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Utskriftsdato (29.6.2017)

Cancer spreading in the peritoneum

Cancer spreading in the peritoneum, known as peritoneal carcinomatosis or peritoneal metastases, is the general term for spreading of tumor cells in the peritoneum often originating from other organs in the abdominal cavity. Spread may also occur when a tumor grows through an organ reaching the surface of the peritoneum. Free cancer cells can implant into different areas of the peritoneum.

The peritoneum is a thin membrane consisting of two layers:Peritoneum cancer, ill.

  • a peritoneal layer which lines the abdominal cavity
  • a visceral layer which wraps around the internal organs in the intraperitoneal cavity

The narrow space between these two layers is filled with a thin fluid keeping the peritoneum moist to allow the two layers to glide freely. Double layer of peritoneum is known as mesentery which houses organs. 

The most common point of origin for peritoneal cancer is the appendix and the colon for both males and females, as well as the gynecologic organs in women.
However, any tumors in the abdominal cavity can cause peritoneal carcinomatosis. Pseudomyxoma peritonei (PMP) is a malignant condition in the appendix characterized by mucinous ascites and peritoneal, mucinous implantations. Mesothelioma is tumor originating from mesothelial cells that lines body cavities.The most common origin is the pleural cavity, but tumor may also originate from the peritoneal cavity.

Incidence

About 5-8 % of patients with primary colon cancer and 2% of patients with rectal cancer have carcinomatosis at the time of diagnosis. Several patients have peritoneal metastases at the time of recurrence. In about half of patients with peritoneal carcinomatosis, there is also distant metastases, which makes it complicated  to cure the disease.

There are about 20 new cases of pseudomyxoma peritonei per year in Norway. (3-4/million/year). Diffuse malignant peritoneal mesothelioma (DMPM) makes up 1/4 of all mesothelioma.

Etiology of cancer spreading in the peritoneum

Cancer in the peritoneum is the result of tumor cells that grow through and into the peritoneum from a primary tumor.

If cancer cells reach the abdominal cavity, they have the ability to implant, create their own blood supply (angiogenesis) and continue to divide enough so that large areas of the abdominal cavity are being affected.

Risk factors

Asbestos exposure may pose a risk factor for mesotheliomas.

Histology of cancer spreading in the peritoneum

Metastasis from carcinoma of the colon or rectum

One can often find infiltrative growth and sometimes also central gland metastasis or metastasis to intra- or extra-abdominal organs, especially to liver and lungs. If tumor produces mucus (mucinous adenocarsinoma), the peritoneal spread is similar to peritoneal mucinous carcinomatosis (PMCA) as seen in pseudomyxoma peritonei.

Carcinomatosis from colon cancer. Click to enlarge. Metastatic mucus-producing andenocarcinoma. Click to enlarge. Metastatic adenocarcinoma of the colon, not mucus-producing. Click to enlarge.

Pseudomyxoma peritonei

Immunohistochemical and molecular genetic studies have shown that pseudomyxoma peritonei usually originate from tumors in the appendix and not from tumors in the ovary. This condition is usually due to low-grade tumors in the appendix, either cystadenoma with atypia or a low-grade mucus-producing adenocarcinoma. 

Appendix with a primary lesion in pseudomyxoma peritonei and a lot of mucinous material in the abdomen. Click to enlarge.

At the histological examination, the amount of atypical cells in relation to the amount of mucus should be considered, as well as cellular atypia, amount of glandular structures and amount of signet ring cells.

Pseudomyxoma peritonei differs from other types of metastatic mucus-producing carcinomas by the fact that the tumor cells do not infiltrate the peritoneal and omental tissue, but rather dissects into the tissue. Only the most malignant types infiltrate into deeper organs or produce lymph node metastases.

There is a classification into three subgroups based on the histological appearance as follows:

  • Disseminated peritoneal adenomucinosis (DPAM) - abundant mucus, sparse epthelium with slight or no atypia, a few mitotic figures and orginating from a cystadenoma.
  • Peritoneal mucinous carcinomatosis, intermediate type (PMCA- I/D) – predominantly DPAM with focal proliferating epithelium with moderate atypia, mitotic figures and originating from a cystadenoma or adenocarcinoma.
  • Peritoneal mucinous carcinomatosis (PMCA) – severe atypical epithelium/signet ring and originating from an adenocarcinoma. Infiltration and lymph node metastasis occurs.

Others combine PMCA-I/D with PMCA into a two-grade system. The grading is not included in WHO classification of intestinal tumors. WHO describe pseudomyxoma peritonei as a condition most probably caused by spreading from a low-grade adenocarcinoma.

Mesothelioma

This tumor does not produce mucus and infiltrates and spreads diffusely into the peritonal cavity. The main differential diagnosis is metastasis from adenocarcinoma. Immunohistochemical investigation can usually establish mesothelioma diagnosis using a few antibodies. In a few occasions there are lymph node metastasis in the cardiophrenic angle in the thoracic cavity.

Malignant mesothelioma in the peritoneum. Click to enlarge. Malignant mesothelioma growing on the colon. Click to enlarge.

