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Utskriftsdato (22.8.2017)

Stomach cancer

95% of all stomach cancers are adenocarcinomas. The rest are distributed between lymphomas, gastrointestinal stromal tumors (GIST), and other more rare forms.

Adenocarcinomas are classified according to growth and spread patterns of intestinal, diffuse, and mixed types and graded by low-grade and high-grade malignancy. This applies primarily to the intestinal type since the diffuse type is by definition considered highly malignant, because of the missing ability to create node structures. 

The stomach consists of the cardia, fundus, corpus, antrum, and pylorus.

Incidence

Compared to other cancers, stomach cancer is relatively rare. Approximately 0.9 percent of men and women will be diagnosed with stomach cancer at some point during their lifetime. Stomach cancer is most frequently diagnosed among people aged 65-74 and is more common in men than women.

In 2017, it is estimated to be 28,000 new cases of stomach cancer in the United States (13).

 

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

Source: National Cancer Institute. Bethesda, MD, USA

 

 

Incidence of cancer of stomach cancer, 1975–2014.

Source: National Cancer Institute. Bethesda, MD, USA

 

Etiology of stomach cancer

  • Chronic infection with Helicobacter pylori
  • Smoking 
  • Stomach resection for benign tumors causes an increase frequency of cancer in the remaining stomach at the anastomosis.
  • In very rare cases, stomach cancer (linitis plastica) is due to a genetic disposition.

The role of diet

Diets containing a high content of plant products, as well as high intake of antioxidants is related to a reduced risk for developing stomach cancer. A high intake of animal products is related to an increased risk.

Stomach cancer occurs more frequently in Japan, Korea, and China compared to the rest of the world. Strongly salted and smoked food is believed partially to be the cause. Water sources are also speculated to cause stomach cancer.

Histology of stomach cancer

The stomach is covered with mucosa, under which there is a loose connective tissue layer (submucosa) and outermost a muscular layer (muscularis propria). The mucosa in the upper part of the stomach contains closely lying glands with parietal and chief cells. Chief cells produce pepsinogen and parietal cells secrete acid. In addition, the glands in corpus and fundus, also contains ECL (enterochromaffin-like) cells. ECL-cells secrete histamine and are involved in the development of endocrine tumors of the corpus and fundus.

In the distal part of the stomach there are less compact glands producing neutral mucus. This part of the stomach contains other types of endocrine cells producing gastrin (G-cells), sertonin (EC-enterochromaffin) and somatostatin (D-cells). The surface and the pits are covered with a mucus-producing epithelium. In a limited zone between the stomach and the esophagus (cardia) the mucosa is very similar to the mucosa in the pyloric region.

Classification of adenocarcinoma precursor lesions

  • Intestinal metaplasia
  • Indefinite for intraepithelial neoplasia
  • Low-grade intraepithelial neoplasia
  • High-grade intraepithelial neoplasia

It is important that intraepithelial neoplasia/dysplasia lesions are evaluated by experienced pathologists before surgery is performed. This is due to the fact that epithelial changes in gastritis and ulcer can imitate dysplasia, and long experience is necessary to evaluate and grade the dysplasia in these specimens.

Classification of adenocarcinoma

  • Intestinal
  • Diffuse
  • Variants of adenocarcinomas (papillary, tubular, signet-ring cell, mucinous, adenosquamous)

The majority of malignant tumors in the stomach are adenocarcinomas. Laureen divided these into a diffuse and intestinal type, a classification which is of epidemiological as well as prognostic impact. Intestinal type metastasizes hematogenously to the liver, whereas the diffuse type has a tendency to spread to the peritoneum with carcinomatosis.

In contrary to adenocarcinoma in the colon, an adenocarcinoma in the stomach is considered an invasive adenocarinoma when infiltrating cells is detected in the lamina propria. This tumor is designated as intramucosal carcinoma. They are included in the terminology ‘early gastric cancer’ and has a relatively good prognosis compared to those with deeper infiltration.

