interact Cardiovasc Thorac Surg 2007; 6(5):661-4.
  8. Rankin SC. Oesophageal cancer: assessment of response and follow up. Cancer Imaging 2007; 7 Spec No A:S67-9.:S67-S69.
  9. Pennathur A, Luketich JD. Resection for esophageal cancer: strategies for optimal management. Ann Thorac Surg 2008; 85(2):S751-S756.
  10. DeMeester SR. New options for the therapy of Barrett's high-grade dysplasia and intramucosal adenocarcinoma: endoscopic mucosal resection and ablation versus vagal-sparing esophagectomy. Ann Thorac Surg 2008; 85(2):S747-S750.
  11. Schuchert MJ, Luketich JD. Management of Barrett's esophagus. Oncology (Williston Park) 2007; 21(11):1382-9, 1392.
  12. Law S, Wong J. The current management of esophageal cancer. Adv Surg 2007; 41:93-119.:93-119.
  13. Rankin SC. Oesophageal cancer: assessment of response and follow up. Cancer Imaging 2007; 7 Spec No A:S67-9.:S67-S69.
  14. Nathwani RA, Kowalski T. Endoscopic stenting of esophageal cancer: the clinical impact. Curr Opin Gastroenterol 2007; 23(5):535-8.
  15. Lin CC, Papadopoulos KP. Novel targeted therapies for advanced esophageal cancer. Dis Esophagus 2007; 20(5):365-71.
  16. Raja SG, Salhiyyah K, Nagarajan K. Does neoadjuvant chemotherapy improve survival in patients with resectable thoracic oesophageal cancer? Interact Cardiovasc Thorac Surg 2007; 6(5):661-4.
  17. Gardner-Thorpe J, Hardwick RH, Dwerryhouse SJ. Salvage oesophagectomy after local failure of definitive chemoradiotherapy. Br J Surg 2007; 94(9):1059-66.
  18. Upponi S, Ganeshan A, Slater A et al. Imaging following surgery for oesophageal cancer. Clin Radiol 2007; 62(8):724-31.
  19. Liao Z, Cox JD, Komaki R. Radiochemotherapy of esophageal cancer. J Thorac Oncol 2007; 2(6):553-68.
  20. Siersema PD. Pathogenesis, diagnosis and therapeutic possibilities of esophageal cancer. Curr Opin Gastroenterol 2007; 23(4):456-61.
  21. Mariette C, Piessen G, Triboulet JP. Therapeutic strategies in oesophageal carcinoma: role of surgery and other modalities. Lancet Oncol 2007; 8(6):545-53.
  22. Kato H, Fukuchi M, Miyazaki T et al. Surgical treatment for esophageal cancer. Current issues. Dig Surg 2007; 24(2):88-95.
  23. Howlader N, Noone AM, Krapcho M, Miller D, Bishop K, Kosary CL, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER Cancer Statistics Review, 1975-2014, National Cancer Institute. Bethesda, MD

Diagnostics of esophageal cancer

Diagnostics are important to assess whether cancer exists and to assess the extent of the disease. It is recommended that the work-up and treatment are discussed by an interdisciplinary team consisting of a radiologist, surgeon, oncologist, and pathologist.   

Most of the esophagus is not available for external inspection. In very rare cases, the tumor can be palpated in the lower part of the throat. More often, there are palpable lymph node metastases in the neck, but this is also rare. 

There is no good serological marker. Blood tests can indicate anemia and reduced nutrition status or disturbances in liver function. There is still a relatively large portion of patients in the catabolic phase at the time of diagnosis, which is evident by a low albumin level.

Hospitals with larger treatment volumes are better at identifying metastases thereby avoiding unnecessary surgery. 

Endoscopy

The diagnosis is made using esophago-gastroscopy with  biopsy. If esophagitis exists with fibrosis, repeated biopsies may be necessary.  In most cases, esophagoscopy provides better and more reliable information than X-ray exams, as well as tissue samples for pathology examinations.

Ultrasound of esophagus

An ultrasound of the esophagus using an endoscope is the most suitable method for assessing the extent of the disease in the esophageal wall. This can be combined with a transesophageal needle biopsy of suspect lymph nodes in the mediastinum. If stenosis is prominent a thin ultrasound probe can be used by inserted  it through the biopsy channel of the scope and through the stenosis. However, the quality of the image is somewhat inferior.

Radiological work-up

  • CT of the thorax is best for assessing extent in the mediastinum, throat, lungs, and liver. There is a higher frequency of inoperability criteria when this is carried out by specialists.
  • X-ray of the esophagus with a contrast agent may be indicated to assess the length of the stenosis, but not for making a diagnosis.
  • Studies indicate that PET can determine lymph node spreading better than other techniques and the method should be a part of the preoperative work-up for esophageal cancer.