 

Metastatic patterns of cancer spreading in the peritoneum

The distribution of cancer cells in the abdominal cavity is partly influenced by gravity and partly follows the current of the peritoneal fluid.

  • Gravity creates an accumulation of cells in the pelvis with growth on the peritoneum in the transition fold in colon/uterus/ovaries/bladder. Additionally the gravity brings tumorcells to both flanks which is the lowest point in lying position.
  • The peritoneal fluid is reabsorbed at the diaphragm and the large and small omentums . The accumulated cells under the diaphragm attach easily to the liver, gallbladder, and surface of the spleen . Tumor in the small omentum often grows on the gastric antrum.

Malignant cells of high and moderate differentiation attach themselves to the mobile small intestine usually only in an advanced stage . In more malignant cases, larger parts of the small intestine are affected. The same occurs if adhesions of intestinal loops (for instance after previous surgery) causes less possibility of movement for the intestine.

The thickness of the peritoneum may in different areas vary from microscopic to thick layers of several centimeters.

  • In DPAM (disseminated peritoneal adenomucinosis), the tumor grows on the peritoneum without infiltrating the underlying tissue and the peritoneum is separated relatively easily when there is no pre-tumoral inflammation.
  • For diseases with infiltrating growth, (PMCA variant of pseudomyxoma, peritoneal carcinomatosis from colon and rectum and mesothelioma) the tumor along with the peritoneum attaches to underlying tissue, which must be resected together with the tumor.

Lymph nodes and distant metastases

  • Pseudomyxoma of an adenomatous type does not spread to lymph nodes or hematogenously.
  • Apparent benign mesothelioma may to some degree spread to lymph nodes or hematogenously. In more malignant types, lymph node involvement in the thorax (cardiophrenic angle) is common.
  • The more malignant a tumor appears to be, the larger the tendency for spreading to lymph nodes and other organs. Synchronous metastases to liver or lungs are more common in peritoneal colorectal cancer.

Staging of cancer spreading in the peritoneum

Classification of extensiveness/peritoneal cancer index (PCI)

Peritoneal cancer varies from nearly microscopic to kilogram scale interperitoneal tumor tissue. It is therefore important to have a classification system to compare studies from various treatment centers.

Sugarbaker's staging

The most common indication in extensiveness of surface for peritoneal disease is developed by Sugar Baker in the US around 1990.The abdomen is separated into 9 regions. The extent in each region is described based on the size of the lesion. The small intestine is separated in the same way into 4 regions. In each of the 13 areas, the size of the lesion is described in lesion score (LS), on a scale from 0 to 3. This is then calculated as Peritoneal Carcinomatosis Index (PCI), which is the sum of the lesion sizes from all 13 areas. PCI index will be a number between 0 and 39.

Regions and scoring used for calculating Peritoneal Carcinomatosis Index (PCI).

Classification of surgical result/degree of cytoreduction

There are multiple classification systems. Some systems indicate complete surgical radicality (R0) which is equivalent to removal of all visible tumor tissue. In another widely used classification system, the cytoreductive surgery is indicated as CC-0 if there is no residual tumor, CC-1 if the largest residual tumor is less than 2.5 mm, CC-2 between 2.5 mm-2.5 cm and CC-3 indicates larger residual lesions. The background for this staging is that chemotherapy will apparently diffuse 2-3 mm into the tissue. 
 

  

Symptoms of cancer spreading in the peritoneum

The clinical profile of pseudomyxoma peritonei is normally increasing abdominal circumference and confirmation of mucous in the abdominal cavity (jelly belly). But, disease history including appendicitis or mucous as coincidental finding are alternative forms of presentation.

Patient with advanced pseudomyxoma peritonei. Click to enlarge.

Distribution of mucous in the abdominal cavity is characteristic. Mucous and attached tumor are usually observed:

  • in the greater omentum
  • under the right diaphragm
  • in the paracolic gutters bilaterally
  • around the liver and gallbladder
  • in the abdominal cavity

With advanced disease, tumor is also seen under the left diaphragm, omental bursa and on the small intestine.

In mildly malignant tumors the characteristic symptoms are :

  • growth of the abdomen with uncharacteristic bloating or pain. In extreme cases, pressure in the diaphragm can cause incapacitating heavy breathing, and susceptibilty for complications such as aspiration pneumonia and deep vein thrombosis/lung embolism.
  • polyuria from pressure on the bladde.
  • iileus due to compression of segment of the intestines.
  • pain resembling the symptoms of appendicitis.
  • hernia with tumor due to intra-abdominal pressure caused by mucous volum.
  • metastases to the ovaries (often diagnosed as primary ovarian cancer).

Few, slightly atypical epithelial cells are often observed in the mucous, and often both ovaries are  involved. It was previously thought that tumor originated from the ovaries, but immunohistochemical examinations indicate that tumor in the ovaries is due to metastasis. For this reasjon tumor is often misinterpreted as low-grade ovarian cancer. The appendix is usually the origin, but other primary localizations have also been reported.

In women with peritoneal metastases, the ovaries are commonly affected. There may be significant tumor growth inside the ovaries or on the surface. For known colorectal cancer, there is more than 50% chance that an ovarian mass is a peritoneal metastasis.(6)

More malignant tumors have a tendency to debut with specific organ symptoms due to infiltration.

