Principles of Surgical Management
As a basic principle, any colorectal cancer is an indication for surgery unless widespread tumor dissemination or general contraindications from the patient's overall health status are present. Furthermore, any precursor pathology with statistical risk for cancer (eg, large sessile polyp in an otherwise healthy individual or dysplasia in a patient with ulcerative colitis) that cannot be managed nonoperatively is an indication for surgery.
The general goal for surgical management is either to achieve cure from the tumor and extension of survival or at least disease-free survival or, in the case of a precursor pathology with or without an underlying disease (eg, ulcerative colitis or FAP), to prevent the cancer and ideally to remove the risk-bearing disease. In a palliative setting, the goal is to prolong the period of symptom-free survival.
Local tumor control generally is the primary treatment objective to prevent local tumor complications, that is, obstruction, perforation, fistula formation, bleeding, and pain. Even in the presence of distant metastases in the liver or lung, resection of the primary tumor remains a reasonable priority. Because solitary or a limited number of metastases in the liver or lung often may be treated surgically by partial organ resection or metastasectomy with a cure rate of up to 35%, their presence should not necessarily alter the surgical approach to do a curative resection at the primary site. However, if there are extensive metastases or peritoneal carcinomatosis and cancer cure is not a reasonable goal, alleviation of symptoms and prevention of impending local complications, for example by restoring the intestinal continuity, is the best palliation.
The specific surgical and oncologic strategy planning is based on a number of factors. It has to take into account the exact localization of the tumor, the tumor stage, the presence of synchronous colonic lesions or an underlying colonic disease, the risk for metachronous lesions, the patient's age and general condition, the extent of the local procedure, and the timing. Only after the extent of the operation has been defined can the method and approach to be used be discussed as to whether the procedure is only suitable for an open laparotomy approach or laparoscopy may be reasonable and beneficial.
In contrast to rectal cancer, neoadjuvant treatment (ie, preoperative chemoradiation) is not indicated in the overwhelming majority of colonic cases. In patients with resectable metastases, preoperative chemotherapy followed by a combined colon and liver resection may be an attractive alternative to a staged resection and may help in assessing the tumor response to a particular chemotherapy regimen. Only rarely is a locally very advanced lesion treated with chemotherapy in anticipation of an otherwise unresectable mass. Adjuvant (ie, postoperative) treatment is discussed in a later section.
When a patient is considered an operative candidate, several preparatory steps need to be addressed.
Most colonic operations can be performed without a blood transfusion. Blood-spearing surgical techniques have reduced the need while the threshold to transfuse has substantially increased. The indication will depend on the starting hemoglobin, the patient's age and physiologic status, a history of ischemic events (coronary, stroke, etc), and the extent of expected and real intraoperative blood loss. As a routine, it is recommended to have the patient's blood typed and screened, but to reserve crossmatching units of blood for these higher-risk situations.
While the risk of blood-borne infections is very low, there is some controversy as to the immunologic effect of blood transfusions on the overall prognosis of colorectal cancer. Because the initial report that transfusion may be associated with an increased likelihood of recurrence,211 many subsequent reports have reached conflicting conclusions. Meta-analysis studies have strongly questioned whether there is a true causal effect present.212 Other factors such as extent of resection required, tumor location, and experience of the surgeon actually may be the more relevant cause for recurrence, but transfusion may be an indirect reflection of extensive disease and surgery. Furthermore, a randomized trial comparing the use of autologous versus allogenic blood in patients undergoing colorectal resections did not show any statistical difference in prognosis.213
Traditionally, bowel cleansing was considered an essential preparation to any elective colon surgery. The rational is based on the colon being a large reservoir for numerous anaerobic and aerobic bacteria. However, recent prospective, randomized, controlled studies and meta-analyses comparing mechanical preparation versus no preparation for elective colorectal surgery have failed to demonstrate any appreciable decrease in infection rates, anastomotic leaks, or mortality rates in patients undergoing mechanical bowel preparation.214–220 Contrasting with the evidence, however, the majority of colorectal surgeons still perform bowel cleansing in their patients. The indisputable advantages of a bowel preparation remain (1) the intraoperative ability to perform a colonoscopy if that were needed, and (2) the absence of a preanastomotic stool load if a primary anastomosis or the tissue quality were unexpectedly less than optimal and asked for a fecal diversion.