Metastatic patterns of stomach cancer

Spreading occurs in different patterns:

  • Spreading by direct invasion of other organs, often the pancreas, possibly transverse colon or left liver lobe.
  • Spreading to the peritoneum or infiltration of serosa. In women, isolated metastases can develop in the ovaries (Krukenberg tumor).
  • Hematogenic spreading usually to the liver and more seldomly to the lungs or bone.
  • Lymphatic spreading to lymph nodes along in the hepatic duodenal ligament, along the celiac trunk and the splenic vessels. Stomach cancer rarely spreads to lymph nodes in the supraclavicular fossa (Wirchow).

Staging of stomach cancer

The TNM classification system is used for staging stomach cancer. TNM assesses the tumor (T), lymph nodes (N), and metastases (M) at the time of diagnosis. To assess the grade of lymph node spreading, at least 15 lymph nodes must be examined microscopically. 

Primary Tumor (T)

  • Tis  Carcinoma in situ: intraepithelial tumor without infiltration of the lamina propria
  • T1   Tumor invades lamina propria or submucosa
  • T2   Tumor invades muscularis propria or subserosa
  • T3   Tumor penetrates serosa (viscerale peritoneum), without invasion of adjacent organs/structures 
  • T4   Tumor invades adjacent organs/structures

 

Regional Lymph Nodes (N)

  • NX   Regional lymph nodes cannot be assessed
  • N0   No regional lymph node metastases
  • N1   Metastases in 1–6 regional lymph nodes 
  • N2   Metastases in 7–15 regional lymph nodes
  • N3   Metastases to at least 16 regional lymph nodes

 
The perigastric nodes along the minor curvature (1) and major curvature (2).
 
Lymph nodes along the left gastric artery (1), common hepatic artery (2), lienalis artery (3) celiac trunk (4) and the hepatoduodenal lymph nodes (5).

Distant Metastasis (M)

  • MX   Distant metastases cannot be assessed
  • M0   No disant metastases 
  • M1   Distant metastases 
Stage Division TNM
Stage T N M
0/IA Tis, T1 N0 M0
IA/IB T1 N0, N1 M0
II

 T1, T2, T3

 N2, N1, N0

M0

IIIA

T2, T3, T4

N2, N1, N0

M0

IIIB T3 N2 M0
IV

T1, T2, T3, T4

N0, N1

M1

 (1)

Symptoms of stomach cancer

Specific symptoms are usually absent early in the disease course. The stomach wall is very mobile and therefor tumors can be large before causing problems.

Early symtoms:

  • Dyspepsia
  • Diffuse pain in the epigastrium

Common symptoms:

  • Fatigue
  • Anemia
  • Loss of appetite
  • Early fullness
  • Vomiting
  • Pain which is not relieved by food intake
  • Moderate weight loss

Symptoms of advanced disease:

  • Pain in the back in the thoracic-lumbar transition when there is invasion of pancreas/posterior abdominal wall.  
  • Retention of solid food in the esophagus or stomach depending on localization of stenosis. 
  • Significant anemia 
  • Ascites from peritoneal carcinosis, (significant spreading to the peritoneum) possibly with ileus.
  • Significant weightloss
  • Icterus

Differential diagnoses of stomach cancer

Benign conditions

  • Dyspepsia due to gastritis/duodenitis, benign ulcer in the upper intestinal tract.
  • Gastro-esophageal reflux with esophagitis.
  • Back pain due to chronic pancreatitis or muscle/bone disease.
  • Anemia from malabsorption, chronic cholitis, diverticulitis (colon), arteriovenous malformations, chronic bleeding from benign ulcer, Meckel's diverticulitis (rare).
  • Stomach retention may be due to distal ulcer with stenosis.
  • Advanced esophagitis with stenosis and retention.
  • Ascites due to liver cirrhosis or portovenous thrombosis.