Differential diagnoses of cancer spreading in the peritoneum

  • Acute appendicitis
  • Other inflammatory conditions in the abdominal cavity
  • Other benign conditions
  • Malignant diseases that do not grow through the intestine wall and thus do not reach the peritoneum

Prognosis of cancer spreading in the peritoneum

Metastases from the colon and rectum

Median survival is usually 6 months if the carcinomatosis  is left untreated. Using modern chemotherapy, the limit may be moved to approximately 2 years for the median patient.

A French study compated CRS-HIPEC with systemic chemotherapy and palliative surgery with oxaliplatin and found a median survival of 23.9 months in the standard group and 62.7 months in the CRS-HIPEC group after complete cytoreductive surgery (CC-0). The equivalent 5-year survival is 13% and 51%. In the study, CRS-HIPEC achieved better results compared to modern chemotherapy (17).

Different centers set different limits for disease extent to accept patients for CRS-HIPEC (which was low in the French study). CRS-HIPEC has been found to be especially effective in patients with low tumor volume measured by PCI, with high or moderately differentiated tumors, and if a complete surgical cytoreduction was possible.

For peritoneal metastases from colorectal cancer (minus appendix) the national treatment results for CRS- HIPEC in Norway show a 5-year survival of 34% with long-term follow-up.(8).

Pseudomyxoma peritonei

The prognosis of pseudomyxoma is good. For carcinomatosis originating from colorectal cancer, CRS-HIPEC has shown promising results in a group with very short long -term survival. In those with limited or moderate carcinomatosis, extensive treatment has increased the survival rate up to 35-50%  of 5-year survival. (8,14, 21)

Significant factors for survival:

  • tumor differentiation, PCI, and grade of cytoreduction (15)
  • number of organ resections has not been found to implicate survival (16)
  • pseudomyxoma peritonei originating from the appendix

Disseminated peritoneal adenomucinous (DPAM)

About 85% 10-year survival after peritonectomy and intraperitoneal chemotherapy. The specific effect of HIPEC compared to other intraperitoneal chemotherapy is not clear. Also, early postoperative intraabdominal chemotherapy may be associated with good results.

Peritoneal mucinous carcinomatosis (PMCA) and peritoneal mucinous carcinomatosis, intermediary type (PMCA-I/D)

About 40% 10-year survival after peritonectomy and intraperitoneal chemotherapy. It is assumed that recurrence in the peritoneum after tumor that is benign in appearance can have malignant transformation over time.

In a study from Oslo University Hospital on cytoreductive surgery 1994-2009, the Norwegian treatment which was implemented in 1994, was assessed and  the results were equivalent to those from international cooperative centers.

If a mucus-filled and distended appendiceal mucoceles is diagnosed, the appendix should be removed without tearing it up to avoid mucus/cells leaking in the pelvis. If this extirpation is successful, and there are no signs of mucus or cells in the abdominal cavity, the patient shall be followed up conservatively and not referred further to CRS-HIPEC. By follow-up at local hospitals, CEA  should be controlled and CT abdomen/pelvis should be  performed after 1, 2, 4 and 6 years. If signs of clinical pseudomyxoma peritonei occurs, the patient should be referred to the national treatment service.

Mesothelioma

The prognosis is poor for the entire group, but there are subgroups which can be treated producing very good results. CRS-HIPEC has become the new treatment strategy. In a study from 8 institutions with together 405 patients given HIPEC (18), the median survival was 53 months with 47% calculated 5-year survival. Four prognostic factors for survival were found:

  • epithelial subtype
  • absence of nodal metastases
  • achievement of CC-0/1
  • performing HIPEC

