At the beginning of the 21st century, rectal cancer continues to be a significant medical and social problem. Currently, there are approximately 135,000 cases of colorectal cancer diagnosed in the United States each year and 50,000 deaths. Approximately 60% of all cases occur in patients older than 65 years of age. Cases that occur prior to age 65 this include 45% of men and 39% of all women diagnosed with colorectal cancer. Significant racial disparities also exist in the incidence and mortality for colorectal cancer, with non-Hispanic blacks (NHB) having the highest incidence and mortality. When compared to non-Hispanic whites (NHW), the NHB population has a 20% higher incidence of colorectal cancer and a 40% higher mortality rate. Overall survival is higher for patients with rectal cancer (67%) than colon cancer (64%), with the most likely explanation being that rectal cancer is more often diagnosed at an earlier localized stage.
Overall, 40% of colorectal tumors are in the proximal colon and 60% are in the distal colon and rectum. However, women are more likely to have proximal lesions (46%) when compared to men (37%), and this disparity increases with advancing age. At younger ages (less than 50), both men (41%) and women (36%) are more likely to be diagnosed with rectal than colon cancer. In fact, there has been a substantial absolute increase in the risk of rectal cancer in patients born after 1970. The reason for the increased risk for rectal cancer in this young population has not been identified but is most likely related to a change in environment, either an exogenous exposure or ingested material in foods such as pesticides or food additives. Increases in the sedentary lifestyle, high-fat diet, and obesity have been suggested etiologic factors as well. As pointed out above, adenocarcinoma of the rectum accounts for nearly 30% of all colorectal cancers. This translates into about 41,000 new diagnoses of rectal cancer each year and greater than 10,000 deaths attributable to this disease within the same time.1,2
The history of modern rectal cancer resection dates to 1884, when Czérny described the first abdominoperineal resection (APR). In 1885, Kraske pioneered the transsacral approach of rectal resection and anastomosis. In 1908, Miles improved on the APR by understanding that there was a “zone of upward spread.”3 He emphasized the importance of performing a wide perineal excision. Consistent with this, current surgical technique includes a cylindrical resection at the level of the levators to include the entire anal canal such that there is not a “coning in” or “waist” on the specimen at the distalmost aspect of the specimen. Furthermore, Miles advocated removal of the rectum with a high ligation of the superior hemorrhoidal artery as well as excision of the abdominal attachments of the rectum and the iliac lymph nodes. Despite the improvements in oncologic resection, operative mortality in Miles’ first series exceeded 42%. Over the next 80 years through the late 1980s, mortality and morbidity for rectal cancer surgery improved markedly in pace with improvements in intra-, peri-, and postoperative care. Unfortunately, there were few, if any, advancements in oncologic techniques during this period. Then, in the late 1980s, William Heald described and began popularizing total mesorectal excision (TME) for carcinoma of the rectum.4 In this technique, he advocates using sharp dissection to perform the complete excision of the mesorectum and its associated lymphatics along the subtle fascial planes that encompass the rectum. Moreover, Heald described a “zone of downward spread” within the mesorectum that requires complete excision to reduce local recurrence. Finally, local excision of small rectal cancers has been used for over 100 years in selected patients. More recently, local excision is being combined with neoadjuvant and adjuvant chemoradiotherapy to maximize local control with a minimally invasive approach.
In Western industrialized nations, the average lifetime risk for an individual to develop colorectal cancer is approximately 6%. This risk increases two- to fourfold if the patient has a personal history of a first-degree relative with colorectal cancer. Inflammatory bowel disease (IBD) is another risk factor. In the first 10 years after the initial diagnosis of ulcerative colitis (UC), the incidence of colorectal cancer increases, and in the past was suggested to be as high as 1% per each year of disease. Recent studies, however, have demonstrated that the cumulative risk is about 2% to 7.5% at 25 to 30 years of disease duration and as high as 13.5% at 45 years of disease.5 Pancolitis is associated with both an earlier and an increased risk for colorectal cancer when compared to left-sided colitis alone. Screening the colon yearly starting at 10 years after the diagnosis with colonoscopy and multiple biopsies in four quadrants every 10 cm from the cecum to the distal rectum is used to predict when a patient is at risk for developing colorectal cancer. If high-grade dysplasia is detected in any of the biopsies, the patient should be advised to have a total proctocolectomy. Some practitioners advocate a surgical resection for low-grade dysplasia as well, whereas some are willing to repeat a colonoscopy with multiple biopsies. If low-grade dysplasia is found on subsequent short-interval colonoscopy, then total proctocolectomy is advised. Ultimately, the most effective method for preventing colon cancer in patients with UC is to remove the colon once any type of dysplasia has been identified. Crohn’s colitis is also associated with an increased risk for colorectal cancer. This is often not appreciated by clinicians because patients with severe Crohn’s colitis often undergo proctocolectomy before their long-term risk becomes an issue. The cumulative risk for colon and rectal cancer in patients with Crohn’s colitis is 2.9% at 10 years, 5.6% at 20 years, and 8.3% at 30 years.5
