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Utskriftsdato (20.11.2017)

Pancreatic cancer

Pancreas

Adenocarcinoma of the ductal type, which originates from exocrine gland tissue, is the most common type of pancreatic cancer and constitutes > 90% of all tumors. Adenocarcinomas in the body and tail are less common than in the head and constitute 25-30% of the total amount.

Endocrine tumors can occur in all parts of the pancreas, but are most common in the body and tail and consitutes 1-2% of all pancreatic tumors. They are separated into functioning and non-functioning tumors, depending on whether the patient has symptoms of hormonal hyperfunction or not.

The pancreas is divided into head of the pancreas, which is closest to the duodenum, the body and tail, as well as a network of ducts.

The pancreas consists of two types of gland tissue:

  • exocrine, which excretes digestive enzymes to the bowel 
  • endocrine, which excretes hormones to the blood system    

Incidence

Compared to other cancers, pancreatic cancer is relatively rare and represents 3.1% of all new cancer cases in the United States. Pancreatic cancer is slightly more common in men than women and is more common with increasing age. The average age at diagnosis is 70 years.

In 2017, it is estimated to be 53,670 new cases of pancreas cancer in the United States (2).

 

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

Source: National Cancer Institute. Bethesda, MD, USA

 

 

Incidence of cancer of pancreatic cancer, 1975–2014.

Source:National Cancer Institute. Bethesda, MD, USA

 

Etiology of pancreatic cancer

In most cases, the cause of pancreatic cancer is unknown.

Risk factors

  • Smoking is the only generally accepted exogenous risk factor of significance. 
  • There is a correlation between long-term chronic pancreatitis and development of pancreatic cancer.
  • Genetic predisposition where there are multiple cases in a family/siblings has occured, but is rare. 

Histology of pancreatic cancer

The pancreas consists of exocrine glands, endocrine glands, connective tissue, nerves, blood vessels, and ducts.

The main "caput" part of this gland is closely attached to the duodenum with main duct, that together with ductus choledochus, opens up in papilla Vateri in the duodenum. The distal part of ductus choledochus and ductus pancreaticus runs together and becomes an integrated part of the dorsal part of the gland.

Tumors originating in the distal part of ductus choleducus, ampulla Vateri or the distal part of the panreatic gland, are often difficult to separate from each other, especially in locally advanced stages. The majority of exocrine tumors in this region are adenocarcinomas and can be differentiated into intestinal or pancreaticobiliary types.

Precursor lesions

According to an international consensus, intraepithelial ductal lesions are designated as Pancreatic Intraepithelial Neoplasia graded, I-III (short for Pan-IN I-III).
This terminology reflects different grades of dysplasia in flat epithelium in small or medium-sized ducts in the pancreatic gland, usually < 5 mm in diameter.
In the pancreatic gland without cancer, Pan-IN grade III is observed in < 5%, although, it is found in 30-50% of pancreas with carcinoma.

Intraductal papillary mucinous neoplasi (IPMN) is a primary neoplastic precancerous lesion with a varying degree of malignant potential. These are characterized by cystic dilatation of the main or secondary ducts with mucin production. IPMN is graded as adenoma (benign), borderline or carcinoma.

There are no known endocrine precursor lesions.

Classification of exocrine neoplasia

The majority of malignant tumors in the pancreas are adenocarcinomas. These originate in the middle-sized ducts within the pancreatic gland. Most of them are differentiated as pancreaticobiliary adenocarcinomas, i.e. they have a phenotype resembling pancreaticobiliary duct epithelium. The other, less frequent, intestinal type demonstrates a intestinal/colon-like phenotype.

In the locally advanced tumors in the caput part of the pancreatic gland, it can be difficult to decide whether they originate in the pancreas ductus choledochus, ampulla Vateri, or duodenum. In these instances immunohistochemistry may be helpful.

Adenocarcinoma in the pancreas has a tendency to produce fibrous connective tissue making them very hard tumors.

Intraductal papillary mucinous carcinomas usually originate in the main pancreatic duct. Also, when pronounced atypia/carcinoma in situ exists in the this tumor type, it is designated as carcinoma. The exact incidence of this tumor type is unknown, but probably accounts for less than 5% of all neoplasias of the pancreas. Malignant IPMN has a better prognosis than ordinary pancreatic adenocarcinomas.

Tumors originating in the exocrine glands are rare, and constitute 1-2 % of all acinic cell carcinoma in the pancreatic gland. Even if this tumor grows more expansive than infiltrative compared to ordinary adenocarcioma, the prognosis is poor with 5-year survival < 10%. 

A solid pseudopapillary tumor (Franz tumor) is a tumor type that mainly exists in younger women. They are usually benign. Metastases have been reported in 15-20% of all patients with this diagnosis.

Serous microcystic adenoma is a tumor without malignant potential in contrast to mucinous cystadenomas.

Blastoma in the pancreas is very rare and is found usually in small children. It consists of epithelial and mesenchymal components.

Endocrine neoplasia

Endocrine neoplasia in the pancreas is rare. Immunhistochemical markers such as synaptophysin, CD56 and chromogranin are important to diagnose these types of tumors. These tumors can produce hormones such as insulin, glucagon, gastrin, somatostatin, and vasoactive intestinal polypeptide.

Staging of pancreatic cancer

Pancreatic cancer is classified by the TNM classification system. This classification applies only to adenocarcinomas in exocrine pancreatic tissue. The TNM system assesses the tumor (T), lymph nodes (N), and metastasis (M) at the time of diagnosis. The TNM classification differentiates between the clinical classification (TNM) and the pathological classification (pTNM).

