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Surgery_Schwartz. treated with epinephrine injection or cautery. Angiography may be diagnostic and therapeutic in this setting. In the rare instance in which diverticular hemorrhage persists or recurs, laparotomy and segmental colectomy may be required.Giant Colonic DiverticulumGiant colonic diverticula are extremely rare. Most occur on the antimesenteric side of the sigmoid colon. Patients may be asymptomatic or may present with vague abdominal com-plaints such as pain, nausea, or constipation. Plain radiographs may suggest the diagnosis. Barium enema is usually diagnos-tic. Complications of a giant diverticulum include perforation, obstruction, and volvulus. Resection of the involved colon and diverticulum is recommended.Right-Sided DiverticulaThe cecum and ascending colon infrequently are involved in diverticulosis coli. Even more uncommon is a true solitary diverticulum, which contains all layers of the bowel wall and is thought to be congenital in origin. Right-sided diverticula occur more often


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Surgery_Schwartz. coli. Even more uncommon is a true solitary diverticulum, which contains all layers of the bowel wall and is thought to be congenital in origin. Right-sided diverticula occur more often in younger patients than do left-sided diver-ticula and are more common in people of Asian descent than in other populations. Most patients with right-sided diverticula are asymptomatic. However, diverticulitis does occur occasionally. Because patients are young and present with right lower quad-rant pain, they are often thought to suffer from acute appendici-tis, and the diagnosis of right-sided diverticulitis is subsequently made in the operating room. If there is a single large diverticu-lum and minimal inflammation, a diverticulectomy may be performed, but an ileocecal resection is usually the preferred operation in this setting. Hemorrhage rarely occurs and should be treated in the same fashion as hemorrhage from a left-sided diverticulum.ADENOCARCINOMA AND POLYPSIncidenceColorectal carcinoma is


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Surgery_Schwartz. operation in this setting. Hemorrhage rarely occurs and should be treated in the same fashion as hemorrhage from a left-sided diverticulum.ADENOCARCINOMA AND POLYPSIncidenceColorectal carcinoma is the most common malignancy of the gastrointestinal tract. Over 130,000 new cases are diagnosed annually in the United States, and more than 50,000 patients die of this disease each year, making colorectal cancer the third most lethal cancer in the United States.75The incidence is similar in men and women and has remained fairly constant over the past 20 years; however, the widespread adoption of current national screening programs is gradually decreasing the incidence of this common and lethal disease in people over 50 years of age. However, people younger than 50 have been experiencing and increase incidence and worse mortality.75 Early detection and improvements in medical and surgical care are thought to be responsible for the decreasing mortality of colorectal cancer observed in recent


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Surgery_Schwartz. incidence and worse mortality.75 Early detection and improvements in medical and surgical care are thought to be responsible for the decreasing mortality of colorectal cancer observed in recent years.Epidemiology (Risk Factors)Identification of risk factors for development of colorectal can-cer is essential to establish screening and surveillance programs in appropriately targeted populations.Aging. Aging is the dominant risk factor for colorectal cancer, with incidence rising steadily after age 50 years. More than 90% of cases diagnosed are in people older than age 50 years. This is the rationale for initiating screening tests of asymptomatic patients at average risk of developing colorectal cancer at age 50 years. However, individuals of any age can develop colorec-tal cancer, so symptoms such as a significant change in bowel Brunicardi_Ch29_p1259-p1330.indd 128823/02/19 2:29 PM 1289COLON, RECTUM, AND ANUSCHAPTER 29habits, rectal bleeding, melena, unexplained anemia, or weight


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Surgery_Schwartz. such as a significant change in bowel Brunicardi_Ch29_p1259-p1330.indd 128823/02/19 2:29 PM 1289COLON, RECTUM, AND ANUSCHAPTER 29habits, rectal bleeding, melena, unexplained anemia, or weight loss require a thorough evaluation.Hereditary Risk Factors. Approximately 80% of colorectal cancers occur sporadically, while 20% arise in patients with a known family history of colorectal cancer. Advances in the understanding of these familial disorders have led to interest in early diagnosis using genetic testing. Because of the medical, legal, and ethical considerations that are involved in this type of testing, all patients should be offered genetic counseling if a familial syndrome is suspected.Environmental and Dietary Factors. The observation that colorectal carcinoma occurs more commonly in populations that consume diets high in animal fat and low in fiber has led to the hypothesis that dietary factors contribute to carcinogenesis. A diet high in saturated or polyunsaturated fats


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Surgery_Schwartz. in populations that consume diets high in animal fat and low in fiber has led to the hypothesis that dietary factors contribute to carcinogenesis. A diet high in saturated or polyunsaturated fats increases risk of colorectal cancer, while a diet high in oleic acid (olive oil, coco-nut oil, fish oil) does not increase risk. Animal studies suggest that fats may be directly toxic to the colonic mucosa and thus may induce early malignant changes. In contrast, a diet high in vegetable fiber appears to be protective. A correlation between alcohol intake and incidence of colorectal carcinoma has also been suggested. Ingestion of calcium; selenium; vitamins A, C, and E; carotenoids; and plant phenols may decrease the risk of developing colorectal cancer. Obesity and sedentary lifestyle dramatically increase cancer-related mortality in a number of malignancies, including colorectal carcinoma. This knowl-edge is the basis for primary prevention strategies to eliminate colorectal cancer by


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Surgery_Schwartz. increase cancer-related mortality in a number of malignancies, including colorectal carcinoma. This knowl-edge is the basis for primary prevention strategies to eliminate colorectal cancer by altering diet and lifestyle.76Inflammatory Bowel Disease. Patients with long-standing colitis from inflammatory bowel disease are at increased risk for the development of colorectal cancer. It is hypothesized that chronic inflammation predisposes the mucosa to malignant changes, and there is some evidence that degree of inflamma-tion influences risk. In general, the duration and extent of colitis correlate with risk. Other factors thought to increase risk include the presence of primary sclerosing cholangitis and family his-tory of colorectal cancer.Other Risk Factors. Cigarette smoking is associated with an increased risk of colonic adenomas, especially after more than 35 years of use. Patients with ureterosigmoidostomy may also be at increased risk for both adenoma and carcinoma


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Surgery_Schwartz. is associated with an increased risk of colonic adenomas, especially after more than 35 years of use. Patients with ureterosigmoidostomy may also be at increased risk for both adenoma and carcinoma formation.77Acromegaly, which is associated with increased levels of circulating human growth hormone and insulin-like growth factor-1, increases risk as well. Pelvic irradiation may increase the risk of developing rectal carcinoma. However, it is unclear whether this represents a direct effect of radiation damage or is instead a correlation between the development of rectal cancer and a history of another pelvic malignancy; for example, among patients who develop prostate cancer and are treated with radia-tion, the risk of rectal cancer increases significantly.78Pathogenesis of Colorectal CancerGenetic Defects. An intense research effort has focused on elucidating the genetic defects and molecular abnormalities asso-ciated with the development and progression of colorectal adeno-mas and


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Surgery_Schwartz. Defects. An intense research effort has focused on elucidating the genetic defects and molecular abnormalities asso-ciated with the development and progression of colorectal adeno-mas and carcinoma. Mutations may cause activation of oncogenes (K-ras) and/or inactivation of tumor suppressor genes (APC, deleted in colorectal carcinoma [DCC], p53). Colorectal carcinoma is thought to develop from adenomatous polyps by accumulation of these mutations in what has come to be known as the adenoma-carcinoma sequence (Fig. 29-22).9,79Defects in the APC gene were first described in patients with Familial Adenomatous Polyposis (FAP). By investigating these families, characteristic mutations in the APC gene were identified. They are now known to be present in 80% of spo-radic colorectal cancers as well.The APC gene is a tumor suppressor gene. Mutations in both alleles are necessary to initiate polyp formation. The majority of mutations are premature stop codons, which result in a truncated APC


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Surgery_Schwartz. well.The APC gene is a tumor suppressor gene. Mutations in both alleles are necessary to initiate polyp formation. The majority of mutations are premature stop codons, which result in a truncated APC protein. In FAP, the site of mutation correlates with the clinical severity of the disease. For example, mutations in either the 3′ or 5′ end of the gene result in attenuated forms of FAP (AFAP), whereas mutations in the center of the gene result in more virulent disease. Thus, knowledge of the specific mutation in a family may help guide clinical decision-making.10APC inactivation alone does not result in a carcinoma. Instead, this mutation sets the stage for the accumulation of genetic damage that results in malignancy. Additional mutations may include activation or inactivation of a variety of genes.One of the most commonly involved genes in colorectal cancer is K-ras. K-ras, a signaling molecule in the epidermal growth factor receptor (EGFR) pathway, is classified as a proto-oncogene


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Surgery_Schwartz. of genes.One of the most commonly involved genes in colorectal cancer is K-ras. K-ras, a signaling molecule in the epidermal growth factor receptor (EGFR) pathway, is classified as a proto-oncogene because mutation of only one allele will perturb the cell cycle. The K-ras gene product is a G-protein involved in intracellular signal transduction. When active, K-ras binds gua-nosine triphosphate (GTP); hydrolysis of GTP to guanosine diphosphate (GDP) then inactivates the G-protein. Mutation of KRAS results in an inability to hydrolyze GTP, thus leaving the G-protein permanently in the active form. It is thought that this then leads to uncontrolled cell division. Because K-ras muta-tion results in uncontrolled downstream signaling, anti-EGFR agents are ineffective in treating K-ras mutant tumors. As such, K-ras mutation status is important in deciding when to utilize anti-EGFR therapies. Other EGFR signaling molecules such as BRAF have also been implicated in colorectal cancer


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Surgery_Schwartz. mutant tumors. As such, K-ras mutation status is important in deciding when to utilize anti-EGFR therapies. Other EGFR signaling molecules such as BRAF have also been implicated in colorectal cancer patho-genesis and progression, and ongoing research is focusing on elucidating their roles in this disease.5NormalepitheliumDysplasticepitheliumEarlyadenomaIntermediateadenomaLateadenomaCarcinomaMetastasisAPCK-RASDCC/DPC4/JV18?p53Other changesFigure 29-22. Schematic showing progression from normal colonic epithelium to carcinoma of the colon.Brunicardi_Ch29_p1259-p1330.indd 128923/02/19 2:29 PM 1290SPECIFIC CONSIDERATIONSPART IIAnother common mutation occurs in the MYH gene on chromosome 1p. MYH is a base excision repair gene, and bial-lelic deletion results in changes in other downstream molecules. Since its discovery, MYH mutations have been associated with an AFAP phenotype in addition to sporadic cancers. Unlike APC gene mutations that are expressed in an autosomal domi-nant