PROSEDYRER

Endoscopic Ultrasound with Aspiration

General

The location of the tumor or lymph node in the mediastinum determines whether an endoscopic ultrasound-guided fine needle aspiration (EUS) from the esophagus or endobronchial ultrasound (EBUS) should be performed.

EUS with aspiration of lymph nodes in the mediastinum is a minimally invasive examination whereby patients can avoid examinations associated with more risk. With EUS, the mediastinal lymph nodes can be sampled at most levels of the mediastinum. 

Indication

  • Enlarged lymph nodes and/or tumor in the mediastinum raising suspicion of a serious lung disease, cancer in the esophagus or stomach. 

Goal

  • Establish a diagnosis 
  • Stage determination

Equipment

  • Endoscope with accessories
  • Needle for puncture
  • Equipment for preparation of cytology specimen

Preparation

  • The patient lies on his/her side and is mildly sedated.
  • Application of local anesthesia in the throat.  

Implementation

  • The scope is inserted into the esophagus via a mouthpiece. 
  • The lymph nodes are visualized using ultrasound.
  • The aspiration needle is inserted through the work channel of the scope and by ultrasound guidance, into the lymph node.
  • Using back-and-forth movements with the needle, cells are sucked out of the lymph node.
  • The material is prepared and assessed by a cytologist.
  • The procedure can be repeated until representative material is obtained.

Follow-up

  • The patient can return home the same day.
  • It may take up to one week before the results are available.

Esophago/gastro/duodenoscopy

General

Esaphago-gastroduodenoscopy (also called upper gastrointestinal scopy) is an examination of the esophagus, stomach, and duodenum.  The examination is carried out by means of a gastroscope, which is a flexible tube equipped with a camera on the end, a light system, and one or two work canals. The mucosa can be inspected and the images are transferred to a monitor.  

During a scopy, the following can also be carried out:

  • biopsy
  • polyp removal
  • treatment for bleeding
  • injection of medication
  • laser treatment of lesions 
  • dilatation of the esophagus

The examination is simple and is carried out at most hospitals. It is important the stomach is empty before the exam.

Indications

  • Diagnose changes in the mucosa (soreness, inflammation, benign or malignant tumors)
  • Monitor a sore in the stomach/duodenum
  • Find source and treat acute bleeding in the upper gastrointestinal tract. 

Goal

  • Diagnose and possibly definitive treatment

Equipment

  • Gastroscope with equipment for biopsy and treatment.
  • Preparation

    Before the examination:

    • Anamnesis:
      • With known valve defect, endocarditis prophylaxis should be considered. 
      • Diabetes requiring insulin should be treated according to guidelines. 
      • Anticoagulation or antiphlogistic drugs should be stopped 5 days before the examination.
    • The stomach should be empty.
    • The patient should fast, starting 6 hours before the examination. Clear fluids are allowed up to 2 hours before the examination.
    • Daily medications can be taken the same day with a sip of water.

    The day of the examination:

    • Premedication with local anesthetic in the pharynx.
    • Possibly general anesthesia.

    Implementation

    • The gastroscope is inserted in through the mouth, down the esophagus and further down to the stomach and duodenum. How far the scope is inserted depends on which organs are inspected or which organ is suspect of tumor growth.
    • Air is blown in to clear the esophagus/stomach and get a better view during insertion of the scope.
    • The mucosa is inspected for abnormalities.
    • Perform necessary procedure.

    The examination usually lasts around 10-30 minutes.

    Follow-up

    Vomiting, pressure, and bloating are normal discomforts during/after the exam.

    The patient should be observed for:

    • bleeding if a biopsy is taken or polyps are removed
    • vomiting blood, black and tar-like stool, or intense stomach pain. If the patient has returned home, the patient is recommended to contact the hospital immediately.

    The patient may eat/drink 1 hour (at the earliest) after the exam due to the local anesthetic in the throat. For an outpatient exam, the patient may return home after 1-2 hours.

    Tissue sample results are available after 1-4 weeks. Further follow-up and treatment should be scheduled, if necessary.

    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 esophageal cancer

    Treatment depends on the stage, the health status of the patient, and symptoms. There is no difference in treatment of squamous cell carcinoma and adenocarcinoma.

    Only 20–25% of all patients with esophageal cancer are appropriate for radical surgery. For the smallest tumors and Barrett's esophagus, photodynamic therapy (PDT) may be the best choice of treatment.

    For about 20–25% of all patients with inoperable localized tumors, curative oncology treatment (chemotherapy/radiation therapy) may be the best choice of treatment.

    This requires:

    • good heart and lung function to complete radical surgery 
    • good kidney function to complete radical oncology treatment

    Chemotherapy and radiation therapy are also used for palliative treatment. Palliation is directed for reducing pain and improving swallowing. Adequate nutrition during treatment is very important for this patient group.