Primary tumor (T)

  • pTX   Primary tumor cannot be assessed
  • pT0   No evidence of primary tumor
  • pTis  Carcinoma in situ

/upload/pankreas/bukspyttkjertel_stadier_t1_t2.gif 

  • pT1   Tumor limited to the pancreas ≤ 2 cm
  • pT2   Tumor limited to the pancreas > 2 cm

/upload/pankreas/bukspyttkjertel_stadier_t3_t4.gif 

  • pT3   Tumor has spread outside the pancreas without involving the coeliac axis or superior mesenteric artery
  • pT4   Tumor infiltrates the coeliac trunk or superior mesenteric artery

Regional lymph nodes (N)

  • pNX   Regionale lymph nodes cannot be assessed
  • pN0   No regional lymph node metastasis
  • pN1   Regional lymph node metastasis 

Metastasis (M)

  • pMX    Metastasis cannot be assessed
  • pM0    No metastasis
  • M1    Metastasis

Metastatic patterns of pancreatic cancer

Adenocarcinoma in the pancreas is an agressive cancer and metastasize early. Spreading occurs both hematogenously and lymphatically. Both local and regional lymph nodes can be infiltrated.  

At the time of diagnosis, there is often metastasis to the liver. Lung and skeletal metastasis are rare.

 

Symptoms of pancreatic cancer

Jaundice

The classic presentation form of pancreatic cancer is referred to as "silent jaundice", meaning the jaundice is not accompanied by other symptoms, as for instance pain. Jaundice is the first symptom in about half of patients with cancer in the head of the pancreas. Among patients who are radically operated, more than 70% have jaundice as one of the first symptoms.  

Pain

Secondary to jaundice, pain is the most common symptom, usually localized centrally in the abdomen. When pain radiates to the back, there is reason to suspect that the tumor has already infiltrated the nerve plexus outside the gland. Pain is commonly the symptom leading the patient to go to the doctor (50–60%). The pain can be described as fatigue in the back which increases when lying on the back. Sitting slightly bent forward may relieve the pain. 

Weight loss

Unintentional weight loss should cause suspicion of pancreatic cancer, especially if it is accompanied by fatigue and recent discomfort in the abdomen or back pain. At the time of diagnosis, almost all patients have lost 2-5 kg of weight, and more than 10 kg is not uncommon.  

Diabetes

Newly diagnosed diabetes may be a warning signal, especially if it is observed in connection with unintentional weight loss or pain in middle-aged people. About 20% of the patients have recently developed diabetes. The connection between pancreatic cancer and diabetes is unclear.  

Stomach retention

Stomach retention may be an early sign of a tumor in the head of the pancreas compressing the duodenum.

Pancreatitis

Patients who receive the diagnosis of acute pancreatitis, without simultaneously having a triggering factor, should be assessed for cancer.

Hormonal symptoms

Endocrine tumors have debut symptoms which deviate from regular adenocarcinomas in the pancreas. Symptoms from functional tumors depend on the excreted hormones.

For example:

  • insulinomas cause episodes of hypoglycemia due to high blood insulin
  • gastrinomas can have debut with ulcer symptoms due do raised levels of gastrin 

Tumors in the body and tail seldom cause early symptoms and are usually diagnosed late in the course of the disease. The tumor is therefore often larger and more advanced at the time of diagnosis. 

Ascites may be a sign of advanced cancer. 

Differential diagnoses of pancreatic cancer

Chronic pancreatitis

Clinically, the most important differential diagnosis is chronic pancreatitis. However, pancreatic cancer cannot always be differentiated from pancreatitis, even by laparotomy. If cancer cannot be excluded and the patient is operable, work-up and treatment should be as if cancer is present. 

Cancer in adjacent organs

Cancer in the Ampulla of Vater, duodenal cancer, and distal (intrapancreatic) cancer of the common bile duct cancer, have a clinical picture which, except for a lesser extent of weight loss, is most closely concurrent with the clinical picture of ductal cancer in the head of the pancreas. Differentiation between these cancer forms in the periampular region is very difficult both pre- and postoperatively. Surgical treatment is, however, the same despite the origin of the tumor. The final diagnosis is obtained from the surgical specimen.  

Metastasis

Metastasis from other tumors to the retroperitoneal space behind and in the head of the pancreas can sometimes be difficult to differentiate from tumors originating from the pancreas itself. For example, metastasis may develop from the kidneys, breast, colon, stomach, and melanoma. In certain cases, a radical resection may cure the disease or prolong recurrence, and in some cases, additional oncological treatment will extend lifetime and long-term absence of symptoms.

Lymphoma

Lymphoma in the pancreas is rare.

Prognosis of pancreatic cancer

The prognosis depends on whether the pancreatic cancer is localized, regional, or metastatic at the time of diagnosis. For pancreatic cancer, only 9.7% are diagnosed at the local stage and the 5-year survival for localized pancreatic cancer is 31.5%. In part because it is difficult to detect early, the average survival time from pancreatic cancer is low and the overall 5-year survival rate for pancreatic cancer patients during the period 2007-2013 was only 8.2%.

Because survival is poor, the population distribution of people who die of pancreatic cancer is similar to that of people who are diagnosed with the disease. Pancreatic cancer deaths is highest among people aged 75-84 and is the third leading cause of cancer death in the United States. Death rates have been stable over 2005-2014.

In 2014, there were an estimated 64,668 people living with pancreas cancer in the United States and in 2017 there are an estimated 43,090 people will die of this disease (2).

