Abeloff's Clinical Oncology, 4th Edition
Part II – Problems Common to Cancer and its Therapy
Section E – Surgical Problems
Chapter 53 – Acute Abdomen, Bowel Obstruction, and Fistula
Chapter 53 – Acute Abdomen, Bowel Obstruction, and Fistula
Sandra L. Wong,Alfred E. Chang
SUMMARY OF KEY POINTS
General surgical problems in the cancer patient require special attention. This chapter reviews common abdominal complications and emergencies that are encountered in patients with a cancer diagnosis. In some cases, these problems might not be related to the cancer itself. For other patients, clinicians must be cognizant of the potential complications associated with progression or treatment of disease. The management of cancer patients has undergone significant changes with the increasing utilization of multimodality therapy. Combined approaches, including surgery, radiation therapy, chemotherapy, and immunotherapy, are now commonplace. Topics having to do with the “acute abdomen” include intestinal obstruction, gastrointestinal (GI) bleeding, and perforation. Other related presentations, such as gastrointestinal inflammatory conditions and fistulae, are also reviewed in this chapter. In addition, unique abdominal problems that are seen in patients undergoing bone marrow transplantation (BMT) are covered.
ACUTE ABDOMEN: GENERAL CONSIDERATIONS
The classic general surgery approach to a patient with acute abdominal pain entails identification of a potentially life-threatening problem and evaluation for emergency exploratory laparotomy. In patients with cancer, the etiology of acute abdominal pain may be directly related to a malignant process, but seemingly unrelated processes must be considered as well. Some GI cancers can present as abdominal emergencies that require surgical intervention. Problems that require surgical consultation include obstruction, perforation, hemorrhage, inflammatory processes, and other miscellaneous problems such as fistulae ( Box 53-1 ).   In a recent prospective analysis of over 1000 consecutive palliative procedures in patients with cancer, over 50% were performed on the GI system, with obstruction and bleeding making up over 75% of the presenting symptoms. Interestingly, surgical intervention resulted in symptom resolution in over 80% of patients. The decision to intervene with surgical therapy is oftendifficult because of abnormal physiologic responses to injury and inflammation, complications associated with previous cancer therapies, and competing risks due to extent or stage of the underlying cancer. In some instances, medical management or utilization of palliative measures make up the mainstay of therapy.
ACUTE ABDOMINAL EMERGENCIES IN CANCER PATIENTS
Abdominal pain is the most common symptom in the patient with an acute abdomen. In patients with a diagnosed intra-abdominal malignancy who are undergoing chemotherapy and/or radiation therapy, abdominal pain must be investigated carefully. Care must be taken not to automatically attribute these complaints to cancer progression. Important considerations in the evaluation of the patient with an acute abdominal process include hemodynamic stability and deterioration of symptoms during the course of examination and workup. Patients taking corticosteroids or who have an altered sensorium warrant special attention because of a potentially unreliable physical examination. Other abdominal complaints, such as vomiting, distention, lack of flatus, and fever, should raise the examiner's index of suspicion that an emergent problem is present.
On physical examination, tenderness to palpation is the most common finding. Peritonitis almost invariably produces tenderness as a localized or diffuse finding, since abdominal pain is transmitted by both visceral and somatic sensory pathways. There is no substitute for a thorough history and physical examination. A careful and thoughtful differential diagnosis is important in directing the course of subsequent evaluation and action. Laboratory tests and diagnostic imaging studies can help to narrow the nature of the problem. Standard laboratory studies should include a complete blood count and electrolyte panel. Leukocytosis will normally be evident if an intra-abdominal infection is present. Unfortunately, chemotherapy-induced neutropenia or immunosuppression might prevent the white cell count from adequately reflecting an inflammatory process. Liver function studies and a serum amylase are helpful in patients with upper abdominal complaints when hepatobiliary or pancreatic etiology is suspected. Patients with evidence of GI bleeding require serial hemoglobins to assess the severity and magnitude of the bleeding; thrombocytopenia and coagulopathy should be corrected when possible.
If an intra-abdominal process is suspected and time permits, diagnostic imaging with plain abdominal films, ultrasonography, and/or computed tomography (CT) could be helpful in making a more definitive diagnosis. With increasing sophistication of CT studies, their importance in identification of abdominal processes, including free fluid, free air, intestinal pneumatosis, portal venous gas, transition points for gastrointestinal obstruction, and localization of abdominal inflammatory processes, is well defined. Importantly, rapid tumor progression and/or metastases can often be assessed at the same setting. Localization of the bleeding source by endoscopy or arteriography can be helpful, and these can often be used as therapeutic modalities as well.
Ultimately, the surgeon must make the determination as to whether the patient has an acute abdominal process that requires surgical intervention. Decisions to operate on acutely ill patients with cancer are difficult and often require a high level of surgical decision making. Due consideration must be given to the stage and prognosis of the cancer itself, since the surgeon's ability to offer a procedure with curative intent versus palliation only may alter the decision-making process. The role of palliative procedures has increased tremendously, with as many as 6% to 21% of cancer operations being classified as palliative in nature.    Even without curative intent, surgeons have a great deal to offer in terms of symptom relief and overall improvement in quality of life. However, attempts at successful palliation must be balanced with inappropriately aggressive attempts, which may carry unacceptable rates of morbidity and mortality.
Perforation of the GI tract mandates operative intervention unless the patient's condition is judged to be extremely poor. Excluding iatrogenic causes of bowel perforation, the causes of perforation can be categorized into the following subgroups: spontaneous tumor rupture or erosion into bowel, drug-induced or associated perforations, and inflammatory conditions. GI tract cancers may present with perforation as the precipitating event, but this is rare and associated with high mortality rates. Primary colon cancers can present as localized perforations or can cause obstruction with subsequent perforation. The perioperative mortality rate following presentation with colon cancer perforation, either at or proximal to the tumor site, ranges from 17% to 48%. Even after accounting for stage, patients tend to have a poorer prognosis.
