- Email: [email protected]
Malignant Bowel Obstruction in Advanced Cancer
Malignant Bowel Ob s tr u ct io n in Ad v an ced Cancer Douglas J. Koo, MD, MPHa,*, Tabitha N. Goring, Kerry-Ann Pinard, BSb, Barbara C. Egan, MDa
MD
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KEYWORDS Malignant bowel obstruction Small bowel obstruction Advanced cancer Prognosis Palliative surgery Total parenteral nutrition
HOSPITAL MEDICINE CLINICS CHECKLIST
1. Malignant bowel obstruction (MBO) is a bowel obstruction distal to the ligament of Treitz in a patient with an intra-abdominal primary cancer with incurable disease or a non–intra-abdominal primary cancer with clear intraperitoneal disease. 2. Patients with advanced ovarian or colorectal cancers have the highest prevalence of MBO. 3. Presenting symptoms may include nausea, vomiting, abdominal pain, or obstipation, whereas the most common physical examination finding is abdominal distention. 4. Laboratory tests should focus on monitoring the metabolic and electrolyte derangements that occur. 5. Computed tomography scan is the current standard for radiographic diagnosis. 6. Prognosis in MBO is generally poor, with median survival depending highly on performance status. 7. There is no consensus regarding the optimal treatment strategy and no evidence supports palliative surgery rather than medical management for improving quality of life or prolonging survival. CONTINUED
Disclosure: The authors have nothing to disclose. a Hospital Medicine Service, Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, 1275 York Avenue, MB 438, New York, NY 10065, USA; b Columbia University College of Physicians and Surgeons, 630 West 168th Street, New York, NY 10032, USA * Corresponding author. 1275 York Avenue, MB 438, New York, NY 10065. E-mail address: [email protected] Hosp Med Clin 5 (2016) 413–424 http://dx.doi.org/10.1016/j.ehmc.2016.02.005 2211-5943/16/$ – see front matter Ó 2016 Elsevier Inc. All rights reserved.
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CONTINUED
8. The mainstays of pharmacologic treatment of inoperable MBO involve opiate analgesia, antiemetics, steroids, antisecretory medications, and intravenous hydration for palliative relief of symptoms. 9. Self-expanding metallic stents or percutaneous endoscopic gastrostomy may be palliative options for patients unable to undergo surgery. 10. Total parenteral nutrition should be discouraged in patients with end-stage disease but may be justified in a select group of patients.
DEFINITION
What is the definition of malignant bowel obstruction (MBO)? MBO was defined by the International Conference on Malignant Bowel Obstruction in 2007 as a condition that fits the following criteria1: Clinical evidence of a bowel obstruction obtained via history, physical examination, or radiography Bowel obstruction distal to the ligament of Treitz Either an intra-abdominal primary cancer with incurable disease or a non–intraabdominal primary cancer with clear intraperitoneal disease EPIDEMIOLOGY
What is the prevalence of MBO in advanced cancer? The prevalence of MBO in advanced cancer is shown in Table 1. PATHOPHYSIOLOGY
What is the mechanism of bowel obstruction? I. Partial or complete bowel blockage Mechanical occlusion: Intraluminal – tumor within the bowel Extraluminal: primary tumor or metastases, adhesion, mesenteric and/or omental tumor, postirradiation fibrosis Table 1 Prevalence of MBO in various cancer types Cancer Type
Prevalence (%)
Ovarian
20–50
Colorectal
10–28
Stomach
6–19
Pancreas
6–13
Bladder
3–10
Extra-abdominal cancers (most often breast and melanoma) Data from Refs.
1–4
2–3
Malignant Bowel Obstruction in Advanced Cancer
II. III. IV. V. VI.
Intramural: including intestinal linitis plastica or tumor Functional obstruction: Motility disorder from tumor involvement of the enteric nervous system or celiac plexus, or paraneoplastic syndrome Increased stasis of luminal contents leading to distention and subsequent damage of bowel wall Increased inflammation, release of prostaglandins and vasoactive peptide Decreased reabsorption of electrolytes and H2O in the bowel Increased bowel edema, hyperemia, and contraction Abdominal pains, cramping, nausea, and vomiting3
What are the differences between proximal small bowel and distal large bowel obstructions? Proximal obstructions present acutely with pain of an intermittent periumbilical nature, vomiting, and with or without abdominal distention. However, more distal obstructions tend to present later with pain of a deeper, localized, and more continuous nature, with abdominal distention and vomiting sometimes being absent.3 DIAGNOSIS
What are the presenting symptoms of malignant small bowel obstruction? Nausea caused by distention and subsequent activation of mechanoreceptors Intermittent or continuous vomiting as a result of nausea or independent of other symptoms Abdominal pain that is continuous (90% of patients) or colicky (75% of patients), periumbilical, and that may increase with palpation Obstipation: complete absence of flatus or feces is suggestive of complete obstruction, whereas paradoxic diarrhea/incontinence is suggestive of a partial obstruction5–7 What are typical physical examination findings of small bowel obstruction? The most frequently encountered physical examination finding is abdominal distention caused by buildup of swallowed air, bacterial fermentation, intraluminal gas, and stasis of luminal contents. With partial obstruction, high-pitched, tinkling, hyperactive bowel sounds can be heard. However, as the obstruction increases, bowel sounds may become hypoactive as abdominal distention progresses and movement of intraluminal contents is blocked. Abdominal tenderness may or may not be present.5 What laboratory tests should be ordered for patients with suspected MBO? A complete blood count with differential and a basic metabolic panel should be ordered for patients presenting with abdominal pain. Routine laboratory testing does not specifically reveal a diagnosis of MBO but should instead be used to monitor the metabolic and electrolyte derangements commonly associated with, or that signal complications of, obstruction, such as hypokalemia, hyponatremia, hypovolemia, and leukocytosis.