 

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References on pancreatic cancer

  1. Nasjonalt handlingsprogram med retningslinjer for diagnostikk, behandling og oppfølging av pasienter med bukspyttkjertel (2014), Helsedirektoratet (National guidelines for diagnostic, treatment and follow-up care of pancreatic cancer, Norwegian Directorate of Health)
  2. Howlader N, Noone AM, Krapcho M, Miller D, Bishop K, Kosary CL, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER Cancer Statistics Review, 1975-2014, National Cancer Institute. Bethesda, MD
  3. Sobin LH, Gospodarowic M, Wettekind C, red. TNM: classification of malignant tumors. 7 utg. Oxford: Willey-BackwII; 2010
  4. Verbeke CS, Gladhaug IP. Resection margin involvement and tumour origin in pancreatic head cancer. Br J Surg 2012;99(8):1036-49
  5. Vincent A, Herman J, Schulick R, Hruban RH, Goggins M. Pancreatic cancer. Lancet 2011;378(9791):607-20
  6. Ghaneh P, Castello E, Neoptolemos JP. Biology and management of pancreatic cancer. Gut 2007;56(8):1134–52
  7. Costello E, Neoptolemos JP. Pancreatic cancer in 2010: new insights for early intervention and detection. Nat Rev Gastroenterol Hepatol 2011;8(2):71-3
  8. Warshaw AL, Lillemoe KD, Fernandez-Del Castillo C. Pancreatic surgery for adenocarcinoma. Curr Opin Gastroenterol 2012;28(5):488-93
  9. Westgaard A, Tafjord S, Farstad IN, Cvancorva M, Eide TJ, Mathisen Ø, et al. Resectable adenocarcinomas in the pancreatic head: the retroperitoneal resection margin is an independent prognostic factor. BMC Cancer 2008;8:5
  10. Westgaard A, Larønningen S, Mellem C, Eide TJ, Clausen OPF, Møller B, et al. Are survival predictions reliable? Hospital volume versus standardisation of histopathological reporting for accuracy of survival estimates after pancreatoduodenectomy for adenocarcinoma. Eur J Cancer 2009, doi: 10.1016/j.ejca.2009.03.019
  11. Carpelan-Helström M, Nordling S, Pukkala E, Sankila R, Lüttges J, Klöppel G, et al. Does anyone survive pancreatic ductal adenocarcinoma? A nationwide study re-evaluating the data of the Finnish Cancer Registry. Gut 2005; 54: 385–387
  12. Michl P, Gress TM. Current concepts and novel targets in advanced pancreatic cancer. Gut 2013;62(2):317-26

Diagnostics of pancreatic cancer

Clinical examinations performed to diagnose pancreatic cancer should focus on jaundice, epigastric tumors, an enlarged liver, ascites, an enlarged gallbladder (Courvoisier's sign), and enlarged lymph nodes in the neck (Virchov's gland). When symptoms, signs, and blood test results cause suspicion of pancreatic cancer, a swift and to-the-point work-up is of importance. 

Imaging diagnostics

  • A transabdominal ultrasound scan is usually the primary examination pancreatic cancer is considered. The examination is sensitive for detection of liver metastasis and ascites, and can show invasion of blood vessels. When ultrasound shows liver metastasis bioptically verified as adenocarcinoma, additional histological diagnostics of the primary tumor in the pancreas are not necessary.  
  • CT is sensitive for detection of the primary tumor and metastasis, and gives good information about the local extension of the tumor, especially the relation of the tumor to surrounding vessels. It is the standard for diagnosis and stage determination. The examination should be performed as a spiral CT with intravenous contrast and imaging of uptake in both early pancreatic parenchymal phase and portal venous phase, which is equivalent to late pancreatic parenchymal phase. This method is suitable for detection of invasion into vessels and/or vessel surrounding growth, as well as detection of variations in vessel anatomy. If the tumor is < 1 cm in diameter, the accuracy decreases significantly for the tumor both with US and CT.   
  • MRI of the pancreas with intravenous contrast can provide good morphological information about the extent of the tumor and invasion of blood vessels. MRCP (magnetic resonance cholangiopancreaticography) completed in the same session provides good visualization of the bile ducts and pancreatic duct. MRCP can be performed without contrast fluid and is non-invasive. Image examples: MRCP overview , MRCP  and MRCP 3D . An MR examination does not necessarily provide better information of the tumor and vessel invasion than a CT scan. For practical purpose, CT often provides better visualization of the blood vessels than MRI. An X-ray of the thorax should be performed early in the work-up even though lung metastasis is relatively rare. In ambiguous cases, a CT of the thorax should be performed.   

Endoscopy

  • Ampullary tumors growing into the duodenum can be visualized and biopsied using duodenoscopy. Pancreatic cancer in advanced cases, can grow into the stomach and may bediagnosed endoscopically. 
  • Endoscopic ultrasound (EUS) has shown to be a relatively good method to assess local invasion and allows for taking specimens for cytology. EUS provides high-resolution images in the parts of the pancreas with proximity to the duodenal wall.

Biopsy

  • In resectable patients, obtaining tissue samples for cytological/histological examination should be avoided. Fine-needle aspiration cytology and/or core biopsy (tissue cylinder) are considered necessary to confirm the diagnosis before chemotherapy for patients who will not be operated.  
  • For an inoperable tumor, a biopsy is recommended to obtain definite diagnosis, especially to clarify whether the tumor is endocrine and not an adenocarcinoma. 
  • In patients with pancreatic cancer, ascites is a sign of an advanced, inoperable disease. A cytological examination of ascites may be of diagnostic value.

Chemical and molecular biological diagnostics, tumor markers

At present, there is no laboratory test of blood or urine, or a combination of tests, which is sufficiently sensitive and specific for this diagnosis.

PROSEDYRER

Endoscopic ultrasound examination of the bile ducts and pancreas

General

In some cases, tumors in the bile ducts or pancreas are difficult to visualize by external ultrasound or CT/MRI. Endoscopic ultrasound-guided fine-needle aspiration (EUS) allows for ultrasound visualization of the area with high resolution and improved possibility for tissue sampling.    