Spontaneous perforation of GI tumors is more common in patients with lymphomas involving the gastrointestinal tract, although this diagnosis is rare. Large malignant retroperitoneal lymphomas, renal cell carcinomas, and testicular cancers metastatic to aortocaval nodes can invade the adjacent duodenum and cause perforation. Patients with GI lymphomas can have symptoms at presentation or can develop symptoms related to regression of their primary tumor during treatment with chemotherapy and/or radiation therapy. Perforation or bleeding from treatment-induced tumor lysis occurs in approximately 3% and 5% of patients, respectively. Although resection of larger, higher-grade GI lymphomas can be associated with increased morbidity, the mortality rate is greater than 50% when surgical intervention is urgently required for perforation or bleeding in the setting of neutropenia and thrombocytopenia.   
Surgical management of bowel perforations varies with the site and etiology. Infectious causes of perforation, such as colitis secondary to cytomegalovirus or Clostridium difficile, have been described but are rare. Treatment includes proper control of the infection and usually necessitates resection with possible enteric diversion. For gastric perforations secondary to benign ulcers, surgical intervention is indicated. For perforated duodenal ulcers, various surgical options can be employed, depending on the patient's underlying disease and clinical status (e.g., hemodynamic stability). Small bowel perforations should be resected with primary anastomosis if possible. Colonic perforations, especially in the setting of the unprepped bowel and in the immunosuppressed patient, should be treated with resection and diversion. One-stage procedures to include primary anastomosis in these situations must be used cautiously and are generally not advised. Aggressive supportive care with control of intra-abdominal infection and sepsis are paramount in the immediate perioperative period.
The true incidence of significant gastrointestinal (GI) bleeding in patients with cancer is not well defined. An estimated 10% to 15% of patients with abdominal emergencies requiring operative intervention had abdominal hemorrhage, most of them secondary to intraluminal bleeding. Patients with lymphoma or leukemia treated with combination chemotherapy regimens can experience GI tract bleeding. While a GI tumor itself could be the source of bleeding, differential diagnosis should include non-tumor-related sources as well. The most common causes of upper GI tract bleeding in patients with cancer are peptic ulcer disease or stress ulceration and complications of anticoagulation or thrombocytopenia.    Rates are likely to be lower in clinical practice, given the availability and increasingly widespread use of H2-receptor blockers and proton pump inhibitors. Other, less common, causes of bleeding include Candida esophagitis, Mallory-Weiss mucosal tears, hemorrhage from inflammatory conditions (e.g., neutropenic enterocolitis), or radiation-associated complications (e.g., arterial-enteric fistulae, radiation enteropathy).
The pathogenesis of upper GI bleeding can be multifactorial. Gastritis or peptic ulcers can be associated with a variety of agents, such as aspirin, alcohol, steroids, indomethacin, or phenylbutazone. Chemotherapeutic agents can depress platelet production as well as damaging or irritating the mucosal surfaces. While the correlation between thrombocytopenia and bleeding is well described, it is difficult to predict which patients might develop transfusion-requiring bleeding or life-threatening hemorrhage. Overall, the incidence of bleeding is low, with one group reporting bleeding episodes with 9% of chemotherapy cycles.   The vast majority of episodes were mild (e.g., epistaxis), but major hemorrhage (including GI bleeding) was seen in approximately 3% of cycles. In that study, administration of certain chemotherapy agents (cisplatin, carboplatin, carmustin, and lomustine) was noted to be significantly related to bleeding episodes:. Others have more recently reported thrombocytopenia, hemorrhage, and hemolysis with oxaliplatin. Prophylactic platelet transfusions should be considered on a case-by-case basis, especially if bleeding has occurred previously.
Hepatic arterial infusion of fluorodeoxyuridine utilizing an implanted pump for the treatment of liver tumors has been reported to result in a significant incidence of upper GI toxicity with biliary sclerosis, gastritis, peptic ulcers, and intra-abdominal bleeding due to catheter displacement.    Other unusual causes of bleeding include hemobilia secondary to presence and/or treatment of hepatobiliary tumors. Arterial-enteric fistulalization may result in severe intraluminal hemorrhage, and operative management should be approached with joint vascular surgery consultation. Communication with vascular structures should always be considered in previous surgical sites and areas of prior radiation treatment.
Intra-abdominal hemorrhage is usually seen as a result of tumor rupture ( Fig. 53-1 ), but spontaneous splenic rupture in patients with hematologic malignancies can be seen as well. Rapid tumor necrosis with subsequent hemorrhage has been reported during chemotherapy and is most commonly seen in patients with GI lymphomas. The incidence of significant GI bleeding in this patient population secondary to tumor lysis from therapy is approximately 5%. Surgical resection of GI lymphoma before systemic or radiation therapy could be beneficial for lesions that are amenable to resection with minimal morbidity.
Figure 53-1 Intra-abdominal hemorrhage from gastrointestinal stromal tumor (GIST). CT scan of the abdomen demonstrating a 10.5-cm proximal jejunal GIST on initial presentation with intra-abdominal perforation and subsequent hemorrhage (inset photo, blood in the pelvis).
Treatment of upper GI tract bleeding requires defining its source. Early endoscopic examination should be performed for diagnosis. In most patients, nonoperative treatment is successful. Supportive measures with antacids, proton pump inhibitors, and blood products will control the bleeding in most patients with gastritis or ulceration. Endoscopic injection with sclerosing agents or endoscopically guided use of coagulative laser or electrocautery can sometimes control bleeding from isolated ulcerations or tumors. If medical management fails to stop bleeding from erosive gastritis or if there is intractable bleeding necessitating ongoing packed red cell transfusion, operative management should strongly be considered. Indications to proceed with surgery should also be predicated on the patient's quality of life and disease prognosis. For erosive gastritis, total or near-total gastrectomy is the most effective means of controlling hemorrhage but is associated with a high morbidity and mortality because of the underlying medical condition of these patients. Bleeding from duodenal ulcer disease in a patient with cancer is probably best treated by oversewing the ulcer and performing a truncal vagotomy with pyloroplasty. When extensive bleeding occurs from a tumor, operative resection might be the only recourse.