Malignant conditions

  • Epigastric pain due to colon cancer (transverse colon) or pancreas.
  • Anemia without other symptoms due to right-sided colon cancer.
  • Ascites may be due to peritoneal carcinosis from other form of cancer.

Prognosis of stomach cancer

The prognosis depends on whether the cancer is localized, regional, or metastatic at the time of diagnosis. For stomach cancer, 27.1% are diagnosed at the local stage and the 5-year survival for localized stomach cancer is 67.2%. The overall 5-year survival rate for liver cancer patients during the period 2007-2013 was 30.6 %. 

The number of stomach cancer deaths is highest among people aged 75-84. Death rates have been falling on average 2.4% each year over 2005-2015.

In 2014, there were an estimated 95,764 people living with stomach cancer in the United States and in 2017 there are an estimated 10,960 people will die of this disease (13).

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References on stomach cancer

  1. Nasjonalt handlingsprogram med retningslinjer for diagnostikk, behandling og oppfølging av pasienter med magekreft (2015), Helsedirektoratet (National guidelines for diagnostic, treatment and follow-up care of stomach cancer, Norwegian Directorate of Health)
  2. Enzinger PC, Benedetti JK, Meyerhardt JA, McCoy S, Hundahl SA, Macdonald JS et al. Impact of hospital volume on recurrence and survival after surgery for gastric cancer. Ann Surg 2007; 245(3):426-34
  3. Macdonald JS, Smalley SR, Benedetti J, Hundahl SA, Estes NC, Stemmermann GN 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. Liakakos T, Roukos DH. More controversy than ever - challenges and promises towards personalized treatment of gastric cancer. Ann Surg Oncol 2008; 15(4):956-60
  5. Patel PR, Mansfield PF, Crane CH, Wu TT, Lee JH, Lynch PM et al. Clinical stage after preoperative chemoradiation is a better predictor of patient outcome than the baseline stage for localized gastric cancer. Cancer 2007; 110(5):989-95
  6. Cunningham D, Allum WH, Stenning SP, Thompson JN, Van DV, Nicolson M et al. MAGIC TP. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med 2006; 355(1):11-20
  7. Brennan MF. Current status of surgery for gastric cancer: a review. Gastric Cancer 2005; 8(2):64-70.
  8. Cunningham D, Chua YJ. East meets west in the treatment of gastric cancer. N Engl J Med 2007; 357(18):1863-5
  9. Hartgrink HH, van de Velde CJ, Putter H, Bonenkamp JJ, Klein Kranenbarg E, Songun I, et al. Extended lymph node dissection for gastric cancer: who may benefit? Final results of the randomized Dutch gastric cancer group trial. J Clin Oncol 2004; 22(11):2069-77
  10. Lim L, Michael M, Mann GB, Leong T. Adjuvant therapy in gastric cancer. J Clin Oncol 2005; 23(25):6220-32
  11. Macdonald JS. Clinical overview: adjuvant therapy of gastrointestinal cancer. Cancer Chemother Pharmacol 2004; 54 Suppl 1:S4-11.:S4-11
  12. Sano T. Tailoring treatments for curable gastric cancer. Br J Surg 2007; 94(3):263-4
  13. 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 stomach cancer

Unfortunately, cancer of the stomach is discovered late, due to few and unspecific symptoms. At time of diagnosis 35% have metastasis to the lymph nodes and 40% have distant metastasis.

The clinical examination will only indicate the disease in an advanced stage, like palpable tumor in the epigastrium, in the peritoneum or lymph nodes in the supraclavicular bone. Ascites and jaundice are late symptoms.

There are no specific tumor markers in the blood. CEA, CA 19-9 and CA 125 can be taken. Blood tests in general do not show much apart from anemia, decreased albumin and elevated liver enzymes and bilirubin levels.