There are a wide variety of laxatives, washouts, and enemas available on the market for mechanical cleansing, but the products used generally are based on either polyethylene glycol (eg, GoLYTELY) or sodium phosphate (Fleet Phospho Soda), the latter of which is contraindicated in patients with renal failure and has come under more broad scrutiny in the United States. In the absence of a consensus regarding the best regimens (ie, orthograde cleansing alone or combined with retrograde enemas), the choice often is a matter of personal preference. Depending on an individual patient's constitution and the degree of obstruction, the bowel cleansing should be started 1 or even 2 days before surgery. The cathartic may result in significant fluid and electrolyte imbalances. Elderly patients, who are more prone to this adverse effect, therefore should preemptively be given intravenous fluids and electrolytes.
Perioperative administration of prophylactic antibiotics aims at reducing colonic and dermal bacterial concentrations and is considered a crucial component of colorectal procedures. The benchmark is the rate of surgical site infections in relation to the level of wound contamination. Prophylaxis has to be distinguished from therapeutic antibiotic treatment in patients who already have an established infection. Prophylaxis (ie, in patients who do not primarily suffer from an infection) should be targeted, adequately dosed, and short (ie, start within 1 hour of the incision and be limited to less than 24 hours) in order to minimize antibiotic side effects and propagation of resistances. Coverage should include both aerobic bacteria (eg, Staphylococcus, Escherichia coli, Klebsiella, Proteus, etc) and anaerobic bacteria (eg, Bacteroides fragilis, Clostridium).
Intravenous administration of broad-spectrum antibiotics is the most common form of prophylaxis and includes several acceptable antibiotic selections: (1) single antibiotics (ertapenem, piperacillin-tazobactam); (2) combination of two antibiotics (second- or third-generation cephalosporin + metronidazole, fluoroquinolone + metronidazole, clindamycin + aminoglycoside, clindamycin + quinolone, clindamycin + aztreonam); or (3) triple combinations such as amoxicillin-clavulanic acid + metronidazole + aminoglycoside. Oral antibiotics (eg, metronidazole combined with nonabsorbable neomycin) in conjunction with a mechanical bowel preparation may yield similar results but may increase the risk of nosocomial superinfections, in particular with Clostridium difficile.
Special considerations according to national guidelines have to be followed for prophylaxis in patients at risk for endocarditis (eg, patients with mechanical heart valve).
Thromboembolic prophylaxis is recommended in all patients undergoing major surgical procedures to reduce the incidence of postoperative deep venous thrombosis and pulmonary embolism. Both pharmacologic and physical prophylaxis (eg, pneumatic calf compression) have been proven to be effective,221 but the use of pharmacologic prophylaxis has recently been endorsed by a task force recommendation.222 Both low-dose unfractionated heparin and low-molecular-weight heparins (LMWHs) have been shown to be equally effective in reducing the incidence of postoperative thromboembolic events without resulting in significant complications.223 A recent randomized study, however, showed that LMWHs have a slightly higher rate of minor bleeding events.224 Based on economic analysis, the data favor the use of subcutaneous heparin as being more cost-effective than LMWHs.225 It is recommended that these drugs be commenced at least 2 hours before surgery and continued postoperatively until the patient has obtained full ambulation. Intermittent pneumatic calf-compression boots are an alternative to heparin that has been demonstrated to be equally successful in preventing deep venous thrombosis and possessing the advantage of no risk of increased bleeding.226 It remains to be determined whether a combination of chemical agents and pneumatic calf-compression boots for patients undergoing colonic resection will be an advantage.
Anticoagulated patients who need to take warfarin (eg, owing to a mechanical heart valve) should be switched perioperatively to intravenous heparin to allow for stopping the warfarin medication and antagonizing its effect with vitamin K. Four hours before incision, the heparin may be discontinued and resumed within 24 hours postoperatively with a stepwise increase in the dose.
After induction of general anesthesia, bladder catheterization should be performed in all major cases to adequately monitor the urine output peri- and postoperatively. In selected patients with a previous history of colorectal or pelvic dissections, placement of ureteral stents allows better intraoperative identification and protection of these crucial structures. Laparoscopic colon procedures do not routinely need ureteral stents; however, selective use of lighted ureteral stents during challenging laparoscopic procedures may facilitate identification of these structures.