Lower GI tract bleeding is infrequently seen from primary cancer sites. Endoscopy, radionuclide imaging, or mesenteric angiography might be required to identify the source. Colonoscopy should be performed as the initial diagnostic study for lower GI bleeding, followed by consideration of upper GI endoscopy. Brisk bleeding can make endoscopic examinations difficult. For GI bleeding at a rate greater than 1 mL/minute, selective mesenteric arteriography might be the most accurate method for localization. Technetium-labeled red blood cell scans can be helpful in localizing the site of hemorrhage when bleeding is more intermittent. Small bowel sources should be entertained if upper and lower endoscopic examination is negative. Primary small bowel tumors (e.g., carcinoids, adenocarcinomas, gastrointestinal stromal tumors) and metastatic lesions (e.g., melanoma, lung) to the small bowel may initially present with an episode of lower GI bleeding. Bloody diarrhea can be seen as a sequelae of radiation treatment for rectal cancer. Radiation enteropathy resulting in bleeding can usually be managed nonoperatively, but in the setting of acute hemorrhage, resection with intestinal diversion might be required.
Operative management of lower GI bleeding is necessary when modalities such as vasopressin infusion or embolization are not indicated or are unsuccessful. In poor-risk patients, these nonoperative therapies are associated with a definitive risk of bowel infarction. Prior localization of the bleeding source is necessary to identify the segment of bowel to resect. When it is not possible to localize the source of colonic bleeding either preoperatively or intraoperatively with inspection or on-table endoscopy, subtotal colectomy should be performed.
ADVERSE EVENTS WITH CYTOTOXIC AGENTS LEADING TO BLEEDING OR PERFORATION
Special consideration should be given to patients receiving targeted molecular therapy agents. Bevacizumab (Avastin), a monoclonal antibody targeting the vascular endothelial growth factor (VEGF)receptor, has been shown to significantly improve overall and progression-free survival rates in patients with metastatic colorectal cancer when used with combination chemotherapy compared to chemotherapy alone   Results of these randomized trials have led to the widespread use of bevacizumab in patients with metastatic colorectal cancers and in selected patients with other solid-organ cancers. Because this drug targets tumor angiogenesis, rare but serious complications, such as bowel perforation, can occur in about 1.5% of patients during treatment. Risk factors for perforation are difficult to define but include longer length of treatment, prior radiation, carcinomatosis, and bowel inflammation from entities such peptic ulcer disease, tumor necrosis, diverticulitis, and chemotherapy-induced colitis.   Bowel perforation can occur at sites that are not affected by malignant disease; perforations were reported in 8% of patients treated with gemcitabine and bevacizumab for pancreas cancer.
Another targeted molecular agent associated with bowel perforation and gastrointestinal bleeding is imatinib (Gleevec), a tyrosine kinase receptor inhibitor that is commonly used in the treatment of chronic myelogenous leukemia and gastrointestinal stromal tumors (GIST). In an early Phase II study of metastatic and/or unresectable GISTs, 5% of patients had hemorrhages into the GI tract or tumor sites.Some of the cases might have been related to tumor rupture. However, episodes were not correlated to imatinib dosing, tumor burden, treatment duration, or platelet count.
With the expanding indications for use of immunotherapeutic agents such as interleukin-2 (IL-2) for metastatic melanoma and renal cell cancer, clinicians should be alert to occasional cases of colonic infarction and perforation. The causes of these perforations are unknown, but it has been postulated that they arise from impaired perfusion due to hypotension, tissue edema, and vasoconstriction secondary to the use of pressor agents. A recent report suggests that bowel perforation might be more commonly seen when IL-2 is used in combination with anti-CTLA 4 antibody and that association can be seen in conjunction with autoimmune colitis.
Bowel necrosis with perforation has been described with the use of cytosine arabinoside. In 50 patients treated for leukemia, seven patients were found to have bowel necrosis and peritonitis at autopsy.Paclitaxel (Taxol), which is commonly used to treat patients with ovarian, breast, and non-small-cell lung cancers, has also been reported as a chemotherapeutic agent that can cause bowel perforation unrelated to tumor lysis. In patients with advanced ovarian cancer, this is a rare but serious complication, and its presentation is associated with a 43% mortality rate. Noncytotoxic drugs are the presumed cause of perforation when bowel wall injury cannot be associated with tumor necrosis or other specific factors in patients with cancer who are undergoing drug therapy. Immunosuppressed patients have a blunted inflammatory response and may have a more subtle presentation of GI perforation. The drugs that are most commonly implicated are corticosteroids, which can give rise to ulcers and perforations in various portions of the GI tract.
INFLAMMATORY CONDITIONS IN THE CANCER PATIENT
Increasingly, aggressive chemotherapeutic regimens are being employed in the treatment of patients with cancer. These treatments can expose patients to life-threatening complications related to bone marrow suppression and neutropenia. The incidence of acute illnesses necessitating surgical intervention in the setting of the neutropenic patient with cancer is approximately 7%. Unique inflammatory abdominal problems in patients with cancer receiving aggressive therapies are reviewed in this section.
Neutropenic enterocolitis is a clinicopathologic syndrome that involves the gastrointestinal tract of patients receiving chemotherapy for hematologic and solid malignancies. The clinical condition has been given a variety of names in the past, including typhlitis, ileocecal syndrome, and necrotizing enteropathy. Most commonly seen in pediatric patients who are undergoing treatment for leukemia, neutropenic enterocolitis is still a relatively rare occurrence in adults, with an incidence of less than 5% in this patient population.   
The pathophysiologic basis of this clinical entity has not been established clearly and is undoubtedly multifactorial. Neutropenic enterocolitis characteristically affects the terminal ileum, cecum, and ascending colon in patients with chemotherapy-induced neutropenia. Although any part of the GI tract can be involved, the cecum appears to be the most severely affected, with mucosal ulceration, gangrene, and perforation. The presence of microorganisms such as Clostridium difficile, Pseudomonas, Escherichia coli, Klebsiella, and Candida in areas of necrotic bowel and in blood cultures suggests that enterocolitis is primarily an infectious process in an immunocompromised host. The invasion of bacteria itself can cause further necrosis of the bowel wall, leading to full-thickness infarction and perforation of the intestine.