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Surgery_Schwartz. molecules. Since its discovery, MYH mutations have been associated with an AFAP phenotype in addition to sporadic cancers. Unlike APC gene mutations that are expressed in an autosomal domi-nant pattern, the requirement for biallelic mutation in MYH results in an autosomal recessive pattern of inheritance.80,81The tumor suppressor gene p53 has been well character-ized in a number of malignancies. The p53 protein appears to be crucial for initiating apoptosis in cells with irreparable genetic damage. Mutations in p53 are present in 75% of colorectal cancers.Deletion of the tumor suppressor phosphatase and ten-sin homolog (PTEN) appears to be involved in a number of hamartomatous polyposis syndromes. Deletions in PTEN have been identified in juvenile polyposis, Peutz-Jeghers syndrome, Cowden’s syndrome, and PTEN hamartoma syndrome, in addi-tion to multiple endocrine neoplasia type IIB. Peutz-Jeghers syndrome is also associated with mutation in STK11, a serine-threonin kinase gene. The


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Surgery_Schwartz. syndrome, and PTEN hamartoma syndrome, in addi-tion to multiple endocrine neoplasia type IIB. Peutz-Jeghers syndrome is also associated with mutation in STK11, a serine-threonin kinase gene. The genetic changes that underlie serratis polyposis syndrome(s) are currently poorly understood.9Genetic Pathways. The mutations involved in colorectal cancer pathogenesis and progression are now recognized to accumulate via one of three major genetic pathways: the loss of heterozygosity (LOH; chromosomal instability) pathway, the microsatellite instability (MSI) pathway, and the CpG island methylation (CIMP; serrated methylated) pathway.The Loss of Heterozygosity Pathway The LOH pathway is characterized by chromosomal deletions and tumor aneu-ploidy. Eighty percent of colorectal carcinomas appear to arise from mutations in the LOH pathway. This pathway was first described in patients with FAP in whom mutations of the APC gene were found to be inherited.Another example of LOH occurs in the region


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Surgery_Schwartz. arise from mutations in the LOH pathway. This pathway was first described in patients with FAP in whom mutations of the APC gene were found to be inherited.Another example of LOH occurs in the region of chromo-some 18q. This region has been found to be deleted in up to 70% of colorectal cancers. Two tumor suppressor genes, DCC and SMAD4, are located in this region, and as such, deletion of 18q may result in the loss of one or both of these genes. DCC is a tumor suppressor gene, and loss of both alleles is required for malignant degeneration. The main role of this molecule appears to be in the central nervous system, where it is involved in neural differentiation and axonal migration. This observa-tion has led to the hypothesis that DCC may be involved in differentiation and cellular adhesion in colorectal cancer, but this theory remains unproven. DCC mutations are present in more than 70% of colorectal carcinomas and may negatively impact prognosis. SMAD4 functions in the signaling


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Surgery_Schwartz. in colorectal cancer, but this theory remains unproven. DCC mutations are present in more than 70% of colorectal carcinomas and may negatively impact prognosis. SMAD4 functions in the signaling cascade of transforming growth factor beta and beta-catenin (also a down-stream effector of the APC gene). Loss of either of these genes is thought to promote cancer progression.82The Microsatellite Instability Pathway. Many of the remain-ing colorectal carcinomas are thought to arise from mutations in the MSI pathway, which is characterized by errors in mismatch repair during DNA replication. These errors in mismatch repair were first described in Hereditary Nonpolyposis Colon Cancer (HNPCC; Lynch syndrome) Lynch 9, but are now recognized to be present in many sporadic tumors as well. A number of genes have been identified that appear to be crucial for recognizing and repairing DNA replication errors. These mismatch repair genes include MSH2, MLH1, PMS1, PMS2, and MSH6/GTBP. A mutation in one


Surgery_Schwartz

Surgery_Schwartz. genes have been identified that appear to be crucial for recognizing and repairing DNA replication errors. These mismatch repair genes include MSH2, MLH1, PMS1, PMS2, and MSH6/GTBP. A mutation in one of these genes predisposes a cell to mutations, which may occur in proto-oncogenes or tumor suppressor genes. Accumulation of these errors then leads to genomic instability and ultimately to carcinogenesis.Microsatellites are regions of the genome in which short base-pair segments are repeated several times, regions that are particularly prone to replication error. Consequently, a mutation in a mismatch repair gene produces variable lengths of these repetitive sequences, a finding that has been described as MSI.Tumors associated with MSI appear to have different bio-logic characteristics than do tumors that result from the LOH pathway. Tumors with MSI are more likely to be in the right colon and possess diploid DNA and are associated with a better prognosis than tumors that arise from the


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Surgery_Schwartz. do tumors that result from the LOH pathway. Tumors with MSI are more likely to be in the right colon and possess diploid DNA and are associated with a better prognosis than tumors that arise from the LOH pathway that are microsatellite stable. Tumors arising from the LOH pathway tend to occur in the more distal colon, often have chromosomal aneuploidy, and are associated with a poorer prognosis.CpG Island Methylation Pathway In the CIMP pathway, genes do not accumulate mutations (deletions or insertions of bases), but instead are activated or inactivated by methylation. This process has been called epigenetic alteration to differenti-ate it from the more traditional genetic alterations or true muta-tions. In normal cells, methylation is critical for regulation of gene expression. In cancer, aberrant methylation (either hyperor hypomethylation), usually of a promoter region, results in abnormal activation or inactivation of genes. This gene silenc-ing or, alternatively, activation


Surgery_Schwartz

Surgery_Schwartz. aberrant methylation (either hyperor hypomethylation), usually of a promoter region, results in abnormal activation or inactivation of genes. This gene silenc-ing or, alternatively, activation results in a phenotype similar to that present with a true gene mutation. This pathway has also been called the serrated methylated pathway because of the observation that serrated polyps often harbor aberrant meth-ylation in contrast to adenomatous polyps that are more often associated with mutations in the APC gene (LOH pathway).83Although these classifications are useful for understanding the mechanisms underlying carcinogenesis, they are not mutu-ally exclusive. For example, a mismatch repair gene may be inactivated by methylation. Errors in mismatch repair may then allow mutations to inactivate a tumor suppressor gene. In addi-tion, there is considerable interest in targeting molecules in each of these pathways in order to design better anticancer agents. Finally, ongoing research is


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Surgery_Schwartz. a tumor suppressor gene. In addi-tion, there is considerable interest in targeting molecules in each of these pathways in order to design better anticancer agents. Finally, ongoing research is focusing on the utility of molecular profiling in predicting prognosis and/or response to treatment.10PolypsIt is now well accepted that the majority of colorectal carcino-mas evolve from adenomatous polyps; this sequence of events is the adenoma-carcinoma sequence. Polyp is a nonspecific clini-cal term that describes any projection from the surface of the intestinal mucosa regardless of its histologic nature. Colorec-tal polyps may be classified as neoplastic (tubular adenoma, villous adenoma, tubulovillous adenomas, serrated adenomas/polyps), hyperplastic, hamartomatous (juvenile, Peutz-Jeghers, Cronkite-Canada), or inflammatory (pseudopolyp, benign lymphoid polyp).Neoplastic Polyps. Adenomatous polyps are common, occur-ring in up to 25% of the population older than 50 years of age in the


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Surgery_Schwartz. Cronkite-Canada), or inflammatory (pseudopolyp, benign lymphoid polyp).Neoplastic Polyps. Adenomatous polyps are common, occur-ring in up to 25% of the population older than 50 years of age in the United States. By definition, these lesions are dysplas-tic. The risk of malignant degeneration is related to both the size and type of polyp. Tubular adenomas are associated with malignancy in only 5% of cases, whereas villous adenomas may harbor cancer in up to 40%. Tubulovillous adenomas are at intermediate risk (22%). Invasive carcinomas are rare in Brunicardi_Ch29_p1259-p1330.indd 129023/02/19 2:29 PM 1291COLON, RECTUM, AND ANUSCHAPTER 29polyps smaller than 1 cm; the incidence of invasive carcinoma increases with size. The risk of carcinoma in a polyp larger than 2 cm is 35% to 50%. Although most neoplastic polyps do not evolve to cancer, most colorectal cancers originate as a polyp. It is this fact that forms the basis for secondary prevention strate-gies to eliminate colorectal


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Surgery_Schwartz. most neoplastic polyps do not evolve to cancer, most colorectal cancers originate as a polyp. It is this fact that forms the basis for secondary prevention strate-gies to eliminate colorectal cancer by targeting the neoplastic polyp for removal before malignancy develops.Polyps may be pedunculated or sessile. Most pedunculated polyps are amenable to colonoscopic snare excision. Removal of sessile polyps is often more challenging. Special colonoscopic techniques, including saline lift, piecemeal snare excision, and endoscopic mucosal resection facilitate successful removal of many sessile polyps. For rectal sessile polyps, transanal opera-tive excision is preferred because it produces an intact, single pathology specimen that can be used to determine the need for further therapy. Interpretation of the precise depth of invasion of a cancer arising in a sessile polyp after piecemeal excision is often impossible. The site of sessile polypectomies should be marked by tattoo marking to


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Surgery_Schwartz. of the precise depth of invasion of a cancer arising in a sessile polyp after piecemeal excision is often impossible. The site of sessile polypectomies should be marked by tattoo marking to guide subsequent endoscopic sur-veillance and to facilitate identification of the involved bowel segment should operative resection be necessary.84 Colectomy is reserved for cases in which colonoscopic removal is impos-sible, such as large, flat lesions, or if a focus of invasive cancer is confirmed in the specimen.Complications of polypectomy include perforation and bleeding. A small perforation (microperforation) in a fully pre-pared, stable patient may be managed with bowel rest, broad-spectrum antibiotics, and close observation. Signs of sepsis, peritonitis, or deterioration in clinical condition are indications for laparotomy. Bleeding may occur immediately after polypec-tomy or may be delayed. The bleeding will usually stop sponta-neously, but colonoscopy may be required to apply endoscopic


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Surgery_Schwartz. are indications for laparotomy. Bleeding may occur immediately after polypec-tomy or may be delayed. The bleeding will usually stop sponta-neously, but colonoscopy may be required to apply endoscopic clips, resnare a bleeding stalk, cauterize the lesion, or inject/apply epinephrine. Occasionally angiography and infusion of vasopressin may be necessary. Rarely, colectomy is required.Hyperplastic Polyps. Hyperplastic polyps are extremely com-mon in the colon. These polyps are usually small (<5 mm) and show histologic characteristics of hyperplasia without any dys-plasia. They are not considered premalignant, but they cannot be distinguished from adenomatous polyps colonoscopically and are therefore often removed. In contrast, large hyperplas-tic polyps (>2 cm) may have a risk of malignant degeneration. Hyperplastic polyposis is a rare disorder in which multiple large hyperplastic polyps occur in young adults. These patients are at increased risk for the development of colorectal


