A 65-year-old man presents with dyspnea on exertion and angina. The patient’s current symptoms have been present for approximately 3 to 4 weeks. He denies any cough, weight loss, and gastrointestinal (GI) tract symptoms. His past medical history is significant for hypertension, stable angina, and colonic polyps that were removed 7 to 8 years ago by colonoscopy. The physical examination reveals a well-nourished man who is in no acute distress. The findings from head and neck, cardiopulmonary, and neurologic examinations are unremarkable. Examination of the abdomen reveals an obese abdomen without tenderness or palpable masses. The rectal examination reveals no masses, a smooth and enlarged prostate, and strongly Hemoccult-positive stool in the vault. The complete blood count reveals a normal white blood cell (WBC) count, hemoglobin 8.7 g/dL, hematocrit 29%, and mean cell volume 72 fL (normal, 76-100 fL). The electrolyte levels and liver function studies are within normal limits. A 12-lead electrocardiogram reveals normal sinus rhythm and mild left ventricular hypertrophy. A chest radiograph reveals a normal cardiac silhouette, no pulmonary infiltrate, no pleural effusion, and no pulmonary mass.
What is the most likely mechanism causing this process?
How would you confirm the diagnosis?
ANSWERS TO CASE 19: Colorectal Cancer and Polyps
Summary: A 65-year-old man presenting with dyspnea on exertion and worsening angina pectoris related to anemia produced by occult GI tract bleeding.
• Most likely mechanism: Anemia caused by occult GI tract bleeding.
• Confirmation of diagnosis: Esophagogastroduodenoscopy (EGD) to evaluate the upper GI tract and colonoscopy to evaluate for a possible colorectal source of bleeding.
1. Learn the clinical presentation and management of colorectal cancer.
2. Know the risk factors for and surveillance of high-risk patients.
This patient presents with angina, dyspnea on exertion, microcytic anemia, and guaiac-positive stool. His presentation is strongly indicative of occult GI tract blood loss. The lower GI tract is the most likely source of bleeding in patients who are not consuming aspirin or other nonsteroidal anti-inflammatory drugs. In this case, the initial treatment should consist of transfusion to improve the patient’s anemia, followed by endoscopic evaluation of the upper and lower GI tract with EGD and colonoscopy. If the source of the blood loss is not identified after these diagnostic procedures, evaluation of the small bowel for a blood loss source by contrast radiography should be performed. Given his previous history of colonic polyps requiring endoscopic removal, this man is at risk for the development of polyps as well as colorectal cancer. Thus, he should have been placed on a regular surveillance schedule 8 years ago, with repeated colonoscopy after 3 years. If negative results were obtained, he should subsequently have been placed on surveillance colonoscopy at 5-year intervals.
APPROACH TO: Colorectal Cancer and Polyps
ABDOMINOPERINEAL RESECTION: Resection of the rectum and anal canal including anal sphincter complex for a low-lying rectal carcinoma. The procedure leaves the patient with a permanent colostomy.
LOW ANTERIOR RESECTION: Resection of the rectum to the level of the levator ani muscles leaving the anal canal and anal sphincter muscles intact so that a stapled or hand-sewn anastomosis can be performed.
BOWEL PREPARATION FOR ELECTIVE COLON SURGERY: A mechanical preparation consisting of a large volume of polyethylene glycol solution or a smaller volume of phospho soda and a broad-spectrum intravenous and/or oral nonabsorbable antibiotic. The goal is to decrease the bacterial count in the event of spillage of colonic contents.
Colorectal cancer is the fourth most common internal malignancy and the second most common cause of cancer death in the United States. (Lung cancer is the most common.) The average American has an approximately 5.5% to 6% lifetime risk of developing colorectal cancer. This cancer is predominantly a disease of the middle-age and elderly population, with only 5% of cancers occurring in patients younger than 40 years. Roughly 70% of colorectal cancers initially develop as adenomatous polyps. Through a series of mutations in protooncogenes and tumor suppressor genes, a malignant transformation occurs leading to the development of carcinoma. Based on the polyp-carcinoma sequence of cancer development, it is possible to prevent cancer by identifying and removing polyps prior to the development of invasive cancer. The rectum and sigmoid colon have long been the most common sites of malignancy; however, this is changing as right-sided colon cancers are steadily increasing in number.