The clinical presentation of neutropenic enterocolitis is extremely variable, and there are no specific criteria on which to make the diagnosis. Furthermore, the symptoms are nonspecific and can be similar to those of a number of other GI processes. Affected patients typically present with fever, abdominal pain and distension, and diarrhea. Abdominal tenderness is frequently localized to the right lower quadrant but can also be diffused. Peritonitis suggests intestinal perforation. Portal venous gas, low serum bicarbonate levels, and generalized peritonitis are ominous findings and suggest a poor outcome.  A right lower quadrant mass might be palpable, indicating a dilated cecum or a focal inflammatory phlegmon or abscess. Advanced cases can present with systemic sepsis and multiorgan failure.
No specific laboratory or radiologic findings are diagnostic for neutropenic enterocolitis. Pneumatosis intestinalis is often seen and is not itself an indication for surgical intervention. The initial treatment for neutropenic colitis is supportive, with the administration of broad-spectrum antibiotics, nasogastric decompression, intravenous fluids, bowel rest, and serial abdominal examinations. In most patients, these measures are sufficient, and symptoms resolve after correction of the neutropenia. Surgical intervention is rarely helpful, but sound surgical judgment should be exercised in determining which patients require an operation ( Box 53-2 ). Specific situations that dictate surgery include uncontrollable GI bleeding, intestinal perforation, and deteriorating clinical course on medical management.
CONDITIONS FOUND AT SURGERY IN NEUTROPENIC PATIENTS WITH CANCER UNDERGOING EMERGENCY LAPAROTOMY
Other intra-abdominal inflammatory conditions, such as appendicitis, can be indistinguishable from neutropenic enterocolitis in patients receiving chemotherapy. In large series of children with leukemia or other malignancies, the incidence of appendicitis has been reported to be between 0.2% and 2%, which is equivalent to the incidence in the general pediatric population. Typically, acute appendicitis presents with right lower quadrant pain and localized tenderness. “Classic” symptoms and clinical findings of appendicitis can be followed by a CT scan to confirm diagnosis. Whereas the treatment of neutropenic enterocolitis is primarily medical, the treatment of acute appendicitis is surgical. Nonoperative management of appendicitis (e.g., intravenous antibiotics with interval appendectomy) is associated with high mortality in patients with leukemia. Delay in treatment results in a higher incidence of perforation, peritonitis, and death. Appendectomy is the treatment of choice for appendicitis. Cases that are complicated by perforation or abscess formation could necessitate the placement of drains, and the surgical incision should be left to close by secondary intention.
Pancreatitis in the patient with cancer is likely to be caused by the same factors that are implicated in the general population, such as gallstones or alcohol abuse. However, pancreatitis can also be a complication of either medical or surgical therapy. Primary adenocarcinoma of the pancreas is seldom a cause of acute pancreatitis. Metastases to the pancreas have been reported from a variety of tumors, including renal cell carcinoma, melanoma, some types of soft tissue sarcoma, and cancers of the prostate, breast, and lung. However, the vast majority of these metastases are asymptomatic.
Pancreatitis is a recognized complication of a number of antineoplastic chemotherapeutic agents, although the drug with which it is most commonly reported is L-asparaginase. Other antineoplastic drugs that are known to induce pancreatitis are corticosteroids, didanosine, and, less commonly, cytarabine, cisplatin, interleukin-2, vincristine, methotrexate, mitomycin C, cyclophosphamide, doxorubicin, and ifosfamide.   The clinical course of patients with chemotherapy-induced pancreatitis is most often mild and self-limiting but can progress to necrotizing pancreatitis or pseudocyst formation. Pancreatitis is also a complication of other cancer treatments. Associated procedures, such as endoscopic retrograde cholangiopancreatography, pancreatectomy, or splenectomy, can also result in pancreatitis. Transarterial embolization of the liver for primary or metastatic tumors can cause pancreatitis by misperfusion of chemotherapeutic agents.
The clinical presentation of pancreatitis includes epigastric pain, nausea, vomiting, generalized ileus, tachycardia, and fever. The diagnosis is usually confirmed by elevations in the serum amylase and lipase levels. CT of the abdomen with intravenous contrast is useful to confirm the presence of pancreatic inflammation or phlegmon and to document necrosis or pseudocyst. The treatment of pancreatitis is generally supportive and includes bowel rest, hydration, and intravenous hyperalimentation. If possible, the causative agent should be eliminated or discontinued, if it can be identified. Necrotizing pancreatitis warrants consideration of pancreatic debridement if there is overwhelming infection.
Perianal and Perirectal Infections in Patients with Cancer
The exact pathogenesis of perianal infections in the patient with cancer is not well defined, though most patients have an underlying neutropenia or immunosuppression. Many patients have a history of pre-existing anorectal problems, including previous perianal or perirectal abscesses, fistula in ano, anal fissures, or hemorrhoids. Once established, the infection can spread into the ischiorectal fossa, supralevator space, retroperitoneum, or perineum. Perianal and perirectal infections develop most frequently in patients with acute leukemia who are being treated with chemotherapy but can also be encountered in some patients with solid tumors or following BMT. In most series in the literature, the incidence of perianal infections in patients with leukemia is between 2% and 8%.  
The most common presenting symptoms are perianal pain and fever. On examination, the perianal region could be erythematous, indurated, and extremely tender to palpation. Often, an abscess does not develop owing to the patient's profound neutropenia or immunosuppression. Spontaneous drainage of an abscess can result in ulceration, purulent discharge, or bleeding. Spread of the infection in the perineum can lead to a fulminant necrotizing fasciitis. The initial course of therapy is administration of broad-spectrum antibiotic and supportive measures such as sitz baths, warm compresses, stool softeners, and analgesics. Most patients can be managed successfully using a nonoperative approach. However, early surgical intervention for complete drainage of pus and debridement of necrotic tissue may be required and should not be delayed when indicated.