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Surgery_Schwartz. degeneration. Hyperplastic polyposis is a rare disorder in which multiple large hyperplastic polyps occur in young adults. These patients are at increased risk for the development of colorectal cancer.Serrated Polyps. Serrated polyps, including sessile serrated adenomas and traditional serrated adenomas, are a recently recognized, histologically distinct group of neoplastic polyps. Endoscopically they are flat lesions and frequently difficult to visualize. These lesions were long thought to be similar to hyperplastic polyps with minimal malignant potential. How-ever, it has become clear that some of these polyps will develop into invasive cancers. In addition, a familial serrated polyposis syndrome has been described. Serrated polyps should be treated like adenomatous polyps.85Hamartomatous Polyps (Juvenile Polyps). In contrast to adenomatous and serrated polyps, hamartomatous polyps (juve-nile polyps) usually are not premalignant. These lesions are the characteristic polyps of


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Surgery_Schwartz. Polyps (Juvenile Polyps). In contrast to adenomatous and serrated polyps, hamartomatous polyps (juve-nile polyps) usually are not premalignant. These lesions are the characteristic polyps of childhood but may occur at any age. Bleeding is a common symptom, and intussusception and/or obstruction may occur. Because the gross appearance of these polyps is identical to adenomatous polyps, these lesions should also be treated by polypectomy. In contrast to adenomatous pol-yposis syndromes, these conditions are often associated with mutation in BMPR1A and SMAD4.Familial juvenile polyposis is an autosomal dominant dis-order in which patients develop hundreds of polyps in the colon and rectum. Unlike solitary juvenile polyps, these lesions may degenerate into adenomas and eventually carcinoma. Annual screening should begin between the ages of 10 and 12 years. Treatment is surgical and depends in part on the degree of rectal involvement. If the rectum is relatively spared, a total abdomi-nal


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Surgery_Schwartz. screening should begin between the ages of 10 and 12 years. Treatment is surgical and depends in part on the degree of rectal involvement. If the rectum is relatively spared, a total abdomi-nal colectomy with ileorectal anastomosis may be performed with subsequent close surveillance of the retained rectum. If the rectum is carpeted with polyps, total proctocolectomy is the more appropriate operation. These patients are candidates for ileal pouch–anal reconstruction to avoid a permanent stoma.Peutz-Jeghers syndrome is characterized by polyposis of the small intestine and, to a lesser extent, polyposis of the colon and rectum. Characteristic melanin spots are often noted on the buccal mucosa and lips of these patients. The polyps of Peutz-Jeghers syndrome are generally considered to be hamar-tomas and are not thought to be at significant risk for malignant degeneration. However, carcinoma may occasionally develop. Because the entire length of the gastrointestinal tract may be affected,


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Surgery_Schwartz. and are not thought to be at significant risk for malignant degeneration. However, carcinoma may occasionally develop. Because the entire length of the gastrointestinal tract may be affected, surgery is reserved for symptoms such as obstruction or bleeding or for patients in whom polyps develop adenoma-tous features. Screening consists of a baseline colonoscopy and upper endoscopy at age 20 years, followed by annual flexible sigmoidoscopy thereafter. Clinicians should ensure patients are screened for associated extraintestinal malignancies (breast, upper gastrointestinal tract, pancreas, cervix, ovaries, and testicles).Cronkite-Canada syndrome is a disorder in which patients develop gastrointestinal polyposis in association with alopecia, cutaneous pigmentation, and atrophy of the fingernails and toenails. Diarrhea is a prominent symptom, and vomiting, mal-absorption, and protein-losing enteropathy may occur. Most patients die of this disease despite maximal medical therapy, and


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Surgery_Schwartz. and toenails. Diarrhea is a prominent symptom, and vomiting, mal-absorption, and protein-losing enteropathy may occur. Most patients die of this disease despite maximal medical therapy, and surgery is reserved for complications of polyposis such as obstruction.Cowden’s syndrome is an autosomal dominant disorder with hamartomas of all three embryonal cell layers. Facial trich-ilemmomas, breast cancer, thyroid disease, and gastrointestinal polyps are typical of the syndrome. Patients should be screened for cancers. Treatment is otherwise based on symptoms.Inflammatory Polyps (Pseudopolyps). Inflammatory pol-yps occur most commonly in the context of inflammatory bowel disease, but they may also occur after amebic colitis, ischemic colitis, and schistosomal colitis. These lesions are not premalig-nant, but they cannot be distinguished from adenomatous polyps based on gross appearance and therefore should be removed. Microscopic examination shows islands of normal, regenerat-ing mucosa


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Surgery_Schwartz. but they cannot be distinguished from adenomatous polyps based on gross appearance and therefore should be removed. Microscopic examination shows islands of normal, regenerat-ing mucosa (the polyp) surrounded by areas of mucosal loss. Polyposis may be extensive, especially in patients with severe colitis, and may mimic FAP.Inherited Colorectal CarcinomaMany of the genetic defects originally described in hereditary cancers have subsequently been found in sporadic tumors. Although the majority of colorectal cancer is sporadic, several hereditary syndromes provide paradigms for the study of this disease. Insight gained from studying inherited colorectal cancer Brunicardi_Ch29_p1259-p1330.indd 129123/02/19 2:29 PM 1292SPECIFIC CONSIDERATIONSPART IIsyndromes has led to better understanding of the genetics of colorectal carcinoma.Familial Adenomatous Polyposis. This rare autosomal dominant condition accounts for only about 1% of all colorec-tal adenocarcinomas. Nevertheless, this


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Surgery_Schwartz. of the genetics of colorectal carcinoma.Familial Adenomatous Polyposis. This rare autosomal dominant condition accounts for only about 1% of all colorec-tal adenocarcinomas. Nevertheless, this syndrome has provided tremendous insight into the molecular mechanisms underlying colorectal carcinogenesis. The genetic abnormality in FAP is a mutation in the APC gene, located on chromosome 5q. Of patients with FAP, APC mutation testing is positive in 75% of cases. While most patients with FAP will have a known family history of the disease, up to 25% present without other affected family members. Clinically, patients develop hundreds to thou-sands of adenomatous polyps shortly after puberty. The lifetime risk of colorectal cancer in FAP patients approaches 100% by age 50 years.Flexible sigmoidoscopy of first-degree relatives of FAP patients beginning at age 10 to 15 years has been the traditional mainstay of screening. Today, following genetic counseling, APC gene testing may be used to


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Surgery_Schwartz. of first-degree relatives of FAP patients beginning at age 10 to 15 years has been the traditional mainstay of screening. Today, following genetic counseling, APC gene testing may be used to screen family members, pro-viding an APC mutation has been identified. If APC testing is positive in a relative of a patient with a known APC mutation, annual flexible sigmoidoscopy beginning at age 10 to 15 years is done until polyps are identified. If APC testing is negative, the relative can be screened starting at age 50 years per average-risk guidelines. If APC testing is refused or unavailable, or if a mutation cannot be identified, annual flexible sigmoidoscopy beginning at age 10 to 15 years is performed until age 24 years. Screening flexible sigmoidoscopy is then done every 2 years until age 34 years, every 3 years until age 44 years, and then every 3 to 5 years.FAP patients are also at risk for the development of adeno-mas anywhere in the gastrointestinal tract, particularly in the


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Surgery_Schwartz. age 34 years, every 3 years until age 44 years, and then every 3 to 5 years.FAP patients are also at risk for the development of adeno-mas anywhere in the gastrointestinal tract, particularly in the duodenum. Periampullary carcinoma is a particular concern. Upper endoscopy is therefore recommended for surveillance every 1 to 3 years beginning at age 25 to 30 years.Once the diagnosis of FAP has been made and polyps are developing, treatment is surgical. Four factors affect the choice of operation: age of the patient; presence and severity of symp-toms; extent of rectal polyposis; and presence and location of cancer or desmoid tumors. Three operative procedures can be considered: total proctocolectomy with an end (Brooke) ileos-tomy; total abdominal colectomy with ileorectal anastomosis; and restorative proctocolectomy with ileal pouch–anal anas-tomosis (IPAA) with or without a temporary ileostomy. Most patients elect to have an ileal pouch–anal anastomosis in the absence of a distal


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Surgery_Schwartz. and restorative proctocolectomy with ileal pouch–anal anas-tomosis (IPAA) with or without a temporary ileostomy. Most patients elect to have an ileal pouch–anal anastomosis in the absence of a distal rectal cancer, a mesenteric desmoid tumor that prevents the ileum from reaching the anus, or poor sphinc-ter function. Mucosectomy has been advocated in patients with FAP undergoing ileal pouch–anal anastomosis because of the risk of neoplasia in the anal transition zone, but the requirement for this procedure remains controversial.86,87 Although patient satisfaction with IPAA remains high, function may not be ideal, and up to 50% of patients experience some degree of incon-tinence. Total abdominal colectomy with an ileorectal anasto-mosis is also an option in these patients, but requires vigilant surveillance of the retained rectum for development of rectal cancer. There is increasing data suggesting that the administra-tion of cyclooxygenase-2 (COX-2) inhibitors (celecoxib, sulin-dac)


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Surgery_Schwartz. surveillance of the retained rectum for development of rectal cancer. There is increasing data suggesting that the administra-tion of cyclooxygenase-2 (COX-2) inhibitors (celecoxib, sulin-dac) may slow or prevent the development of polyps.88,89FAP may be associated with extraintestinal manifesta-tions such as congenital hypertrophy of the retinal pigmented epithelium, desmoid tumors, epidermoid cysts, mandibular osteomas (Gardner’s syndrome), and central nervous system tumors (Turcot’s syndrome). Although they arise in a minority of FAP patients, desmoid tumors in particular can make surgi-cal management difficult and are a source of major morbidity and mortality in these patients. These lesions arise from fibro-blasts, and although technically benign, can be highly locally invasive. These tumors often involve the bowel mesentery, pel-vis, and abdominal wall. In some cases, surgery is thought to be the “trigger.” Local recurrence after attempted resection is common; therefore, surgery


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Surgery_Schwartz. tumors often involve the bowel mesentery, pel-vis, and abdominal wall. In some cases, surgery is thought to be the “trigger.” Local recurrence after attempted resection is common; therefore, surgery is to be avoided if at all possible. Desmoid tumors are often hormone responsive, and growth may be inhibited in some patients with tamoxifen. COX-2 inhibitors and nonsteroidal, anti-inflammatory drugs may also be benefi-cial in this setting. A recent report suggests that imatinib may also be effective.90,91Attenuated Familial Adenomatous Polyposis. AFAP is a recognized variant of FAP. Patients present later in life with fewer polyps (usually 10–100) predominantly located in the right colon, when compared to classic FAP. Colorectal carci-noma develops in more than 50% of these patients, but occurs later (average age, 55 years). Patients are also at risk for duo-denal polyposis. However, in contrast to FAP, APC gene muta-tions are present in only about 30% of patients with AFAP. When


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Surgery_Schwartz. but occurs later (average age, 55 years). Patients are also at risk for duo-denal polyposis. However, in contrast to FAP, APC gene muta-tions are present in only about 30% of patients with AFAP. When present, these mutations are expressed in an autosomal dominant pattern.Mutations in MYH also result in the AFAP phenotype but are expressed in an autosomal recessive pattern. It has been sug-gested that MYH mutations may be responsible for AFAP in patients who do not have a detectable APC gene mutation.80,81Genetic testing is often offered to patients with suspected AFAP. When positive, genetic counseling and testing may be used to screen at-risk family members. If the family mutation is unknown, screening colonoscopy is recommended beginning at age 13 to 15 years, then every 4 years to age 28 years, and then every 3 years. These patients are often candidates for a total abdominal colectomy with ileorectal anastomosis because the limited polyposis in the rectum can usually be treated by