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Which imaging modalities should be used for diagnosis? Computed tomography (CT) scan has a sensitivity and specificity greater than 90% for high-grade obstruction and it is the current gold standard of bowel obstruction diagnosis. However, because of its accessibility and low cost, plain abdominal radiography is a good first diagnostic tool to identify high-grade bowel obstruction, although its sensitivity and specificity are lower than those of CT scans, being diagnostic in only 50% to 60% of cases.8 PROGNOSIS IN ADVANCED CANCER
What is the prognosis associated with the development of MBO? Survival after development of MBO is generally poor, with median survival reported to be 1 to 3 months.9 Large survival ranges have been reported; a subset of patients with MBO can benefit from chemotherapy and/or surgery and can survive for greater than 1 year. In an observational study of patients hospitalized with MBO, excluding patients with gynecologic malignancies, median survival was most strongly predicted by Eastern Cooperative Oncology Group (ECOG) performance status (PS) at the time of diagnosis of MBO, with results shown in Table 2. In addition, a low serum blood urea nitrogen level or a high albumin level at the time of presentation was also associated with prolonged survival.10 In another observational study of patients with nongynecologic malignancies and MBO, the median survival was 80 days, with a large range, from 7 to 873 days. Thirty-four percent of patients received surgical intervention, palliative systemic chemotherapy was given to 37% of patients, total parenteral nutrition (TPN) was administered to 43% of patients for a median of 13 days, and a venting gastrostomy tube was placed in 26% of patients. With respect to the incident admission, 74% of patients were discharged home, 17% died in the acute care setting, and 9% were transferred to a palliative care unit for terminal care. There was a cohort of patients (17%) who survived for greater than 1 year, and, again, ECOG PS was tightly linked to survival. Median survival was greater than 200 days for ECOG 0 to 1, 63 days for ECOG 2, 28 days for ECOG 3, and 7 days for ECOG 4. Median length of stay for the incident admission was 16 days, and readmission was common (58%).9 A large retrospective review of admissions for MBO inclusive of all cancer types revealed in-hospital mortalities of 21.4% to 24.5%. Factors that were associated with higher in-hospital mortality were male gender, surgical management, lack of insurance, and multiple comorbidities; specifically, liver disease, a history of weight loss, renal failure, congestive heart failure, and metastatic disease were all associated
Table 2 Median survival in MBO ECOG PS
Median Survival (d)
0–1
222
2
63
3–4
27
Data from Wright FC, Chakraborty A, Helyer L, et al. Predictors of survival in patients with noncurative stage IV cancer and malignant bowel obstruction. J Surg Oncol 2010;101:425–9.
Malignant Bowel Obstruction in Advanced Cancer
with increased in-hospital mortality. In contrast, obesity was associated with a lower risk of in-hospital mortality, and obese patients were more likely to receive nonsurgical management.11 MANAGEMENT
What are the general principles of management of MBO caused by malignancy? There is no consensus regarding the optimal treatment strategy and no evidence supports palliative surgery compared with medical management for improving quality of life or prolonging survival. The decision to proceed with surgical intervention in patients with advanced cancer involves careful consideration of risk and benefits, goals of care, and prognosis. The clinical decision-making process in advanced cancer depends on level of obstruction, the presence of single or multiple points of obstruction, the extent of cancer, comorbidities, and the PS of the patient.2 When should a surgeon be consulted during the medical management of an MBO? The authors suggest early consultation with a surgeon familiar and experienced with patients with advanced cancer to assist in determining whether prompt surgical intervention is necessary if consistent with goals of care and the patient is a candidate for surgery. The primary oncologist and primary care provider, if appropriate and available, can also be helpful in considering the optimal course for the patient by contributing important oncologic medical history as well as patient preferences. It may be a good option for patients with early stage cancer with preserved PS and a single point of occlusion. Patients who are in the middle of chemotherapy may need additional deliberation with the primary oncologist to determine systemic therapy logistics around a possible surgical intervention. Indications for immediate surgery may include: Bowel ischemia or infarction Volvulus Bowel perforation In addition, closed-loop small bowel obstructions and most large bowel obstructions are unlikely to resolve with conservative medical management and may necessitate early involvement of a surgeon. Palliative surgery should always be considered but should not be routinely performed because it may not improve survival or palliate the patient and is associated with a high complication rate.2 Case series of patients with MBO have shown a 30-day mortality of 25% (9%–40%), postsurgical morbidity of 50% (9%–90%), reobstruction rate of 48% (39%–57%), and a median survival of 7 months (2–12 months).2,12–15 Indicators of poor prognosis in patients are listed in Box 1 and should limit the indication of surgery in patients with MBO. Which endoscopic interventions are available for patients unfit for surgery? Self-expanding metallic stents are an option in MBO of the gastric outlet, proximal small bowel, and colon (areas accessible by endoscopic devices) in patients with a single point of obstruction in whom palliative surgery has been ruled out or those who do not want to undergo surgery.3 Percutaneous endoscopic gastrostomy is also an option for patients unable to undergo surgery or enteral stenting and who cannot control symptoms without aspiration or drainage of gastric contents.
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Box 1 Indicators of poor prognosis with surgical management of MBO Elderly age Malnutrition or cachexia Peritoneal carcinomatosis Multiple occlusive levels of obstruction Palpable abdominal masses Refractory ascites Symptomatic extra-abdominal metastatic disease Deteriorated general status/ECOG PS Renal or hepatic insufficiency Previous abdominal pelvic radiation therapy Absence of possible specific oncologic treatments Data from Refs.3,16,17
Which medications are useful in medical management of MBO? The objective of medical management in MBO is for palliative treatment to achieve symptomatic control of pain, nausea, and vomiting. The mainstays of pharmacologic treatment of inoperable MBO involve opiate analgesia, antiemetics, steroids, antisecretory medications, and intravenous (IV) hydration. IV, subcutaneous, sublingual, and transdermal routes should frequently be used because nausea, vomiting, and impaired absorption may not allow oral administration (Table 3). When should a nasogastric tube (NGT) be used? Insertion of an NGT can lead to quick resolution of intractable vomiting and gastric distention, as well as allow for decompression of the intraluminal contents, which can aid in spontaneous resolution of the obstruction. An NGT should only be used temporarily while other treatment is pursued given the complications (eg, nasal passage ulcers, gastric irritation) and discomfort with long-term use. Expert consensus states that the removal of the NGT should not be considered if secretions/output exceeds 1 L in 24 hours, suggesting ongoing obstruction.21 Removal of the NGT can be considered after a period of observation off suction. When is a venting gastrostomy indicated? If pharmacologic therapy fails to relieve symptoms, a venting gastrostomy (also called drainage percutaneous endoscopic gastrostomy [PEG]) may be placed endoscopically or surgically to allow decompression of gastrointestinal (GI) secretions without the discomfort of an NGT, in certain circumstances. This venting gastrostomy may allow oral intake for palliative use and even oral medication administration depending on the level of obstruction. Its use would be consistent with palliation plans to minimize aspiration and symptom exacerbations from irresolvable obstruction. This technique allows a more comfortable and safe long-term GI decompression. In rare cases, the