Complete or partial obstruction of the GI tract is a common problem in patients with cancer. Typical presentation includes abdominal pain, nausea, and vomiting. Intestinal obstruction is one of the most common indications for emergency laparotomy.   Intestinal obstruction can occur at any site along the GI tract, and symptoms are often dictated by the level of obstruction. Initial symptoms may be identical to those of adynamic ileus, a condition that needs to be distinguished from obstruction. Adynamic ileus in patients with cancer can be related to chemotherapeutic agents or can be secondary to other metabolic problems. Vincristine sulfate and the vinca alkaloids are known to produce peripheral neuropathies and a paralytic ileus. Drug-induced ileus is estimated to occur in 10% of patients receiving these agents and could be due to their neurotoxic effects. Clinical presentation and radiologic studies are very helpful in differentiating adynamic ileus from a mechanical obstruction. With an adynamic ileus, generalized small bowel and colonic distension is apparent on plain films without the multiple air-fluid levels and absence of colonic gas that are seen with mechanical obstruction. Cross-sectional imaging with CT is now the adjunctive study of choice, since it can provide information simultaneously about the presence, level, severity, and cause of obstruction.  
Therapeutic options include nasogastric decompression with bowel rest (e.g., NPO with intravenous fluid support). Adjunctive treatment with analgesics, antiemetics, somatostatin, or motility agents have been used with varying success. Patients with a history of previous malignancy who present with bowel obstruction should be treated like any other patient with intestinal obstruction. In the case of a first presentation with obstructive symptoms, the etiology is benign (e.g., due to adhesions or herniation) in up to one third of patients. Many patients who require laparotomy to treat their obstructions are found to have benign disease, and some even have a new primary malignancy. Given a good baseline performance status, surgical exploration for benign causes of obstruction have a high rate of success.
Recurrence of cancer, either locally or as diffuse peritoneal disease, is a more common problem and, unfortunately, is more difficult to treat. Surgical intervention is required if bowel strangulation and infarction are suspected because of fever, leukocytosis, and localized peritoneal tenderness. Radiographic evidence of complete bowel obstruction with loss of air in the distal large bowel and absence of flatus may likewise prompt an urgent laparotomy. Patients with partial obstructions can be managed expectantly. Further evaluation to include CT scan or other contrast studies may be helpful in delineating level(s) or extent of obstruction ( Fig. 53-2 ).
Figure 53-2 Small bowel obstruction in a patient with metatstatic appendiceal carcinoma. A, CT scan of the abdomen demonstrating a widely patent–stapled anastomosis from a prior right colectomy; B, Decompressed bowel distal to the point of obstruction (arrow).Findings at laparotomy were consistent with intractable bowel obstruction due to adhesions from small tumor implants.
Successful nonoperative management of malignant bowel obstruction is reported in up to 29% of cases; however, recurrent episodes of obstruction are commonplace. Operative mortality and successful intervention rates for patients with cancer undergoing exploratory laparotomy for intestinal obstruction are difficult to measure, since patient selection bias tends to skew the reported results. The extent of disease and failing performance status are associated with high perioperative morbidity and mortality.   Even with early relief of symptoms, durability of palliation can be short.
Retrospective studies have identified presence of ascites and multiple sites of obstruction as factors predictive of unsuccessful surgical intervention. Conversely, long disease-free interval, good nutritional status (albumin >3.0 mg/dL), and good performance status are predictive of successful laparotomy. However, each patient must be approached on an individual basis, and it is of paramount importance to combine surgical decision making with basic principles of palliative care in forming a treatment plan. The reported results of surgical treatment for intestinal obstruction in this patient population vary significantly. The site of the primary tumor may also influence the clinician's approach to management, since the natural history of a cancer should also be taken into account.
Stomach and Duodenum
The most common causes for upper GI obstruction involving the stomach or proximal duodenum in patients with cancer are benign peptic ulcer disease, primary carcinoma of the gastric antrum, and gastric outlet obstruction secondary to an upper GI, pancreatic, or biliary tract cancer. Symptoms due to obstruction at this level include nonbilious vomiting, postprandial pain, and epigastric fullness. On physical examination, a succussion splash or palpable mass is present in approximately one third of cases, reflecting ascites and tumor burden. Endoscopy is helpful for defining the site and cause of upper GI obstruction.
Benign, obstructive ulcer disease is uncommonly seen in the modern era of H2-receptor blockers and proton pump inhibitors. Operative therapy is generally required after initial stabilization with fluid resuscitation and nasogastric decompression in uncontrolled cases. Vagotomy with pyloroplasty is the treatment of choice, particularly for patients with cancer who might be debilitated. For obstructing primary gastric carcinomas, a curative resection with gastrojejunostomy reconstruction is recommended if the patient is stable and if the procedure is technically feasible. In cases of advanced disease, gastrostomy tube placement, with or without gastrojejunostomy (intestinal bypass), may be the best course of action. When gastric outlet obstruction is due to an unresectable pancreatic or biliary tract neoplasm, prognosis is typically poor owing to the extent of disease. Creation of a gastrojejunostomy via an open or laparoscopic approach can be considered for bypassing the obstruction and maintaining gastrointestinal continuity, but outcomes are not uniform. Many patients have poor emptying of stomach contents even with a mechanically patent anastomosis. Therapeutic endoscopic options are in their infancy, and success has been seen with endoscopically deployed metal endoluminal stents. This procedure is gaining widespread acceptance, and reports show 70% relief of symptoms with low complication rates. Common complications include perforation (0% to 15%) and stent migration (0% to 40%).   In patients with concomitant biliary obstruction from a cancer in the head of the pancreas, an endoscopic retrograde cholangiopancreatography can be performed at the same setting to accomplish biliary stenting with plastic or metal prostheses.
Most malignant obstructions of the small intestines are a result of metastatic deposits from other cancers; primary tumors of the small bowel are rare. The most common malignancies that give rise to obstructive metastatic deposits are intra-abdominal tumors, such as colorectal, ovarian, pancreatic, and gastric cancers. Carcinomatosis with resultant malignant bowel obstruction from appendiceal primaries (including pseudomyxoma peritonei) are seen less commonly. Symptoms of small bowel obstruction include crampy abdominal pain, distension, nausea, and vomiting. Physical examination usually reveals percussion tympany and high-pitched bowel sounds. Plain films of the abdomen reveal multiple air-fluid levels within the small intestine. A contrast study of the large bowel should be performed to determine whether distal obstruction is present, as carcinomatosis can involve multiple sites. If a partial small bowel obstruction is diagnosed (e.g., presence of gas in the large bowel), then nonoperative management is generally recommended.