Indications

  • Cancer in the liver/bile ducts
  • Cancer in the pancreas
  • Tissue sampling of small lesions which are not suitable for a percutaneous examination.

Goal

  • Diagnostics
  • Survey the relationship of the tumor to adjacent structures, for example blood vessels, focusing on operability.

Equipment

  • Ultrasound duodenoscope with accessories
  • Fine needle and equipment for preparing cytological specimens

Preparation

  • If the patient is treated with the anticoagulant warfarin, this must be discontinued 3 days before the examination when tissue sampling is an option.
  • The patient must be fasting for 6 hours before the examination.
  • The examination is normally performed under light sedation or local anesthesia sprayed in the throat.
  • The patient lies on their left side on the examination table.
  • A hollow mouth piece is put between the teeth for insertion of the scope.

Implementation

  • The scope is carefully inserted through the mouth down to the stomach and the duodenum.
  • The ultrasound probe on the end of the endoscope is placed toward the stomach/intestinal wall. The rest of the examination focuses on the ultrasound images.
  • If necessary, a needle can be inserted through the endoscope for aspiration of test material. The specimen is prepared and assessed by a cytologist. 

Follow-up care

  • The patient may eat/drink at the earliest 1 hour after the procedure due to the local anesthesia of the throat.
  • The examination is performed on an outpatient basis and the patient may return home after 1–2 hours.
  • The result is usually available within a week.

Treatment of pancreatic cancer

The only possibility to cure the disease is by surgical resection of the tumor. Due to the limited number of patients who are suitable for surgery with a curative intent, the tendency internationally is that these patients are centralized to centers of excellence for diagnosis and treatment by an interdisciplinary team. The teams should consist of highly qualified surgeons, radiologists, anesthesiologists, oncologists, pathologists, and specialized nurses. Today, there is convincing data showing a positive correlation between the number of operated patients and short and long-term results.

Pancreatic cancer has long been considered a chemotherapy resistant tumor form. A large number of studies, including large randomized multi-center studies, have been completed in recent years, but these have generally shown only marginal effects on tumor response and survival.

Preoperative radiation and chemotherapy are not routinely given but only within the framework of controlled studies.

Palliative treatment

At the time of diagnosis, about 15% of patients have a potentially resectable tumor. For the remaining 85% of the patients, palliative treatment is appropriate. Additionally, most operated patients will have recurrence of the disease. Therefore, nearly all patients will receive treatment for symptom relief.  

Treatment of pain and nausea follows general principles, but a few other alternatives are appropriate for pancreatic cancer:

  • Celiac plexus neurolysis
  • Splanchnic nerve resection – division of the splanchnic nerves, which drive pain impulses from the pancreas, is now performed by a thoracoscopic technique. The procedure is done bilaterally and good initial results have been reported without side effects. 
  • Radiation treatment – For extensive metastasis and pain which is difficult to treat, it has been well documented that radiation treatment provides good pain relief for some patients. Unfortunately, the effect is delayed for a few weeks.
  • Treatment of gastroduodenal stenosis
  • Treatment of jaundice

Surgery/Intervention of pancreatic cancer

Surgery

For operable pancreatic cancer, appropriate surgical procedures are:

  • Pancreaticoduodenectomy (Whipple procedure)
  • Distal pancreatectomy - for cancer in the body or tail.
  • Total pancreatectomy is only performed in special cases.

Endoscopic intervention

With endoscopic retrograde cholangiopancreatography (ERCP) it is possible to perform:

  • Stenting
  • Endoscopic loop resection

Most patients with pancreatic cancer experience loss of weight and commonly malnutrition. In such cases, nutritional supplementation is applied from the time of the work-up until the operation. Resectable patients having a delay in the operation due to lasting jaundice or limited capacity, should have their fluid, electrolyte, and energy balance improved during the delay. Potassium should always be given preoperatively to jaundiced patients with prolonged bleeding time or too high INR.  

Marking and fixing the operation specimen

For assessment of surgical results, a high-quality histopathological examination of the operation specimen is necessary. This should be done in a standardized way and the pathologist and surgeon should agree on which histopathological variables are significant.

Conferring regularly with a pathologist appears to significantly improve histological quality. In addition, the surgeon's understanding of the cancer's spreading pattern increases.  

The specimens of distal resections (body and tail) are fixed in an ordinary way with 10 units of formalin per unit of tissue. Whipple specimens should preferably be delivered unfixed to the pathology department immediately after the operation. All important vessels, ductal structures, and resection surfaces (especially posterior resection surfaces) should be marked. 

Pathology results

  • Tumor localization
  • Tumor size
  • Histology type
  • Grading
  • Resection margins (especially posterior/retroperitoneal surface)
  • Vessel infiltration
  • Perineural infiltration
  • Lymph node metastasis 
  • Pan-IN
  • pTNM

Since the pancreas is partially a retroperitoneal organ, local spreading to the posterior resection surface is very critical. It is therefore important that this resection surface is examined for tumor tissue and reported.

PROSEDYRER

Endoscopic retrograde cholangiopancreatography (ERCP)

General

Endoscopic retrograde cholangiopancreatography (ERCP) provides an X-ray image of the bile ducts and pancreatic ductal system by direct injection of contrast into the ductal system.

The technique also provides access to both extended diagnostics and therapeutic procedures for the bile ducts and pancreas.

The procedure can be performed on an outpatient basis and is similar to gastroscopy. If a therapeutic procedure is performed, the patient often stays in the hospital for observation. 

For ERCP, a duodenoscope is used which is a special gastroscope with side viewing optic. This makes it significantly more suitable to manipulate the duodenal papilla, however navigation is more difficult. Various customized instruments can be passed through the instrument canal of the endoscope and further on through the papilla.