Genetic risk factors also have been implicated in the development of colorectal cancer. One is familial adenomatous polyposis (FAP), an autosomal dominant syndrome with 100% lifetime risk of developing colorectal cancer. The abnormality is caused by a defect in the APC gene located on chromosome 5q21. Patients with FAP develop hundreds or thousands of adenomas by their twenties, and colorectal cancer develops in all patients by age 50 years if untreated. Extraintestinal manifestations of this genetic defect include desmoid tumors, periampullary masses, osteomas, and medulloblastomas. A second genetic abnormality associated with the development of colorectal cancer is related to defects in the mismatch repair genes MLH1, MSH2, MSH6, and PMS2. Genetic defects in these mismatch repair genes affect the repair of DNA replication errors and spontaneous base repair loss and contribute to hereditary nonpolyposis colorectal cancer (HNPCC) that is also known as Lynch syndrome. Despite the name, these cancers arise from adenomas and may account for 5% of all colorectal malignancies. In this autosomal dominant syndrome, cancers occur more often on the right side of the colon. Despite developing at a younger age, there is a better prognosis with these cancers when compared with age-matched controls with a non-HNPCC colorectal cancer. In theory, a patient with HNPCC living to age 80 years would have an 80% risk for developing colorectal cancer; additionally, there is a substantial risk of endometrial cancer (50%), ovarian cancer (15%). urinary tract cancer (10%), and gastric cancer (5%). There is a smaller but substantial risk of small intestinal (1%) and hepatopancreaticobiliary (1%) tumors as well. Family members should be screened initially at age 25 years or 10 years prior to the age at which the first family member was diagnosed with a neoplasm. Screening should include yearly colonoscopy and esophagogastroduodenoscopy (EGD) every 3 years (unless there is a family history of gastric cancer when yearly EGD is advised). If an endoscopically unresectable polyp or cancer is detected, a total abdominal colectomy with an ileorectal anastomosis is recommended. Urine cytology to rule out dysplastic cells in the genitourinary tract (which is at risk for transitional cell carcinoma) is recommended. Women who desire to retain fertility should get at least once-yearly transvaginal pelvic ultrasounds and CA-125 levels. Any affected woman who has finished childbearing should consider having a total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH-BSO). Any affected woman who requires a colectomy should be advised to undergo simultaneous prophylactic TAH-BSO. Finally, there is MUTYH polyposis, which is an autosomal recessive genetic defect that predisposes to colon and rectal cancer as well. This is often referred to as the autosomal recessive FAP, as this disease has very similar features to FAP. Patients who are carriers of MYH genetic defects are also at increased risk of colorectal cancer even though they do not carry genetic defects in both alleles. These patients should have colonoscopy every 5 years.
Dietary fats, especially red-meat fats, have been implicated as a risk factor for colon and rectal cancer.6 People who consume less than 15% of their diet as fat have a lower incidence of colorectal cancer, whereas those who take in 20% of their diet as fat, either as unsaturated animal fat or as highly saturated vegetable oils, have an increased risk of colorectal malignancy.
In the past few decades, several studies have linked alcohol consumption and tobacco use with an increased risk of colorectal neoplasia. Moreover, there appears to be a synergistic effect with an even greater increased risk of adenomatous polyps in people who are both smokers and drinkers.7
The concept that colorectal cancers develop from polyps, or the “adenoma-to-carcinoma sequence,” was first described by Dukes in 1926. Most patients with rectal cancer have no inherited component; instead, there is an initiating genetic mutation, such as of an oncogene like Kras, that leads to abnormal cell growth. Subsequently, mutations resulting in inactivation of tumor suppressor genes, such as p53, loss of heterozygosity (LOH) on the long arm of chromosome 18 and the APC gene (even in non-FAP patients), allows for progression to cancer. In fact, in sporadic cancers, mutations in the APC gene are the most common initial genetic alteration.8
The time course for polyp development and transformation to cancer is thought to be 5 to 10 years. Most adenomas remain benign; however, histologic type, polyp size, and evidence of dysplasia are associated with transformation. Data from the National Polyp Study and St. Mark’s Hospital in London show that approximately 75% to 85% of adenomas are tubular, 8% to 15% are tubulovillous, and 5% to 10% are villous. Tubular adenomas usually form a stalk, whereas villous adenomas have a broad base (Fig. 54-1). Villous histology is associated with an increased risk of cancer development. Only 1% of polyps less than 1 cm in diameter show evidence of malignant transformation, whereas 50% of polyps greater than 2 cm in diameter harbor areas of carcinoma.
Clinically, it is important to diagnose the type, size, and number of polyps to risk-stratify patients for treatment and future surveillance. Endoscopic treatment likely reduces or eliminates the risk of colorectal cancer in patients. Rigid sigmoidoscopy and flexible sigmoidoscopy are all that are necessary to screen the rectum. Sigmoidoscopic screening should be followed by a complete colonoscopy if biopsy of a small rectal or sigmoid polyp shows adenomatous changes. Colonoscopy screening as the first study is indicated in high-risk populations such as those with a family history of colorectal cancer, a personal history of IBD, or a known familial genetic mutation (FAP/HNPCC/MUTYH). Autopsy studies have reported that adenomas are present in 20% to 60% of patients with a colorectal cancer, and synchronous cancers are found in 3% to 9% of patients. In patients who cannot undergo a preoperative colonoscopy, either a virtual colonoscopy or barium enema should be performed. If both procedures are contraindicated in these patients, colonoscopy evaluation should be performed 3 months after resection.
Treatment of the malignant rectal polyp is becoming more common with the increase in colonoscopy screening and the early diagnosis of small distal rectal cancers. Surgical treatment in part depends on the morphology of the polyp and the histologic evaluation of the resected lesion. Pedunculated malignant polyps are classified by Haggitt per the depth of invasion of the cancer within the head of the polyp and stalk9 (see Fig. 54-1). Malignant polyps completely resected with greater than 2-mm margins and without stalk invasion are considered adequately treated with colonoscopic removal, provided there are no poor prognostic histologic features such as lymphovascular invasion or poor differentiation (high grade). Tumors with poor differentiation and/or lymphatic/venous invasion are associated with an increased incidence of involved lymph nodes.10
The type of therapy offered to a patient with rectal cancer depends not only on the stage of the tumor but also on its location within the pelvis and its relation to the anal sphincters. Compared with colon cancer, knowledge and appreciation of anatomic landmarks are critical in determining resectability and sphincter preservation.