Disease screening can most effectively be accomplished by complete colonoscopy. For average-risk individuals, the American College of Gastroenterology screening recommendation is colonoscopy every 10 years beginning at 50 years of age. If an adenomatous polyp bigger than 1 cm is identified and removed, repeat colonoscopy should be done in 3 years. When the colon is clear of polyps, colonoscopy can be done every 5 years.
Symptoms of colorectal cancer vary depending on the location of the tumor. The most common presenting symptom is rectal bleeding (occult or gross). After bleeding, symptoms include chronic changes in bowel habits in 77% to 92% of patients, obstruction in 6% to 16%, and perforation with peritonitis in 2% to 7%. Characteristic changes in bowel habits are a decrease in the caliber of stools and diarrhea. These are more commonly seen with left-sided tumors and rectosigmoid tumors. Tumors of the right side are less likely to cause obstructive symptoms until late in the course of the disease. Anemia is a more common presentation in these patients.
The TNM (tumor-node-metastasis) system and the Astler-Coller modification of the Duke classification are the most common staging systems used for colorectal carcinoma (Tables 19–1 and 19–2).
Table 19–1 • TNM STAGING SYSTEM
Table 19–2 • ASTLER-COLLER MODIFICATION OF THE DUKE CLASSIFICATION
Patients with colonic polyps can be treated with endoscopic resection. Endoscopic therapy is considered definitive when the resection of the polyp is complete. Cancer risks increase with larger polyps, with the risk of carcinoma approximately 1.3% for adenomatous polyps smaller than 1 cm, 9.5% for polyps 1 to 2 cm, and 46% for polyps bigger than 2 cm. Polypectomy alone is considered curative if the tumor has not penetrated the submucosa, whereas submucosal penetration increases the likelihood of regional lymph node metastasis.
Invasive adenocarcinoma of the colon requires segmental resection of the involved colon. Colon resections performed laparoscopically have been found to be associated with improved postoperative quality of life and more rapid recoveries in comparison to open resections. Although once considered less ideal for cancer control, laparoscopic colectomy for colorectal cancer has been demonstrated to provide similar disease-free survival, overall survival, and local-recurrence rates as open operations in four published randomized controlled trials. A patient with a reasonable life expectancy should undergo a preoperative metastatic workup, including chest radiography and abdomen and pelvic computed tomography (CT) scans. The amount of colon resected is based on blood supply and regional lymphatic drainage (Figure 19–1). Primary anastomosis can be performed with stapling devices or via a hand-sewn technique. Both methods have equal risks of anastomotic dehiscence and stricture. Following recovery from colon resection, patients with lymph node involvement (stage III disease) have improved survival and a reduced possibility of recurrence when they are given adjuvant chemotherapy. Current standard therapy is the FOLFOX4 regimen: 5-FU (fluorouracil), leucovorin, and oxaliplatin. The approximate 5-year survival of patients by stage is as follows: stage I, 80% to 90%; stage II, 60% to 70%; stage III, 40% to 60%; and stage IV, 4% to 9%.
Figure 19–1. Resection of colon cancer. Right colectomy (A), right hemicolectomy with division of middle colic pedicle (B), transverse colectomy (C), resection of splenic flexure sparing left colic artery (D), left hemicolectomy (E), sigmoid colectomy sparing left colic artery (F). (Reproduced, with permission, from Niederhuber JE, ed. Fundamentals of Surgery. Stamford, CT: Appleton & Lange; 1998:322 as modified from Schwartz SI, Ellis H. Maingot’s Abdominal Operations. 10th ed. Norwalk, CT: Appleton & Lange; 1989:1053.)