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Surgery_Schwartz. 28 years, and then every 3 years. These patients are often candidates for a total abdominal colectomy with ileorectal anastomosis because the limited polyposis in the rectum can usually be treated by colo-noscopic snare excision.92 Prophylaxis with COX-2 inhibitors also may be appropriate. Because of the more subtle phenotype in these patients, it is important to rule out other familial syn-dromes such as HNPCC (Lynch syndrome) and the more com-mon familial colorectal cancer.Lynch Syndrome (Hereditary Nonpolyposis Colon Cancer; HNPCC). Lynch syndrome is more common than FAP, but it is still extremely rare (1–3% of all colon cancers). The genetic defects associated with Lynch syndrome arise from errors in mismatch repair, the phenotypic result being MSI. Lynch syn-drome is inherited in an autosomal dominant pattern and is char-acterized by the development of colorectal carcinoma at an early age (average age, 40–45 years). Approximately 70% of affected individuals will develop


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Surgery_Schwartz. in an autosomal dominant pattern and is char-acterized by the development of colorectal carcinoma at an early age (average age, 40–45 years). Approximately 70% of affected individuals will develop colorectal cancer. Cancers appear in the proximal colon more often than in sporadic colorectal cancer and have a better prognosis regardless of stage. The risk of syn-chronous or metachronous colorectal carcinoma is 40%. Lynch syndrome may also be associated with extracolonic malignan-cies, including endometrial carcinoma, which is most com-mon in women, and ovarian, pancreas, stomach, small bowel, biliary, and urinary tract carcinomas. The diagnosis is made based on family history. The Amsterdam I criteria for clini-cal diagnosis of Lynch syndrome are three affected relatives Brunicardi_Ch29_p1259-p1330.indd 129223/02/19 2:29 PM 1293COLON, RECTUM, AND ANUSCHAPTER 29with histologically verified adenocarcinoma of the large bowel (one must be a first-degree relative of one of the others)


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Surgery_Schwartz. 129223/02/19 2:29 PM 1293COLON, RECTUM, AND ANUSCHAPTER 29with histologically verified adenocarcinoma of the large bowel (one must be a first-degree relative of one of the others) in two successive generations of a family with one patient diagnosed before age 50 years. The presence of other related carcinomas should raise the suspicion of this syndrome. Revised criteria Amsterdam II requires three or more relatives with an HNPCC related malignancy in which at least one is a first degree relative of the others, two generations are affected, at least one cancer occurred before age 50, FAP has been excluded, and pathology of the tumors has been reviewed and confirmed. In a patient with an established diagnosis of colorectal cancer, tumor testing for presence of mismatch repair gene products (immunohisto-chemistry) and/or MSI can sometimes serve as screening for this syndrome.10,93,94Lynch syndrome results from mutations in mismatch repair genes, and like FAP, specific mutations are


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Surgery_Schwartz. (immunohisto-chemistry) and/or MSI can sometimes serve as screening for this syndrome.10,93,94Lynch syndrome results from mutations in mismatch repair genes, and like FAP, specific mutations are associated with different phenotypes. For example, mutations in PMS2 or MSH6 result in a more attenuated form of Lynch syndrome when compared to mutations in other genes. MSH6 inactivation also appears to be associated with a higher risk for endometrial cancer. Further significance of these specific mutations remains to be determined.Screening colonoscopy is recommended annually for at-risk patients beginning at either age 20 to 25 years or 10 years younger than the youngest age at diagnosis in the family, which-ever comes first. Because of the high risk of endometrial carci-noma, transvaginal ultrasound or endometrial aspiration biopsy is also recommended annually after age 25 to 35 years. Because there is a 40% risk of developing a second colon cancer, total colectomy with ileorectal


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Surgery_Schwartz. ultrasound or endometrial aspiration biopsy is also recommended annually after age 25 to 35 years. Because there is a 40% risk of developing a second colon cancer, total colectomy with ileorectal anastomosis is recommended once adenomas or a colon carcinoma is diagnosed. Annual proctos-copy is necessary because the risk of developing rectal cancer remains high. Similarly, prophylactic hysterectomy and bilateral salpingo-oophorectomy should be considered in women who have completed childbearing.93-95Familial Colorectal Cancer. Nonsyndromic familial colorec-tal cancer accounts for 10% to 15% of patients with colorec-tal cancer. The lifetime risk of developing colorectal cancer increases with a family history of the disease. The lifetime risk of colorectal cancer in a patient with no family history of this disease (average-risk population) is approximately 6%, but rises to 12% if one first-degree relative is affected and to 35% if two first-degree relatives are affected. Age of onset


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Surgery_Schwartz. history of this disease (average-risk population) is approximately 6%, but rises to 12% if one first-degree relative is affected and to 35% if two first-degree relatives are affected. Age of onset also impacts risk, and a diagnosis before the age of 50 years is associated with a higher incidence in family members. Screening colonoscopy is recommended every 5 years beginning at age 40 years or begin-ning 10 years before the age of the earliest diagnosed patient in the pedigree. While there are no specific genetic abnormalities that are associated with familial colorectal cancer, any of the defects found in either the LOH pathway or MSI pathway may be present in these patients.Prevention: Screening and SurveillanceBecause the majority of colorectal cancers are thought to arise from adenomatous polyps, preventive measures focus on identi-fication and removal of these premalignant lesions. In addition, many cancers are asymptomatic, and screening may detect these tumors at an early and


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Surgery_Schwartz. polyps, preventive measures focus on identi-fication and removal of these premalignant lesions. In addition, many cancers are asymptomatic, and screening may detect these tumors at an early and curable stage (Table 29-1). Although screening for colorectal cancer decreases the incidence of can-cer and cancer-related mortality, the optimal method of screen-ing remains controversial. Screening guidelines are meant for asymptomatic patients.95-98 Any patient with a gastrointestinal complaint (bleeding, change in bowel habits, pain, etc) requires a complete evaluation, usually by colonoscopy.Fecal Occult Blood Testing and Fecal Immunohistochemical Testing. FOBT is known to reduce colorectal cancer mortality by 33% and metastatic disease by 50%. However, FOBT is rela-tively insensitive, missing up to 50% of cancers and the majority of adenomas. Its specificity is low because 90% of patients with positive tests do not have colorectal cancer. FIT is more sensitive and specific for cancer.


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Surgery_Schwartz. up to 50% of cancers and the majority of adenomas. Its specificity is low because 90% of patients with positive tests do not have colorectal cancer. FIT is more sensitive and specific for cancer. Mortality benefits for its use are inferred from FOBT literature. Compliance with annual testing is low and costs are significant if one includes the colonoscopy examina-tions done to evaluate patients with positive FOBT/FIT. Nonethe-less, the direct evidence that FOBT screening is efficacious and decreases both the incidence and mortality of colorectal cancer is so strong that national guidelines recommend annual FOBT/FIT screening for asymptomatic, average-risk Americans older than 50 years of age as one of several accepted strategies. A positive FOBT/FIT should be followed by colonoscopy.97-100Stool DNA. Neoplastic lesions of the colon shed cells into the lumen posing an opportunity for detection via DNA testing. A commercially available multitarget stool DNA test evaluates stool samples


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Surgery_Schwartz. DNA. Neoplastic lesions of the colon shed cells into the lumen posing an opportunity for detection via DNA testing. A commercially available multitarget stool DNA test evaluates stool samples for mutant KRAS, methylated BMP3 and the pro-moter region of NDRG4. In a large North American prospective study, this test has recently been found to be 92% sensitive for detection of colorectal cancer. Compared to FIT, stool DNA testing has a lower specificity (74%) raising concerns about how to manage stool DNA-positive patients who have a negative colonoscopic evaluation. Sensitivity for advanced precancerous lesions was 42%.100,101 This test, in combination with FIT, is supported as a screening modality every 1 to 3 years by the U.S. Preventative Task Force, and every 3-year utilization is sup-ported by NCCN guidelines.100 Nevertheless, additional studies will be necessary to determine if these tests are comparable or superior to more traditional methods has been techniques.Flexible


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Surgery_Schwartz. is sup-ported by NCCN guidelines.100 Nevertheless, additional studies will be necessary to determine if these tests are comparable or superior to more traditional methods has been techniques.Flexible Sigmoidoscopy. Screening by flexible sigmoidos-copy every 5 years may lead to a 60% to 70% reduction in mor-tality from colorectal cancer, chiefly by identifying high-risk individuals with adenomas. However, it is important to recog-nize that lesions in the proximal colon cannot be identified, and for this reason, flexible sigmoidoscopy has often been paired with air-contrast barium enema to detect transverse and right colon lesions. Patients found to have a polyp, cancer, or other lesion on flexible sigmoidoscopy will require colonoscopy.101-102Fecal Occult Blood Testing and Flexible Sigmoidoscopy. Several trials have shown that FOBT screening is least effec-tive at detecting rectosigmoid cancers.97-99 This is precisely the area screened by flexible sigmoidoscopy; thus, the combination


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Surgery_Schwartz. Several trials have shown that FOBT screening is least effec-tive at detecting rectosigmoid cancers.97-99 This is precisely the area screened by flexible sigmoidoscopy; thus, the combination of the two tests has been suggested as a reasonable screening strategy. Winawer and colleagues, in a study of 12,479 subjects, showed that the combination of FOBT annually with flexible sigmoidoscopy every 5 years resulted in lower mortality from colorectal cancer and better survival in patients with colorectal cancer.99 A similar benefit was confirmed in long-term (11-year) follow-up from the Norwegian Colorectal Cancer Prevention Trial. Such data led to the American Cancer Society recommen-dations that one of the acceptable screening regimens for aver-age-risk Americans is the combination of FOBT/FIT annually and flexible sigmoidoscopy every 5 years; this combination was preferred over either test alone. Recent NCCN guidelines offer the option of flexible sigmoidoscopy with stool-based testing


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Surgery_Schwartz. annually and flexible sigmoidoscopy every 5 years; this combination was preferred over either test alone. Recent NCCN guidelines offer the option of flexible sigmoidoscopy with stool-based testing Brunicardi_Ch29_p1259-p1330.indd 129323/02/19 2:29 PM 1294SPECIFIC CONSIDERATIONSPART IIevery 10 years. The addition of air-contrast barium enema to assess the proximal colon may improve sensitivity as well.96Colonoscopy. Colonoscopy is currently the most accurate and most complete method for examining the large bowel. This procedure is highly sensitive for detecting even small polyps (<1 cm) and allows biopsy, polypectomy, control of hemor-rhage, and dilation of strictures. However, colonoscopy does require mechanical bowel preparation, and the discomfort asso-ciated with the procedure requires conscious sedation in most patients. Colonoscopy is also considerably more expensive than other screening modalities and requires a well-trained endos-copist. The risk of a major complication