The rectum, usually 15 to 20 cm in length, extends from the rectosigmoid junction, marked by fusion of the taenia coli into a completely circumferential muscular layer, to the anal canal. In males, the rectum tends to be longer (18 cm) when compared to females (15 cm). The rectum transitions from being intraperitoneal to being completely extraperitoneal 10 to 12 cm from the anus and the root of the sigmoid mesentery is approximately 19 cm from the anal verge on rigid sigmoidoscopy.11 The rectum is “fixed” posteriorly and laterally by Waldeyer’s fascia and the lateral stalks, respectively. In the male patient, the anterior rectum is fixed to Denonvilliers’ fascia, a fold of two layers of peritoneum that separates the rectum from the posterior prostate and seminal vesicles. In the female patient, the peritoneal cavity descends to the pouch of Douglas, with its most dependent point being adjacent to the cervix anteriorly and mid-rectum posteriorly.12 When seen endoscopically, the rectum has three valves of Houston, the middle of which corresponds to the anterior peritoneal reflection (Fig. 54-2A).
While many surgical descriptions for rectal cancer refer to the distance of the lesion from the anal verge or the dentate line, a more accurate description for distal (palpable lesions) is the distance above the anorectal ring as palpated by the examining surgeon. For nonpalpable lesions, we use a rigid sigmoidoscope to localize the lesion and then ascertain the distance from the anal verge to the mass. At the muscular level, the anal canal starts at the top of the “high-pressure zone” that is at the proximal aspect of the anorectal ring, a muscular structure consisting of the internal sphincter, external sphincter, and puborectalis (Figs. 54-2A and B). The high-pressure zone descends beyond the dentate line to the junction of the anal mucosa and the perianal skin; this junction is often referred to as the anal verge. To achieve an adequate distal margin (≥1 cm) with sphincter preservation, the lower border of a tumor must be located high enough above the top of the anorectal ring. The closer the tumor is to the anorectal ring the less likely the surgeon will be able to get extra length with rectal mobilization. This will often make sphincter preservation more difficult. This caveat even holds true with neoadjuvant chemoradiation, as scarring in the distal rectum after radiation and a lack of mesorectum fixes the tissues posteriorly, making it technically more difficult for the surgeon to gain extra length even with mobilization down to the levator ani complex. Hence, some tumors that are 1 to 2 cm above the anorectal ring and seem at initial exam to be amenable to sphincter preservation are not. Once in the operating room, the surgeon is not able to gain distal mobilization and an adequate margin is difficult to achieve and thereby sphincter preservation can prove challenging or not possible. If curative resection compromises perfect function of the sphincter apparatus, or if an adequate distal margin cannot be obtained while preserving the anorectal ring, an APR with a permanent colostomy should be constructed. Although a patient may assume that a colostomy indicates a hopelessly incurable cancer, we must emphasize that the colostomy is necessary because of the anatomic location, not necessarily the severity of the rectal cancer.
Arteriography demonstrates extensive intramural anastomoses between the superior, middle, and inferior rectal arteries. The superior rectal artery originates from the inferior mesenteric artery and descends in the mesorectum to supply the upper and middle rectum (Fig. 54-3). The inferior rectal arteries, branches of the internal pudendal arteries, enter posterolateral and provide blood supply to the anal sphincters and epithelium. The middle rectal artery, often depicted in anatomic drawings as a large and significant artery branching off the internal iliac artery on each side, is seldom greater than 1 mm in diameter.13 In one study, the middle rectal artery was observed in only 22% of cadaver specimens.12 When present, the middle rectal artery is located near the lateral rectal stalks. These stalks are primarily nerves but have been confused previously with arterial supply.
The superior rectal vein drains the upper and middle thirds of the rectum and empties into the portal system via the inferior mesenteric vein. The middle rectal veins drain the lower rectum and upper anal canal into the internal iliac veins. The inferior rectal veins drain the lower anal canal, emptying into the internal iliac veins via the pudendal veins. Because the venous systems communicate, low rectal cancers may spread via the portal and systemic circulations.
Local recurrence after resection is common and can occur with and without distant metastatic disease. Rectal cancer can spread locally via lymphatics that follow cranially along the superior hemorrhoidal vessels. This “zone of upward spread” was described initially by Miles in his landmark paper describing the APR. Heald has described a “zone of downward spread” within the mesorectum4; this zone can encompass as much as 4 cm beyond the distal mucosal edge of the tumor.14,15 Although some surgeons and pathologists describe tumor within this zone of downward spread as tumor implants, others believe that these implants are replaced nodes. Appreciation of the zones of upward and downward spread has influenced the extent of dissection surgeons now perform for curative resection of rectal cancers.
Lymph from the upper and middle rectum drains into the inferior mesenteric nodes (Fig. 54-4). Lymph from the lower rectum may drain into the inferior mesenteric system or into the network along the middle and inferior rectal arteries, posteriorly along the middle sacral artery, and anteriorly through the channels to the retrovesical or rectovaginal septum, to the iliac nodes, and ultimately, to the periaortic nodes. In a Japanese study, the obturator nodes, external to the hypogastric nerve plexus, were found to be involved with cancer in 8% of tumors located in the distal rectum, whereas these nodes were rarely, if ever, involved with proximal tumors.16 Lymphatics from the anal canal above the dentate line usually drain via the superior rectal lymphatics to the inferior mesenteric lymph nodes and laterally to the obturator and internal iliac nodes. Below the dentate line, lymph drains primarily to the inguinal nodes but may empty into the inferior or superior rectal lymph nodes. In most cases of rectal cancer, spread to the inguinal lymph nodes should be considered stage IV disease. In our experience, however, some patients whose distal rectal adenocarcinoma invades the anal canal can have regional nodal spread to the inguinal lymph nodes. These select few patients may remain curable and their radiation fields should include the involved inguinal lymph node basins.