Invasive adenocarcinoma of the rectum accounts for approximately 30% of all colorectal carcinoma. The rectum is classically described as the lowest 15 cm of the GI tract. Because of the close proximity of the rectum to the surrounding structures, patients with rectal cancer are not only at risk for distant metastasis but also for local tumor recurrence. Preoperative evaluation of patients with rectal carcinoma should include chest radiography and a CT scan of the abdomen and pelvis. In addition, endoscopic ultrasonography should be performed to determine the depth of tumor invasion and the status of the perirectal lymph nodes. Several surgical treatment options for rectal cancer are available depending on the location in the rectum and the depth of invasion. For most patients with superficial invasion (T1), the risk of lymph node metastasis is low. If the tumor is low in the rectum, a transanal resection of the tumor with tumor-free margins is the standard therapy. For maximal benefit from this approach, patients generally should have a tumor involving less than a third of the rectal circumference, less than transmural involvement, a well to moderately differentiated histologic grade, and unaffected rectal lymph nodes. For patients with deeper invasion (T2 and T3) and higher risk of lymph node metastases, surgical resection of the involved rectum and surrounding lymph nodes is necessary. A low anterior resection (LAR) is performed for rectal cancers above the anal sphincter complex. For those tumors near the sphincter complex, an abdominoperineal resection (APR) with permanent colostomy is usually necessary.
Patients with locally invasive rectal carcinoma (stage III) experience a reduction in pelvic tumor recurrence when they complete a course of radiation therapy in addition to surgical resection (adjuvant therapy). Neoadjuvant chemoradiation (given preoperatively) therapy appears to have additional benefits over postoperative chemoradiation therapy in preventing local recurrences. Patients with stage III rectal carcinoma also benefit from systemic adjuvant systemic chemotherapy.
The incidence of metachronous (subsequent) colorectal cancer is 1.1% to 4.7%. It is not clear how often and by what means patients should be evaluated following the successful treatment of colorectal cancers. One such surveillance colonoscopy program advocates initial colonoscopy at 6-month intervals up to 1 year, followed by yearly colonoscopy for 2 years, and subsequent surveillance colonoscopy every 3 years. In addition, patients should undergo a regular evaluation involving history and physical examinations and serial carcinoembryonic antigen (CEA) measurements.
High-Risk Patient Groups
Patients at high risk for colorectal cancer include those with familial adenomatous polyposis (FAP) syndrome, familial cancer (first-degree relatives), hereditary nonpolyposis colorectal cancer (HNPCC) syndrome, and a history of inflammatory bowel disease, particularly ulcerative colitis. Screening recommendations differ depending on the disease. Children of persons with FAP should have a flexible sigmoidoscopy every 1 to 2 years beginning at 10 to 12 years of age. Individuals with a strong family history of colorectal cancer should have an initial colonoscopy at 40 years of age or when they are 10 years younger than the age at which the relative was diagnosed, whichever comes first. For patients with HNPCC syndrome, the initial colonoscopy is recommended at 25 years of age, followed by yearly fecal occult blood testing and colonoscopy every 3 years (Table 19–3). Patients with a history of ulcerative colitis of more than 7 to 8 years’ duration should have a colonoscopy with biopsies every 1 to 2 years.
Table 19–3 • RECOMMENDED SCREENING AND SURVEILLANCE GUIDELINES
The presence of metastatic disease to the liver or lungs generally indicates the presence of disseminated disease. However, there are subsets of patients who may develop isolated metastasis to these sites and can be treated appropriately by surgical resection. The approach to patients with metastatic colorectal carcinomas has continued to evolve over the past 10 years. There have been significant advances in the development and application of cytotoxic chemotherapy regimens and target-molecular therapies for patients with stage III and stage IV diseases. When managing patients with metastatic diseases, it is important for the surgeons to coordinate with the medical oncologists regarding the indications and timing of surgery. Chemotherapy regimen such as the FOLFOX and FOLFIRI can induce liver injuries; therefore, the timing of liver resections has to be closely coordinated. Similarly, the preoperative administration of a bevacizumab can increase bleeding and wound complications.
The role of surgery directed toward the primary tumor in patients with synchronous stage IV colorectal cancers is becoming much more limited. This change in approach has been prompted by observations reported from the Memorial Sloan-Kettering Cancer Center, where over 200 patients with stage IV disease underwent initial systemic therapy without operative treatment of the primary tumors. During follow-up 93% of the patients never required surgical palliation of their primary tumors.