Table 3 Pharmacologic treatment of MBO Drug
Dose
Side Effects
Analgesia Pain control
Morphine
2.5–10 mg IV q 2–6 h prn
Sedation, myoclonus, respiratory Use other opiates in renal and liver dysfunction. depression No difference in rates of spontaneous resolution between patients receiving opiate pain medications (ie, hydromorphone, fentanyl) vs those who did not2,18
Antiemetics Reduce nausea and vomiting
Ondansetron
8 mg IV q 8 h
QT prolongation
Haloperidol
0.5–5 mg IV q 6 h
Compazine
5–10 mg IV q 6 h
QT prolongation, dystonia, extrapyramidal symptoms Dystonia, akathisia, sedation
Metoclopramide 5–20 mg IV TID–QID
Antisecretory Reduce secretions, distention, and peristalsis19
Octreotide
Hyoscyamine Scopolamine Glycopyrrolate
Anti-inflammatory Dexamethasone Reduce peritumor inflammation and edema20
Dystonia, akathisia
100–300 mg SC BID–TID or Bradycardia, headache, fatigue 10–40 mg/h IV continuous infusion 0.25–0.5 mg SC or IV q 4 h Dry mouth, blurry vision, ileus, urinary retention, confusion 1.5 mg transdermal Dry mouth, blurry vision, ileus, patch every 3 d urinary retention, confusion 0.1–0.2 mg IV TID–QID Dry mouth, blurry vision, ileus, urinary retention, confusion 4 mg IV TID–QID
Hyperglycemia, fluid retention
Comments
Antagonizes receptors in gut that mediate sensations of mechanical stretch and mucosal injury (5-HT3 serotonin receptor) Central dopamine antagonists control nausea via chemoreceptor trigger zone Central dopamine antagonists control nausea via chemoreceptor trigger zone Use only if incomplete/partial bowel obstruction without colic because it may increase gastrointestinal motility Expensive. Requires continuous dosing. Depot formulations take weeks for effect — — — Discontinue if no improvement in 3–5 d
Abbreviations: 5-HT3, 5-hydroxytryptamine-3; BID, twice a day; prn, as needed; q, every; QID, 4 times a day; SC, subcutaneous; TID, 3 times a day. Data from Refs.2,3,18–20
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Clinical Effect
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gastrostomy can be reversed if normal bowel function is regained; for instance, by definitive surgical management or exceptional systemic treatment responses. Does MBO ever resolve spontaneously? Spontaneous resolution of MBO occurs in 30% to 40% of patients with inoperable MBO and little is known about factors affecting it. One study showed that the most relevant clinical factors influencing nonresolution of MBO were cognitive failure, cachexia, dyspnea at rest, palpable abdominal tumor, hepatic failure, upper intestinal obstruction, and dehydration.2 COMPLICATIONS
What are the complications of MBO?
Bowel perforation/necrosis Sepsis/bacteremia/peritonitis Aspiration pneumonitis Intractable pain Intractable nausea and vomiting Diarrhea or constipation Electrolyte derangements Inability to deliver oral medications because of erratic absorption or vomiting Malnutrition
SUPPORTIVE MEASURES
What is the role of nutrition and TPN in patients with MBO? Nutrition is always a consideration in patients who develop MBO and the absence of a consistent nutrition plan can be distressing to the patient and family. Questions that influence nutrition management are:
Is the obstruction partial or complete? Is the obstruction involving the small bowel or the large bowel or both? Is the patient experiencing nausea and/or vomiting and to what degree? Does the patient have anorexia from the underlying malignancy versus the obstruction itself? Does the patient have abdominal pain associated with oral intake? In the setting of an MBO, there is an erratic and an unknown degree of absorption of nutrients. If the patient’s obstruction is known to be partial, the patient may be able to tolerate liquid oral intake only. When nausea, vomiting, or pain limits oral intake, a venting gastrostomy (or drainage PEG) may be considered for palliative relief knowing that this could create loss of nourishment. In addition, loss of gastric and biliary fluids can potentiate malnutrition and ongoing fluid losses can result in dehydration. Although the use of TPN in patients with cancer is controversial, it is generally not recommended for patients with MBO. There are several possible complications associated with TPN that can cause significant morbidity and mortality (Box 2). TPN may be indicated in a select group of patients with MBO and may prolong survival in some, but at the cost of frequent complications. Although no randomized trials have been performed, 1 small observational study showed significantly higher
Malignant Bowel Obstruction in Advanced Cancer
Box 2 Complications with TPN Bacteremia Fungemia Septic shock Deep venous thrombosis/pulmonary embolus Volume overload Fatty liver Electrolyte derangements Refeeding syndrome Hyperglycemia Biliary sludge
complications with TPN in malignant GI failure compared with nonmalignant GI failure.22,23 A retrospective study of patients with end-stage ovarian cancer found a modest increase in median survival measured in days in patients who received TPN, but considering the possible complications the investigators recommended routine use be discouraged in patients with end-stage ovarian cancer.24 A prospective multicenter European observational study examined the median survival of patients with incurable cancer with MBO on home TPN and not undergoing any further disease-directed therapy and found a median survival of 3 months, which is consistent with prior retrospective studies.24,25 Overall, TPN in MBO should be discouraged in patients with end-stage bowel or ovarian cancer, but may be justified in a select group of patients with an excellent PS (Karnofsky score >50) who have a median survival of more than 2 to 3 months and in whom death from malnutrition would precede death from the disease.24 The risks and benefits need to be weighed in each patient on a case-by-case basis, and should only be decided on after multidisciplinary evaluation. What is the role of IV fluid hydration on discharge in patients with inoperable MBO? In patients with MBO and limited oral intake, dehydration is an inevitable consequence and a result of disease progression. The need to provide supplemental IV hydration to terminally ill patients with MBO remains controversial and home hydration is often considered as a short-term supplement. Hydration is thought to meet the water/electrolyte requirements and to correct thirst, dry mouth, altered mental status, constipation, postural hypotension, and asthenia.26,27 However, there is little evidence to determine the value and outcomes of chronic IV fluid hydration in patients with MBO. One prospective randomized trial of 17 patients explored the role of scopolamine and octreotide with a variable amount of IV hydration on the outcomes of patients with inoperable bowel obstruction. There was a trend toward a decreased intensity of nausea and a nonsignificant downward trend toward less drowsiness in patients who received more IV hydration, but no significant difference in the sensation of dry mouth, daily thirst intensity, the feeling of abdominal distention, or intensity of dyspnea.26 Consideration about pulmonary edema, peripheral edema, and respiratory distress need to be balanced against the comfort of decreased urine output, less GI secretions, and less time connected to an IV line.