Indications

Cancer in the pancreas or liver/bile ducts:

  • Diagnostic technique for ambiguous cases (visualization of ductal system and possible brush sampling or biopsy)
  • Preoperative bile/pancreatic duct decompression 
  • Symptom relieving drainage of bile/pancreatic ductal system  in cases of inoperable cancer
  • Local removal of early stage cancer in duodenal papilla 

A common feature is that all of these indications include therapy. Diagnostic ERCP is applied to a diminishing degree, but may still be used for collecting tissue samples (cytology or biopsy).

Goals

  • Obtain a diagnosis
  • Drain stenotic ductal systems

Equipment

  • Side optic endoscope (duodenoscope) with accessories 

Preparation

Plavix®, Clopidogrel®, Brillique®, Pradaxa®, Xarelto®, Eliquis®, Fragmin® or Marevan® (warfarin) should be stopped  to reduce the risk of bleeding during the procedure, if the patients general practitioner doesn´t decides otherwise.

  • Plavix®, Clopidogrel® and Brilique® may be taken up to seven days before the procedure.
  • Pradaxa®, Xarelto® and Eliquis® may be taken up to 48 hours before the procedure.
  • Marevan® (warfarin) may be taken up to 48 hours before the procedure, and the patient must also have an INR control at least an hour before the examination.
  • The patient may continue to take Albyl-E® (acetylsalicylic acid).
  • Fragmin® injections may be taken until the night before the procedure.
  • If the patient has an artificial heart valve, contact the ward in charge of the excamination.

The stomach must be empty before the procedure.

  • The patient can´t eat or drink anything in the last six hours before the procedure.
  • If the patient is very thirsty he/she may drink 1-2 glasses of water until two hours before the procedure, and then only rinse the mouth without swallowing anything.

If the patient have diabetes and use insulin or other essential medecines that can´t be postponed, the patient can get an appointment early in the day.

The procedure is usually carried out under light sedation with Dormicum®/Pethidin®, however propofol-anesthesia is becoming more common. General anesthesia is only exceptionally use.

Implementation

  • The procedure is performed with the patient on the stomach with the right side slightly raised.
  • The endoscope is inserted carefully through the mouth and stomach to the duodenal papilla.
  • A thin plastic tube is manipulated into the bile duct or pancreatic duct and contrast fluid is injected to visualize the ductal system, and an X-ray picture is taken simultaneously. 
  • If necessary, a brush or biopsy forceps is inserted into the duct for sampling.
  • If necessary stenotic areas can be expanded with a balloon, plastic tubing, or a stent.

Follow-up

The patient can often return home the same day, unless a procedure is performed which increases the risk for complications. This is determined on an individual basis.  

Results from biopsies are usually available after 1 week.

If a stent is inserted, this must usually be removed or changed after 2–3 months by a repeated ERCP procedure.

Complications

Most ERCP procedures are carried out without complications. It is common to have a sore throat and light abdominal pain (including gas pain) after the procedure.

Pancreatitis is the most threatening complication and occurs in 4–15% of cases. There are some known risk factors, most significantly previous ERCP pancreatitis and possibly ampullary dysfunction. However, pancreatitis occurs for unknown cause. Fortunately, most cases are mild with only abdominal pain requiring a few extra days in the hospital. However, necrotizing pancreatitis also occurs with significant mortality.

Other, less frequent complications are cholangitis, bleeding, or perforations after endoscopic papillotomy. If any of these are discovered during the examination, they are usually treated conservatively without the need for surgery or other intervention. Delayed bleeding (within 24 hours) also occurs and will often require a repeat endoscopic procedure for treatment.

Whipple procedure

General

A Whipple procedure is performed when there is suspicion of a malignant tumor in the head of the pancreas or adjacent organs such as the duodenum or bile ducts. The operation is also carried out for some cases of chronic pancreatitis.  

A Whipple procedure is not performed if there is spreading of cancer to other organs or to peripheral lymph nodes. Invasion of blood vessels (especially the mesenteric artery and greater mesenteric vein) is also a contraindication. In some cases of limited vessel invasion, the operation can still be carried out in combination with vascular surgery.

The head of the pancreas is removed. Since the pancreas shares blood supply and lymphatic drainage with adjacent organs, some of the common bile duct is removed along with the entire duodenum and often the distal stomach . Finally, a reconstruction is performed where the small intestine is anastomosed to the remaining bile ducts, stomach, and remaining pancreas. 

Mortality of the procedure is low, but postoperative morbidity is still significant. To reduce postoperative mortality, the patient should be operated at a hospital with a large volume of operations and after critical preoperative assessment of the patients. 

Indications

  • Tumor in the pancreas
  • Tumor in the duodenum
  • Tumor in distal end of the common bile duct 

Goal

  • Cure of the disease

Preparation

  • Antibiotic prophylaxis
  • Thrombosis prophylaxis
  • Urinary bladder catheter 
  • Epidural catheter is installed for postoperative pain relief.
  • The patient lies in the supine position.
  • The operation is performed under general anesthesia.

Implementation

A Whipple procedure consists of three steps:

  • Dissection
  • Resection
  • Reconstruction

Dissection

  • The procedure is performed via an angled, epigastric transverse incision.
  • The abdominal cavity is inspected and palpated thoroughly.
  • Inoperability criteria are:  
    • liver metastasis
    • peritoneal metastasis
    • invasion of the base of the mesentery
    • infiltration of the peritoneal surface
    • growth into adjacent organs (not the duodenum)
  • Kocherization is completed when the duodenum and head of the pancreas are dissected off the underlying structures.
  • The hepatic artery and the base of the gastroduodenal artery are dissected and identified by vessel loops.
  • The common bile duct is dissected and the area of division is identified with a vessel loop.
  • The superior mesenteric vein is dissected at the lower edge of the pancreas.
  • The lesser sac is divided and the omental bursa is opened, and the caudal edge of the pancreas is isolated.
  • The portal vein is bluntly dissected behind the pancreas to isolate the portal vein. The dissected pancreas is identified with a vessel loop.