During an exploratory laparotomy when intestinal bypass is being considered, it is preferable to perform the simplest procedure with maximal conservation of bowel length. Ileostomy or colostomy might be unavoidable, depending on the level of obstruction. At least one third of patients with symptomatic relief of malignant small bowel obstruction experience recurrence of the obstruction at a later point in time. Survival after bypass surgery for malignant obstruction is often short, and is a marker of advanced malignancy.
Colon and Rectum
Obstruction of the colon and rectum occurs approximately half as frequently as small bowel obstruction in the cancer patient population. Large bowel obstruction is more often a result of malignancy (i.e., primary or recurrent tumor) than of benign causes such as volvulus or diverticulitis. Symptoms include vomiting, crampy abdominal pain, bleeding, lack of flatus or stool, or change in bowel habits. Flat and upright abdominal films are important in the initial assessment of these patients. Follow-up contrast studies are helpful in delineating the site of obstruction.
Initial treatment should consist of nasogastric tube decompression and fluid resuscitation. If a total colonic obstruction is present, dilation of the proximal colon can lead to perforation of the cecum, especially if a competent ileocecal valve is present. Cecal dilation of 12 to 14 cm is associated with a high risk of perforation, and a decompressive procedure should be performed urgently to avoid this complication. A diverting colostomy may be the surgical therapy of choice if there is evidence of peritoneal carcinomatosis. If the obstruction is related to a primary colon cancer, resection with primary anastomosis or ostomy should be performed. Obstructive tumors of the rectum are often a harbinger of locally advanced primary rectal tumors or recurrent carcinomas after a previous low anterior resection. These tumors are often associated with evidence of distant metastatic disease or a high local recurrence rate if resection is performed. Therapeutic endoscopy with colonic stenting offers an alternative to surgical diversion, providing excellent palliation and allowing an elective procedure to be performed following bowel decompression and other treatments if necessary. There is no apparent difference in long-term survival rates with stents compared to an emergent operation.
Palliation Issues in Bowel Obstruction
Heterogeneity of patient populations, coupled with lack of evidence-based medicine in this area, makes appropriate patient selection one of the biggest challenges in palliative surgery. End-stage cancer patients are diverse in multiple facets: symptoms experienced, tumor biology, extent of underlying disease, previous treatments received, type of palliative procedure performed, and psychosocial circumstances, to name a few. Deterioration of a patient's general medical condition can make operative treatment of bowel obstruction prohibitive or inappropriate. A patient might also wish to avoid further operative interventions in the face of terminal disease. In these patients, optimal medical management should be considered to help alleviate suffering from abdominal pain, nausea, vomiting, and dehydration.
Because of the nature of the underlying disease process, surgical resection and/or bypass might not yield durable palliation. Proper patient selection is paramount to successful palliative efforts. Recent series have reported effective palliation in up to 80% of patients with obstruction. Another approach that has been described for the therapy of these patients is the use of a decompressive gastrostomy tube in conjunction with either enteral or parenteral fluids. Management of malignant bowel obstruction has to be coordinated with end-of-life care in some patients. Time to mortality with malignant bowel obstruction is short; small series report mean durations of survival ranging from 35 to 64 days regardless of intervention.    
GASTROINTESTINAL PROBLEMS FOLLOWING BONE MARROW TRANSPLANTATION
Evaluation of acute abdominal complaints in patients who have had BMT represents a major diagnostic challenge for the surgeon. Virtually all patients who have undergone BMT will experience gastrointestinal problems at some point in the post-transplant period; these can include nausea, vomiting, alterations in liver function tests, diarrhea, and abdominal pain. Such findings in an acutely ill patient following BMT may herald a broad spectrum of acute abdominal processes. There are, however, several disease entities that are unique to the BMT patient, and these warrant special consideration.
There are three common causes of abdominal complaints in the BMT patient that are unique:
High-dose induction chemotherapy or chemoradiation therapy given before transplantation
Acute intestinal graft-versus-host disease (GVHD) in recipients of allogeneic transplants
Infections of the gut that occur before bone marrow recovery
The post-transplant period at which each of these potential complaints becomes problematic differs. Injury to the gastrointestinal tract and liver after high-dose chemotherapy and radiation is usually present by day 10; the process is transient and usually resolves after several weeks. Acute GVHD appears between 2 and 8 weeks after allogeneic BMT, while chronic GVHD is manifest from 3 to 15 months after BMT. In patients receiving HLA-mismatched marrow, the onset of acute GVHD could be as early as 7 days. Lower GI tract involvement with acute GVHD is characterized by diarrhea and abdominal cramping and is often severe in its presentation. GVHD affecting the upper GI tract is characterized by anorexia, dyspepsia, nausea, and vomiting. Biopsies of affected portions of the GI tract for histologic examination are diagnostic, though diagnosis is often made on clinical grounds. Immunosuppression with combination therapy is the cornerstone of treatment.
Infections of the gut caused by bacteria and fungus are most often seen before post-transplant day 30, while viral infections are usually seen after 30 days, although there are reports of late (5 months to 1 year) reactuation of varicella zoster infection associated with acute abdominal pain, hepatitis and pancreatitis, or disseminated disease. Mortality rates are from 50% to 100%.  
GVHD is a process in which donor T-cells react to recipient cells; it develops in 30% to 50% of patients receiving allogeneic grafts.   Despite the prominence of intra-abdominal organs and symptoms in the manifestations of GVHD, it is rare that surgical intervention is necessary. The most common indications for abdominal surgery in patients with GVHD are gastrointestinal bleeding and obstruction.  Perforation of the bowel is uncommon. The finding of pneumatosis intestinalis on abdominal radiography has been reported to be present in as many as 18% of BMT patients with acute GVHD;the majority of these cases do not require operation.     Although usually an indication for surgery, free air in the peritoneal cavity need not be associated with a frank bowel perforation, and there are reports of managing this problem without an operation.