The pelvic autonomic nerves consist of the paired hypogastric (sympathetic), sacral (parasympathetic), and inferior hypogastric nerves (Fig. 54-5). Sympathetic nerves originate from L1 to L3, form the inferior mesenteric plexus, travel through the superior hypogastric plexus, and descend as the hypogastric nerves to the pelvic plexus. The parasympathetic nerves, or nervi erigentes, arise from S2 to S4 and join the hypogastric nerves anterior and lateral to the rectum to form the pelvic plexus and ultimately the periprostatic plexus. The inferior hypogastric nerve plexus arises from interlacing sympathetic and parasympathetic nerve fibers and forms a fenestrated rhomboid plate on the lateral pelvic sidewall. Fibers from this plexus innervate the rectum as well as the bladder, ureter, prostate, seminal vesicles, membranous urethra, and corpora cavernosa. Therefore, injury to these autonomic nerves can lead to impotence, bladder dysfunction, and loss of normal defecatory mechanisms.
The walls and floor of the pelvis are covered by the endopelvic, or parietal, fascia (Fig. 54-6). The fascia propria, an extension of the endopelvic fascia, encloses the rectum and its mesorectal fat, lymphatics, and vascular supply as a single unit; forms the lateral stalks of the rectum; and connects to the parietal fascia on the pelvic sidewall. The presacral fascia is the parietal fascia that covers the sacrum and coccyx, presacral plexus, pelvic autonomic nerves, and the middle sacral artery. Posteriorly, a thickening of this fascia, called Waldeyer’s fascia, is the anteroinferior fascial reflection from the presacral fascia at the level of S4. Anteriorly, Denonvilliers’ fascia separates the anterior rectal wall from the prostate and seminal vesicles in the male and is thought to be an entrapped extension of the peritoneum.17
The preoperative evaluation is critically important to treat the cancer optimally and achieve sphincter preservation. With this information, surgeons must individualize the treatment and care of each patient.
The patient with rectal cancer usually presents to the surgeon after a definitive endoscopic diagnosis. The patient’s initial complaint may include rectal bleeding, a change in bowel habits or stool caliber, rectal pain, a sense of rectal “fullness,” weight loss, nausea, vomiting, fatigue, or anorexia; however, many patients are completely asymptomatic. Specific symptoms may assist the surgeon in deciding on the optimal approach to therapy. Tenesmus, the constant sensation of needing to move one’s bowels, usually is indicative of a large and possibly fixed stage II or III cancer. Pain with defecation suggests involvement of the anal sphincters; cancers growing directly into the anal sphincter usually are not amenable to sphincter-sparing procedures. Information pertaining to anal sphincter function is invaluable when one is contemplating a low anastomosis. If patients are incontinent, they are better served with an ostomy. Preoperative sexual function is important to know because one must discuss the risks of the procedure and the likelihood of sexual dysfunction postoperatively. Patients who have preexisting sexual dysfunction are at increased risk for worse postoperative function. Diabetics, smokers, and patients who require neoadjuvant radiation are also at increased risk of postoperative sexual dysfunction.
A comprehensive medical history should be aimed at identifying other medical conditions, such as cardiopulmonary, renal, and nutritional issues that may require additional evaluation before surgical intervention. A comprehensive evaluation allows for more accurate risk stratification. Family history or factors predisposing the patient to rectal cancer, such as FAP, HNPCC, MUTYH, and IBD, are important to consider as one plans the operative procedure. For patients with UC/FAP/MUTYH and rectal cancer, the preferred operation is a total proctocolectomy with ileoanal J-pouch reconstruction or end ileostomy, depending on age and sphincter function. One must carefully consider the role of neoadjuvant chemoradiotherapy in patients with rectal cancer and these diseases because once an ileoanal J-pouch is constructed, if radiation has not been given preoperatively, postoperative radiation will severely damage the reconstruction, resulting in poor function and often in the need to remove the J-pouch. In HNPCC, the subsequent lifetime risk of a metachronous cancer is approximately 10% so either a low anterior resection or APR or total proctocolectomy with an ileoanal J-pouch reconstruction can be considered. Whenever an ileoanal J-pouch is created, careful consideration of preoperative radiation is necessary due to the difficulty using radiation on a small bowel reconstruction in the pelvis.
A careful and accurate digital rectal examination (DRE) is critical in determining the clinical stage and any plans for neoadjuvant therapy. Digital exam of a palpable lesion allows for the assessment of tumor size, mobility and fixation, anterior or posterior location, relationship to the sphincter mechanism and top of the anorectal ring, and distance from the anal verge.
Rigid proctoscopy is also essential to the evaluation of patients with rectal cancer because it demonstrates the proximal and distal levels of the mass from anal verge, extent of circumferential involvement, orientation within the lumen, and relationship to the vagina, prostate, or peritoneal reflection. All this information aids in determining the feasibility of local excision if indicated. Rigid proctoscopy also allows one to obtain an adequate tissue biopsy. Flexible sigmoidoscopy is not used routinely because the flexibility of the instrument can give a false distance between the tumor and the dentate line. Furthermore, a mass will often be described as a sigmoid or rectosigmoid tumor on flexible colonoscopy and then when the patient is evaluated in the office with rigid sigmoidoscopy, the lesion is often found to be much lower and in fact is often a true rectal cancer that qualifies for neoadjuvant chemoradiotherapy. Hence, rigid sigmoidoscopy is mandatory for all distal left-sided lesions. A complete colonoscopy to the cecum is essential to rule out synchronous cancers, which occur 2% to 8% of the time. We prefer colonoscopy over virtual colonoscopy so that we may not only diagnose but also excise any amenable polyps. For anterior lesions, women should undergo a complete pelvic examination to determine vaginal invasion.