Endoscopic Examinations

  • Gastroscopy, based on visual understanding and biopsies for pathological examinations, provides diagnosis in nearly 100% of the cases.
  • When malignancy is confirmed, gastroscopy with endoscopic ultrasound is the best method for determining infiltration into the stomach and metastasis to local lymph nodes. This is of practical importance for the further handling.
  • Preoperative laparoscopy is used to diagnose peritoneal carcinosis or superficial liver metastasis. Laparoscopy can determine inoperability criteria in up to 20-30%.

Radiological Exams 

  • Spiral CT scan of thorax and upper abdomen (stomach and liver protocol) is done at confirmed disease. The examination is sensitive towards metastasis in lung parenchyma and mediastinum, and can identify tumors smaller than 5 mm in the liver.
  • The liver can also be examined with dedicated MRI.
  • Ultrasound-guided liver biopsy is an important supplement by uncertainty.
  • Ultrasound of liver with contrast also helps when the diagnosis is uncertain. 
  • PET scan has a higher sensitivity towards distant metastases than CT/MRI.
  • Skeletal scintigraphy is now less used if there is suspicion of spread to the bone.

PROSEDYRER

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.

    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.

    Treatment of stomach cancer

    Surgery is the only treatment that can cure the disease. However, this cancer type is often advanced at the time of diagnosis as 75% of the patients have lymph node metastasis or distant metastasis. The possibility for curative surgery is therefore limited and chemotherapy or radiation therapy is the best option.

    Advanced stomach cancer with extensive lymph node metastasis or distant metastasis is considered to be a disease that is relatively sensitive to chemotherapy.

    Surgery of stomach cancer

    Treatment of localized illness

    For localized stomach cancer, radical surgery may cure the disease. The percentage of patients offered surgery is about 70% and of these, about half are potentially curable.

    Tumors in the cardia/body of the stomach are operated for a total gastrectomy. A frozen section is used for pathological assessment during the procedure to ensure sufficient margins proximally (1). The spleen should also be removed with these proximal tumors in the cardia and on the major curvature. It is common to remove some lymph node stations, especially those along the left gastric artery and the minor and major sides of the stomach (modified D2 resection). Both the greater and lesser omentum should be removed.  

    If the tumor is localized in the antrum/pylorus, only the lower portion of the stomach is removed and the small intestine is connected to the upper portion (Billroth I or II variations). The spleen can then often be spared. For invasion into surrounding organs, the tumor should be removed en bloc along with the invaded organ.  

    Neoadjuvant therapy

    A large randomized study (MAGIC) (6) has shown extended 5-year survival when the patient is offered chemotherapy both preoperatively (neoadjuvant) and postoperatively (adjuvant). This is now standard treatment in Norway and is given in form of ECX or EOX regimens.  

    Treatment of inoperable illness 

    The chance of inoperability is great if the tumor grows: 

    • in the posterior abdominal wall toward the main artery or pancreas or
    • there is metastasis to the liver, lungs, peritoneum, or
    • there are ascites with malignant cells 

    Chemotherapy can in some cases make the tumor operable at a later time. Chemotherapy treatment with EOX is administered. Alternatively, milder treatments are given depending on age, health status, and comorbidity.

    Treatment for metastatic illness

    Surgical treatment may provide relief by securing passage and removing bleeding. This is appropriate mostly for younger patients with an expected survival time of 4-5 months.     

    PROSEDYRER

    Stomach Resection/Total Gastrectomy

    General

    A stomach resection/total gastrectomy is mostly performed for cure. There is no agreement on how extensive the lymph node dissection should be. In Japan and some treatment centers in the West, an extensive dissection is performed (D2 resection). This has not been common in Norway. It has been shown that a splenectomy or particulary distal resection of the pancreas should not be routinely performed as either may increase morbidity and mortality. Studies have shown that an extensive lymph node dissection can be performed with low mortality and morbidity when it is centralized to departments with a high volume of treatments and special competence.