References on cancer spreading in the peritoneum

  1. Ronnett BM, Shmookler BM, Sugarbaker PH, Kurman RJ. Pseudomyxoma peritonei: new concepts in diagnosis, origin, nomenclature, and relationship to mucinous borderline (low malignant potential) tumors of the ovary. Anat Pathol 1997; 2:197-226.
  2. Moran BJ, Meade B, Murphy E. Hyperthermic intraperitoneal chemotherapy and cytoreductive surgery for peritoneal carcinomatosis of colorectal origin: a novel treatment strategy with promising results in selected patients. Colorectal Dis 2006; 8(7):544-50.
  3. Moran BJ, Mukherjee A, Sexton R. Operability and early outcome in 100 consecutive laparotomies for peritoneal malignancy. Br J Surg 2006; 93(1):100-4.
  4. Mahteme H, von Heideman A, Grundmark B, Tholander B, Påhlman L, Glimelius B et al. Heterogeneous activity of cytotoxic drugs in patient samples of peritoneal carcinomatosis. Eur J Surg Oncol 2007; Jun 15; : 17574369
  5. Nasjonalt handlingsprogram med retningslinjer for diagnostikk, behandling og oppfølging av kreft i tykktarm og endetarm. IS-2283, feb 2015 (ISBN 978-82-8081-367-1)
  6. Evers DJ, Verwaal VJ. Indication for oophorectomy during cytoreduction for intraperitoneal metastatic spread of colorectal or appendiceal origin. Br J Surg. 2011 Feb;98(2):287-92.
  7. Carr NJ, Cecil TD, Mohammed F, Sobin LH, Sugarbaker PH, Gonzalez-Morene,S et al. A consensus for classification and pathologic reporting of pseudomyxoma peritonei and associated appendiceal neoplasia. Am J Surg Pathol 2016; 40:14-26.
  8. Froysnes IS1, Larsen SG1, Spasojevic M, Dueland S, Flatmark K.. Complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastasis in Norway: Prognostic factors and oncologic outcome in a national patient cohort. J Surg Oncol 2016;DOI 10.1002/jso.24290.
  9. Van Leeuwen BL, Graf W, Pahlman L, Mahteme H. Swedish Experience with Peritonectomy and HIPEC. HIPEC in Peritoneal Carcinomatosis. Ann Surg Oncol 2007; 12(5).
  10. Sugarbaker PH. Surgical treatment of peritoneal carcinomatosis: 1988 Du Pont lecture. Can J Surg 1989; 32(3):164-70.
  11. Sugarbaker PH. Peritonectomy procedures. Ann Surg 1995; 221:29-42.
  12. Sugarbaker PH, Chang D. Results of treatment of 385 patients with peritoneal surface spread of appendiceal malignancy. Ann Surg Oncol 1999; 6(8):727-31.
  13. Sugarbaker PH. A curative approach to peritoneal carcinomatosis from colorectal cancer. Semin Oncol 2005; 32(6 Suppl 9):S68-S73.
  14. Elias D, Bedard V, Bouzid T, Duvillard P, Kohneh-Sharhi N, Raynard B et al. Malignant peritoneal mesothelioma: treatment with maximal cytoreductive surgery plus intraperitoneal chemotherapy. Gastroenterol Clin Biol 2007; 31(10):784-8.
  15. Yan TD, Morris DL. Cytoreductive  surgery and perioperative intraperitoneal chemotherapy for isolated colorectal peritoneal carcinomatosis: Experimental therapy or standard of care? Ann Surg 2008; 248(5):829-835.
  16. Franco J et al. Multivisceral resection does not affect morbidity and survival after cytoreductive surgery and chemoperfusion for carcinomatosis from colorectal cancer.   Ann Surg Oncol 2008;15(11):3065-3072.
  17. Elias DJ et al. Coplete cytoreductive surgery plus intraperitoneal chemohyperthermia with oxaliplatin for peritoneal carcinomatosis of colorectal origin. Clin Oncol 2009;27(5):681-685.
  18. Yan TD et al. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for malignant peritoneal mesothelioma: Multi-institutial experience. J Clin Oncol 2009;27(36):6237-6242.
  19. L-OUS-033 Perfusjonskjemoterapi: Nasjonal behandlingstjeneste for hyperterm intraperitoneal kjemoterapi ved kolorektal kreft, pseudomyxoma peritonei og peritonealt mesoteliom).
  20. Sorensen O. Flatmark K, Dueland S, Giercksky K-E, Larsen SG.. Evaluation of complete cytoreductive surgery and two intraperitoneal chemotherapy techniques in pseudomyxoma peritonei. Eur J Surg Oncol. 2012 Oct;38(10):969-76.
  21. Mirnezami R, Mehta AM, Chandrakumaran K, Cecil T, Moran BJ, Carr N, Verwaal VJ, Mohamed F, Mirnezami AH. Cytoreductive surgery in combination with hyperthermic intraperitoneal chemotherapy improves survival in patients with colorectal peritoneal metastases compared with systemic chemotherapy alone. Br J Cancer. 2014 Oct 14;111(8):1500-8.
  22. Elias D, Lefevre JH, Chevalier J, Brouquet A, Marchal F, Classe JM et al. Complete cytoreductive surgery plus intraperitoneal chemohyperthermia with oxaliplatin for peritoneal carcinomatosis of colorectal origin. J Clin Oncol 2009;27:681-85.
  23. Verwaal VJ, Bruin S, Boot H, Van Slooten G, Van Tinteren H. 8-year follow-up of randomized trial: cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy in patients with peritoneal carcinomatosis of colorectal cancer. Ann Surg Oncol 2008;15:2426-2432.


Diagnostics of cancer spreading in the peritoneum

Clinical Examination

  • Clinical examination of abdomen
  • Rectal/vaginal exam

Blood tests

  • CEA - often raised in pseudomyxoma from the appendix, and in 50% with colorectal cancer
  • CA 19-9 - marker for peritoneal involvement
  • CA 125 - the levels of CEA and CA-125 (or HE4) should always be measured if ovarian tumor is suspected. Increased CEA for suspected ovarian cancer will in most cases be a metastasis from a primary tumor in the bowel.      
  • General parameters (renal function, liver function, Hb, white, thrombocytes)

Image diagnostics

  • CT of abdomen/pelvis for possible lymph node-/liver metastasis.
  • CT of thorax to exclude lung metastases.
  • PET scans have low sensitivity for mucinous tumors, but may be important to exclude central nodal metastases or distant metastases.