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Surgery_Schwartz. conscious sedation in most patients. Colonoscopy is also considerably more expensive than other screening modalities and requires a well-trained endos-copist. The risk of a major complication after colonoscopy (perforation and hemorrhage) is extremely low (0.2–0.3%). Nevertheless, deaths have been reported.Air-Contrast Barium Enema. Air-contrast barium enema is also highly sensitive for detecting polyps greater than 1 cm in diameter (90% sensitivity). Unfortunately, there are no studies proving its efficacy for screening large populations. Accuracy is greatest in the proximal colon but may be compromised in the sigmoid colon if there is significant diverticulosis. The major disadvantages of barium enema are the need for mechanical bowel preparation and the requirement for colonoscopy if a lesion is discovered.Computed Tomography Colonography (Virtual Colonos-copy). Advances in imaging technology have created a num-ber of less invasive, but highly accurate tools for screening. CT


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Surgery_Schwartz. if a lesion is discovered.Computed Tomography Colonography (Virtual Colonos-copy). Advances in imaging technology have created a num-ber of less invasive, but highly accurate tools for screening. CT colonography makes use of helical CT technology and three-dimensional reconstruction to image the intraluminal colon. At present, patients require a mechanical bowel preparation. The colon is then insufflated with air, a spiral CT is performed, and both two-dimensional and three-dimensional images are gener-ated. In the hands of a qualified radiologist, sensitivity appears to be as good as colonoscopy for colorectal cancers and polyps greater than 1 cm in size.103 Colonoscopy is required if a lesion is identified. CT colonography has also been used for imag-ing the proximal colon in cases of obstruction or if a colonos-copy cannot be completed in selected patients. Limitations of this technique include false-positive results from retained stool, diverticular disease, haustral folds, motion


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Surgery_Schwartz. or if a colonos-copy cannot be completed in selected patients. Limitations of this technique include false-positive results from retained stool, diverticular disease, haustral folds, motion artifacts, and an inability to detect flat adenomas.Guidelines for Screening. Current American Cancer Society guidelines advocate screening for the average-risk population (asymptomatic, no family history of colorectal carcinoma, no personal history of polyps or colorectal carcinoma, no familial syndrome) beginning at age 50 years. Recommended proce-dures include yearly FOBT/FIT, flexible sigmoidoscopy every Table 29-1Advantages and disadvantages of screening modalities for asymptomatic individuals ADVANTAGESDISADVANTAGESFecal occult blood testing (FOBT)Ease of use and noninvasiveLow costGood sensitivity with repeat testingMay not detect most polypsLow specificityColonoscopy required for positive resultPoor compliance with serial testingThree successive stools requiredFecal immunohistochemical test


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Surgery_Schwartz. with repeat testingMay not detect most polypsLow specificityColonoscopy required for positive resultPoor compliance with serial testingThree successive stools requiredFecal immunohistochemical test (FIT)Ease of use and noninvasiveLow costMore sensitive and specific than FOBTOnly one stool sample requiredMay not detect most polypsColonoscopy required for positive resultMultitarget stool DNAEase of use and noninvasiveMore sensitive than FITMay not detect most polypsColonoscopy required for positive resultLess specific than FITSigmoidoscopyExamines colon most at riskVery sensitive for polyp detection in left colonDoes not require full bowel preparation (enemas only)InvasiveUncomfortableSlight risk of perforation or bleedingMay miss proximal lesionsColonoscopy required if polyp identifiedColonoscopyExamines entire colonHighly sensitive and specificTherapeuticMost invasiveUncomfortable and requires sedativeRequires bowel preparationRisk of perforation or bleedingCostlyDouble-contrast


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Surgery_Schwartz. entire colonHighly sensitive and specificTherapeuticMost invasiveUncomfortable and requires sedativeRequires bowel preparationRisk of perforation or bleedingCostlyDouble-contrast barium enemaExamines entire colonGood sensitivity for polyps >1 cmExamines entire colonRequires bowel preparationLess sensitivity for polyps <1 cmMay miss lesions in the sigmoid colonColonoscopy required for positive resultComputed tomography colonography (virtual colonoscopy)NoninvasiveSensitivity may be as good as colonoscopyRequires bowel preparationInsensitive for small polypsMinimal experience and dataColonoscopy required for positive resultBrunicardi_Ch29_p1259-p1330.indd 129423/02/19 2:29 PM 1295COLON, RECTUM, AND ANUSCHAPTER 295 years, FOBT/FIT and flexible sigmoidoscopy in combination, air-contrast barium enema every 5 years, or colonoscopy every 10 years. Patients with other risk factors should be screened earlier and more frequently (Table 29-2).93-96,104,105Routes of Spread and Natural


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Surgery_Schwartz. barium enema every 5 years, or colonoscopy every 10 years. Patients with other risk factors should be screened earlier and more frequently (Table 29-2).93-96,104,105Routes of Spread and Natural HistoryCarcinoma of the colon and rectum arises in the mucosa. The tumor subsequently invades the bowel wall and eventually adja-cent tissues and other viscera. Tumors may become bulky and circumferential, leading to colon obstruction. Local invasion (especially in the rectum or sigmoid colon) may occasionally cause obstruction of other organs such as the ureter.Regional lymph node involvement is the most common form of spread of colorectal carcinoma and usually precedes distant metastasis or the development of carcinomatosis. The likelihood of nodal metastasis increases with tumor size, poorly differentiated histology, lymphovascular invasion, and depth of invasion. The T stage (depth of invasion) is the single most significant predictor of lymph node spread. Carcinoma in situ (Tis) in which


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Surgery_Schwartz. histology, lymphovascular invasion, and depth of invasion. The T stage (depth of invasion) is the single most significant predictor of lymph node spread. Carcinoma in situ (Tis) in which there is no penetration of the muscularis mucosa (basement membrane) has also been called high-grade dysplasia and should carry no risk of lymph node metastasis. Small lesions confined to the bowel wall (T1 and T2) are associated with lymph node metastasis in 5% to 20% of cases, whereas larger tumors that invade through the bowel wall or into adja-cent organs (T3 and T4) are likely to have lymph node metas-tasis in more than 50% of cases. The number of lymph nodes with metastases correlates with the presence of distant disease and inversely with survival. Four or more involved lymph nodes (N2 disease) predict a poor prognosis. In colon cancer, lym-phatic spread usually follows the major venous outflow from the involved segment of the colon. Lymphatic spread from the rectum follows two routes. In the


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Surgery_Schwartz. a poor prognosis. In colon cancer, lym-phatic spread usually follows the major venous outflow from the involved segment of the colon. Lymphatic spread from the rectum follows two routes. In the upper rectum, drainage ascends along the superior rectal vessels to the inferior mesen-teric nodes. In the lower rectum, lymphatic drainage may course along the middle rectal vessels. Nodal spread along the inferior rectal vessels to the internal iliac nodes or groin is rare unless the tumor involves the anal canal or the proximal lymphatics are blocked with tumor (Fig. 29-23).The most common site of distant metastasis from colorec-tal cancer is the liver. These metastases arise from hematog-enous spread via the portal venous system. Like lymph node metastasis, the risk of hepatic metastasis increases with tumor size and tumor grade. However, even small tumors may pro-duce distant metastasis. The lung is also a site of hematogenous spread, but this rarely occurs in isolation. Carcinomatosis


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Surgery_Schwartz. with tumor size and tumor grade. However, even small tumors may pro-duce distant metastasis. The lung is also a site of hematogenous spread, but this rarely occurs in isolation. Carcinomatosis (dif-fuse peritoneal metastases) occurs by peritoneal seeding and has a dismal prognosis.Staging and Preoperative EvaluationClinical Presentation. Symptoms of colon and rectal can-cers are nonspecific and generally develop when the cancer is locally advanced. The classic first symptoms are a change in bowel habits and rectal bleeding. Abdominal pain, bloating, and other signs of obstruction typically occur with larger tumors and Table 29-2Screening guidelines for colorectal cancerPOPULATIONINITIAL AGERECOMMENDED SCREENING TESTAverage risk50 yAnnual FOBT orFlexible sigmoidoscopy every 5 y orAnnual FOBT and flexible sigmoidoscopy every 5 y orAir-contrast barium enema every 5 y orColonoscopy every 10 yAdenomatous polyps50 yColonoscopy at first detection; then colonoscopy in 3 yIf no further polyps,


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Surgery_Schwartz. and flexible sigmoidoscopy every 5 y orAir-contrast barium enema every 5 y orColonoscopy every 10 yAdenomatous polyps50 yColonoscopy at first detection; then colonoscopy in 3 yIf no further polyps, colonoscopy every 5 yIf polyps, colonoscopy every 3 yAnnual colonoscopy for >5 adenomasColorectal cancerAt diagnosisPretreatment colonoscopy; then at 12 mo after curative resection; then colonoscopy after 3 y; then colonoscopy every 5 y, if no new lesionsUlcerative colitis, Crohn’s colitisAt diagnosis; then after 8 y for pancolitis, after 15 y for left-sided colitisColonoscopy with multiple biopsies every 1–2 yFAP10–12 yAnnual flexible sigmoidoscopyUpper endoscopy every 1–3 y after polyps appearAttenuated FAP20 yAnnual flexible sigmoidoscopyUpper endoscopy every 1–3 y after polyps appearHNPCC20–25 yColonoscopy every 1–2 yEndometrial aspiration biopsy every 1–2 yFamilial colorectal cancer first-degree relative40 y or 10 y before the age of the youngest affected relativeColonoscopy every 5


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Surgery_Schwartz. yColonoscopy every 1–2 yEndometrial aspiration biopsy every 1–2 yFamilial colorectal cancer first-degree relative40 y or 10 y before the age of the youngest affected relativeColonoscopy every 5 yIncrease frequency if multiple family members are affected, especially before 50 yFAP = familial adenomatous polyposis; FOBT = fecal occult blood testing; HNPCC = hereditary nonpolyposis colon cancer.Data from Smith et al,79 Pignone et al,97 and Levin et al.67Brunicardi_Ch29_p1259-p1330.indd 129523/02/19 2:29 PM 1296SPECIFIC CONSIDERATIONSPART IIsuggest more advanced disease. Because of the caliber of the bowel and the consistency of the stool, left-sided tumors are more likely to cause obstruction than are right-sided tumors. Rectal tumors may cause bleeding, tenesmus, and pain. How-ever, it is important to note that many patients may be asymp-tomatic and/or present with unexplained anemia, weight loss, or poor appetite.Staging. Colorectal cancer staging is based on tumor depth and the