    Surgery has two phases:

    • Resection of stomach tumor with lymph nodes en bloc
      • Either stomach resection of distal tumor in the stomach
      • Or total gastrectomy for proximal tumor (cardia/body) or diffuse growing tumor
    • Reconstruction of digestive tract

    Contraindications

    • Distant metastasis and peritoneal carcinosis
    • Local invasion of pancreas, aorta, transverse colon, and hepatoduodenal ligament 
    • Other complicating illness 

    Goal

    • Curative

    Equipment

    • Laparotomy tray
    • Self-retaining retractor which lifts the costal arch 
    • Staple instruments: closing-splitting/long cross-stapling  

    Preparation

    • Thrombosis prophylaxis 
    • Antibiotic prophylaxis
    • Epidural catheter is placed for postoperative pain treatment.  
    • Preoperative bowel emptying is not done.

    Implementation

    Resection

    • A midline incision is made in the epigastrium to below the umbilicus. 
    • The abdomen is examined for metastasis. 
    • The major omentum is divided from the transverse colon, the minor omentum from the liver.
    • The duodenum is mobilized and devided with a stapling instrument distal to the pylorus.  
    • The coeliac trunk is identified with lymph nodes.
    • Thel left gastric artery is identified and divided.
    • If necessary, the short gastric vessels are cut and the stomach is isolated to the esophagus.
    • The stomach is divided at the desired level with stapler.
    • Lymph nodes are dissected around the coeliac trunk, along the splenic vessels, and liver hilus according to the local policy.
    • The vagus nerves are cut at the cardia for total gastrectolmy.

    Reconstruction

    After the stomach resection, the proximal stomach can be anastomosized to:

    • (Billroth-I operation) the duodenal stump, end-end
    • (Billroth-II operation) proximal jejunum, end-side with or without side-side enteroanastomosis
    • (Roux-en-Y) proximal jejunum end-side with end-side enteroanastomosis

    After a total gastrectomy, the esophagus is anastomosized to the proximal jejunum  (Roux-en-Y).

    In certain cases, a feeding tube is inserted for early enteral nutrition in the jejunum.

    Follow-up

    • Nasogastric tube, if used, is removed when the bowel has resumed function.
    • After a total gastrectomy, a contrast X-ray examination is performed only if there is suspect anastomosis failure. The patient may eat early.
    • After a gastric resection, the patient may usually drink/eat immediately after the operation.
    Stomach Resection/Total GastrectomyStomach Resection/Total GastrectomyStomach Resection/Total GastrectomyStomach Resection/Total Gastrectomy

    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 stomach cancer

    Operable stomach cancer

    For patients with operable stomach cancer in stage II–III, who are < 75 years and in good health, we recommend neoadjuvant and adjuvant chemotherapy with ECX (epirubicin, cisplatin, and capecitabine), or alternatively EOX (epirubicin, oxaliplatin, and capecitabine) (1).

    Primary local inoperable cancer or advanced/metastatic illness

    Chemotherapy is indicated for locally advanced stomach cancer with sign of invasion of other organs/structures which are not able to be removed surgically. Chemotherapy has been shown to be effecting for downstaging, sometimes with the possibility of a later resection with a curative intention. However, there are large differences in results. 

    Advanced stomach cancer with distant metastasis is not possible to cure and the purpose of all treatment is palliative. The illness becomes stabilized for many patients and symptoms are relieved. The treatment can also extend illness-free periods and survival time. In most, the illness will progrediate after a few months. There is no defined chemotherapy regimen, but patients with good health status and < 75 years should be informed of the possibility of chemotherapy.

    For younger patients with good health status, we recommend the EOX or ECX regimen. For older patients (>70–75 years), or patients with reduced health status, we recommend ELF (etoposide, 5-FU, calcium folinate).

    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 stomach cancer

    Postoperative adjuvant combined radiation and chemotherapy is assessed for histological resection borders which are not free. However, the survival gain is not well documented (1).