    Surgery of esophageal cancer

    Surgical treatment is usually performed with the goal of curing the patient. The treatment is associated with cardiopulmonary complications and with a greater risk for anastomosis leakage than for regular bowel surgery. Poor health status will therefore more often be considered a criterion for inoperability than for other bowel surgery.

    Recent studies indicate that using thoracoscopy to remove the thoracic part of the esophagus can reduce the frequency of cardiopulmonary complications. This, however, has not been performed at the Norwegian Radium Hospital, and will not be mentioned further here.

    Endoscopic treatment with a sling resection is an alternative to surgery in severe dysplasia and in certain cases of T1 without lymph node metastases. Endoscopic treatment has the advantage of low morbidity and mortality in addition to preserving digestive function. About 50% of these patients, however, do not have the correct stage diagnosis with findings of invasive tumors in the resected material. At treatment centers where these tumors are rare, surgical treatment is the safest alternative.  

    PROSEDYRER

    Esophagus Resection

    General

    During a resection of the esophagus, the portion aboral part of the esophagus with the tumour is resected and the stomach is pulled up into the thorax, if necessary all the way up into the collum, and is anastomosed with the remaining esophagus.

    Access can be:

    • transthoracic by creating an opening between the ribs. This provides the best access in the thorax and the easiest lymph node dissection. 
    • transhiatal by operating in the thorax via an opening in the diaphragm and finally anastomosing to the throat. This technique may caus less cardiopulmonary complications.

    Cervical esophagus:

    • from the cricoid cartilage to thorax opening (about 15–25 cm from the teeth).
    • regional lymph nodes: cervical, peri-esophageal, internal jugular, scalene, and supraclavicular

    Thoracic esophagus:

    • upper: from the opening of the thorax to the tracheal bifurcation (approx. 25–35 cm from the teeth)
    • lower: the distal half between the tracheal bifurcation and cardia (approx. 35–45 cm from the teeth) regional lymph nodes: upper and lower peri-esophageal, subcarinal, mediastinal, and perigastric

    The impact of an extensive lymph node dissection is uncertain. In Japan, in the last few decades, it has been emphasized that a lymph node dissection must be performed in the thorax, abdomen, and neck. This has achieved a 40-50% 5 year survival. Western studies have not been able to obtain similar results, therefore lymph node dissections have not been performed to a similar extent. 

    Indications

    • Transthoracic access: tumor in all parts
    • Transhiatal access: tumor in upper or lower part of esophagus

    Contraindications

    • Metastases to the lungs, liver, or other metastases
    • Infiltration in the lungs, trachea, pericardia, aorta
    • Spreading to supraclavicular lymph nodes
    • Heart/lung disease to a relative severe degree

    At the time of diagnosis, over half of the patients will meet one or more criteria for inoperability, therefore only palliative treatment is offered.

    Goal

    • Cure

    Equipment

    • Self-retaining retractor for ribs
    • Retractors for access to thorax via diaphragm
    • Double tube for separate intubation of main bronchia
    • Forceps 
    • Laparotomy tray
    • Bookwalters self-retaining retractor
    • Staple instruments: cross-stapling  / closing-dividing , possibly circular stapler
    • Clips

    Preparation

    • Preoperative bowel evacuation is not performed as this does not improve the frequency of anastomosis leakage or infection. 
    • High-dosage low molecular weight heparin is administered as a thrombosis prophylactic. The first dose is given the evening before the operation to hinder the risk of bleeding from the epidural catheter.
    • Antibiotic prophylaxis is administered.
    • Epidural catheter is installed for postoperative pain treatment.
    • For transthoracic access the patient should be placed in an oblique position with the right side up on the operation table. For transhiatal access, the patient lies in the supine position.
    • The patient is placed under general anesthesia. For transthoracic access, separate intubation of the main bronchis is preferred to be able to collapse the right lung.

    Implementation

    The operation usually starts by mobilizing the stomach via a mid-line incision in the abdomen.

    The lymph nodes around the coeliac arteries are palpated and a frozen section is taken for suspicion of metastasis.

    The stomach is divided from the greater omentum while preserving the vessels along the greater curve. The short gastric vessels are divided. The vessels along the lesser curve are cut. The pylorus and duodenum are mobilized. The stomach is divided from the angulus to the top pf the fundus with a stapling instrument, preparing a tube of the gastric remnant. This can also be made in to a type of tube. Splitting of the pylorus fibers is done to facilitate emptying of the stomach (pyloroplasty).

    The opening in the diaphragm (hiatus) is widened for the stomach to enter the thorax.