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DISCHARGE PLANNING
What are the considerations for discharge planning in patients with bowel obstruction? Discharge planning 1. Following surgical intervention (lysis of adhesions, intestinal diversion, ileostomy/ colostomy creation): provide diet instructions, level of activity, possible ostomy instructions. 2. Following endoscopic intervention (small bowel or colonic stenting): patient should be maintained on soft diet, stool softeners, and laxatives. 3. Patients going home with a chronic MBO: expectation setting, advance directives, and a clear goals-of-care discussion should take place involving the patient and primary caregiver by a multidisciplinary team. A chronic MBO is, in general, a terminal condition. A delicate but important discussion may be beneficial to consider the concerns about clinical deterioration that suggests prognosis of time is shorter. If concepts of hospice and end-of-life scenarios have not been explored, this could be an appropriate opportunity. The multidisciplinary team should include the inpatient management team, primary oncologist, palliative care specialist, nurse case manager, social worker, and hospice services liaison. The following should be provided: psychosocial support for the patient and a plan to address caregiver burden, pain management, nursing care for all tubes/drains, and an infusion company if hydration or TPN are within the scope of the goals of care. Hospice services can usually manage all of the discharge care needs, depending on the geographic location of the patient, but family involvement is paramount, because the family is the mainstay of patient support with home hospice. Inpatient hospice services remain an option for those with the insurance benefit if it is in keeping with the patient’s goals of care. PERFORMANCE IMPROVEMENT
Care of patients with MBO requires consideration not only of the obstruction, malignancy, and its complications but also other factors that affect quality of life in terminal illness. Coordinating care in patients with MBO remains paramount, and hospitalists are experts in hospital-based care processes and can efficiently organize care between a patient’s oncologist, surgical consultant, nursing staff, social work, and case management. Moreover, because MBO represents a highly severe illness with high intensity of services (compared with other reasons for hospitalization), hospitalists may note increased length of stay, more frequent readmissions, and increased resource use. Effective coordination of care by hospitalists may improve these outcomes. CLINICAL GUIDELINES
The National Comprehensive Cancer Network has published clinical guidelines for symptom management in MBO as part of their palliative care resources.28 REFERENCES
1. Anthony T, Baron T, Mercadante S, et al. Report of the Clinical Protocol Committee: development of randomized trials for malignant bowel obstruction. J Pain Symptom Manage 2007;34:S49–59.
Malignant Bowel Obstruction in Advanced Cancer
2. Tuca A, Guell E, Martinez-Losada E, et al. Malignant bowel obstruction in advanced cancer patients: epidemiology, management, and factors influencing spontaneous resolution. Cancer Manag Res 2012;4:159–69. 3. Ripamonti CI, Easson AM, Gerdes H. Management of malignant bowel obstruction. Eur J Cancer 2008;44:1105–15. 4. Mercadante S, Casuccio A, Mangione S. Medical treatment for inoperable malignant bowel obstruction: a qualitative systematic review. J Pain Symptom Manage 2007;33:217–23. 5. Ripamonti C, Bruera E. Palliative management of malignant bowel obstruction. Int J Gynecol Cancer 2002;12:135–43. 6. Goldstein NE, Morrison RS. Evidence-based practice of palliative medicine. Philadelphia: Elsevier/Saunders; 2013. 7. O’Connor B, Creedon B. Pharmacological treatment of bowel obstruction in cancer patients. Expert Opin Pharmacother 2011;12:2205–14. 8. Silva AC, Pimenta M, Guimaraes LS. Small bowel obstruction: what to look for. Radiographics 2009;29:423–39. 9. Chakraborty A, Selby D, Gardiner K, et al. Malignant bowel obstruction: natural history of a heterogeneous patient population followed prospectively over two years. J Pain Symptom Manage 2011;4:412–20. 10. Wright FC, Chakraborty A, Helyer L, et al. Predictors of survival in patients with non-curative stage IV cancer and malignant bowel obstruction. J Surg Oncol 2010;101:425–9. 11. Alese OB, Kim S, Chen Z, et al. Management patterns and predictors of mortality among US patients with cancer hospitalized for malignant bowel obstruction. Cancer 2015;121:1772–8. 12. Miller G, Boman J, Shrier I, et al. Small bowel obstruction secondary to malignant disease: an 11-year audit. Can J Surg 2000;43:353–8. 13. Blair SL, Chu DZ, Schwarz RE. Outcome of palliative operations for malignant bowel obstruction in patients with peritoneal carcinomatosis from nongynecological cancer. Ann Surg Oncol 2001;8:632–7. 14. Lau PW, Lorentz TG. Results of surgery for malignant bowel obstruction in advanced, unresectable, recurrent colorectal cancer. Dis Colon Rectum 1993; 36:61–4. 15. Yazdi GP, Miedema BW, Humphrey LJ. High mortality after abdominal operation in patients with large-volume malignant ascites. J Surg Oncol 1996;62:93–6. 16. Ripamonti C, Twycross R, Baines M, et al, Working Group of the European Association for Palliative Care. Clinical-practice recommendations for the management of bowel obstruction in patients with end-stage cancer. Support Care Cancer 2001;9:223–33. 17. Helyer L, Easson AM. Surgical approaches to malignant bowel obstruction. J Support Oncol 2008;6:105–13. 18. Hanks GW, Conno F, Cherny N, et al. Morphine and alternative opioids in cancer pain: the EAPC recommendations: Expert Working Group of the Research Network of the European Association for Palliative Care. Br J Cancer 2001;84: 587–93. 19. Wood GJ, Shega JW, Lynch B, et al. Management of intractable nausea and vomiting in patients at the end of life: “I was feeling nauseous all of the time. nothing was working.” JAMA 2007;298:1196–207. 20. Feuer DJ, Broadley KE. Corticosteroids for the resolution of malignant bowel obstruction in advanced gynaecological and gastrointestinal cancer [review]. Cochrane Database Syst Rev 2000;(2):CD001219.
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21. Laval G, Marcelin-Benazech B, Guirimand F, et al, French Society for Palliative Care, French Society for Digestive Surgery, French Society for Gastroenterology, French Association for Supportive Care in Oncology, French Society for Digestive Cancer. Recommendations for bowel obstruction with peritoneal carcinomatosis. J Pain Symptom Manage 2014;48:75–91. 22. Chermesh I, Mashiach T, Amit A, et al. Home parenteral nutrition (HTPN) for incurable patients with cancer with gastrointestinal obstruction: do the benefits outweigh the risks? Med Oncol 2011;28:83–8. 23. Abu-Rustum NR, Barakat RR, Venkatraman E, et al. Chemotherapy and total parenteral nutrition for advanced ovarian cancer with bowel obstruction. Gynecol Oncol 1997;64:493–5. 24. Bozzetti F. Nutritional support of the oncology patient. Crit Rev Oncol Hematol 2013;87:172–200. 25. Bozzetti F, Santarpia L, Pironi L, et al. The prognosis of incurable cachectic cancer patients on home parenteral nutrition: a multi-centre observational study with prospective follow-up of 414 patients. Ann Oncol 2014;25:487–93. 26. Ripamonti C, Mercadante S, Groff L, et al. Role of octreotide, scopolamine butylbromide, and hydration in symptom control of patients with inoperable bowel obstruction and nasogastric tubes: a prospective randomized trial. J Pain Symptom Manage 2000;19:23–34. 27. Bruera E, Hui D, Dalal S, et al. Parenteral hydration in patients with advanced cancer: a multicenter, double-blind, placebo-controlled randomized trial. J Clin Oncol 2013;31:111–8. 28. NCCN clinical practice guidelines in oncology: palliative care. Version 2.2013. 2013. Available at: http://www.nccn.org/professionals/physician_gls/f_guidelines. asp. Accessed December 1, 2015.