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Surgery_Schwartz. is important to note that many patients may be asymp-tomatic and/or present with unexplained anemia, weight loss, or poor appetite.Staging. Colorectal cancer staging is based on tumor depth and the presence or absence of nodal or distant metastases. Older staging systems, such as the Dukes’ Classification and its Astler-Coller modification, have been replaced by the tumor-node-metastasis (TNM) staging system described by the American Joint Committee on Cancer (AJCC). The AJCC TNM classification has recently been updated to reflect sur-vival outcomes based upon the Surveillance Epidemiology and End Results (SEER) registry (Table 29-3).106-109 Stage I disease includes adenocarcinomas that are invasive through the muscu-laris mucosa but are confined to the submucosa (T1) or the mus-cularis propria (T2) in the absence of nodal metastases. Stage II disease consists of tumors that invade through the bowel wall into the subserosa or nonperitonealized pericolic or perirectal tissues (T3) or


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Surgery_Schwartz. propria (T2) in the absence of nodal metastases. Stage II disease consists of tumors that invade through the bowel wall into the subserosa or nonperitonealized pericolic or perirectal tissues (T3) or into other organs or tissues or through the vis-ceral peritoneum (T4) without nodal metastases. Stage III dis-ease includes any T stage with nodal metastases, and stage IV disease denotes distant metastases.The preoperative imaging evaluation usually identifies stage IV disease. In colon cancer, differentiating stages I, II, and III depends on histologic examination of the resected specimen. In rectal cancer, endorectal ultrasound or MRI may predict the stage (ultrasound stage, uTxNx) preoperatively, but the final determination depends on pathologic examination of the resected tumor and adjacent lymph nodes (pathologic stage, pTxNx). Dis-ease stage correlates with 5-year survival. Patients with stages I and II disease can expect excellent survival rates. The pres-ence of nodal metastases


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Surgery_Schwartz. lymph nodes (pathologic stage, pTxNx). Dis-ease stage correlates with 5-year survival. Patients with stages I and II disease can expect excellent survival rates. The pres-ence of nodal metastases (stage III) decreases survival. In rectal cancer, staging has been further refined, and outcomes suggest that subgroups of patients within each stage may have very dif-ferent prognoses. If the mesorectum around a rectal cancer is involved or threatened (only 1–2 mm of clearance), there is a very high likelihood of local recurrence and a poor prognosis. This circumferential or radial margin is probably best assessed preoperatively by MRI. Although nodal involvement is the sin-gle most important prognostic factor in colorectal carcinoma, tumor characteristics, such as degree of differentiation, muci-nous or signet-ring cell histology, vascular invasion, and DNA aneuploidy, also adversely affect prognosis. Preoperative CEA also has been suggested to be a prognostic indicator.8 Molecular


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Surgery_Schwartz. muci-nous or signet-ring cell histology, vascular invasion, and DNA aneuploidy, also adversely affect prognosis. Preoperative CEA also has been suggested to be a prognostic indicator.8 Molecular profiling is currently being studied in an effort to further improve prognostic indicators.110 The 5-year survival rate with stage IV disease is low. However, in well-selected patients, metastasec-tomy, especially of isolated liver or lung lesions, can result in cure. In these patients, the involvement of a multidisciplinary team and/or tumor board is highly recommended (Fig. 29-24).Preoperative Evaluation. Once a colon or rectal carcinoma has been diagnosed, a staging evaluation should be undertaken. The colon must be evaluated for synchronous tumors, usually by colonoscopy. Synchronous disease will be present in up to 5% of patients. For rectal cancers, digital rectal examination and rigid or flexible proctoscopy with biopsy should be performed to assess tumor size, location, morphology,


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Surgery_Schwartz. will be present in up to 5% of patients. For rectal cancers, digital rectal examination and rigid or flexible proctoscopy with biopsy should be performed to assess tumor size, location, morphology, histology, and fixa-tion. Endorectal ultrasound or MRI can be invaluable in staging rectal cancer and is used to classify the ultrasound T and N stage of rectal cancers (see Fig. 29-24). A chest/abdominal/pelvic CT scan should be obtained to evaluate for distant metastases. Pelvic CT scan, and sometimes MRI, can be useful in large rec-tal tumors and in recurrent disease to determine the extent of local invasion. Among patients with obstructive symptoms, a water-soluble contrast study (Gastrografin enema) may be use-ful for delineating the degree of obstruction. It is important to avoid mechanical bowel preparation (for either colonoscopy or surgery) in a patient who appears to be obstructed. PET scan may be useful in evaluating lesions seen on CT scan and in patients in whom a risky or


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Surgery_Schwartz. bowel preparation (for either colonoscopy or surgery) in a patient who appears to be obstructed. PET scan may be useful in evaluating lesions seen on CT scan and in patients in whom a risky or highly morbid operation is planned (pelvic exenteration, sacrectomy). Preoperative CEA is often obtained and may be useful for postoperative follow-up.Therapy for Colonic CarcinomaPrinciples of Resection. The objective in treatment of car-cinoma of the colon is to remove the primary tumor along with its lymphovascular supply. Because the lymphatics of the colon accompany the main arterial supply, the length of bowel resected depends on which vessels are supplying the segment involved with the cancer. Any adjacent organ or tissue, such as the omentum, that has been invaded should be resected en bloc with the tumor. If all of the tumor cannot be removed, a palliative procedure should be considered, although it impor-tant to note that “debulking” is rarely effective in colorectal adenocarcinoma.The


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Surgery_Schwartz. the tumor. If all of the tumor cannot be removed, a palliative procedure should be considered, although it impor-tant to note that “debulking” is rarely effective in colorectal adenocarcinoma.The presence of synchronous cancers or adenomas or a strong family history of colorectal neoplasms suggests that the entire colon is at risk for carcinoma (often called a field defect), and a subtotal or total colectomy should be considered. Meta-chronous tumors (a second primary colon cancer) identified during follow-up studies should be treated similarly. However, the surgeon must be aware of which mesenteric vessels have been ligated at the initial colectomy because that may influence the viability of the remaining colon and the choice of procedure.The number of lymph nodes recovered in the surgical specimen has long served as a proxy for the oncologic adequacy of resection. A number of studies previously have suggested that Inferiormesenteric a.Superiorrectal a.Middlerectal a.Inferiorrectal


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Surgery_Schwartz. specimen has long served as a proxy for the oncologic adequacy of resection. A number of studies previously have suggested that Inferiormesenteric a.Superiorrectal a.Middlerectal a.Inferiorrectal a.Common iliac a.Figure 29-23. Lymphatic drainage of the rectum. a. = artery.Brunicardi_Ch29_p1259-p1330.indd 129623/02/19 2:29 PM 1297COLON, RECTUM, AND ANUSCHAPTER 29STAGETNM0TisN0M0IT1, T2N0M0IIAT3N0M0IIBT4aN0M0IICT4bN0M0IIIAT1–T2N1/N1cM0IIIAT1N2aM0IIIBT3–T4aN1/N1cM0IIIBT2–T3N2aM0IIIBT1–T2N2bM0IIICT4aN2aM0IIICT3–T4aN2bM0IIICT4bN1–N2M0IVAAny TAny NM1aIVBAny TAny NM1bIVCAny TAny NM1cUsed with the permission of the American College of Surgeons. Amin MB, Edge SB, Greene FL, et al. (Eds.) AJCC Cancer Staging Manual, 8th Ed. Springer New York, 2017.Table 29-3TNM Staging of colorectal carcinoma DEFINITIONTumor Stage (T)TXPrimary tumor cannot be assessedT0No evidence of primary tumorTisCarcinoma in situ, intramucosal carcinoma (involvement of lamina propria with no extension through


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Surgery_Schwartz. Stage (T)TXPrimary tumor cannot be assessedT0No evidence of primary tumorTisCarcinoma in situ, intramucosal carcinoma (involvement of lamina propria with no extension through muscularis mucosae)T1Tumor invades the submucosa (through the muscularis mucosa but not into the muscularis propria)T2Tumor invades the muscularis propriaT3Tumor invades through the muscularis propria into pericolorectal tissuesT4Tumor invades the visceral peritoneum or invades or adheres to adjacent organ or structure T4aTumor invades through the visceral peritoneum (including gross perforation of the bowel through tumor and continuous invasion of tumor through areas of inflammation to the surface of the visceral peritoneum) T4bTumor directly invades or adheres to adjacent organs or structuresNodal Stage (N)NXRegional lymph nodes cannot be assessedN0No regional lymph node metastasisN1One to three regional lymph nodes are positive (tumor in lymph nodes measuring ≥0.2 mm), or any number of tumor deposits are


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Surgery_Schwartz. lymph nodes cannot be assessedN0No regional lymph node metastasisN1One to three regional lymph nodes are positive (tumor in lymph nodes measuring ≥0.2 mm), or any number of tumor deposits are present and all identifiable lymph nodes are negative N1aOne regional lymph node is positive N1bTwo or three regional lymph nodes are positive N1cNo regional lymph nodes are positive, but there are tumor deposits in the• subserosa• mesentery• or nonperitonealized pericolic, or perirectal/mesorectal tissues.N2Four or more regional nodes are positive N2aFour to six regional lymph nodes are positive N2bSeven or more regional lymph nodes are positiveDistant Metastasis (M)M0No distant metastasis by imaging, etc.; no evidence of tumor in distant sites or organs (This category is not assigned by pathologists.)M1Metastasis to one or more distant sites or organs or peritoneal metastasis is identified M1aMetastasis to one site or organ is identified without peritoneal metastasis M1bMetastasis to two or


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Surgery_Schwartz. to one or more distant sites or organs or peritoneal metastasis is identified M1aMetastasis to one site or organ is identified without peritoneal metastasis M1bMetastasis to two or more sites or organs is identified without peritoneal metastasis M1cMetastasis to the peritoneal surface is identified alone or with other site or organ metastasesBrunicardi_Ch29_p1259-p1330.indd 129723/02/19 2:29 PM 1298SPECIFIC CONSIDERATIONSPART IIFigure 29-24. A. Endorectal ultrasonography showing a T3 rectal carcinoma. The dotted line is being used to measure the diameter of the lesion. B. Rectal cancer MRI. (A, Used with permission from Charles O. Finne III, MD, Minneapolis, MN.) a minimum of 12 lymph nodes in the resected specimen are nec-essary for adequate staging. In addition, patients in whom more nodes are harvested have better long-term outcome. As such, a 12-node minimum has been suggested as an appropriate bench-mark for assessing quality of care. However, several investi-gators recently


Surgery_Schwartz

Surgery_Schwartz. nodes are harvested have better long-term outcome. As such, a 12-node minimum has been suggested as an appropriate bench-mark for assessing quality of care. However, several investi-gators recently have called this into question, noting that the number of lymph nodes examined does not correlate with stag-ing, use of adjuvant chemotherapy, or patient survival. Others have suggested that the number of negative lymph nodes and/or the lymph node ratio (positive lymph nodes to total lymph nodes) may further improve staging.106,111-114If unexpected metastatic disease is encountered at the time of a laparotomy, the decision about whether to proceed with resection of the primary tumor depends on the volume of dis-tant disease, location and size of the primary tumor, the opera-tion required to remove the primary tumor, and the operative approach. If the metastatic disease is low volume (isolated or potentially resectable liver lesions) and the resection of the primary tumor is straightforward