Following the initial history, DRE, and rigid proctoscopy, additional preoperative staging studies can help to determine the appropriate treatment for each patient, whether radical resection or local excision is warranted, and whether preoperative chemoradiation is recommended. Accurate preoperative staging is gaining increasing importance as combined-modality therapy and sphincter-preserving surgical approaches are considered.
Abdominal and pelvic computed tomography (CT) scans can demonstrate regional tumor extension, lymphatic and distant metastases, and tumor-related complications such as perforation or fistula formation. Its accuracy in determining the depth of invasion, however, is less than that of endorectal ultrasound (ERUS) or specialized magnetic resonance imaging (MRI). Pelvic CT scan therefore is not recommended as the only modality for evaluation of a patient’s primary tumor. For example, the sensitivity of CT scan for detecting distant metastasis is higher (75%-87%) than that for detecting perirectal nodal involvement (45%) or the depth of transmural invasion (70%). If a node is seen on CT scan, it should be presumed to be malignant because benign adenopathy is not normally seen around the rectum.
Intravenous contrast given at the time of a CT scan is important to assess the liver for metastatic disease, as well as to evaluate the size and function of the kidneys. Ureteral involvement by the tumor can be assessed and allows for planning of ureteral stent placement preoperatively. Also, invasion of contiguous structures such as the vagina, prostate, and bladder can be initially evaluated on CT scan. Most importantly, lateral pelvic sidewall invasion must be ascertained as this can be very challenging to resect if the disease burden does not regress substantially with neoadjuvant chemoradiation. All patients should undergo a chest CT scan to exclude pulmonary metastases. Because of newer chemotherapies (Oxaliplatinum, Irinotecan, Avastin, and Cetuximab) and multiple treatment regimens, patients with multiple sites of metastatic disease are more likely to receive chemotherapy alone if the pelvic disease is asymptomatic and/or chemoradiation (symptomatic pelvic disease) followed by chemotherapy and may avoid a surgical resection if they have a large burden of distant disease or multiple sites of metastatic disease.
Complete blood count and electrolytes often are obtained. Liver enzymes may be normal in the setting of small hepatic metastases and are not a reliable marker for liver involvement.
Guidelines published by the American Society for Clinical Oncology (ASCO) recommend that serum carcinoembryonic antigen (CEA) levels be obtained preoperatively in patients with rectal cancer to aid in staging, surgical treatment planning, and assessment of prognosis. Although neither sensitive nor specific enough to serve as a screening method for the detection of colorectal cancer, preoperative CEA levels greater than 5 ng/mL signify a worse prognosis, stage for stage, than those with lower levels. In addition, elevated preoperative CEA levels that do not normalize following surgical resection imply the presence of persistent disease and the need for further evaluation. CEA is most helpful in identifying recurrent disease with an overall sensitivity rate of 70% to 80%.
Compared with CT scanning, transrectal endoluminal or endoscopic ultrasound (TRUS) permits a more accurate characterization of the primary tumor and the status of the perirectal lymph nodes. Localized cancers involving only the mucosa and submucosa usually can be distinguished from tumors that penetrate the muscularis propria or extend through the rectal wall into the perirectal fat.
ERUS is an office-based procedure that is well tolerated and can be performed by the surgeon for preoperative planning. Figure 54-7 shows the schematic layers seen in TRUS.
Several studies comparing the accuracy of TRUS with CT scan and MRI suggest that TRUS is superior for T staging of rectal cancer. The range of the accuracy of TRUS is 80% to 95% compared with 65% to 75% for CT scan, 75% to 85% for MRI, and 62% for DRE. In one review, the accuracy of TRUS was greatest (95%) in distinguishing whether a tumor was confined to the rectal wall (T1, T2) versus invading into the perirectal fat (T3 or greater) and less able to distinguish accurately T1 from T2 cancers.18 It is important to understand that all of the above methods are operator dependent; if an institution regularly utilizes ERUS instead of endorectal coil MRI (ecMRI), then that modality will lead to more accurate staging for that institution, and vice-versa if it more regularly utilizes ecMRI. Sometimes, if the lymph nodes are negative and there is a question of whether the tumor is a T2 or T3 lesion, it can be beneficial to get both an ERUS and an ecMRI. Figure 54-8 demonstrates a uT2 lesion. In addition, in patients who have received prior radiation, the accuracy decreases owing to edema and fibrosis.
Despite these data, there is considerable inter-observer variability and a significant learning curve associated with performing TRUS. For these reasons, TRUS under-stages more frequently than over-stages the primary rectal tumor. However, TRUS under-stages the cancer less often than CT scan (15% vs 39%). A modified tumor-node-metastasis (TNM) classification for rectal cancer has been proposed based on TRUS-derived T stage (Table 54-1).
| uT1 | Invasion confined to the mucosa and submucosa |
| uT2 | Penetration of the muscularis propria but not through to the mesorectal fat |
| uT3 | Invasion into the perirectal fat |
| uT4 | Invasion into the adjacent organ |
| uN0 | No enlargement of lymph nodes |
| uN1 | Perirectal lymph nodes enlarged |
TRUS is less useful in predicting the status of perirectal lymph nodes. In several comparative studies, the accuracy of TRUS (70%-75%) was like that of CT scan (55%-65%) and MRI (60%-65%). The accuracy of nodal staging with TRUS requires the nodes to be larger than 5 mm. The contribution of TRUS-guided fine-needle aspiration (FNA) biopsy to N-staging accuracy for rectal cancer is controversial.