Another intra-abdominal complication of BMT that presents with abdominal pain is venoocclusive disease (VOD) of the liver.   The etiology of VOD is thought to be damage to the endothelium of hepatic venules and centrilobular hepatic necrosis, leading to fibrosis and occlusion of the central hepatic veins. VOD is associated with significant mortality. The differential diagnosis of VOD is lengthy and includes any disorder that could result in right upper quadrant pain, jaundice, or ascites. A partial list would include such disorders as hepatitis, drug- or parenteral nutrition-induced liver dysfunction, acute cholecystitis, cholangitis, or liver abscess; careful workup should be undertaken. The diagnosis of VOD can usually be made on clinical signs, liver biopsy being reserved for patients in whom the diagnosis is not certain ( Fig. 53-3 ). Because of underlying hematologic disorders, liver biopsies are associated with acute bleeding and must be performed with care. The treatment of VOD is supportive, with emphasis on maintaining intravascular volume and renal perfusion while limiting the amount of sodium and extravascular fluid accumulation.
Figure 53-3 Venoocclusive disease following bone marrow transplant. A, CT scan of the abdomen demonstrating no abnormalities of the liver. B, Following allogeneic peripheral stem cell transplant for refractory large B-cell lymphoma, this patient developed increasing fatigue, abdominal distention, and elevated liver function tests. CT scan showed new findings of ascites and low-density diffusion of the liver. Subsequent laparoscopic biopsy of the liver confirmed venoocclusive disease.
In summary, BMT has become a proven and accepted treatment for a number of hematologic and solid malignancies. Transplant-related complications, such as GVHD and VOD, remain a major cause of morbidity and mortality. The presentation and sequelae of both these disease entities present difficult diagnostic and management challenges for the clinician. Although the management of GVHD and VOD is primarily medical, surgical consultation could be required for evaluation of abdominal pain and distension, nausea, vomiting, diarrhea, hyperbilirubinemia, or other gastrointestinal complaints. An understanding of the manifestations of these complications, together with vigilant clinical evaluation, is paramount to determine when surgical intervention is necessary in this complex patient population.
A fistula is an abnormal connection between two epithelialized surfaces, and fistula formation is an important complication of cancer and its treatment. Fistulae that complicate cancers have been reported between the stomach and pericardium, the biliary and bronchial trees, the portal and systemic circulations, and the alimentary canal and vascular system, to name a few. This overview concentrates on the more routine fistulae connecting the skin, alimentary canal, and genitourinary tract in various combinations.
Fistulae are seen as complications in patients with cancer because multiple risk factors for fistula development are often present in these patients. Fistulae are rarely the presenting symptom of an intra-abdominal malignancy; they most often present as complications during or after treatments. Most clinicians agree that contributing factors include prior abdominal surgery, inflammatory bowel disease, use of radiation therapy, cancer, malnutrition, and intra-abdominal sepsis. Unfortunately, many of these factors are prevalent in patients with cancer and are not often reversible. Despite the use of total parenteral nutrition, enteral nutrition, antibiotics, and highly sophisticated bioengineered wound care adjuncts, mortality and morbidity rates from gastrointestinal fistulae remain high. Although mortality rates as low as 7% are reported, numbers in the range of 10% to 30% are more representative.   The exact incidence of GI fistula formation in patients with cancer is not known but is likely quite low.
Enterocutaneous fistulae commonly occur in patients who have received radiation therapy. Direct invasion with subsequent tumor necrosis can result in an abnormal connection between viscera and the skin. Ischemic necrosis secondary to neoplastic vascular invasion or secondary to small vessel occlusion from host reaction and sclerosis likewise can lead to fistula formation. Finally, tumor-induced perforation with abscess and subsequent erosion can result in fistula formation. This latter mechanism is particularly troublesome, as it can lead to diagnostic confusion and can complicate management. Ionizing radiation could have both acute and chronic effects on the GI tract. The acute effects—a result of the depletion of rapidly proliferating mucosal cells causing diarrhea, nausea, vomiting, abdominal pain, and GI tract bleeding—are generally self-limiting. However, chronic radiation damage can become evident as early as 1 month after radiation therapy, or it might not be clinically apparent for as long as 30 years after treatment.   Although radiation injury to the bowel can arise as a complication in as many as 15% of patients receiving treatment to abdominal fields, fistulae occur more rarely. Factors related to the incidence of radiation-induced injury include the total radiation dose and fractionation, the sensitivity of exposed normal organs within the radiation port, anatomic considerations, the presence of comorbid conditions, and concomitant administration of other drugs.
Bowel tolerance of radiation therapy is limited. The small bowel, stomach, and colon are the least tolerant organs, with a maximum tolerated dose of 45 Gy. The greater the amount and extent of exposure to the radiation beam, the greater is the risk of injury. Factors that tend to fix the bowel in a single location, such as postoperative adhesions, increase the likelihood of radiation enteritis. Pre-existent large-vessel atherosclerosis and small-vessel diabetic vasculopathy can increase sensitivity to radiation injury. Finally, the effects of many chemotherapeutic agents—especially doxorubicin, 5-fluorouracil, gemcitibine, and mitomycin-C—can potentiate the effects of radiation therapy, increasing its toxicity. In this regard, pyrimidine analogs such as bromodeoxyuridine and iododeoxyuridine are being studied as tumor-selective radiation sensitizers. Many techniques have been developed to limit GI tract exposure to radiation, including the use of shielding and conformal mapping techniques as well as intra-operative radiation therapy, whereby normal visceral structures can be better shielded from the radiation ports.
Fistulae that complicate cancer generally occur during active treatment or subsequent follow-up. To reduce the risk of fistula formation following surgical procedures, adherence to good surgical principles and techniques is thought to be helpful. Systemic antibiotics might help to prevent complications (including fistulae) in these situations. Intra-operative risk factors for fistula formation include active infection, extensive adhesions, creation of serosal injuries, prior radiation therapy, prior fistulization, and presence of ischemic tissue. Thorough drainage of all intra-abdominal infection and debridement of all devitalized and ischemic tissue can reduce the incidence of fistulae. Protection of sites of anastomosis or extensive dissection could also be important, particularly in the previously irradiated abdomen. Vascularized flaps, including serosa, omentum, and muscle, have all been described to fill soft tissue defects and exclude small bowel from areas of dissection. Many investigators have demonstrated the relationship of nutritional status to operative morbidity and mortality, including fistulae. In patients with cancer who developed postoperative gastrointestinal fistulas, an albumin level of less than 3.0 g/dL was a poor prognostic factor for fistula closure.