Surgery_Schwartz

Surgery_Schwartz. the primary tumor, and the operative approach. If the metastatic disease is low volume (isolated or potentially resectable liver lesions) and the resection of the primary tumor is straightforward (segmental abdominal colec-tomy), it is probably reasonable to proceed with resection. On the other hand, if the metastatic disease is high volume (carci-nomatosis), especially if the primary tumor is minimally symp-tomatic, the operation should be aborted in order to facilitate early systemic chemotherapy. Some centers favor starting the operation with a diagnostic laparoscopy in cases where risk of discovering metastasis is high in order to minimize the magni-tude of the operation should surgery be aborted. With recent advances in chemotherapy, many of these patients will never develop a complication from the primary tumor requiring surgi-cal intervention. Other palliative approaches include a bypass or proximal stoma for obstructing lesions.115,116Stage-Specific Therapy Stage 0 (Tis, N0,


Surgery_Schwartz

Surgery_Schwartz. from the primary tumor requiring surgi-cal intervention. Other palliative approaches include a bypass or proximal stoma for obstructing lesions.115,116Stage-Specific Therapy Stage 0 (Tis, N0, M0) Polyps containing carcinoma in situ (high-grade dysplasia) carry no risk of lymph node metastasis. However, the presence of high-grade dysplasia increases the risk of finding an invasive carcinoma within the polyp. For this reason, these polyps should be excised completely, and patho-logic margins should be free of dysplasia. Most pedunculated polyps and many sessile polyps may be completely removed endoscopically. These patients should be followed with fre-quent colonoscopy to ensure that the polyp has not recurred and that an invasive carcinoma has not developed. In cases where the polyp cannot be removed entirely, a segmental resection is recommended.Stage I: The Malignant Polyp (T1, N0, M0) Occasionally a polyp that was thought to be benign will be found to harbor invasive carcinoma after


Surgery_Schwartz

Surgery_Schwartz. be removed entirely, a segmental resection is recommended.Stage I: The Malignant Polyp (T1, N0, M0) Occasionally a polyp that was thought to be benign will be found to harbor invasive carcinoma after polypectomy. Treatment of a malig-nant polyp is based on the risk of local recurrence and the risk of lymph node metastasis.59 The risk of lymph node metastases depends primarily on the depth of invasion. Invasive carcinoma in the head of a pedunculated polyp with no stalk involvement carries a low risk of metastasis (<1%) and may be completely resected endoscopically. For sessile polyps, the depth of inva-sion predicts risk of lymphovascular spread. A recent classifica-tion stratifies risk by depth of submucosal spread. Superficial lesions (submucosa 1; Sm1) are low risk, whereas Sm2 and Sm3 are intermediate and high risk.117 Lymphovascular inva-sion, poorly differentiated histology, tumor budding, or tumor within 1 mm of the resection margin greatly increases the risk of local


Surgery_Schwartz

Surgery_Schwartz. and Sm3 are intermediate and high risk.117 Lymphovascular inva-sion, poorly differentiated histology, tumor budding, or tumor within 1 mm of the resection margin greatly increases the risk of local recurrence and metastatic spread. Segmental colectomy is then indicated. Invasive carcinoma arising in a sessile polyp extending into the submucosa and is usually best treated with segmental colectomy (Fig. 29-25).Stages I and II: Localized Colon Carcinoma (T1-3, N0, M0) The majority of patients with stages I and II colon cancer will be cured with surgical resection. Few patients with completely resected stage I disease will develop either local or distant recur-rence, and adjuvant chemotherapy does not improve survival in these patients.117 However, up to 46% of patients with com-pletely resected stage II disease will ultimately die from colon cancer. For this reason, adjuvant chemotherapy has been sug-gested for selected patients with stage II disease (young patients, tumors with


Surgery_Schwartz

Surgery_Schwartz. resected stage II disease will ultimately die from colon cancer. For this reason, adjuvant chemotherapy has been sug-gested for selected patients with stage II disease (young patients, tumors with “high-risk” histologic findings). It remains contro-versial as to whether chemotherapy improves survival rates in these patients. In some cases, molecular profiling may predict prognosis, although it is important to note that these tools have not been shown to predict response to therapy. At present, Brunicardi_Ch29_p1259-p1330.indd 129823/02/19 2:29 PM 1299COLON, RECTUM, AND ANUSCHAPTER 29molecular profiling for selecting patients to receive chemother-apy remains unproven.Stage III: Lymph Node Metastasis (Tany, N1, M0) Patients with lymph node involvement are at significant risk for both local and distant recurrence, and adjuvant chemotherapy has been recommended routinely in these patients. 5-Fluorouracil–based regimens (with leucovorin) and oxaliplatin (FOLFOX) reduce recurrences and


Surgery_Schwartz

Surgery_Schwartz. and distant recurrence, and adjuvant chemotherapy has been recommended routinely in these patients. 5-Fluorouracil–based regimens (with leucovorin) and oxaliplatin (FOLFOX) reduce recurrences and improve survival in this patient popula-tion. It is important to note, however, that a subgroup of patients with stage III disease will do well without chemotherapy. MSI status in particular predicts good prognosis. Subset analysis from the CRYSTAL trial has shown that patients with MSI-high stage III disease do not benefit from 5-fluorouracil–based chemotherapy. Molecular profiling, therefore, may be helpful in determining which stage III patients can safely avoid systemic chemotherapy.118Stage IV: Distant Metastasis (Tany, Nany, M1) Survival is extremely limited in stage IV colon carcinoma. Systemic che-motherapy is recommended in almost all cases of distant spread. However, unlike many other malignancies, highly selected patients with isolated, resectable metastases may benefit from


Surgery_Schwartz

Surgery_Schwartz. Systemic che-motherapy is recommended in almost all cases of distant spread. However, unlike many other malignancies, highly selected patients with isolated, resectable metastases may benefit from resection (metastasectomy). The most common site of metasta-sis is the liver. Of patients with systemic disease, approximately 15% will have metastases limited to the liver. Of these, 20% are potentially resectable for cure. Survival is improved in these patients (20–40% 5-year survival) when compared to patients who do not undergo resection. Hepatic resection of synchronous metastases from colorectal carcinoma may be performed as a combined procedure or in two stages. The second most com-mon site of metastasis is the lung, occurring in approximately 20% of patients with colorectal carcinoma. Although very few of these patients will be potentially resectable, among those who are (about 1–2% of all colorectal cancer patients), long-term survival benefit is approximately 30% to 40%. There are


Surgery_Schwartz

Surgery_Schwartz. very few of these patients will be potentially resectable, among those who are (about 1–2% of all colorectal cancer patients), long-term survival benefit is approximately 30% to 40%. There are limited reports of successful resection of metastases in other sites (ovary and retroperitoneum are most common). Cytore-ductive surgery and intraperitoneal chemotherapy (HIPEC) has been suggested for patients with carcinomatosis, but remains unproven for colorectal cancer and carries high morbidity.119,120The remainder of patients with stage IV disease cannot be cured surgically, and therefore, the focus of treatment should be palliation. Methods such as colonic stenting for obstruct-ing lesions of the left colon also provide good palliation. More limited surgical intervention such as a diverting stoma or bypass procedure may be appropriate in patients with stage IV disease who develop obstruction. Hemorrhage in an unresectable tumor can sometimes be controlled with angiographic embolization.


Surgery_Schwartz

Surgery_Schwartz. stoma or bypass procedure may be appropriate in patients with stage IV disease who develop obstruction. Hemorrhage in an unresectable tumor can sometimes be controlled with angiographic embolization. External beam radiation also has been used for palliation. The involvement of a palliative care team in the management of these patients is critical.116Therapy for Rectal CarcinomaPrinciples of Resection. The biology of rectal adenocarci-noma is thought to be similar to the biology of colonic adeno-carcinoma, and the operative principles of complete resection of the primary tumor, its lymphatic bed, and any other involved organ apply to surgical resection of rectal carcinoma. However, the anatomy of the pelvis and proximity of other structures (ureters, bladder, prostate, vagina, iliac vessels, and sacrum) make resection more challenging and often require a different approach than for colonic adenocarcinoma. Moreover, it is more difficult to achieve negative radial margins in rectal


Surgery_Schwartz

Surgery_Schwartz. and sacrum) make resection more challenging and often require a different approach than for colonic adenocarcinoma. Moreover, it is more difficult to achieve negative radial margins in rectal cancers that extend through the bowel wall because of the anatomic limita-tions of the pelvis. Therefore, local recurrence is higher than with similar stage colon cancers. However, unlike the intraperi-toneal colon, the relative paucity of small bowel and other radi-ation-sensitive structures in the pelvis makes it easier to treat rectal tumors with radiation. Therapeutic decisions, therefore, are based on the location and depth of the tumor and its relation-ship to other structures in the pelvis.Local Therapy. The distal 10 cm of the rectum are accessible transanally. For this reason, several local approaches have been proposed for treating rectal neoplasms. Transanal excision (full thickness or mucosal) is an excellent approach for noncircum-ferential, benign, villous adenomas of the rectum.


Surgery_Schwartz

Surgery_Schwartz. approaches have been proposed for treating rectal neoplasms. Transanal excision (full thickness or mucosal) is an excellent approach for noncircum-ferential, benign, villous adenomas of the rectum. Transanal endoscopic microsurgery (TEM) and transanal minimally invasive surgery (TAMIS) make use of a specially designed proctoscope, magnifying system, and instruments similar to those used in laparoscopy to allow local excision of lesions higher in the rectum (up to 15 cm). Although this technique has been used for selected T1, and some T2, carcinomas, local excision does not allow pathologic examination of the lymph nodes and might therefore understage patients. Moreover, local recurrence rates are high after transanal excision, and salvage surgery, while often curative, has been reported to be associ-ated with poorer survival than with initial radical surgery. Cur-rent recommendation is to limit local excision of T1 lesions to patients with well to moderately differentiated small


Surgery_Schwartz

Surgery_Schwartz. to be associ-ated with poorer survival than with initial radical surgery. Cur-rent recommendation is to limit local excision of T1 lesions to patients with well to moderately differentiated small lesions (<3 cm) and/or in patients medically unfit for radical resection. In general, local excision of any rectal neoplasm should be con-sidered an excisional biopsy because final pathologic examina-tion of the specimen may reveal an invasive carcinoma that then mandates more radical therapy.120,121Ablative techniques, such as electrocautery or endocavi-tary radiation, also have been used. The disadvantage of these techniques is that no pathologic specimen is retrieved to confirm the tumor stage. Fulguration is generally reserved for extremely high-risk, symptomatic patients with a limited life span who cannot tolerate more radical surgery.120Radical Resection. Radical resection is preferred to local therapy for most rectal carcinomas. Radical resection involves removal of the involved