There is no non-invasive method to diagnose extensiveness of peritoneal spreading at a relatively early stage. All imaging techniques tend to underestimate the prevalence of disease extensiveness in the abdominal cavity. Examinations with imaging techniques are more effective for inspecting diseases within the organs, and less so for inspecting organs superficially.

Invasive diagnostics

  • Aspiration of ascites
    • Mucinous fluid without cells indicates adenomucinosis.
    • Serous fluid with tumor cells indicates peritoneal carcinomatosis.
    • Separated cancer cells can provide accurate diagnosis.
  • Laporoscopy is the best method to evaluate extent. The laparoscopy findings should describe extensivenss as precisely as possibly, especially in the small intestine. It is helpful the examination can be recorded. The method is of lesser value if there are prominent adherances. 
  • Biopsy is performed for assessment of malignancy grade.

Other investigations are performed depending on what organs are involved.

Treatment of cancer spreading in the peritoneum

Historically, the common treatment for spread to the abdominal cavity from different tumors has been systemic chemotherapy based on which organ the spread is originating from. In some cases the treatment has also been combined with surgery with varying degrees of removal of tumor tissue. If there is residual tumor tissue, the surgery is indicated as palliative. The goal of these treatments is increased lifespan and improved quality of life.

In recent years there have been a new treatment where the surgeon attemps to remove any visible residual tumor (maximal cytoreductive surgery (CRS)) followed by chemotherapy in the abdominal cavity at the end of surgery. The chemotherapy is heated and delivered over a short time (hyperthermic intraperitoneal chemotherapy (HIPEC)).

Different tumors can be treated, but particularly peritoneal carcinomatosis from pseudomyxoma peritonei, colorectal cancer and abdominal mesothelioma. Spread from ovarian cancer to the peritoneum is an increasing field internationally, but so far, few with this diagnosis have received treatment.

In Norway, CRS-HIPEC is since 2009 rooted as a national treatment service (19) related to the surgical ward at Oslo University Hospital. Norway is among the few countries that have national  guidelines ensuring equal treatment regardless of residency. The guidelines were created in cooperation with the Directorate of Health and Norwegian Gastrointestinal Cancer Group (NGICG) (5).

Radiation therapy is not administered for peritoneal carcinomatosis.

Surgery of cancer spreading in the peritoneum

At Oslo University Hospital in Norway, maximal cytoreductive surgery (CRS) has been performed since 1994 for pseudomyxoma peritonei. For cases of peritoneal carcinomatosis from colorectal cancer, CRS has been performed since 2005.

Since 2003 chemotherapy has been given as hyperthermic intraperitoneal chemotherapy (HIPEC). In 2016, 120 patients underwent surgery and HIPEC was performed in 80 of these patients. Oslo University Hospital is currently the national center for this multimodality treatment (19).

When detecting carcinomatosis during primary surgery of an abdominal tumor in local hospitals, it is essential to minimize the separation. Tumor tissue tends to adhere to fibrous adhesions and complicate final surgery. In Norway, these patients should be referred to Oslo University Hospital for maximal cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). For relevant patients, x rays and anamnesis is discussed and evaluated in a weekly specialist meeting involving radiologists, oncologists and surgeons.

PROSEDYRER

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC)

General

In principle all of the parietal peritoneum with visible tumor is resected. On the bowel, small tumor foci are carefully cauterized or excised. With more advanced involvement, the bowel segment is removed. Tumor tissue on the surface of the liver can be burned away or removed by capsulectomy.  A splenectomy is performed if there are tumors on the spleen. Peritoneum on the bladder can also be removed. The surgeon operates in one region at a time and removes all involved tissue. Normal peritoneum is usually not removed. Anastomosis is usually not carried out on the rectum due to the risk of leakage. A permanent or temporary colostomy may be necessary. After resection, HIPEC is performed and the abdomen is closed.

Resection of the peritoneum is often extensive surgery. The multimodality treatment is time consuming and duration of general anaesthesisa for 6-12 hours is customary, median time of surgery is 8 hours. With such comprehensive surgery, reoperations may be necessary due to complications such as infection, ileus or anastomotic leak. Approximately 10% are being reoperated after primary surgery.

Indication

Pseudomyxoma peritonei orginating from lesions in appendix

  • For possible treatment, normal intestinal sections must be present peroperatively.
  • Good general condition (ECOG 0-1). Patients with significant comorbidity and high age (> 75 year) are poor candidates.
  • The patient must be considered able to tolerate extensive surgery and subsequent chemotherapy with the drug applicable at the time.
  • There is not an upper limit of tumor extent for performing the surgery.

CRS-HIPEC for carcinomatosis from colorectal cancer

  • Confined stage IV colon/rectal cancer without Central lymph node metastases or systemic metastases.
  • Confined tumor spreading in an organ is acceptable in special situations.

The indications are the same as for pseudomyxoma from the appendix, with addition of:

  • The patient may have received first line chemotherapy at an earlier stage, but without any disease progression during ongoing chemotherapy.
  • The extent should be confined (PCI ≤ 20-25) with limited involvement of small intestine.
  • Histologically low-differentiated tumors or signet ring cell tumors have a very poor prognosis and are accepted only in exceptional cases.
  • It may be recommendable to perform second-look surgery 12 months after primary surgery in patients operated for localized carcinomatosis without HIPEC, or who had ovarian metastases at that time. Such patients are given 6 months of chemotherapy before 6 months of observation. Surgery may be appropriate if the extent of the disease is limited. Sometimes laparoscopy is performed to estimate the extent of the disease.  