GI fistulae occur commonly during the treatment of gynecologic malignancies. Although less common, they also occur in the settings of bladder and rectal cancer. Postoperative irradiation after the extensive pelvic operations exposes the bowel to high doses of ionizing radiation. Fistulae resulting from the treatment of other cancers are much less common.
A number of factors decrease the likelihood of spontaneous closure of a fistula. The most common are undrained infections and luminal obstruction distal to the fistula. Other factors include prior radiation or chemotherapy, epithelialization of the fistula tract, cancer within the tract, granulomatous disease (e.g., inflammatory bowel disease or mycobacterial infection) within the fistula, presence of a foreign body, and malnutrition. Although predictive of morbidity due to fistulae, fistula output does not necessarily appear to be related to the probability of spontaneous fistula closure. Given proper nutritional support and attention to these factors, as many as 60% of GI fistulae can close spontaneously.  
Complications that are routinely encountered with GI fistula include fluid and electrolyte disorders, sepsis, malnutrition, and impaired skin integrity. The frequency and severity of these complications relate to the daily volume of fistula output and to the composition of the output. High-output fistulae (>1 L/day) tend to originate more proximally in the GI tract. Because of the specialized composition of gastric juice, bile, and succus pancreaticus, these more proximal fistulae not only tend to lead to dehydration but also are more prone to cause electrolyte and acid-base imbalances. Low-output fistulae generally originate more distally in the alimentary canal, resulting in low-volume outputs that are generally isotonic. For these reasons, the classification of fistulae according to their daily output volume can help to predict the likelihood and kinds of complications to be expected.
Resuscitation of patients with GI fistulae follows the principles of general fluid and electrolyte assessment and management. A urinary catheter and, if necessary, central venous pressure monitoring are quite helpful. Specific fluid, electrolyte, and acid-base disturbances, organ dysfunction, and nutritional status should be identified with the initial bloodwork and treated appropriately. Subsequent diagnostic and therapeutic maneuvers must await completion of the resuscitation phase, so these issues must be dealt with promptly, over the initial 12 to 48 hours after presentation.
Patients who exhibit signs of sepsis must be evaluated aggressively to identify the source. Intra-abdominal and perifistular abscesses are common and must be identified quickly. Thorough physical examination (including digital examination of the rectum, vagina, stomas, and wounds) is absolutely necessary. CT scanning of the abdomen and pelvis using intravenous and enteric contrast and contrast in the rectum, fistula tract, and drainage tubes is often the most enlightening radiologic study ( Fig. 53-4 ). Any undrained foci of infection must be addressed aggressively and drained either percutaneously or operatively. Once the acute electrolyte imbalances have been corrected and the fistula output has stabilized, intravenous fluid and nutritional infusions may be combined to simplify fluid management. Definitive treatment of fistulae ultimately requires the reestablishment of normal skin integrity; macerated skin and large open wounds complicate and delay spontaneous or operative closure. Techniques such as sump drainage, stoma bag application, and barrier protection of the skin using special adhesives or pastes should be used liberally.
Figure 53-4 Arterioenterocutaneous fistula. Patient with a multiply recurrent high-grade liposarcoma of the spermatic cord treated with radical surgical resection and radiation therapy. After the most recent surgery, the patient developed an enterocutaneous fistula that was managed conservatively. He later presented with brisk bleeding from the fistula and per rectum. A, CT scan of the pelvis demonstrating recurrent tumor and tract (arrows) of enterocutaneous fistula. B, Arteriogram with contrast extravasation from the left external iliac artery and communication of the bowel (arrow).
Malnutrition either pre-exists or will develop in nearly all patients with GI fistulae unless specific, aggressive nutrition support is initiated early in the treatment course. Either enteral or parenteral nutrition support can generally be started as soon as the initial resuscitative and stabilization measures have been accomplished. Formal nitrogen balance studies and indirect calorimetric measurement of energy expenditure are the gold standards for adjusting protein and calorie intake to meet needs. Once requirements have been determined, the route of administration that is chosen depends on overall patient status and the nature of the fistula. In general, early initiation of parenteral nutrition is helpful to ensure adequate support without delay. Subsequent aggressive attempts should be made to meet some or all of the patient's nutritional requirements enterally.
Fistulae can be managed appropriately only when their anatomic features are well defined. Reversible causes for fistulae failing to close spontaneously must be identified. Careful examination of the fistula with appropriate biopsies is necessary to rule out epithelialization or the presence of cancer. Generally, the entire GI tract should be investigated with radiographic contrast studies to rule out distal obstruction, to determine the origin of the fistula accurately, and to identify all involved organs and poorly drained associated abscesses. A fistulogram, obtained in the presence of an experienced surgeon, can provide valuable anatomic information and can help in the formulation of surgical plans. In patients with cancer, a thorough search for recurrent and metastatic disease is also important.
In patients who are stable and in whom no factors preventing spontaneous fistula closure are present, a trial period of nonsurgical management is generally indicated. The availability of parenteral and enteral nutrition support programs should be coordinated with home care services to allow for spontaneous closure. In some patients, adequate stabilization cannot be achieved. Ongoing fistula output or sepsis in these patients precludes nutritional repletion, adequate skin care, and protection of end-organ function. In this setting, early operation is mandatory.
The operative goals for treating intestinal fistulae are to effect excision of the fistula tract and associated diseased tissue, restore continuity of the GI tract, and prevent recurrent fistulae. Use of vascularized omental, mesenteric, bowel, or muscular flaps to fill inflamed cavities and protect anastomoses is often helpful and should be planned for in conjunction with appropriate consultants preoperatively. The definitive operation is a good opportunity to simplify subsequent management of the patient through the insertion of enteric tubes for feeding and GI drainage. Bypass of fistulae can be a useful palliative technique when definitive resection is technically impossible or is thought to be associated with prohibitive morbidity.
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