MRI offers some advantages compared with TRUS when it comes to staging rectal cancer. It permits a larger field of view, it may be less operator- and technique-dependent (although it is reader-dependent), and it allows study of stenotic tumors that may not be even amenable to DRE or passage of the ERUS probe.19 Figure 54-9 illustrates a T3 lesion. Like TRUS, ecMRI or phased-array MRI can discriminate small-volume nodal disease and subtle transmural invasion. These specialized MRI techniques can identify involved perirectal nodes based on characteristics other than size, with reported accuracy rates of up to 95%. Another advantage over TRUS is identification of foci not only within the mesorectum but also outside the mesorectal fascia, such as the pelvic sidewall. We currently prefer phased-array MRI for staging of rectal cancers because it provides equal accuracy in staging compared to ecMRI but without the intrarectal coil.
Figure 54-9
Endorectal MRI of a T3 lesion. Arrowhead indicates the site of the endorectal coil. Large arrow demonstrates fingerlike projections of carcinoma invading into the mesorectal fat. Small arrow points to the anterior rectal wall. (Used with permission from Koenraad J. Mortele, MD, Beth Israel Deaconess Medical Center, Boston, MA.)
Double-contrast MRI may permit more accurate T staging of rectal cancer by allowing better distinction between normal rectal wall, mucosa, muscularis, and perirectal tissues. In one report, the specificity and sensitivity of ecMRI with combined intravenous and endorectal contrast material to predict infiltration of the anal sphincter were 100% and 90%, respectively. However, N staging was not improved with this approach.
Phased-array surface coil MRI also may be beneficial in predicting the likelihood of a tumor-free resection margin by visualizing tumor involvement of the mesorectal fascia. If confirmed in other series, preoperative MRI may prove useful in selecting patients at high risk of local recurrence for therapy prior to resection.
Fluorine-18 fluorodeoxyglucose–positron emission tomography (FDG-PET) is effective in assessing the extent of pathologic response of primary rectal cancer to preoperative chemoradiation and may predict long-term outcome.20 In addition, it has an accuracy of 87% for detecting recurrence of rectal cancer after surgical resection and full-dose external-beam radiation therapy.21 While PET scans are positive in 90% of primary and recurrent tumors and in distant metastatic disease, they are relatively inaccurate for nodal metastases. Rectal cancer rarely metastasizes to the bones or to the brain, and without symptoms these two areas are not included routinely in surveillance imaging. They will, however, light up on PET scan. Current guidelines recommend that PET scans not be used routinely in the standard workup of a rectal cancer.
The purpose of staging any cancer is to describe the anatomic extent of the lesion. Staging by clinical examination, radiology, and pathology aids in planning treatment, evaluating response to treatment, comparing the results of various treatment regimens, and determining prognosis. Currently, the most widely accepted staging system for rectal cancer in the United States is the TNM classification system.
In 1987, the American Joint Committee on Cancer (AJCC) and the International Union Against Cancer (IUC) introduced the TNM staging system for colorectal cancer. The seventh edition was published in 2009 (Tables 54-2 and 54-3). The TNM staging system is based on depth of tumor invasion as well as presence of lymph node or distant metastases. In stage I disease, the tumor may invade into the muscularis propria. In stage II disease, the tumor invades completely through this layer into the perirectal fat (T3) or adjacent organs (T4). Any lymph node metastasis represents stage III disease, and metastatic spread denotes stage IV disease. Depth of invasion (T stage) of the primary tumor is an important prognostic variable as increasing depth of invasion is correlated with an increasing chance of lymph node metastases. For instance, early-stage cancers extending into the muscularis mucosa (T1) will have up to a 10% to 13% incidence of metastasizing to perirectal lymph nodes.22,23 In 805 pathology specimens, Sitzler noted that 5.7% of T1 lesions, 19.6% of T2 lesions, 65.7% of T3 lesions, and 78.8% of T4 lesions had lymph node metastases.24
Generally, the biologic behavior of rectal cancer cannot be predicted by its location or size although there is a consensus among experts that the more distal cancers have a poorer outcome when compared stage for stage with more proximal lesions. Poorly differentiated cancers have a worse long-term prognosis than well or moderately differentiated tumors. Other factors that portend a poor prognosis include direct tumor extension into adjacent structures (T4 lesions), lymph node metastases, lymphatic, vascular, or perineural invasion, and bowel obstruction.