MD
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KEYWORDS Malignant bowel obstruction Small bowel obstruction Advanced cancer Prognosis Palliative surgery Total parenteral nutrition
HOSPITAL MEDICINE CLINICS CHECKLIST
1. Malignant bowel obstruction (MBO) is a bowel obstruction distal to the ligament of Treitz in a patient with an intra-abdominal primary cancer with incurable disease or a non–intra-abdominal primary cancer with clear intraperitoneal disease. 2. Patients with advanced ovarian or colorectal cancers have the highest prevalence of MBO. 3. Presenting symptoms may include nausea, vomiting, abdominal pain, or obstipation, whereas the most common physical examination finding is abdominal distention. 4. Laboratory tests should focus on monitoring the metabolic and electrolyte derangements that occur. 5. Computed tomography scan is the current standard for radiographic diagnosis. 6. Prognosis in MBO is generally poor, with median survival depending highly on performance status. 7. There is no consensus regarding the optimal treatment strategy and no evidence supports palliative surgery rather than medical management for improving quality of life or prolonging survival. CONTINUED
Disclosure: The authors have nothing to disclose. a Hospital Medicine Service, Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, 1275 York Avenue, MB 438, New York, NY 10065, USA; b Columbia University College of Physicians and Surgeons, 630 West 168th Street, New York, NY 10032, USA * Corresponding author. 1275 York Avenue, MB 438, New York, NY 10065. E-mail address: [email protected] Hosp Med Clin 5 (2016) 413–424 http://dx.doi.org/10.1016/j.ehmc.2016.02.005 2211-5943/16/$ – see front matter Ó 2016 Elsevier Inc. All rights reserved.
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CONTINUED
8. The mainstays of pharmacologic treatment of inoperable MBO involve opiate analgesia, antiemetics, steroids, antisecretory medications, and intravenous hydration for palliative relief of symptoms. 9. Self-expanding metallic stents or percutaneous endoscopic gastrostomy may be palliative options for patients unable to undergo surgery. 10. Total parenteral nutrition should be discouraged in patients with end-stage disease but may be justified in a select group of patients.
DEFINITION
What is the definition of malignant bowel obstruction (MBO)? MBO was defined by the International Conference on Malignant Bowel Obstruction in 2007 as a condition that fits the following criteria1: Clinical evidence of a bowel obstruction obtained via history, physical examination, or radiography Bowel obstruction distal to the ligament of Treitz Either an intra-abdominal primary cancer with incurable disease or a non–intraabdominal primary cancer with clear intraperitoneal disease EPIDEMIOLOGY
What is the prevalence of MBO in advanced cancer? The prevalence of MBO in advanced cancer is shown in Table 1. PATHOPHYSIOLOGY
What is the mechanism of bowel obstruction? I. Partial or complete bowel blockage Mechanical occlusion: Intraluminal – tumor within the bowel Extraluminal: primary tumor or metastases, adhesion, mesenteric and/or omental tumor, postirradiation fibrosis Table 1 Prevalence of MBO in various cancer types Cancer Type
Prevalence (%)
Ovarian
20–50
Colorectal
10–28
Stomach
6–19
Pancreas
6–13
Bladder
3–10
Extra-abdominal cancers (most often breast and melanoma) Data from Refs.
1–4
2–3
Malignant Bowel Obstruction in Advanced Cancer
II. III. IV. V. VI.
Intramural: including intestinal linitis plastica or tumor Functional obstruction: Motility disorder from tumor involvement of the enteric nervous system or celiac plexus, or paraneoplastic syndrome Increased stasis of luminal contents leading to distention and subsequent damage of bowel wall Increased inflammation, release of prostaglandins and vasoactive peptide Decreased reabsorption of electrolytes and H2O in the bowel Increased bowel edema, hyperemia, and contraction Abdominal pains, cramping, nausea, and vomiting3
What are the differences between proximal small bowel and distal large bowel obstructions? Proximal obstructions present acutely with pain of an intermittent periumbilical nature, vomiting, and with or without abdominal distention. However, more distal obstructions tend to present later with pain of a deeper, localized, and more continuous nature, with abdominal distention and vomiting sometimes being absent.3 DIAGNOSIS
What are the presenting symptoms of malignant small bowel obstruction? Nausea caused by distention and subsequent activation of mechanoreceptors Intermittent or continuous vomiting as a result of nausea or independent of other symptoms Abdominal pain that is continuous (90% of patients) or colicky (75% of patients), periumbilical, and that may increase with palpation Obstipation: complete absence of flatus or feces is suggestive of complete obstruction, whereas paradoxic diarrhea/incontinence is suggestive of a partial obstruction5–7 What are typical physical examination findings of small bowel obstruction? The most frequently encountered physical examination finding is abdominal distention caused by buildup of swallowed air, bacterial fermentation, intraluminal gas, and stasis of luminal contents. With partial obstruction, high-pitched, tinkling, hyperactive bowel sounds can be heard. However, as the obstruction increases, bowel sounds may become hypoactive as abdominal distention progresses and movement of intraluminal contents is blocked. Abdominal tenderness may or may not be present.5 What laboratory tests should be ordered for patients with suspected MBO? A complete blood count with differential and a basic metabolic panel should be ordered for patients presenting with abdominal pain. Routine laboratory testing does not specifically reveal a diagnosis of MBO but should instead be used to monitor the metabolic and electrolyte derangements commonly associated with, or that signal complications of, obstruction, such as hypokalemia, hyponatremia, hypovolemia, and leukocytosis.