    Transhiatal technique

    • The opening for the esophagus in the diaphragm is widened.  
    • The esophagus is dissected up in the thorax via the opening in the diaphragm as far up towards the neck as possible. 
    • Small blood and lymph vessels are divided between clips.
    • An incision is made on the left side of the neck.
    • The cervical esophagus is dissected carefully through an incision on the left of the collum, to prevent damage to the recurrent laryngeal nerves, and divided.
    • A tube is inserted through the thorax aperture into the abdomen. The gastric remnant is sutured to this and carefully pulled and pushed into the collum. An anastomosis is manually performed.
    • A tube is pulled via the nose down into the rest of the stomach.
    • A vacuum drain is installed to the mediastinum.
    • The incisions are closed.

    Transthoracic technique

    • An incision is made in the fifth right intercostal room.
    • The lung is collapsed to facilitate better access.
    • The pleura is divided over the esophagus. The esophagus with mediastinal tissue and lymph nodes are sharply dissected.
    • The azygos vein is divided and sutured.
    • The esophagus is cut in a suitable place oral to the tumor and the stomach is pulled up and anastomosed.
    • A tube is pulled through the nose to the stomach.
    • Two separate vacuum drains are placed in the upper and lower part of the thoracic cavity.
    • The incisions are closed.
    • If the tumor is located high in the thorax, it may be appropriate to dissect through the neck to achieve dissection margin above the tumor.

    Handling the removed specimen

    It is advantageous to bring the specimen unfixed to the pathology department. The specimen should always be cut up, but allow the tumor area to remain undisturbed to be stretched onto a cork disc for fixing. An unopened esophagus in the tumor area contributes to achieve adequate sections for the microscopic assessment of the "circumferential" resection margin. 

    The operation specimen description should include information about the localization (upper, middle, lower 1/3 of esophagus) and the size of the specimen (maximum diameter).

     

    Follow-up

    • Relatively often, patients stay on a respirator for a few days after the operation.
    • The thorax drain is removed when health status is good enough and no more than 200 ml/day collects.
    • The nastogastric tube is removed when the bowel resumes activity, or a couple of days.
    • X-ray contrast examination is performed after 6-7 days to check the anastomosis. After this, the patient may eat.
    • The patient is discharged after 10-14 days.

    Complications from surgery

    • Pneumonia with or without heart failure occurs relatively often. 
    • Anastomosis failure occurs more frequently than after other intestinal  surgery. Anastomosis failure can cause mediastinitis with a high mortality. The condition requires surgical installation of thoracic drain or is treated with a covered stent.
    • Stenosis in the anastomosis may be caused by fibrosis or tumor recurrence. This should be treated with endoscopic blocking or a stent.
    • For large remains of the stomach, some patients may have a delay in stomach emptying.
    • Some patients have a tendency to have the "dumping syndrome" or rapid empty of stomach content.
    • Damage to the vagus nerve (vagotomy) can cause intractable diarrhea in a very few patients.
    Esophagus ResectionEsophagus ResectionEsophagus ResectionEsophagus Resection

    Esophageal dilatation

    General

    Esophageal dilatation is for patients who have undergone an esophagus resection where anastomosis is made between the remainder of the esophagus and stomach. Scar tissue around the anastomosis often leads to a shrinking in the passage making it painful to swallow. 

    Dilatation is usually performed 6 weeks after the operation and it is common to repeat the procedure 6-8 times.

    The procedure is carried out using a gastroscope, which is a flexible tube equipped with a camera on the end, light system, and one or two work canals. Using this, the mucosa can be inspected and the images are transferred to a monitor.

    Indications

    • Postoperative narrowing of the surgical anastomosis
    • Routine procedure following esophageal resection 

    Goal

    • Enlarge space in the esophagus

    Equipment

    • Gastroscope with accessories
    • Equipment for unblocking (esophageal balloon, dilator, pistol)

    Preparation

    The patient must:
    • Inform the health personnel if he/she is aware of a valve defect in their heart. In this case, an endocarditis prophylactic is given.
    • Inform the health personnel if he/she is being treated with insulin.
    • Inform the health personnel if he/she is being treated with an anticoagulant or arthritis medication. This should not be taken for 5 days prior to the examination.
    Before the examination:
    • The patient must fast for 6 hours before the examination. Clear fluids are allowed for up to the last 2 hours before the examination.  
    • Medications may be taken the same day with a sip of water.
    Examination day:
    • A premedication is given.
    • The patient lies on their left side on the examination table.
    • Dental prosthetics must be removed before the examination.
    • Before the examination, a local anesthetic is sprayed in the throat. This will work for about 30 minutes.

    Implementation

    • Sedative and pain medication is given.
    • The gastroscope is inserted through the mouth, down the esophagus, and to the constriction/anastomosis.
    • Air is blown in to rinse the esophagus/stomach to obtain better overview during insertion of the scope.
    • A dilatation balloon is inserted down the esophagus through a canal in the gastroscope.
    • The balloon is placed in the middle of the constriction.
    • When the balloon is filled with water under pressure, the tissue is stretched. The pressure remains for about 3 minutes.
    • The balloon is emptied and retrieved together with the gastroscope.