Surgery_Schwartz

Surgery_Schwartz. life span who cannot tolerate more radical surgery.120Radical Resection. Radical resection is preferred to local therapy for most rectal carcinomas. Radical resection involves removal of the involved segment of the rectum along with its lymphovascular supply. Although any microscopically nega-tive margin has been suggested to be adequate, most surgeons Pedunculated polypInvasive caSessile polypStalkNeckMuscularismucosaFigure 29-25. Levels of invasive carcinoma in pedunculated and sessile polyps. ca = carcinoma.Brunicardi_Ch29_p1259-p1330.indd 129923/02/19 2:29 PM 1300SPECIFIC CONSIDERATIONSPART IIstill attempt to obtain a 2-cm distal mural margin for curative resections.Total mesorectal excision (TME) is a technique that uses sharp dissection along anatomic planes to ensure complete resection of the rectal mesentery during low and extended low anterior resections. For upper rectal or rectosigmoid resections, a partial mesorectal excision of at least 5 cm distal to the tumor


Surgery_Schwartz

Surgery_Schwartz. resection of the rectal mesentery during low and extended low anterior resections. For upper rectal or rectosigmoid resections, a partial mesorectal excision of at least 5 cm distal to the tumor appears adequate. TME both decreases local recurrence rates and improves long-term survival rates. Moreover, this tech-nique is associated with less blood loss and less risk to the pel-vic nerves and presacral plexus than is blunt dissection. The principles of TME should be applied to all radical resections for rectal cancer.Recurrence of rectal cancer generally has a poor prog-nosis. Extensive involvement of other pelvic organs (usually occurring in the setting of tumor recurrence) may require a pelvic exenteration. The rectal and perineal portions of this operation are similar to an APR, but en bloc resection of the ureters, bladder, and prostate or uterus and vagina are also per-formed. A permanent colostomy and an ileal conduit to drain the urinary tract may be necessary. The sacrum may


Surgery_Schwartz

Surgery_Schwartz. bloc resection of the ureters, bladder, and prostate or uterus and vagina are also per-formed. A permanent colostomy and an ileal conduit to drain the urinary tract may be necessary. The sacrum may also be resected if necessary (sacrectomy) up to the level of the S2-S3 junction. These operations are best performed in tertiary centers with multidisciplinary teams consisting of a colon and rectal surgeon, urologist, neurosurgeon, and plastic surgeon.Stage-Specific Therapy (Fig. 29-26). Pretreatment staging of rectal carcinoma often relies on endorectal ultrasound or MRI to determine the T and N status of a rectal cancer. Ultrasound is highly accurate at assessing tumor depth, but it is less accurate in diagnosing nodal involvement. Ultrasound evaluation can guide choice of therapy in most patients. MRI is useful to assess mesorectal involvement. When the radial margin is threatened or involved, neoadjuvant chemoradiation is recommended.122Stage 0 (Tis, N0, M0) Villous adenomas harboring


Surgery_Schwartz

Surgery_Schwartz. MRI is useful to assess mesorectal involvement. When the radial margin is threatened or involved, neoadjuvant chemoradiation is recommended.122Stage 0 (Tis, N0, M0) Villous adenomas harboring carci-noma in situ (high-grade dysplasia) are ideally treated with local excision. A 1-cm margin should be obtained. Rarely, radical resection will be necessary if transanal excision is not techni-cally possible (large circumferential lesions).Stage I: Localized Rectal Carcinoma (T1-2, N0, M0) Although local excision has been used for small, favorable ses-sile uT1N0 and uT2N0 rectal cancers, local recurrence rates may be as high as 20% and 40%, respectively. Local excision increasingly is offered to patients with small, low-risk lesions, but it does not allow physicians to assess regional lymph nodes. For this reason, radical resection is recommended in all good-risk patients. Lesions with unfavorable histologic characteristics and those located in the distal third of the rectum, in particular,


Surgery_Schwartz

Surgery_Schwartz. For this reason, radical resection is recommended in all good-risk patients. Lesions with unfavorable histologic characteristics and those located in the distal third of the rectum, in particular, are prone to recurrence. In high-risk patients and in patients who refuse radical surgery because of the risk of need for a permanent colostomy, local excision may be adequate, but strong consideration should be given to adjuvant or neoadju-vant chemoradiation to improve local control. The efficacy of adjuvant or neoadjuvant chemoradiation followed by transanal excision in patients who can tolerate radical surgery has been High risk orrefuses radicalresectionTransanalexcision +/–neoadjuvant oradjuvantchemoradiationRadicalresectionRadicalresectionRadicalresectionContinuechemotherapyConsiderresectionChemoradiationvs. palliativeprocedurestent, laserablation, stoma,resectionLow risk andaccepts


Surgery_Schwartz

Surgery_Schwartz. palliativeprocedurestent, laserablation, stoma,resectionLow risk andaccepts radicalresectionNeoadjuvantchemoradiationNeoadjuvantchemoradiationAsymptomaticSymptomaticRestageRestageUnresectable/multiplemetastaticsitesResectable/singlemetastatic siteChemotherapyNo metastasesNo metastasesRectal adenocarcinomaStage II(T3-4, N0, M0)Stage III(Tany, N1-3, M0)Staging evaluationCT chest/abdomen/pelvisEndorectal U/S+/– MRIColonoscopy/CT colonography (if possible)Stage IV(Tany, Nany, M1)Stage I(T1-2, N0, M0)RestageFigure 29-26. Diagnostic algorithm for rectal cancer. CT = computed tomography; MRI = magnetic resonance imaging; U/S = ultrasound.Brunicardi_Ch29_p1259-p1330.indd 130023/02/19 2:29 PM 1301COLON, RECTUM, AND ANUSCHAPTER 29controversial. Early results from ACOSOG Z6041, in which patients with T2 rectal cancers received neoadjuvant chemo-radiation followed by transanal excision, showed a pathologic complete response rate of 44%.123 At 3 years, disease-free sur-vival was 88%, which is


Surgery_Schwartz

Surgery_Schwartz. with T2 rectal cancers received neoadjuvant chemo-radiation followed by transanal excision, showed a pathologic complete response rate of 44%.123 At 3 years, disease-free sur-vival was 88%, which is comparable to cancer outcomes after a formal resection. However, population-based data suggests that survival after local excision for rectal cancer is suboptimal and should not be offered as a matter of routine.124Locally Advanced Rectal Cancer (Stages II and III) Stage II: Localized Rectal Carcinoma (T3-4, N0, M0). Larger rectal tumors, especially if located in the distal rectum, are more likely to recur locally. There are two schools of thought, each differing in their approach, concerning how to control local recurrences. Advocates of total mesorectal resection sug-gest that optimization of operative technique will obviate the need for any adjuvant chemoradiation to control local recur-rence after resection of stages I, II, and III rectal cancers. The opposing school suggests that


Surgery_Schwartz

Surgery_Schwartz. of operative technique will obviate the need for any adjuvant chemoradiation to control local recur-rence after resection of stages I, II, and III rectal cancers. The opposing school suggests that stages II and III rectal cancers will benefit from chemoradiation. They argue that such therapy reduces local recurrences and prolongs survival whether given preoperatively or postoperatively. The advantages of preopera-tive chemoradiation include tumor shrinkage, increased likeli-hood of resection and of a sphincter-sparing procedure, tumor downstaging by treating locally involved lymph nodes, and decreased risk to the small intestine. Disadvantages include possible overtreatment of early-stage tumors, impaired wound healing, and pelvic fibrosis increasing the risk of operative com-plications. Postoperative radiation allows accurate pathologic staging of the resected tumor and lymph nodes and avoids the wound healing problems associated with preoperative radiation. However, bulky tumors,


Surgery_Schwartz

Surgery_Schwartz. Postoperative radiation allows accurate pathologic staging of the resected tumor and lymph nodes and avoids the wound healing problems associated with preoperative radiation. However, bulky tumors, tumors involving adjacent organs, and very low rectal tumors may be much more difficult to resect without preoperative radiation and may require a more exten-sive operation.124-127Stage III: Lymph Node Metastasis (Tany, N1, M0). Many surgeons now recommend chemotherapy and radiation either preor postoperatively for node-positive rectal cancers. The advantages and disadvantages are similar to those listed for stage II disease, except that the likelihood of overtreating an early-stage lesion is considerably less.Over the past two decades, a wide variety of studies have addressed the issue of adjuvant and neoadjuvant therapy for locally advanced rectal cancer. Many of these studies demon-strated both improved local control and prolonged survival and resulted in the 1990 National Institutes of


Surgery_Schwartz

Surgery_Schwartz. and neoadjuvant therapy for locally advanced rectal cancer. Many of these studies demon-strated both improved local control and prolonged survival and resulted in the 1990 National Institutes of Health (NIH) con-sensus conference recommendation for postoperative chemo-radiation therapy in these patients. There is little controversy regarding chemoradiation therapy for stage III (node-positive) disease. However, advances in surgical technique, such as TME, for locally advanced node-negative cancers (T3-4, N0; stage II) have improved local control with surgery alone, prompting some to abandon adjuvant chemoradiation in these patients, especially for those with cancers in the proximal rectum. Although the data from these studies are intriguing, other reports have shown that chemoradiation improves local control and survival even in patients who undergo TME. Thus, most colorectal surgeons in the United States continue to recommend adjuvant or neo-adjuvant therapy for patients with locally


Surgery_Schwartz

Surgery_Schwartz. local control and survival even in patients who undergo TME. Thus, most colorectal surgeons in the United States continue to recommend adjuvant or neo-adjuvant therapy for patients with locally advanced disease. Many European surgeons now rely heavily on MRI staging to determine the need for neoadjuvant chemoradiation. They use neoadjuvant chemoradiation if the radial margin is threatened or involved by the cancer or if anal sphincter or other local organ invasion is present. In the United States, chemoradia-tion therapy is still recommended for all patients with stage III disease and the majority of patients with stage II disease. In select patients with T3 tumors, favorable histology, and nega-tive radial margins, chemoradiation may not be necessary, but larger prospective studies are required before this approach can be recommended.125-127Appropriate timing of chemoradiation for locally advanced rectal cancer has been debated. Historically, preopera-tive chemoradiation has been


Surgery_Schwartz

Surgery_Schwartz. required before this approach can be recommended.125-127Appropriate timing of chemoradiation for locally advanced rectal cancer has been debated. Historically, preopera-tive chemoradiation has been advocated based on tumor shrink-age/downstaging, improved resectability, and the possibility of performing a sphincter-sparing operation in some patients. In addition, the absence of small bowel adhesions in the pelvis may decrease toxicity. However, preoperative radiation therapy may increase operative complications and impairs wound heal-ing. Although preoperative endorectal ultrasound and MRI have improved our ability to stage rectal cancer, clinical “overstag-ing” can be problematic, and neoadjuvant therapy may there-fore overtreat patients with pT1-2, N0 tumors. Advocates of postoperative radiation therapy cite more accurate pathologic staging and fewer operative/postoperative complications. How-ever, large, bulky tumors may be unresectable or require a more extensive operation (APR,