    Radiation treatment should be done with three-dimensional dosage planning and include the operation area with nearest lymph drainage area. The total radiation dose is 50 Gy and is combined with 5-FU and calcium folinate or capecitabine.

    Patients with a palliative status with symptoms from a primary tumor can have palliative radiation treatment, for example 3 Gy fractions to total dosage 30–36 Gy.

    Complication treatment of stomach cancer

    Surgery, chemotherapy, 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 gain 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.

    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.

    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.

    Intravenous Extravasation of Cytotoxic Drugs

    General

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

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

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

    Risk factors for intravenous extravasation:

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

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

    • Non-cytotoxic/irritating
    • Tissue irritant
    • Cytotoxic

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

    Indication

    • Intravenous extravasation of cytotoxic drugs. 

    Goal

    • Limit damage of tissue from intravenous extravasation.

    Definitions

    Non-cytotoxic drugs or non-irritants

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

    Irritants

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

    Cytotoxic drugs

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

    DNA-binding

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

    • Anthracycline
    • Alkylating drugs
    • Other

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

    Non DNA-binding

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

    • Vinca alkaloids
    • Taxanes

     

    Chemotherapy cytotoxicity (1)
    Cytotoxic, necrosis

    Irritant, can cause flaking or inflammation

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

     * = Anthracycline

    ** = Alkylating agents

    *** = Vinca alkaloids

    **** = Taxanes

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

    All chemotherapy drugs can damage tissue in high concentrations.

    References

     

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

    Preparation

    Identification of an extravasal injection

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

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

     

    Implementation

    Flow chart for treatment of intravenous extravasation of cytotoxic drugs:

    Emergency response:

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

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

    Conservative treatment

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

    Localize and neutralize:

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

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

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

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

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

    Treatment 

    Dexrazoxan (Savene®)

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

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

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

    Cost

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

    Dimethylsulfoxide (DMSO)

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

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

    Hyaluronidase

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

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

    Surgical treatment

    "Wash-out"

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

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

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

    References

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

    Follow-Up

    For conservative treatment 

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

    For emergency surgical treatment

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

     

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

    Smoking cessation in connection with cancer treatment

    General

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

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

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

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

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

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

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

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


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

     

    Indication

    Weaning of nicotine in connection to cancer treatment. 

    Goal

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

    Preparation

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

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

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

    Implementation

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

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

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

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

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

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

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

    Treatment with nicotine replacement therapy

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

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

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

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

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

    Side effects

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

    Precautions

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

    Treatment with non-nicotine medications

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

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

    Side effects

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

    Precautions

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

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

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

    Side effects

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

    Precations

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

    Follow-up

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

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

    References

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    Follow-up care after treatment of stomach cancer

    Endoscopy check

    • For intestinal metaplasia, endoscopy is not indicated. This condition is quite common and the risk for adenocarcinoma is very low. These patients often have gastritis with dyspepsia and are followed up clinically with appropriate treatment (for example acid neutralization/antibiotic treatment against helicobacter pylori).
    • Patients with dysplasia (Barrett's esophagus) should be check with endoscopy and new biopsies after 3-6 months.
    • After a total gastrectomy, the anastomsis is checked for stenosis about 3 months after the operation.

    Subsequent checks for the next 5 years are done with a general practitioner. X-ray of the lungs and ultrasound of the liver may be taken as well as measurement of Hb and vitamin B12.  

    After stomach surgery

    • Vitamin B12 deficiency: After a total gastrectomy, the patient must have intravenous vitamin B12 supplements (one ampule) every 3 months for the rest of their life.

    • If there is stenosis in the anastomosis due to fibrosis or tumor reoccurrence: dilatation, stent, or reoperation
    • For malnutrition: small, frequent meals and supplements
    • For "dumping" with rapid emptying of stomach content, abdominal pain, and diarrhea: reduce intake of fluid at mealtimes and lie down for a short period after mealtime.

    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