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Which imaging modalities should be used for diagnosis? Computed tomography (CT) scan has a sensitivity and specificity greater than 90% for high-grade obstruction and it is the current gold standard of bowel obstruction diagnosis. However, because of its accessibility and low cost, plain abdominal radiography is a good first diagnostic tool to identify high-grade bowel obstruction, although its sensitivity and specificity are lower than those of CT scans, being diagnostic in only 50% to 60% of cases.8 PROGNOSIS IN ADVANCED CANCER
What is the prognosis associated with the development of MBO? Survival after development of MBO is generally poor, with median survival reported to be 1 to 3 months.9 Large survival ranges have been reported; a subset of patients with MBO can benefit from chemotherapy and/or surgery and can survive for greater than 1 year. In an observational study of patients hospitalized with MBO, excluding patients with gynecologic malignancies, median survival was most strongly predicted by Eastern Cooperative Oncology Group (ECOG) performance status (PS) at the time of diagnosis of MBO, with results shown in Table 2. In addition, a low serum blood urea nitrogen level or a high albumin level at the time of presentation was also associated with prolonged survival.10 In another observational study of patients with nongynecologic malignancies and MBO, the median survival was 80 days, with a large range, from 7 to 873 days. Thirty-four percent of patients received surgical intervention, palliative systemic chemotherapy was given to 37% of patients, total parenteral nutrition (TPN) was administered to 43% of patients for a median of 13 days, and a venting gastrostomy tube was placed in 26% of patients. With respect to the incident admission, 74% of patients were discharged home, 17% died in the acute care setting, and 9% were transferred to a palliative care unit for terminal care. There was a cohort of patients (17%) who survived for greater than 1 year, and, again, ECOG PS was tightly linked to survival. Median survival was greater than 200 days for ECOG 0 to 1, 63 days for ECOG 2, 28 days for ECOG 3, and 7 days for ECOG 4. Median length of stay for the incident admission was 16 days, and readmission was common (58%).9 A large retrospective review of admissions for MBO inclusive of all cancer types revealed in-hospital mortalities of 21.4% to 24.5%. Factors that were associated with higher in-hospital mortality were male gender, surgical management, lack of insurance, and multiple comorbidities; specifically, liver disease, a history of weight loss, renal failure, congestive heart failure, and metastatic disease were all associated
Table 2 Median survival in MBO ECOG PS
Median Survival (d)
0–1
222
2
63
3–4
27
Data from Wright FC, Chakraborty A, Helyer L, et al. Predictors of survival in patients with noncurative stage IV cancer and malignant bowel obstruction. J Surg Oncol 2010;101:425–9.
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with increased in-hospital mortality. In contrast, obesity was associated with a lower risk of in-hospital mortality, and obese patients were more likely to receive nonsurgical management.11 MANAGEMENT
What are the general principles of management of MBO caused by malignancy? There is no consensus regarding the optimal treatment strategy and no evidence supports palliative surgery compared with medical management for improving quality of life or prolonging survival. The decision to proceed with surgical intervention in patients with advanced cancer involves careful consideration of risk and benefits, goals of care, and prognosis. The clinical decision-making process in advanced cancer depends on level of obstruction, the presence of single or multiple points of obstruction, the extent of cancer, comorbidities, and the PS of the patient.2 When should a surgeon be consulted during the medical management of an MBO? The authors suggest early consultation with a surgeon familiar and experienced with patients with advanced cancer to assist in determining whether prompt surgical intervention is necessary if consistent with goals of care and the patient is a candidate for surgery. The primary oncologist and primary care provider, if appropriate and available, can also be helpful in considering the optimal course for the patient by contributing important oncologic medical history as well as patient preferences. It may be a good option for patients with early stage cancer with preserved PS and a single point of occlusion. Patients who are in the middle of chemotherapy may need additional deliberation with the primary oncologist to determine systemic therapy logistics around a possible surgical intervention. Indications for immediate surgery may include: Bowel ischemia or infarction Volvulus Bowel perforation In addition, closed-loop small bowel obstructions and most large bowel obstructions are unlikely to resolve with conservative medical management and may necessitate early involvement of a surgeon. Palliative surgery should always be considered but should not be routinely performed because it may not improve survival or palliate the patient and is associated with a high complication rate.2 Case series of patients with MBO have shown a 30-day mortality of 25% (9%–40%), postsurgical morbidity of 50% (9%–90%), reobstruction rate of 48% (39%–57%), and a median survival of 7 months (2–12 months).2,12–15 Indicators of poor prognosis in patients are listed in Box 1 and should limit the indication of surgery in patients with MBO. Which endoscopic interventions are available for patients unfit for surgery? Self-expanding metallic stents are an option in MBO of the gastric outlet, proximal small bowel, and colon (areas accessible by endoscopic devices) in patients with a single point of obstruction in whom palliative surgery has been ruled out or those who do not want to undergo surgery.3 Percutaneous endoscopic gastrostomy is also an option for patients unable to undergo surgery or enteral stenting and who cannot control symptoms without aspiration or drainage of gastric contents.
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Box 1 Indicators of poor prognosis with surgical management of MBO Elderly age Malnutrition or cachexia Peritoneal carcinomatosis Multiple occlusive levels of obstruction Palpable abdominal masses Refractory ascites Symptomatic extra-abdominal metastatic disease Deteriorated general status/ECOG PS Renal or hepatic insufficiency Previous abdominal pelvic radiation therapy Absence of possible specific oncologic treatments Data from Refs.3,16,17
Which medications are useful in medical management of MBO? The objective of medical management in MBO is for palliative treatment to achieve symptomatic control of pain, nausea, and vomiting. The mainstays of pharmacologic treatment of inoperable MBO involve opiate analgesia, antiemetics, steroids, antisecretory medications, and intravenous (IV) hydration. IV, subcutaneous, sublingual, and transdermal routes should frequently be used because nausea, vomiting, and impaired absorption may not allow oral administration (Table 3). When should a nasogastric tube (NGT) be used? Insertion of an NGT can lead to quick resolution of intractable vomiting and gastric distention, as well as allow for decompression of the intraluminal contents, which can aid in spontaneous resolution of the obstruction. An NGT should only be used temporarily while other treatment is pursued given the complications (eg, nasal passage ulcers, gastric irritation) and discomfort with long-term use. Expert consensus states that the removal of the NGT should not be considered if secretions/output exceeds 1 L in 24 hours, suggesting ongoing obstruction.21 Removal of the NGT can be considered after a period of observation off suction. When is a venting gastrostomy indicated? If pharmacologic therapy fails to relieve symptoms, a venting gastrostomy (also called drainage percutaneous endoscopic gastrostomy [PEG]) may be placed endoscopically or surgically to allow decompression of gastrointestinal (GI) secretions without the discomfort of an NGT, in certain circumstances. This venting gastrostomy may allow oral intake for palliative use and even oral medication administration depending on the level of obstruction. Its use would be consistent with palliation plans to minimize aspiration and symptom exacerbations from irresolvable obstruction. This technique allows a more comfortable and safe long-term GI decompression. In rare cases, the
Table 3 Pharmacologic treatment of MBO Drug
Dose
Side Effects
Analgesia Pain control
Morphine
2.5–10 mg IV q 2–6 h prn
Sedation, myoclonus, respiratory Use other opiates in renal and liver dysfunction. depression No difference in rates of spontaneous resolution between patients receiving opiate pain medications (ie, hydromorphone, fentanyl) vs those who did not2,18
Antiemetics Reduce nausea and vomiting
Ondansetron
8 mg IV q 8 h
QT prolongation
Haloperidol
0.5–5 mg IV q 6 h
Compazine
5–10 mg IV q 6 h
QT prolongation, dystonia, extrapyramidal symptoms Dystonia, akathisia, sedation
Metoclopramide 5–20 mg IV TID–QID
Antisecretory Reduce secretions, distention, and peristalsis19
Octreotide
Hyoscyamine Scopolamine Glycopyrrolate
Anti-inflammatory Dexamethasone Reduce peritumor inflammation and edema20
Dystonia, akathisia
100–300 mg SC BID–TID or Bradycardia, headache, fatigue 10–40 mg/h IV continuous infusion 0.25–0.5 mg SC or IV q 4 h Dry mouth, blurry vision, ileus, urinary retention, confusion 1.5 mg transdermal Dry mouth, blurry vision, ileus, patch every 3 d urinary retention, confusion 0.1–0.2 mg IV TID–QID Dry mouth, blurry vision, ileus, urinary retention, confusion 4 mg IV TID–QID
Hyperglycemia, fluid retention
Comments
Antagonizes receptors in gut that mediate sensations of mechanical stretch and mucosal injury (5-HT3 serotonin receptor) Central dopamine antagonists control nausea via chemoreceptor trigger zone Central dopamine antagonists control nausea via chemoreceptor trigger zone Use only if incomplete/partial bowel obstruction without colic because it may increase gastrointestinal motility Expensive. Requires continuous dosing. Depot formulations take weeks for effect — — — Discontinue if no improvement in 3–5 d
Abbreviations: 5-HT3, 5-hydroxytryptamine-3; BID, twice a day; prn, as needed; q, every; QID, 4 times a day; SC, subcutaneous; TID, 3 times a day. Data from Refs.2,3,18–20
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Clinical Effect
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gastrostomy can be reversed if normal bowel function is regained; for instance, by definitive surgical management or exceptional systemic treatment responses. Does MBO ever resolve spontaneously? Spontaneous resolution of MBO occurs in 30% to 40% of patients with inoperable MBO and little is known about factors affecting it. One study showed that the most relevant clinical factors influencing nonresolution of MBO were cognitive failure, cachexia, dyspnea at rest, palpable abdominal tumor, hepatic failure, upper intestinal obstruction, and dehydration.2 COMPLICATIONS
What are the complications of MBO?