CRS-HIPEC for carcinomatosis from abdominal mesotheliom

Indications are the same as for colon and rectal cancer. In addition must be excluded

  • whether the patient has mesothelioma in pleura with invasion to the abdominal cavity.
  • whether there is metastases to lymph nodes in the cardiophrenic angle of the thorax.

Goal

  • Curative treatment

 

Preparation

  • The patient is informed that a colostomy may be necessary. Its location is marked preoperatively on the skin.
  • Patients to have a resection with anastomosis in the rectum should have a thorough preoperative bowel preparation.
  • The patient is given a preoperative dose of low molecular weight heparin and support hose with inflatable cuffs for the lower extremities to reduce the risk of thrombosis.
  • Epidural catheter is placed for postoperative pain treatment.
  • A bladder catheter is inserted.
  • The patient lies supine with the legs in stirrups.
  • The operation is carried out under general anaesthesia.

Implementation

A few principles are demonstrated in the film.
  • The abdomen is opened with a long mid-line incision.
  • Extent of carcinomatosis is surveyed thoroughly.
  • It is assessed whether the cancer grows infiltratingly or only on the peritoneum. A frozen section may be helpful .

Maximal cytoreductive surgery (CRS) techniques

The procedure often starts with an omentectomi.Thereafter, a final surgery in the pelvis including a peritonectomy is often performed, along with a resection of rectum and genitalia interna if necessary. Any affected peritoneum in the flank is resected if necessary and the need for colon surgery is considered.The need for resection of the peritoneum at the diaphragm is then considered. On the right side it may be necessary to perform a cholecystectomy and resection of tissue on the surface of the liver and subhepatically. On the left side, the spleen sometimes must be removed and a gastrectomy may be necessary.

Hyperthermic intraperitoneal chemotherapy (HIPEC) techniques

  • A rubber drape is attached to the edges of the incision.
  • The heart-lung machine is assembled to administer the chemotherapy.
  • The rubber drape must be carefully attached to the skin around the entire circumference of the opening. Confirm there is no leakage of chemotherapy.
  • The lavage fluid is warmed until the abdominal fluid has a temperature > 40.0°C. When the system functions optimally, the gel port is fixed on the plastic surface and chemotherapy is added to the perfusion circuit.
  • The chemotherapy is administered for 90 minutes.
  • The abdominal cavity is then perfused with NaCl and the equipment is disassembled.
  • The abdomen is closed.

Follow-up

The average length of hospital stay after surgery is 11 days, but may be considerably longer for some patients.

Complications

  • Extensive operation with multiple resections as well as blood transfusion increase the danger for infections and anastomosis leakages. There is evidence that both intraperitoneal chemotherapy and hyperthermia may increase the risk for this. Reoperations may therefore be necessary in some cases.
  • In rare cases, HIPEC may cause neutropenia and thrombocytopenia.
  • Other complications can occur depending on which organs are removed.

Patients with widespread peritoneal surface malignancies or aggressive histology have a significant risk of recurrence. These patients are also at risk for distant metastases to the liver and lung.

PeritonectomyPeritonectomyCRS-HIPECCRS-HIPEC
PeritonectomyPeritonectomy

Stoma

General

Intestinal stoma is often required during treatment of rectal cancer and sometimes for colon cancer. The stoma is either permanent or temporary. Stoma is also constructed for temporary relief of distal anastomosis or ileus.

Permanent stoma is prepared when the rectum is removed or when there is an inoperable tumor or ileus due to extreme adherences. Preferably, it is placed as close to the anus as possible to provide the best possible reabsorption of nutrition and fluid.

The procedure may be performed by laparoscopy.

A stoma can have with one or two openings. The type of stoma depends on the purpose of the stoma and anatomical conditions in the abdomen.

End stoma 

The colon is divided and the oral end is brought out. The end stoma is easier to handle and is better looking than a loop stoma. The end stoma is usually performed for permanent stomas and for relief of fistulas.

Loop stoma 

The colon is not divided but is pulled out like a loop through the abdominal wall. An opening is made in the top of the loop. The stoma has two openings: one oral and one aboral. The stoma can be prepared in two ways:

  • symmetrical—an opening is made on the top of the extracted "backwards U." The ingoing and outgoing openings of the bowel looks similar. Symmetric loop stoma are usually performed for colostomy  .
  • asymmetrical—the oral part of the bowel is brought forward and empties easier into the bag while the aboral part of the bowel is at the skin level and the opening is small. Asymmetric loop stoma is usually created for an ileostomy .

Sigmoid colostomy 

Sigmoid colostomy is the most common form of colostomy. The stoma is installed if it is not technically possible or sensible to anastomose the colon to the rectum/anal canal. It is then constructed as a permanent end stoma. This is done in 15-30% of patients with rectal cancer.