| Primary Tumor (T) | |
| TX | Primary tumor cannot be assessed |
| T0 | No evidence of primary tumor |
| Tis | Carcinoma in situ, intramucosal carcinoma (involvement of lamina propria with no extension through muscularis mucosae) |
| T1 | Tumor invades the submucosa (through the muscularis mucosa but not into the muscularis propria) |
| T2 | Tumor invades the muscularis propria |
| T3 | Tumor invades through the muscularis propria into pericolorectal tissues |
| T4 | Tumor invades the visceral peritoneum or invades or adheres to adjacent organ or structure |
| T4a | Tumor 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) |
| T4b | Tumor directly invades or adheres to adjacent organs or structure |
| Regional lymph nodes (N) | |
| NX | Regional lymph nodes cannot be assessed |
| N0 | No regional lymph node metastasis |
| N1 | One 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 |
| N1a | One regional lymph node is positive |
| N1b | Two or three regional lymph nodes are positive |
| N1c | No regional lymph nodes are positive, but there are tumor deposits in the
|
| N2 | Four or more regional nodes are positive |
| N2a | Four to six regional lymph nodes are positive |
| N2b | Seven or more regional lymph nodes are positive |
| Distant metastasis (M) | |
| M0 | No distant metastasis by imaging, etc.; no evidence of tumor in distant sites or organs (This category is not assigned by pathologists.) |
| M1 | Metastasis to one or more distant sites or organs or peritoneal metastasis is identified |
| M1a | Metastasis to one site or organ is identified without peritoneal metastasis |
| M1b | Metastasis to two or more sites or organs is identified without peritoneal metastasis |
| M1c | Metastasis to the peritoneal surface is identified alone or with other site or organ metastases |
| When T is… | And N is… | And M is… | Then the stage group is… |
| Tis | N0 | M0 | 0 |
| T1, T2 | N0 | M0 | I |
| T3 | N0 | M0 | IIA |
| T4a | N0 | M0 | IIB |
| T4b | N0 | M0 | IIC |
| T1-T2 | N1/N1c | M0 | IIIA |
| T1 | N2a | M0 | IIIA |
| T3-T4a | N1/N1c | M0 | IIIB |
| T2-T3 | N2a | M0 | IIIB |
| T1-T2 | N2b | M0 | IIIB |
| T4a | N2a | M0 | IIIC |
| T3-T4a | N2b | M0 | IIIC |
| T4b | N1-N2 | M0 | IIIC |
| Any T | Any N | M1a | IVA |
| Any T | Any N | M1b | IVB |
| Any T | Any N | M1c | IVC |
Surgical resection is the cornerstone of curative therapy. Following a potentially curative resection, the 5-year survival rate varies per disease extent25,26 (Table 54-4). However, these survival figures may improve with the increased use of adjuvant therapy.
Surgical and oncologic management varies greatly depending on the stage and location of the tumor within the rectum. Superficially invasive, small cancers may be managed effectively with local excision. However, most patients have more deeply invasive tumors that require major surgery, such as low anterior resection (LAR) or APR. Yet others present with locally advanced tumors adherent to adjoining structures such as the sacrum, pelvic sidewall, vagina, uterus, cervix, prostate, or bladder, requiring an even more extensive operation.
After establishing the diagnosis and completing the staging workup, a decision is made whether to pursue immediate resection or administer preoperative chemoradiotherapy. For patients with stage II and III rectal cancer, the authors advocate for combined preoperative chemoradiotherapy. The authors recommend this for all stage II and III patients with tumors located in the distal two-third of the rectum. For patients with rectal cancer in the proximal one-third of the rectum, the authors use preoperative chemoradiotherapy on a case-by-case basis depending on the size and bulkiness of the tumor and the number of involved lymph nodes as well as the patient’s medical and surgical history.
The high bacterial load in the intestinal tract requires preoperative bowel decontamination to reduce the incidence of infectious complications. Prior to the routine use of mechanical bowel preparation and preoperative antibiotics, the reported rate of infection following colorectal surgery was 60%.27 A standard bowel preparation includes a clear-liquid diet 24 hours prior to surgery, laxatives and/or enemas, oral antibiotics (erythromycin base and neomycin base) and gastrointestinal tract irrigation with a solution of polyethylene glycol electrolyte lavage (GoLYTELY or Miralax). In two separate surveys of North American colorectal surgeons, almost two-thirds preferred the polyethylene glycol electrolyte solutions because of the reliability of the cleansing results.28,29 Certain preparations are contraindicated in patients with certain medical conditions. For example, patients with elevated creatinine or congestive heart failure should avoid the magnesium citrate preparation, whereas patients with gastroparesis should not take a large-volume polyethylene glycol preparation.
Recent studies have shown that mechanical bowel preparation in conjunction with oral antibiotics, a chlorhexidine shower, and a clean closure protocol grouped together as an infection protection bundle have reduced the overall surgical site infection (SSI) rate from 19.7% to 8.2%. The chlorhexidine shower, the oral antibiotics, and the mechanical bowel preparation were all associated with decreased SSI. Moreover, patients who received both oral antibiotics and a mechanical bowel prep had an SSI of 2.7% versus 15.8% for all other patients.30 Furthermore, a mechanical bowel preparation should be performed in large part because it allows for easier manipulation of the colon and rectum with both open and laparoscopic surgery.31
Oral antibiotics are also used to further decrease the incidence of postoperative infectious complications. Although mechanical cleansing decreases the total volume of stool in the colon, it does not affect the concentration of bacteria per milliliter of effluent. The most commonly used regimen is the Nichols/Condon preparation: neomycin 1 g and erythromycin base 1 g, both non-absorbable antibiotics, by mouth at 5:00 pm and 10:00 pm on the day prior to surgery. In addition to oral antibiotics, perioperative systemic antibiotics should be given prior to incision time. A typical choice to cover both aerobic and anaerobic intestinal bacteria is a second- or third-generation cephalosporin in combination with metronidazole. Postoperative antibiotic prophylaxis is not indicated.
Perioperative systemic antibiotic coverage is broadened in patients with high-risk cardiac lesions such as prosthetic heart valves, previous history of endocarditis, or a surgically constructed systemic-pulmonary shunt, and with intermediate-risk cardiac lesions such as mitral valve prolapse, valvular heart disease, or idiopathic hypertrophic subaortic stenosis. Intravenous ampicillin 2 g and gentamycin 1.5 mg/kg are administered 30 to 60 minutes before the procedure, and ampicillin is repeated once 6 hours postoperatively in place of cefazolin; metronidazole is administered as usual. Vancomycin is substituted for ampicillin if the patient is allergic to penicillin or cephalosporin.