    The procedure usually lasts 10–30 minutes.

    Follow-Up

    Pain and tendency for vomiting, pressure, and bloating are normal discomforts during/immediately following the exam.

    The patient should be observed for: 

    • Intense pain, vomiting blood. In rare circumstances, the tissue splits and air seeps out into the mediastinum and moves around in the corium of the throat (crepitation). If the patient has returned home, he/she must contact the hospital directly for X-ray of the thorax.
    • Bleeding if a biopsy is taken or polyps are removed.

    The patient may eat/drink at the earliest 1 hour after the procedure due to the local anesthesia in the throat. For outpatient procedures, the patient may return home after 2-4 hours.

    Self-expanding stent in the upper GI tract

    General

    A self-expanding stent is installed when passage of food in the upper GI tract is constricted. This procedure is an important option especially for patients with an inoperable tumor in the esophagus. It is important the patient avoids palliative surgery as much as possible to minimize time spent at the hospital.

    A stent is installed using a scope. The stent serves as a grating which expands when pushed out of its casing. Using X-ray, the stent is guided down a guide-wire. Because of tension in the metal wires, a larger opening is made through the tumor area. The stent is usually covered with a plastic membrane to keep the tumor tissue from growing in the openings of the metal grating.  

    Indications

    • Stenosis – many patients with cancer in the esophagus or stomach have stenosis as the most prominent symptom and therefore do not receive nutrition orally. Endoscopic installation of a self-expanding stent enables most patients to obtain nutrition by mouth.
    • Fistula – an esophago-tracheal fistula can be treated with a stent in both the esophagus and trachea. A fistula from the esophagus to the pleura can be covered with a stent in the esophagus. External drainage on the outside of the esophagus is usually necessary for healing to occur.

    Goal

    • The patient obtains nutrition orally
    • Palliation

    Equipment

    • Gastroscope with accessories
    • Stent equipment with guide wire and weights

    Preparation

    Installation of a stent is performed on an outpatient and inpatient basis.

    The patient must:

    • inform the health personnel if they have a known heart valve defect. If so, the patient will be administered a prophylaxis for endocarditis.
    • inform the health personnel if they are treated with insulin.
    • Inform the health personnel if they are treated with an anticoagulant or arthritis medications. These should be stopped 5 days before the procedure. 
    • take an X-ray and EKG if he/she is > 60 years and/or has heart disease 

    Before stent installation:

    • Fast for the last 6 hours before the operation 

    The day of stent installation

    • Premedication is administered.
    • The patient lies in the supine position on the examination table.
    • Dentures are removed. 
    • A local anesthetic is sprayed in the throat. This will take effect immediately.
    • The patient is placed under general anesthesia.

    Implementation

    • The scope is inserted in the mouth and down the esophagus.  
    • The tumor area is localized.
    • The upper and lower part of the tumor is marked with lead balls on the skin using X-ray.
    • The guide-wire is inserted down and the scope is pulled out.
    • An insertion case with the self-expanding stent is inserted down over the guide-wire and placed according to the lead balls (still using X-ray).
    • The stent is released and the insertion case is retrieved. 
    • X-ray and endoscopy are used to check that the stent is situated correctly.

    The procedure usually lasts for 30 minutes.

    Follow-up

    It usually takes 2-3 days for the stent to fully expand to the optimal size. During this period, the patient will usually have increasing pain.

    The patient is transferred immediately after the procedure as long as there are no complications. Normal hospital stay is 1-3 days.

    The patient should be observed for:

    • pain – adequate pain medication should be administered.
    • respiration – serious breathing difficulty may be a sign of perforation in the esophagus.
    • creptiation (when air leaks to surrounding tissue) –  this is a sign of subcutaneous emphysema and can occur as a complication from perforation in the esophagus. 
    • rise in body temperature – this indicates a perforation in the esophagus.

    An X-ray of the stent is performed to check that the contrast fluid passes the stent the first day after installation.

    An X-ray might be taken of the stent before the patient starts to eat. Often, the patient can eat/drink until the X-ray is taken.

    Complications from a self-expanding stent

    Dislocation of the stent is rare, but still the most common complication.

    In some cases, the tumor grows over the upper or lower edge. This requires a new stent to be placed partially in the old stent.

    Stents which are placed through the cardia will make an opening from the stomach to the esophagus where there is risk of regurgitation of stomach content causing aspiration and pneumonia. There are stents available with an anti-reflux mechanism.

    Abcesses can develop on the outside of the esophagus if the stent closes a fistula path from the inside without simultaneous drainage from the outside.