Bowel perforation/necrosis Sepsis/bacteremia/peritonitis Aspiration pneumonitis Intractable pain Intractable nausea and vomiting Diarrhea or constipation Electrolyte derangements Inability to deliver oral medications because of erratic absorption or vomiting Malnutrition
SUPPORTIVE MEASURES
What is the role of nutrition and TPN in patients with MBO? Nutrition is always a consideration in patients who develop MBO and the absence of a consistent nutrition plan can be distressing to the patient and family. Questions that influence nutrition management are:
Is the obstruction partial or complete? Is the obstruction involving the small bowel or the large bowel or both? Is the patient experiencing nausea and/or vomiting and to what degree? Does the patient have anorexia from the underlying malignancy versus the obstruction itself? Does the patient have abdominal pain associated with oral intake? In the setting of an MBO, there is an erratic and an unknown degree of absorption of nutrients. If the patient’s obstruction is known to be partial, the patient may be able to tolerate liquid oral intake only. When nausea, vomiting, or pain limits oral intake, a venting gastrostomy (or drainage PEG) may be considered for palliative relief knowing that this could create loss of nourishment. In addition, loss of gastric and biliary fluids can potentiate malnutrition and ongoing fluid losses can result in dehydration. Although the use of TPN in patients with cancer is controversial, it is generally not recommended for patients with MBO. There are several possible complications associated with TPN that can cause significant morbidity and mortality (Box 2). TPN may be indicated in a select group of patients with MBO and may prolong survival in some, but at the cost of frequent complications. Although no randomized trials have been performed, 1 small observational study showed significantly higher
Malignant Bowel Obstruction in Advanced Cancer
Box 2 Complications with TPN Bacteremia Fungemia Septic shock Deep venous thrombosis/pulmonary embolus Volume overload Fatty liver Electrolyte derangements Refeeding syndrome Hyperglycemia Biliary sludge
complications with TPN in malignant GI failure compared with nonmalignant GI failure.22,23 A retrospective study of patients with end-stage ovarian cancer found a modest increase in median survival measured in days in patients who received TPN, but considering the possible complications the investigators recommended routine use be discouraged in patients with end-stage ovarian cancer.24 A prospective multicenter European observational study examined the median survival of patients with incurable cancer with MBO on home TPN and not undergoing any further disease-directed therapy and found a median survival of 3 months, which is consistent with prior retrospective studies.24,25 Overall, TPN in MBO should be discouraged in patients with end-stage bowel or ovarian cancer, but may be justified in a select group of patients with an excellent PS (Karnofsky score >50) who have a median survival of more than 2 to 3 months and in whom death from malnutrition would precede death from the disease.24 The risks and benefits need to be weighed in each patient on a case-by-case basis, and should only be decided on after multidisciplinary evaluation. What is the role of IV fluid hydration on discharge in patients with inoperable MBO? In patients with MBO and limited oral intake, dehydration is an inevitable consequence and a result of disease progression. The need to provide supplemental IV hydration to terminally ill patients with MBO remains controversial and home hydration is often considered as a short-term supplement. Hydration is thought to meet the water/electrolyte requirements and to correct thirst, dry mouth, altered mental status, constipation, postural hypotension, and asthenia.26,27 However, there is little evidence to determine the value and outcomes of chronic IV fluid hydration in patients with MBO. One prospective randomized trial of 17 patients explored the role of scopolamine and octreotide with a variable amount of IV hydration on the outcomes of patients with inoperable bowel obstruction. There was a trend toward a decreased intensity of nausea and a nonsignificant downward trend toward less drowsiness in patients who received more IV hydration, but no significant difference in the sensation of dry mouth, daily thirst intensity, the feeling of abdominal distention, or intensity of dyspnea.26 Consideration about pulmonary edema, peripheral edema, and respiratory distress need to be balanced against the comfort of decreased urine output, less GI secretions, and less time connected to an IV line.