Enhanced recovery after surgery (ERAS) protocols have become popularized in the last several years in colorectal surgery programs across the United States. ERAS protocols have been very successful in decreasing length of stay as well as postoperative surgical complications. These protocols include a preoperative bowel preparation as outlined above while allowing the patient to continue to consume clear liquids up to 2 hours prior to surgery. This aims to limit preoperative dehydration and thereby limit the need for intraoperative fluid administration, which itself leads to third spacing and tissue edema, and as a result, a slower recovery. Patients are also instructed to refrain from taking ACE inhibitors and diuretics the morning of surgery to prevent hypotension and thereby obviate the need for excess intraoperative fluids. In addition to the bowel preparation, a complex carbohydrate load is often given 2 hours prior to the surgery and it is hypothesized that this decreases insulin resistance because it prevents starvation physiology and thereby limits the catabolic effects of starvation generally seen around surgery.
Preoperative pain control is initiated with 1000 mg of Tylenol and a COX-2 inhibitor such as Celebrex and gabapentin (age- and sex-related dosing) in the holding area. Intraoperatively, fluid administration is limited and goal-directed fluid therapy is utilized. Goal-directed fluid therapy is achieved by monitoring urine output (0.25 cc/kg/h) and cardiac stroke volume as monitored with a transesophageal probe. Intraoperative narcotics are minimized. Epidurals and transversus abdominus plane (TAP) blocks and catheters are utilized to further decrease postoperative reliance on narcotics. Exogenous fluid administration is stopped within 6 hours of surgery and patients are immediately started on clear liquids and advanced to regular diet on postoperative day one. This allows for earlier usage and absorption of oral pain medicines. Liberal use of Tylenol and NSAIDs is recommended as well. ERAS protocols have resulted in a dramatic decrease in length of stay and wound infections, among other complications. An ERAS protocol is an integral part of any program in colon and rectal surgery.
The primary goal of surgical treatment for rectal cancer is complete eradication of the primary tumor along with the adjacent mesorectal tissue and the superior hemorrhoidal artery pedicle. Although reestablishment of bowel continuity at the time of surgery has become routine, cancer removal should not be compromised in an attempt to avoid a permanent colostomy.
For tumors located in the extraperitoneal rectum, resection margins are limited by the bony confines of the pelvis and the proximity of the bladder, prostate, and seminal vesicles in men and vagina in women. Although locoregional recurrence may be inevitable, local recurrence, cure, mortality, anastomotic leaks, and colostomy rates after rectal cancer surgery are related to surgical technique as well as to the experience and volume of the individual surgeon and institution.
The optimal distal resection margin for surgically treated rectal cancer remains controversial. Although the first line of rectal cancer spread is upward along the lymphatics, tumors below the peritoneal reflection can spread distally via intra- or extramural lymphatic and vascular routes.
The use of APR for low rectal cancers traditionally has been based on the need for a 5-cm distal margin of normal tissue. However, in retrospective studies, margins as short as 1 cm have not been associated with an increased risk of local recurrence.32–34 Distal intramural spread usually is limited to within 2.0 cm of the tumor unless the lesion is poorly differentiated or widely metastatic. Data from a randomized, prospective trial conducted by the National Surgical Adjuvant Breast and Bowel Project demonstrated no significant differences in survival or local recurrence when comparing distal rectal margins of less than 2, 2 to 2.9, and greater than 3 cm.32 Therefore, a 1- to 2-cm distal margin is acceptable for resection of rectal carcinoma, although a 5-cm proximal margin is still recommended.34,35
The importance of obtaining an adequate circumferential or radial margin has been appreciated more in the last 15 years. In fact, the circumferential radial margin (CRM) is more critical than the proximal or distal margin for local control. Tumor involvement of the circumferential margin has been shown to be an independent predictor of both local recurrence and survival. The Norwegian Rectal Cancer group reported on circumferential resection margins with 29-month median follow-up in 686 patients who had curative intent LAR with TME alone (no adjuvant radiotherapy) for rectal adenocarcinoma. The Norwegian group found that the overall local recurrence rate was 7% (22% with positive CRM and 5% with a negative CRM). Moreover, 40% of patients with a positive CRM developed distant metastases whereas only 12% of those with negative CRM developed distant disease.36 In this study, a positive CRM clearly affected survival. In another report of 90 patients undergoing resection for rectal cancer, when the radial margins were histologically positive, the hazard ratio (HR) for local recurrence was 12.2, and the HR for death was 3.2 when compared with those with clear circumferential margins. Furthermore, the length of mesorectum beyond the primary tumor that needs to be removed is thought to be 5 cm because tumor implants usually are seen no further than 4 cm from the distal edge of the tumor within the mesorectum.9,15 Therefore, in proximal rectal cancers, distal mesorectal excision 5 cm below the lower border of the tumor should be the goal. There is ample evidence, however, that in more distal tumors where there is less mesorectum, a 1- to 2-cm margin is acceptable to achieve sphincter preservation.34,35
Several retrospective studies of local excision since the 1970s have demonstrated a local recurrence rate of 7% to 33% and survival rates of 57% to 87%. Many of these reviews are limited, small, single-institution studies, often combining patients with tumors of different depths, including T3 lesions, positive margins, or those who underwent different forms of local therapy, such as fulguration and snare cautery. Despite these limitations, many of these studies have demonstrated that local excision for superficial tumors with negative margins may provide similar survival and local control but without the morbidity of the APR. Major risk factors for local recurrence include positive surgical margins, transmural extension, lymphovascular invasion, and poorly differentiated/high grade histology. These retrospective studies suggest that local excision of selected distal rectal adenocarcinomas may provide adequate oncologic control at considerably less morbidity than APR.
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