Resection

  • The gastroduodenal artery is divided at the origin from the hepatic artery.
  • The small intestine is divided 8–10 cm distal to the ligament of Treitz using a GIA stapler. This apparatus inserts two double rows of staples and divdes the tissue between them in one operation.
  • The stomach is divided at the angulus, also with a GIA. The staple suture is inverted manually with sutures.
  • A cholecystectomy is performed.
  • The pancreas is divided with a knife between the head and body.
  • The loop around the common bile duct is removed and the duct is divided.
  • The tissue between the head of the pancreas and the portal vein and superior mesenteric artery is divided by dissection towards the vessels. The specimen is now free to be removed. 

Reconstruction

  • The pancreas is anastomosed end-to-side to the distal small intestine with interrupted sutures. 
  • The common bile duct is anastomosed end-to-side further down on the small intestine. The anastomosis is performed with running sutures posteriorly and interrupted sutures anteriorly.  
  • The stomach is anastomosed side-to-side to the small bowel. The anastomosis is created with a GIA or with sutures. The opening from the GIA is closed with running sutures. 
  • The abdomen is flushed and a drain is placed in the anastomosis area.
  • The abdominal wall is closed by two layers of running sutures. The skin is closed with staples.
  • The surgical specimen is marked by the surgeon and sent to the pathologist.

Follow-up

  • Epidural pain relief is usually given for 3–5 days and helps the mobilization of the patient.
  • The patient often has a naso-gastric tube for the first 24 hours.
  • The patient may drink as soon as he/she would like to.

Possible serious complications are often due to:

  • Failure in one or more anastomoses
  • Abscess and/or sepsis 
  • Bleeding

Less serious complications involve delayed gastric emptying. Thus, long-lasting delay of stomach emptying should raise the suspicion of an underlying intraabdominal complication.

The patient

After a complication-free postoperative stay, the patient is usually transferred to a local hospital after about 1 week and is discharged after 10–14 days.

When histology report from the surgical specimen is available, treatment with chemotherapy will be considered.

The patient is usually followed up by their primary care physician after treatment is completed.

After

  • Patients having stomach resections may develop vitamin B12 and iron deficiencies. Hemoglobin should be checked every 4 months and a B12 injection is recommended.
  • Exocrine insufficiency can occur. This is treated with pancreatic enzymes in tablet form.  
  • After a pancreatic resection, there is an increased risk for developing diabetes and the patient must be informed about the initial symptoms of diabetes mellitus.
Whipples Procedure

Distal pancreatectomy (body and tail)

General

For cancer in the body or tail of the pancreas, a pancreatectomy can cure the disease. In a distal pancreatectomy, the spleen is also removed. 

Distal pancreatectomies at Oslo University Hospital, Rikshospitalet, are usually performed by a laparoscopic technique.

Indications

  • Detection or suspicion of cancer in the body or tail of the pancreas where there is no evidence of advanced cancer (metastasis or invasion of blood vessels). 
  • Precancerous conditions 

Goal

  • Cure the disease

Equipment

  • Laparoscopy rack
  • Ultrasound probe
  • Electrosurgical equipment (LigaSure®) or ultrasound scalpel (AutoSonix®, Harmonic® or SonoSurge®)
  • Laparatomy tray and possibly a vascular tray for the operating room
  • Preparation

  • Thrombosis prophylaxis
  • The patient lies in the supine position with their left side raised about 30°
  • The procedure is carried out under general anesthesia
  • Implementation

    • The first trocar (12 mm) is placed in the umbilicus. A total of 4 ports are routinely used. The last three are placed through the abdominal wall in an arc around the area of the tumor.
    • The left colon flexur is mobilized medially and the omental bursa is opened to expose the anterior distal end of the pancreas. For sufficient exposure, the stomach is mobilized medially and the transverse colon caudally, in order for the short gastric vessels between the speen and stomach as well as the gastrocolic ligament to be divided. 
    • Peroperative ultrasound is used to precisely localize the tumor.
    • The splenic artery and vein are dissected from the pancreas proximal to the tumor. The vessels are dissected to the origin of the splenic artery. The vessels are then split with a linear vessel stapler (artery before vein). In cases where the tumor invades toward neighboring organs - if there are no other contraindications - an èn-bloc resection of the infiltrated organs (adrenal gland, kidney, partial resection of colon and stomach) can be performed.
    • After resection the specimen is placed in an endocatch bag and pulled out in an extended umbilical incision.
    • Finally, a drain is installed near the incision on the pancreas, before closing the abdomen.

    Follow-up

    • The most common complication is leakage from the remainder of the pancreas. This is monitored by measuring amylase from the drain. A fistula is a complication which occurs when there is lasting production of larger fluid volumes with high levels of amylase from the drain. These usually close spontaneously over time (weeks to months). In some cases, the fluid production from the fistula can be reduced with octreotide analog drugs.
    • In uncomplicated cases, the patient may return home after about 5 days. If a fistula forms, the patient may return home with a drain installed.
    • The sutures are removed 2 weeks after the operation. 
    • Exocrine insufficiency can occur. This is treated with pancreatic enzymes in tablet form. In certain cases where large parts of the pancreas are removed, there is a small risk for developing diabetes. In this case, the patient will be dependent on insulin. 

    Further follow-up is determined based on the histology.