Indications

Permanent:

  • for rectal amputation
  • to avoid permanent incontinence of poor anal sphincter function (Hartmann's operation)
  • to relieve an inoperable fistula anally from the stoma

Temporary:

  • for preoperative radiation
  • relief of rectal ileus

Sigmoid colostomies are easy to maintain. The stools usually has a normal consistency and causes little irritation to the skin.

Transverse colostomy 

The transverse colon is brought out in the right rectus muscle. This is a loop stoma and is often temporary. It is often difficult to maintain because the stoma is voluminous and the feces is thin and foul-smelling. This type of stoma is associated with more complications than a sigmoidostomy. As a temporary stoma it has similar frequency of complications as ileostomas.

There is a risk that the bowel content may pass into the distal opening with an incomplete relief of stools.

Indications

  • relieve stenosis in the left colon
  • relieve low anastomosis or rectum resection
  • allow rinsing of the left colon through the stoma in limited anastomosis leakage

Ileostomy

The ileum is brought out  20-30 cm from the cecum and preferably in the right rectus muscle as an asymmetrical loop stoma. It is relatively simple to construct but can be difficult to maintain due to thin fecal content. The longer nipple will help avoiding damage to the skin.

Indications

  • protect anastomoses after rectosigmoid resection
  • relieve bowel obstruction
  • relieve preoperative radiation of stenosis due to colorectal cancer
  • relieve fistula

Indications for stomas

  • Cancer in the rectum (rectum amputation, Hartmann)
  • Cancer in the colon

Goals

  • Facilitate output of bowel contents
  • Relieve the bowel/stenosis/fistula

Equipment

  • Laparotomy tray and possibly laparoscopy equipment.
  • A device to place under the loop.

Preparation

The patient should be prepared for:
  • anatomical and physiological changes following the operation
  • what a stoma involves
  • stoma equipment and how it functions
  • the stoma is edematous the first weeks after the operation and that it will normalize

Stoma marking

The patient is informed of the purpose of the stoma marking. The goal is to find appropriate placement in order for the patient to maintain the stoma.

It is important to see the patient, lying, sitting, standing, and during movement. By seeing the abdomen in different positions, the abdomen's shape is emphasized such that individual considerations are taken during marking. The patient should be able to address their own wishes and desires.

Factors influencing the location

  • the stoma should be visible to the patient.
  • the stoma should be placed within the rectus muscle
  • the stoma disc and stoma should not come in conflict with skin folds, groin, hollow areas, iliac crest, scars, hernias, the navel, or straps for prosthesis or binder
  • the stoma should not hamper the clothing
  • choice of stoma type

Marking:

  • The rectus muscle is identified on the side where the stoma will be placed
  • The appropriate stoma location is adjusted by using a piece of tape which is moved about on the abdomen when the patient lies down, sits, and stands.
  • The patient must be offered to walk with the disc and bag to check that the stoma marking is optimal.
  • Final marking for placement is done with a waterproof marker.

Implementation

  • When the stoma is not brought out through the abdominal inscision but through a separate hole in the abdominal wall it will be easier to handle. For transversostomy: an incision is made in the right rectus muscle and the omentum is dissected off the attachment to the relevant part of the colon. It may be difficult to obtain sufficient length of the bowel without damaging the vessel supply if the abdominal wall is thick. For an ileostomy, this is more simple.
  • The least amount of skin is removed if the stoma is not brought out through the abdominal inscision.
  • The bowel is pulled out as a backwards "U" and is not divided.
  • The bowel is sutured to the peritoneum.
  • The bowel is sutured to the anterior fascia.
  • A tube or skin bridge is placed under the loop at the skin level to prevent the bowel from retracting.
  • The bowel lumen is opened at the top and the bowel wall is everted and sutured to the skin.
  • For a section in the right rectus chain, the stoma is placed out through a separate incision to facilitate stoma hygiene.
  • Colostomy should preferably be pulled 1-2 cm out over the skin level. Ileostomy: 2-3 cm.

End sigmoid colostomy:

  • A mid-line incision to the right of the navel is made.
  • The bowel is divided with a closing-dividing stapler.
  • The bowel is mobilized by adequate division of the vessels without damaging the vessel archade to permit the bowel to be pulled out through the skin without tightening.
  • In the abdominal wall, the peritoneum and posterior fascia leaf are split.
  • The musculature is split length-wise and as much as necessary transversally.
  • The anterior fascia leaf is split in a cross.
  • A skin cylinder with underlying fatty tissue is removed up to the fascia.
  • The extracted bowel opening is sutured to the fascia and everted with sutures  in the bowel tube, mucosa  and skin.

Follow-up

The very first stoma changes after an operation should be performed on the third postoperative day. If the stoma bandage leaks, this must be changed earlier. The change should be carried out by a stoma nurse/nurse while the patient is in the supine position. The stoma is observed for possible infection, necrotizing mucosa or abdominal wall, loosening of sutures, and for leakage of air and bowel content. Bag inflation is a signs of bowel activity. It is appropriate to use a colorless, drainable bag in the first period since the bowel content is thinner in the beginning. If a bag with a filter is used, the filter should be covered.

As soon as the patient is ready for it, the patient is trained for stoma changing/cleaning. Training should occur daily until the patient has mastered it.