    Drug Therapy of esophageal cancer

    Curative oncology treatment (chemotherapy and radiation therapy) is administered to patients when the disease is localized and inoperable. Chemotherapy in the form of CiFu treatments is administered before starting radiation therapy as well as during and after.

    The Scandinavian Esophagus Group is currently performing a randomized study with preoperative oxaliplatin-FU with and without preoperative 40 Gy of radiation therapy.

    Palliative chemotherapy

    Palliative chemotherapy is appropriate when the disease is advanced. Expected survival time is often short and the patient's general health status is weakened. Side effects should be minimal, therefore CiFu treatment is often contraindicated. A combination of docetaxel (Taxotere®) and capecitabine (Xeloda®), which are currently being used in a phase ll study, is a good alternative for patients with aWHO function level of 0–2.

    PROSEDYRER

    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.

    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.

    Radiation Therapy of esophageal cancer

    Even if surgery is often considered the only curative treatment, good results have been published with radiation therapy in combination with chemotherapy (1). Today, this is standard treatment localized inoperable cancer in the esophagus.   

    If the patient's general health status is reduced and/or blood values are too low, radiation therapy is the only option. The treatment is administered in hyperfractionated high doses and the goal is to cure the disease. Biologically, this is based on the high proliferation rate of the squamous cells (Tpot). The treatment is well-tolerated, however the disadvantage is that microscopic spreading is not treated. It is considered too toxic to combine this radiation treatment with chemotherapy.

    Palliative radiation therapy

    The purpose is to keep the esophagus open and the patients swallowing ability for the rest of the patient's life, or long as it is possible.

    The treatment is administered either as external or endocavital radiation therapy.

    PROSEDYRER

    External Radiation Therapy

    General

    External radiation therapy is used in combination with chemotherapy for curative purposes. It can also be used in combination with endocavitary therapy for curative and palliative purposes, or alone as palliative treatment.

    It is normal to group squamous cell carcinomas and adenocarcinomas as one with regards to radiation therapy. Both are moderately sensitive to radiation. Radiation therapy serves both curative and palliative treatment purposes.

    For curative radiation therapy, it is important to uphold the planned treatment duration.

    Indication

    • Esophageal cancer

    Goal

    • Eliminate tumor - cure
    • Reduce tumor volume – palliation
    • Relieve tumor symptoms - palliation

    Definitions

    The tumor, including enlarged lymph nodes, in the ipsilateral hilus and mediastinum are defined as the target volume (GTV). Outside of this, 1–5 cm margins are placed to include microscopic spreading, tumor movement during respiration, and variations in tuning (CTV and PTV). The volume of the risk organs in the radiation field such as medulla, heart, and lungs must be minimalized with regarding maximal tolerable dosage.

    Target Volume

     

    Definitions of target volume according to ICRU
    (International Commission on Radiation Units and Measurements)
    GTV (Gross Tumor Volume) Palpable or visible/demonstrative area of malignant growth.

    CTV (Clinical Target Volume)

    Tissue volume containing GTV and/or subclinical microscopic malignant disease.

    ITV (Internal Target Volume)

    Volume containing CTV plus inner margin taking into account inner movement and changes in CTV.

    PTV (Planning Target Volume) Geometric volume containing ITV with set-up margin taking into account patient movement, variation in patient positioning, and field modeling.

     

    Preparation

    Target volume and radiation technique

    The radiation area is set based on the CT images.

    • The patient is not restrained, but stabilized on a wingboard with their arms up next to their head.
    • A CT for image-taking in a dedicated CT machine is performed and preferably with a contrast agent.
    • The localization of the tumor and risk organs are drawn directly in on the images and create a 3-dimensional radiation volume. The risk organs in the thorax are the spinal cord and lungs. Many patients with this diagnosis also have chronic obstructive pulmonary disease (COPD). 
    • The radiation therapists create a suggestion for the radiation field which must be adjusted and approved by both the medical physicist and treating doctor. Ideally, a uniform dosage distribution over the target volume is desired and no radiation to the critical organs. In reality, this is impossible to achieve. The dosage distribution is therefore a compromise between what is possible and what is desired.  
    • For the CT-taking, it is very important the patient is well medicated for pain and is able to lie still on their back. A premedication is administered or an extra dose of opiates if necessary.
    • The patient lies on a flat bench with only a thin mattress.

    Preparation for simulation including tuning and tracing of fields takes about 1 week. After this, the patient is ready to start radiation therapy.

    The patient must go to the simulator for tracing of the field about 1 week after the CT is taken. The field shape is drawn with a maker on the patient's skin. For simulation, it is also important the patient is well medicated for pain and is able to lie still. The simulator tuning often lasts for 1 hour. The simulator is an X-ray apparatus with set-up and dimensions like a radiation apparatus. This allows for the possibility of taking control images of the field set-up. These will be used for comparing the shade images of the radiated fields obtained on the radiation apparatus.