    Treatment of jaundice

    General

    Generally, only jaundice which causes symptoms is treated. Itching which is not relieved by antihistamines and socially unacceptable jaundice are indications for treatment. Patients with long-lasting jaundice should receive potassium to reduce the risk for bleeding disturbances. This should be administered parentally due to poor intestinal uptake. 

    Endoscopic drainage

    Drainage of the bile ducts with a stent using endoscopy is the primary option. Compared to open surgery, this procedure has low acute morbidity, but cholangitis and recurrence of jaundice is more common than after surgical anastomosis. The total morbidity throughout the entire disease period should therefore not be underestimated. Plastic endo-prostheses are usually changed after 3 months due to deposition of bile salts, which can obstruct the stent and cause recurrence of jaundice. An alternative is to install a self-expanding metal stent for patients with a longer survival.

    Percutaneous transhepatic drainage

    Percutaneous transhepatic drainage combined with external/internal transhepatic drainage is reserved for patients where the endoscopic technique is unsuccessful. PTC treatment is painful for the patient and is often carried out under sedation and analgesia, or possibly under general anesthesia. In addition, there is a risk for both bleeding and sepsis. This technique should therefore be secondary to the ERCP technique. 

    Surgical drainage

    Surgical enterobiliar anastomosis has a higher treatment mortality and morbidity than an endoscopic tent but usually remains open for the patient`s remaining survival time. A cholecystojejunostomy can be performed if the cystic duct is well expanded and opens sufficiently into the bile duct with a safe distance from the tumor. A choledochal duodenostomy gives successful results if the tumor does not grow too high into the hepatoduodenal ligament. Alternatively, an anastomosis can be made between the common hepatic duct and either the duodenum or a jejunal Roux loop.  

    Exploration is not recommended if only installing an enterbiliary anastomosis. In these cases, endoscopic or percutaneous drainage should be performed instead. If a non-resectable tumor is found by laparotomy, surgical by-pass is recommended as routine treatment.

    Treatment of gastric retention

    General Information

    Gastric and/or duodenal retention can occur due to: 

    • tumor-compression of the duodenum
    • development of stricture caused by infiltration from tumor
    • duodenal stenosis 
    • reduced motility

    To relieve an identified anatomical obstruction in the stomach/duodenum, an operation with gastro-entero-anastomosis is an option. An operation involving gastro-enterostoma relief can be performed laparoscopically. 

    Endoscopically installed self-expanding metal stents may be an option for patients with advanced disease.

    The functional outcome is not always satisfactory, patients may have nausea and vomiting caused by metabolic factors associated with tumor disease. Indications for surgery must be weighed against life expectancy without surgery.

    It is not proven that parenteral nutrition provides better tumor treatment effect or generally increases the quality of life or life expectancy in patients.

    Due to nausea and anorexia, enteral tube feeding can be useful for some patients, although many may find the tube troublesome. 

    Different nutritional supplements and vitamins can be seen as beneficial by many patients and relatives, but there is no proven efficacy in studies. Recently, it is shown that some omega-3 polyunsaturated fatty acids, especially eicosapentaenoic acid, increases the effect of oral nutrition supplements, and may be given a place in supporting the treatment.

    Drug therapy of pancreatic cancer

    Adjuvant treatment

    The purpose of adjuvant treatment is to prevent or prolong time to recurrence after pancreatectomy for pancreatic cancer. Patients who are operated radically for pancreatic cancer, and where there is no sign of disseminated cancer, may be candidates for adjuvant treatment.

    The treatment consists of 6 months of Nordic FLv which is administered every other week for 13 treatments.

    The patient should be under 75 years and have a general health status equivalent to ECOG 0–1 or Karnofsky 70 or better. Nordic FLv is generally a mildly toxic regimen, but the toxicity must be continually assessed during the treatment period since, based on experience, these patients do not tolerate chemotherapy well.

    Tumor-directed palliation

    5-FU has been the reference treatment in randomized studies for andvanced pancreatic cancer. From the end of the 1990's, gemcitabine has been the first-line choice for advanced cancer is some countries including the USA and Germany.

    In Norway, gemcitabine is recommended to certain patients with non-resectable pancreatic cancer. 

    • The dose is 1000 mg/m2 body surface and is given once a week by intravenous infusion. 

    • The first cycle consists of 7 weeks of treatment followed by a 1 week break.

    • Thereafter, 4-week cycles are administered with 3 treatment weeks and a 1 week break.

    The dose is adjusted according to the degree of bone marrow suppression, as well as creatinine and liver tests.

    The side effect is primarily vomiting lasting for a few days after the infusion. This can be relieved by serotonin-receptor antagonists and glucocorticosteroids. A small portion of these patients lose their hair after long-term treatment and some have temporary influenza-like symptoms. If the patient is clinically stable, a CT scan should be done every 3 months for objective assessment of the tumor effect. For tumor progression or worsened general health condition, chemotherapy should be stopped, which should be discussed with the patient before starting treatment. For a stable tumor disease, the treatment should continue until the disease symptoms are suppressed.

    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 pancreatic cancer

    It is recommened that the patient does not receive adjuvant radiation treatment either with or without concomitant chemotherapy.

    This also applies to patients who have resection margins which are not free of microscopic cancer, or have metastasis to regional lymph nodes.

    Complication treatment of pancreatic cancer

    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

    Celiac Plexus Neurolysis

    General

    Neurolytic procedures can produce long-term blocking by destroying nerve tissue. This kind of nerve blockage lasts until the nerves regenerate. Pain is not only conducted by the afferent and sensory nerve fibers, but also the sympathetic nerve system. Most neurolysis procedures are directed toward the sympathetic nerve structures.