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DISCHARGE PLANNING
What are the considerations for discharge planning in patients with bowel obstruction? Discharge planning 1. Following surgical intervention (lysis of adhesions, intestinal diversion, ileostomy/ colostomy creation): provide diet instructions, level of activity, possible ostomy instructions. 2. Following endoscopic intervention (small bowel or colonic stenting): patient should be maintained on soft diet, stool softeners, and laxatives. 3. Patients going home with a chronic MBO: expectation setting, advance directives, and a clear goals-of-care discussion should take place involving the patient and primary caregiver by a multidisciplinary team. A chronic MBO is, in general, a terminal condition. A delicate but important discussion may be beneficial to consider the concerns about clinical deterioration that suggests prognosis of time is shorter. If concepts of hospice and end-of-life scenarios have not been explored, this could be an appropriate opportunity. The multidisciplinary team should include the inpatient management team, primary oncologist, palliative care specialist, nurse case manager, social worker, and hospice services liaison. The following should be provided: psychosocial support for the patient and a plan to address caregiver burden, pain management, nursing care for all tubes/drains, and an infusion company if hydration or TPN are within the scope of the goals of care. Hospice services can usually manage all of the discharge care needs, depending on the geographic location of the patient, but family involvement is paramount, because the family is the mainstay of patient support with home hospice. Inpatient hospice services remain an option for those with the insurance benefit if it is in keeping with the patient’s goals of care. PERFORMANCE IMPROVEMENT
Care of patients with MBO requires consideration not only of the obstruction, malignancy, and its complications but also other factors that affect quality of life in terminal illness. Coordinating care in patients with MBO remains paramount, and hospitalists are experts in hospital-based care processes and can efficiently organize care between a patient’s oncologist, surgical consultant, nursing staff, social work, and case management. Moreover, because MBO represents a highly severe illness with high intensity of services (compared with other reasons for hospitalization), hospitalists may note increased length of stay, more frequent readmissions, and increased resource use. Effective coordination of care by hospitalists may improve these outcomes. CLINICAL GUIDELINES
The National Comprehensive Cancer Network has published clinical guidelines for symptom management in MBO as part of their palliative care resources.28 REFERENCES
1. Anthony T, Baron T, Mercadante S, et al. Report of the Clinical Protocol Committee: development of randomized trials for malignant bowel obstruction. J Pain Symptom Manage 2007;34:S49–59.
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2. Tuca A, Guell E, Martinez-Losada E, et al. Malignant bowel obstruction in advanced cancer patients: epidemiology, management, and factors influencing spontaneous resolution. Cancer Manag Res 2012;4:159–69. 3. Ripamonti CI, Easson AM, Gerdes H. Management of malignant bowel obstruction. Eur J Cancer 2008;44:1105–15. 4. Mercadante S, Casuccio A, Mangione S. Medical treatment for inoperable malignant bowel obstruction: a qualitative systematic review. J Pain Symptom Manage 2007;33:217–23. 5. Ripamonti C, Bruera E. Palliative management of malignant bowel obstruction. Int J Gynecol Cancer 2002;12:135–43. 6. Goldstein NE, Morrison RS. Evidence-based practice of palliative medicine. Philadelphia: Elsevier/Saunders; 2013. 7. O’Connor B, Creedon B. Pharmacological treatment of bowel obstruction in cancer patients. Expert Opin Pharmacother 2011;12:2205–14. 8. Silva AC, Pimenta M, Guimaraes LS. Small bowel obstruction: what to look for. Radiographics 2009;29:423–39. 9. Chakraborty A, Selby D, Gardiner K, et al. Malignant bowel obstruction: natural history of a heterogeneous patient population followed prospectively over two years. J Pain Symptom Manage 2011;4:412–20. 10. Wright FC, Chakraborty A, Helyer L, et al. Predictors of survival in patients with non-curative stage IV cancer and malignant bowel obstruction. J Surg Oncol 2010;101:425–9. 11. Alese OB, Kim S, Chen Z, et al. Management patterns and predictors of mortality among US patients with cancer hospitalized for malignant bowel obstruction. Cancer 2015;121:1772–8. 12. Miller G, Boman J, Shrier I, et al. Small bowel obstruction secondary to malignant disease: an 11-year audit. Can J Surg 2000;43:353–8. 13. Blair SL, Chu DZ, Schwarz RE. Outcome of palliative operations for malignant bowel obstruction in patients with peritoneal carcinomatosis from nongynecological cancer. Ann Surg Oncol 2001;8:632–7. 14. Lau PW, Lorentz TG. Results of surgery for malignant bowel obstruction in advanced, unresectable, recurrent colorectal cancer. Dis Colon Rectum 1993; 36:61–4. 15. Yazdi GP, Miedema BW, Humphrey LJ. High mortality after abdominal operation in patients with large-volume malignant ascites. J Surg Oncol 1996;62:93–6. 16. Ripamonti C, Twycross R, Baines M, et al, Working Group of the European Association for Palliative Care. Clinical-practice recommendations for the management of bowel obstruction in patients with end-stage cancer. Support Care Cancer 2001;9:223–33. 17. Helyer L, Easson AM. Surgical approaches to malignant bowel obstruction. J Support Oncol 2008;6:105–13. 18. Hanks GW, Conno F, Cherny N, et al. Morphine and alternative opioids in cancer pain: the EAPC recommendations: Expert Working Group of the Research Network of the European Association for Palliative Care. Br J Cancer 2001;84: 587–93. 19. Wood GJ, Shega JW, Lynch B, et al. Management of intractable nausea and vomiting in patients at the end of life: “I was feeling nauseous all of the time. nothing was working.” JAMA 2007;298:1196–207. 20. Feuer DJ, Broadley KE. Corticosteroids for the resolution of malignant bowel obstruction in advanced gynaecological and gastrointestinal cancer [review]. Cochrane Database Syst Rev 2000;(2):CD001219.
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21. Laval G, Marcelin-Benazech B, Guirimand F, et al, French Society for Palliative Care, French Society for Digestive Surgery, French Society for Gastroenterology, French Association for Supportive Care in Oncology, French Society for Digestive Cancer. Recommendations for bowel obstruction with peritoneal carcinomatosis. J Pain Symptom Manage 2014;48:75–91. 22. Chermesh I, Mashiach T, Amit A, et al. Home parenteral nutrition (HTPN) for incurable patients with cancer with gastrointestinal obstruction: do the benefits outweigh the risks? Med Oncol 2011;28:83–8. 23. Abu-Rustum NR, Barakat RR, Venkatraman E, et al. Chemotherapy and total parenteral nutrition for advanced ovarian cancer with bowel obstruction. Gynecol Oncol 1997;64:493–5. 24. Bozzetti F. Nutritional support of the oncology patient. Crit Rev Oncol Hematol 2013;87:172–200. 25. Bozzetti F, Santarpia L, Pironi L, et al. The prognosis of incurable cachectic cancer patients on home parenteral nutrition: a multi-centre observational study with prospective follow-up of 414 patients. Ann Oncol 2014;25:487–93. 26. Ripamonti C, Mercadante S, Groff L, et al. Role of octreotide, scopolamine butylbromide, and hydration in symptom control of patients with inoperable bowel obstruction and nasogastric tubes: a prospective randomized trial. J Pain Symptom Manage 2000;19:23–34. 27. Bruera E, Hui D, Dalal S, et al. Parenteral hydration in patients with advanced cancer: a multicenter, double-blind, placebo-controlled randomized trial. J Clin Oncol 2013;31:111–8. 28. NCCN clinical practice guidelines in oncology: palliative care. Version 2.2013. 2013. Available at: http://www.nccn.org/professionals/physician_gls/f_guidelines. asp. Accessed December 1, 2015.