    After the simulation, the final treatment plan is transferred to the radiation machines, and the treatment is initiated usually after 1-2 days.

    Implementation

    Curative radiation treatment 

    The dosage speed is 0.5–5 Gy per minute. A homogeneous dose is striven for, possibly using compensation. All fields (most often 3) are treated with each fraction.

    Conventional fractioning combined with chemotherapy

    50 Gy is distributed into 25 fractions over 5 weeks combined with 3–4 CiFu courses (cisplatin, 5-FU). Risk areas obtain 46 Gy over 23 fractions.

    Hyperfractionated treatment

    Hyperfractionated treatment is used with the intention of curing the disease (radiation only).

    The treatment is administered twice daily with 35 Gy distributed over 20 fractions over 2 weeks toward ITV. After a pause in treatment of 2 weeks, 28 Gy is distributed over 14 fractions over 9 days toward GTV. This gives a total dosage of 64 Gy.

    Two weeks later, the treatment is concluded with an endocavitary dosage of 8 Gy. The total dosage is then 72 Gy over 7½ weeks, which is a curative dosage for squamous cell carcinomas. The treatment is well tolerated. The disadvantage is that microscopic cancer cells are not treated; It is considered too toxic to combine this radiation treatment with chemotherapy.

    Palliative radiation therapy 

    Radiation therapy is administered in dosages of 30–36 Gy over 10–12 fractions daily. When an external dosage of 30 Gy is given, it is often supplemented with an endocavitary treatment of 8 Gy after a 1 week break.  

    Follow-up

    The patient is checked with endoscopy for the first time 6 weeks after concluded treatment. Later checks are individual and occur at the patient's local hospital.

    Side effects which can occur after external radiation treatment are:

    • problems swallowing due to soreness and pain

    • skin reactions

    • fatigue

    • reduced lung capacity

    • leukopenia – induced by chemotherapy

    • thrombocytopenia – induced by chemotherapy

    • fibrosis in the esophagus - delayed effect

    • fistulas - usually due to infiltration of the tumor to respiratory passage – delayed effect

    External radiation therapyExternal radiation therapy

    Endocavitary Radiation Therapy

    General

    Endocavitary radiation therapy is given in addition to external radiation therapy for curative purposes, or alone for palliative purposes.

    The tumor area is radiated using iridium which is programmed to take in pre-defined time intervals in the length of the target volume. The dosage rate and radiation time depend on the age of the iridium which has a half-life of 74 days. The iridium is changed every 3 months.

    The effect of the endocavitary technique usually appears later than for stenting, but improves swallowing which will last the rest of the patient's life. The stent may be installed at a later time. Follow-up after radiation treatment is therefore important to assess who needs a stent.

    In Norway, the Norwegian Radium Hospital is the only hospital performing endocavitary radiation treatment for esophageal cancer.

    Indication

    • Tumor in the esophagus without tumor component in the stomach

    Goal

    • Curative therapy in conjunction with external radiation treatment
    • Palliation

    Definitions

    Some CT dosage plans are carried out for endocavitary radiation therapy, but this is not routinely used. 

    Preparation

    • This type of radiation treatment is a collaboration between anesthesia personnel, surgeon, oncologist, physicist, and radiation therapist. The treatment requires specific radiation equipment.
    • Based on the endoscopic description of the tumor and CT, the target volume is defined as 1 cm deep from the esophageal mucosa, and as the endoscopic tumor length plus 1 cm cranial and 1 cm caudal.
    • The patient must fast on the day of the treatment.

    Implementation

    The patient is sedated.

    Endocavitary radiation treatment is performed in two steps. The first radiation step is done in an endoscopy room:

    • The tumor's upper and lower borders are localized using a gastroscope and X-ray.
    • A hollow applicator is placed in the esophagus with space for the radioactive iridium source .

    The patient is immediately moved, in the same position, to the radiation department for the next step:

    • The iridium source is programmed for position and time frame to release an even radiation dose to the tumor, plus 1 cm cranial and caudal.
    • Each treatment lasts 5-10 minutes depending on the volume of the radiation and age of the iridium.

    The treatment is administered in 8 Gy fractions.

    • For curative purposes, 1 fraction is administered 1 week after external radiation treatment is concluded.
    • For palliative purposes, 3 fractions are administered with 1 week intervals.

    Follow-up

    Follow-up occurs at the patient's local hospital with individual adjustments of intervals.