    Today, by means of CT guidance, the neurolytic drug can be injected with high precision with a minimal risk of exposing the surrounding structures to the neurolytic chemicals. CT guidance also provides for a better possibility for optimal placement of the needle in cases where tumor masses have changed the normal anatomical conditions of the retroperitoneal room. The procedure is performed in cooperation with interventional radiologists.

    Invasive techniques still play an important role in treating cancer pain in a correct selected group of patients. The quality of the blockages increases when the procedure is guided by imaging and with the help of an interventional radiologist. Neurolytic blockades should never be considered an isolated treatment form, but as part of a broader treatment strategy, where one of the goals is to reduce the need of strong opioids and other analgesic.

    Celiac plexus neurolysis is the most common neurolytic blockage for patients with pain associated with cancer. It has been shown that patients with pancreatic cancer can obtain significant pain relief from a single (sympathetic nerve) blockade for the remainder of their life, on condition that distribution to sympathetic nerves are satisfactory.

    Access to the celiac plexus is reached by:

    • Posterior antecrural or retrocrural access. May be done with C-bow, but preferably CT.
    • Endoscopic ultrasound-guided access (via gastroscopy with ultrasound.)
    • Open abdominal.  Neurolysis can be performed preoperatively (in connection to exploratory laparotomy.)

    Indications

    Pain, often deep, diffuse and localized to the upper abdomen with radiating pain to the back. This treatment is primarily for patients with pancreatic cancer, but also those with malignant tumors in the upper abdomen, suffering from visceral pain, may benefit from this blockage.

    Refractory nausea for the same patient group.

    Neurolysis of the celiac plexus (sympathetic nerves) may be appropriate for different cancer types in the upper abdomen, but is mostly utilized for pancreatic cancer. Visceral pain is the one that can be alleviated by this blockade. Sensory and sympathetic nerve fibers from all organs in the upper part of the abdominal cavity, including bowel up to and including proximal part of colon, goes through the celiac plexus.

    Goals

    Improved pain control and reduced side effects from opioid pain relievers due to dosage reduction.



    Equipment

    • Needles (22 G) and equipment for local anesthesia.
    • Contrast medium to confirm correct position before the neurolysis.
    • Local skin anesthetic also for testing effect ahead of the neurolysis.
    • Alcohol, concentration minimum 50%.
    • Intensive care with vital signs (pulse rate, blood pressure, EKG and SaO2).
    • Medications for sedation and pain relief.

    Preparation

    • Blood tests: INR, thrombocytes and  hematological tests, leukocytes, CRP, electrolytes and kidney function.
    • Agreement for possible cessation of anticoagulants and antiplatelet agents is made individually.
    • Any fasting ahead is agreed individually for each patient. Some sedation is common in addition to local anesthesia. If the patient requires deep sedation/sleep, fasting for 6 hours before the procedure is necessary.
    • Prone, supine, or lateral position. Anterior access is primarily used when the patient cannot lie on their abdomen or the lateral decubitus position or when anatomical conditions do not allow posterior access.

    Implementation

    The celiac plexus (sympathetic nerve fibers) lies retroperitoneal at the level of the L1 vertebra. The fibers are arranged as a network in front of the aorta and around the celiac trunk.

    • With the patient in the prone or lateral position, the needle is inserted at level of the T12 and L1 vertebrae using local anesthesia.
    • The direction of the needle is guided by CT. The needle is guided a few cm to the side of the midline on each side of the spine with the tip close to both sides of the aorta.
    • After a test dose of  local anesthesia, and confirmation of correct position by injection of contrast medium, 75-95% alcohol is injected, 20-30 ml on each side.
    • In some cases it may be difficult to achieve good dispersion of the neurolysis because of tumor masses filling up the retroperitoneal space. In such cases the blockade may be inserted  retrocrurally, also at level of the T12 and L1, but with less volume. The effect is then substantially as a result of blockade of the splanchnic nerves proximally to the celiac plexus.

    Follow-up

    Complications can occur but are uncommon.

    • Temporary side effects in the form of orthostatic hypotension and diarrhea are relatively common the first 24-48 hours.
    • Back pain, usually in the form of soreness for 2-4 days is experienced by some.
    • Retroperitoneal bleeding, aortic dissection and paraplegia are very rare, but have been reported.
    Celiac plexus neurolysisCeliac plexus neurolysisCeliac plexus neurolysis

    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.

    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.

    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.

    Smoking cessation in connection with cancer treatment

    General

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

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

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

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

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

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

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

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


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

     

    Indication

    Weaning of nicotine in connection to cancer treatment. 

    Goal

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

    Preparation

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

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

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

    Implementation

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

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

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

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

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

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

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

    Treatment with nicotine replacement therapy

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

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

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

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

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

    Side effects

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

    Precautions

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

    Treatment with non-nicotine medications

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

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

    Side effects

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

    Precautions

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

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

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

    Side effects

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

    Precations

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

    Follow-up

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

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

    References

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

    Follow-up care after treatment of pancreatic cancer

    Follow-up care should be adapted for each individual patient based on the disease development.

    After a surgical procedure, the patient will be offered a consultation with the surgeon when the histology result is available. Further follow-up is performed every 3-4 months with the patient's general practitioner. A clinical examination should be done as well as blood tests.

    After a Whipple procedure, many patients will need an injection of vitamin B12 .

    For a total pancreatectomy, the patient should have a consultation with a diabetologist/endocrinologist because of the high risk for insulin overdose. Blood sugar should be held somewhat higher than for other diabetics. For an increasing problem with blood sugar regulation, recurrence should be suspected, unless an infection is present.

    Adjuvant treatment should be completed and followed-up at a local hospital.

    Inoperable patients are referred to a local hospital for palliative chemotherapy and follow-up care.

     

    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