19.1 Which of the following patients has the highest risk of developing colorectal cancer?
A. A 45-year-old man whose younger brother has a history of colon cancer
B. A 30-year-old woman with a BRCA1 mutation
C. A 55-year-old man with a 15-year history of ulcerative colitis
D. A 50-year-old man with a history of resected adenomatous colonic polyps
E. A 44-year-old man with FAP syndrome (polyposis coli)
19.2 Which of the following is the most appropriate treatment for a 40-year-old man with a T3 N1 carcinoma of the cecum?
A. Preoperative chemoradiation therapy followed by right hemicolectomy
B. Right hemicolectomy and postoperative chemotherapy with 5-FU, leucovorin, and oxaliplatin
C. Endoscopic removal of the tumor followed by chemoradiation therapy
D. Right hemicolectomy and postoperative tamoxifen therapy
E. Definitive treatment with six cycles of FOLFOX and remove the colon only if the patients develops symptoms
19.3 Which of the following is the most appropriate follow-up for a 60-year-old man who underwent a colonoscopy and complete endoscopic removal of a 2-cm adenomatous polyp from the sigmoid colon?
A. Annual colonoscopy.
B. Repeated colonoscopy at 3 years and, if the results are negative, repeated every 5 years.
C. CT scan and repeated colonoscopy at 3 years and, if the results are negative, repeated every 5 years.
D. Repeated colonoscopy every 2 years.
E. Examine the stool for occult blood every 6 months.
19.4 A 58-year-old woman with a history of stage III colon cancer that was treated with primary colectomy and adjuvant FOLFOX therapy develops a rise in serum CEA and is found on CT scan to have a 2-cm localized lesion in the greater omentum. Biopsy of the lesion reveals metastatic carcinoma. Which of the following is the most appropriate treatment?
A. Radiation therapy
B. Operative resection of the mass
C. Additional systemic chemotherapy
E. Completion colectomy and omentectomy
19.1 E. BRCA1 does not confer an increased risk of colon cancer, whereas BRCA2 does. The other conditions are associated with increased risks of developing colorectal cancer, but a patient with FAP syndrome (the colon is filled with thousands of polyps) has nearly a 100% risk of developing colon cancer.
19.2 B. Right hemicolectomy with postoperative adjuvant chemotherapy using FOLFOX4 (5-FU, leucovorin, and oxaliplatin) is indicated for this patient with stage III colon cancer. Radiation therapy is generally indicated for patients with rectal carcinoma. Tamoxifen therapy is not useful for colorectal carcinoma. Definitive systemic treatment for colorectal cancer without surgery is indicated only in patients with relative asymptomatic stage IV disease.
19.3 B. The current recommendations for colonic polyp follow-up are as follows: Once the colon is cleared of polyps, repeated colonoscopy at 3 years and, if the results are negative, repeated colonoscopy every 5 years. A CT scan is not recommended for the follow-up of patients with polyps. Occult blood screening has not been shown to be an effective strategy for the early identification of colorectal cancers.
19.4 C. This patient has an intraperitoneal recurrence that signifies stage IV disease. Local or radical resections of intraperitoneal recurrences generally do not improve survival and should be done only to palliate significant symptoms. Additional systemic chemotherapy or targeted molecular therapies could be considered at this time. Alternatively, the patient can be observed for disease progression and treated if the tumor grows.
Many of the symptoms associated with colorectal cancer are nonspecific, including postprandial bloating, distension, and constipation.
Patients with FAP syndrome are at high risk for adenomas and adenocarcinomas of the duodenum in addition to colorectal cancers, and these patients require surveillance EGD.
Approximately 70% of colon cancers are thought to arise from adenomatous polyps. The larger the adenomatous polyp, the greater the risk of colon cancer.
For rectal cancer, neoadjuvant chemotherapy seems to be helpful in reducing local recurrence.
Andre T, Boni C, Navarro M, et al. Improved overall survival with oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment in stage II or III colon cancer in the MOSAIC trial. J Clin Oncol. 2009;27:3109-3116.
Bullard Dunn KM, Rothenberger DA. Colon, rectum, and anus. In: Brunicardi FC, Andersen DK, Billiar TR, et al, eds. Schwartz’s Principles of Surgery. 9th ed. New York, NY: McGraw-Hill; 2010:1013-1072.
Luglio G, Nelson H. Laparoscopy for colon cancer: state of the art. Surg Oncol Clin N Am 2010;19:777-791.
Poultsides GA, Servais EL, Saltz LB, et al. Outcome of primary tumor in patients with synchronous stage IV colorectal cancer receiving combination chemotherapy without surgery as initial treatment. J Clin Oncol. 2009;20:3379-3384.