    Side effects which can occur after endocavitary radiation are:

    • problems swallowing 
    • pain  
    • fibrosis in the esophagus - delayed effect
    Endocavitary radiation therapyEndocavitary radiation therapyEndocavitary radiation therapyEndocavitary radiation therapy

    Complication Treatment of esophageal cancer

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

    It may be necessary to provide supportive care in order for the patient to complete and obtain the full effect of planned treatment. Supportive care can also be provided to reduce side effects and improve the patient's quality of life during and after treatment.

    Adequate nutrition is essential to enable patients with esophageal cancer to complete radical treatment. These patients have often experienced dramatic weight loss because of the disease, therefore nutrition probeor PEG is recommended from the start of treatment.

    PROSEDYRER

    Treatment of Nausea Induced by Chemotherapy

    General

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

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

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

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

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

    Indication

    • Nausea induced by chemotherapy drugs.

    Goal

    • Prevention and treatment of nausea and vomiting.

    Definitions

    Chemotherapies according to emetic potential

    High emetogenicity   

    Group 1

    Moderate emetogenicity   

     Group 2

    Low/minimal emetogenicity

    Group 3

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

    CHOP (cyclophosfamide, doxorubicin, vincristine, prednisolone)
    Gemcitabine

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

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

    References

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

    Preparation

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

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

    Implementation

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

    Antiemetic regimens

    Mildly emetic chemotherapy

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

    Moderately emetic chemotherapy

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

    Highly emetic chemotherapy, or if other treatment does not help

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

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

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

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

    Delayed nausea

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

    Conditional nausea

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

    Follow-up

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

    Smoking cessation in connection with cancer treatment

    General

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

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

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

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

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

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

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

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


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

     

    Indication

    Weaning of nicotine in connection to cancer treatment. 

    Goal

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

    Preparation

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

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

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

    Implementation

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

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

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

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

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

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

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

    Treatment with nicotine replacement therapy

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

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

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

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

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

    Side effects

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

    Precautions

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

    Treatment with non-nicotine medications

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

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

    Side effects

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

    Precautions

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

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

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

    Side effects

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

    Precations

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

    Follow-up

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

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

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    Nutrition during Cancer Treatment

    General

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

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

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

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

    Indication

    • Cancer treatment (chemotherapy, radiation, surgery).

    Goal

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

    Definitions

    Subjective Global Assessment (SGA)

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

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

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

    Calculation of nutrition and fluid requirements

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

    Nutritionally enriched diet / enrichment of food and beverages

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

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

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

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

    Tube feeding

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

    Tube feeding is used in the event of

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

    Tube feeding must not be used for the following conditions.

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

    Tube feeding solutions

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

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

    Parenteral nutrition

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

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

    Preparation

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

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

    Tube feeding

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

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

    Parenteral nutrition

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

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

    Implementation

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

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

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

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

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

    Tube feeding

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

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

    For a running feeding tube:

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

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

    Bolus supply

    Initiation of tube feeding with bolus supply is only recommended

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

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

    Continuous supply

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

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

    Parenteral nutrition

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

    The patient must be monitored closely in relation to

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

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

    Follow-up

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

    Transfusions

    General

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

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

    Normal values

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

    Indications

    Blood transfusion

    Assessment for a blood transfusion based on:

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

    Platelet transfusion

    The patient is assessed for thrombocyte transfusion based on:

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

    Prophylactic platelet transfusion

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

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

    Goal

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

    Definitions

    Blood

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

    Platelets

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

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

    Radiation

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

    This is done for:

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

    Preparation

    Blood tests

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

    Compatibility

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

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

    Implementation

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

    Observations

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

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

    Follow-up

    Hemoglobin and thrombocytes are checked.

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

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

    Bone Marrow Stimulation with G-CSF

    General

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

    Indications 

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

    Goal

    • Maintain treatment intensity

    Preparation

    The patient should be adequately informed about the treatment.

    Implementation

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

     

    Follow-up Care

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

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

    Febrile Neutropenia

    General

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

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

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

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

    Indications

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

    Goals

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

    Definitions

    Fever is defined as:

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

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

    Preparation

    The following diagnostic tests should be performed:

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

    Information

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

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

    Use of an isolated or private room

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

     

    Implementation

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

    Antibiotic regimen

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

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

    • age
    • sex
    • kidney function
    • fat index   

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

    Serum concentration of tobramycin and gentamycin

    For single dose in 24 hours

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

    For multiple doses in 24 hours

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

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

    Systemic fungal treatment

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

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

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

    Follow-up

    Observe for symptoms of a new infection.

    Follow-up care after treatment of esophageal cancer

    Patients who have been treated with an esophagus resection or oncology treatment have endoscopy 6 weeks after the treatment is terminated. Later checks occur at the patient's local hospital and are individualized.

    The follow up should determine the health status of the patient, need for nutritional supplementation, and pain treatment. Further assessment of new stenosis or metastases requiring stenting or palliative radiation therapy should also be made.

    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