Transverse colostomies and ileostomies can be closed after about six weeks. For closing of ileostomy, there is a higher chance of postoperative ileus and possibly also for bowel leakage than with colostomy.

For Hartmann's operation, the goal in some instances is to perform a re-anastomosis of the bowels and to avoid permanent stoma.

Complications of stoma

Early

  • Infection in the subcutaneous tissues occurs relatively often and more commonly with obesity.
  • Necrotizing of mucosa or the entire abdominal wall occurs more frequently in patients with a thick subcutaneous fat layer.
  • Loosening of eversion sutures along the edge occurs relatively frequently.
  • Retraction of stoma to the skin level or under occurs relatively rarely, but more frequently for loop colostomy. Retraction can cause overflow to the disconnected bowel. This is especially unfortunate in fistula relief.
  • Colo-cutaneous/ileo-cutaneous fistulas occur rarely.

Delayed

  • Peristomal hernia is a complication where the stoma bulges out like lump on the skin. This can make attachment of the stoma bag more difficult and the stoma may have to be moved.
  • Stenosis in the stoma opening occurs relatively rarely. It occurs if the bowel opening is not adequately inverted or if the tip of the stoma necrotizes down to or under the skin level.
  • Retraction of the stoma down to or under the skin level occurs relatively rarely.
  • Prolapse of stoma is a relatively rare complication where the bowel turns itself 10 cm or more out through the stoma opening. This happens most often in transverse colostomy stomas. The herniation can cause increased pressure to the bowel vessels through the abdominal wall and possible cause bowel necrosis. This complication can be treated conservatively but may relapse.
Stoma placementStoma placementStoma placementStoma placement
Stoma placementStoma placementStoma placement

Drug therapy of cancer spreading in the peritoneum

Systemic chemotherapy has little effect on mucinous masses in the abdomen. Patients who cannot undergo cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC), or those with inoperable recurrence may still be candidates for systemic chemotherapy.

Intraoperative chemotherapy

If maximal cytoreduction (CC 0-1) is achieved, hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) may be given as direct continuation of the operation. This extends the time of surgery with three hours. By administering chemotherapy intraperitoneally, the concentration of the rinse fluid can be increased as opposed to intravenous administration. To enhance the effect of chemotherapy, the solution in the peritoneum maintained at 41,5–42.0°C.

Pseudomyxoma peritonei from appendix and carcinomatosis from colon and rectum 

  • At Oslo University Hospital, mitomycin C is currently used and is dosed based on body surface:35 mg/m², max 70 mg.
  • 50% of the dose is added to the lavage fluid when the correct intraabdominal temperature is reached, thereafter 25% after 30 minutes, and the remaining 25% after 60 minutes.
  • The perfusion is stopped after 90 minutes. The abdominal cavity is rinsed, the abdomen is closed and the patient is awakened.

Carcinomatosis from abdominal mesothelioma

  • At the Oslo University Hospital, cisplatin is used currently and is dosed based on body surface, 50 mg/m², max 100 mg and doxorubicin 15 mg/m², max 30 mg.
  • 50% of the dose is added to the perfusion circuit when the correct intraabdominal temperature is reached, thereafter 25% after 30 minutes, and the remaining 25% after 60 minutes.
  • The perfusion is stopped after 90 minutes.The abdominal cavity is rinsed, the abdomen is closed and the patient is awakened.

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


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  4. Liffrig, JR. Phototrauma prevention. Wilderness Environ Med 2001;12:195-200.
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  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
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  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 cancer spreading in the peritoneum

Radiation therapy is not administered for peritoneal carcinomatosis.

Complication treatment for spread of cancer in the peritoneum

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

Support treatment is usually necessary in order for the patient to complete and obtain the full effect of planned treatment.

Support treatment may also be given to reduce side effects and raise the patient's quality of life during and after treatment.

PROSEDYRER

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.

Smoking cessation in connection with cancer treatment

General

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

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

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

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

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

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

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

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


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

 

Indication

Weaning of nicotine in connection to cancer treatment. 

Goal

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

Preparation

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

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

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

Implementation

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

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

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

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

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

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

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

Treatment with nicotine replacement therapy

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

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

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

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

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

Side effects

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

Precautions

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

Treatment with non-nicotine medications

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

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

Side effects

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

Precautions

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

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

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

Side effects

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

Precations

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

Follow-up

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

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

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Follow-up care after treatment of cancer spreading in the peritoneum

The first follow-ups are performed after 3 months.
  • Radically treated pseudomyxoma peritonei is evaluated yearly for 5 years, thereafter less frequently up to 10 years.
  • Adenocarcinomas/mesothelioma is evaluated every 3 months for the first year. Thereafter after 1½, 2, 3, 4 and 5 years, or until disease progression. The first follow-up takes place at the hospital where the treatment was performed, thereafter at local hospitals.

Checks consist of:

  • clinical examination of the abdomen
  • rectal/vaginal exploration
  • Hb, CEA, CA 19-9, CA-125, creatinine, ALP
  • CT abdomen/pelvis
  • CT thorax/abdomen/pelvis
  • other examinations as needed
Patients with pseudomyxoma peritonei are usually followed-up at Oslo University Hospital.