Placement of a nasogastric tube is not necessary on a routine basis for patients undergoing resection of the colon or rectum and should be avoided unless they present with a complete or partial bowel obstruction.227
Preoperative Marking of Ostomy Site.
In patients who may need permanent or temporary placement of an ostomy during the surgical procedure, preoperative marking of the ideal stoma site by a stoma nurse helps to facilitate postoperative ostomy handling by the patient.
Preemptive Pain Management.
Effective pain management is an important factor not just for patient comfort but to reduce the incidence of postoperative pulmonary complications. Preoperative placement of epidural analgesia is a very valuable strategy, which, in addition to its pain-relieving effect, promotes the earlier resumption of postoperative bowel function as a result of its suppression of sympathetic nerves. The relevant segments that need to be blocked for an abdominal incision are located at a thoracic level (T6–T12).
General Technical Principles
The objective of surgery for colonic cancer is to perform a curative resection by removing the cancerous segment of colon, the mesentery with the primary feeding vessel and the lymphatics, and any organ with direct tumor involvement. Because the lymphatics run with the arterial supply of the colon, the primary artery supplying the segment of the colon to be resected is divided at its origin. Ligation at the origin of the vessel ensures inclusion of apical nodes, which may convey prognostic significance for the patient.228 While careful dissection in the right place is the mainstay of a successful surgery, the historical Turnbull no-touch technique with early vascular ligation and occlusion of the bowel with tapes to prevent embolization of tumor and improve survival has not shown any advantage.229
The length of bowel and mesentery resected is dictated by tumor location and distribution of the primary artery (Table 36-14), but a radical resection of a colonic tumor should achieve at least a 5-cm clearance at the proximal and distal margin. Extended resections for confined tumors outside of high-risk patients have not been shown to confer additional survival benefit230; however, tumors located in “border zones” should be resected with both neighboring lymphatics to encompass possible bidirectional spread. If a tumor is adherent to or invading an adjacent organ such as the kidney or small bowel, an en bloc resection should be performed where technically feasible. Because adhesions between the tumor and adjacent organ may not necessarily be inflammatory, but, because of carcinoma, mere division or “pinching” of a tumor from an adjacent organ is not an acceptable surgical technique because it may reduce the chance of cure.
When synchronous cancers are present in the colon, an extended resection or even total colectomy, with ideally only one anastomosis, should be performed. Occasionally, two separate resections (eg, right hemicolectomy and low anterior resection) with two anastomoses are preferable to preserve colon length and to avoid postcolectomy diarrhea. Cancer on the basis of an underlying pancolonic disease (eg, ulcerative colitis or FAP) requires a total proctocolectomy with either an ileoanal pull-through procedure or an ileostomy80; young patients (<50 years, with/without proven HNPCC gene constellation) presenting with tumors proximal to the sigmoid colon should be offered a total abdominal colectomy to reduce the risk of metachronous cancers and to facilitate surveillance.231
A limited wedge resection may be considered for an unfit patient or for palliative resection in those with widespread tumor. This will relieve the patient's symptoms and prevent future obstruction and bleeding from the primary tumor.
Table 36-14: Standard Resections of the Colon ||Download (.pdf)
Table 36-14: Standard Resections of the Colon
|Tumor Location||Resection||Description of Extent||Major Blood Vessel||Safety Margin (cm)|
|Cecum||Right hemicolectomy||Terminal ileum to midtransverse colon, right flexure included||Ileocolic artery, right colic artery, right branch of mid colic artery||5|
|Ascending colon||Right hemicolectomy||Terminal ileum to midtransverse colon, right flexure included||Ileocolic artery, right colic artery, right branch of midcolic artery||5|
|Hepatic flexure||Extended right hemicolectomy||Terminal ileum to descending colon (distal to left flexure)||Ileocolic artery, right colic artery, midcolic artery||5|
|Transverse colon||Extended right hemicolectomy||Terminal ileum to descending colon (distal to left flexure)||Ileocolic artery, right colic artery, midcolic artery||5|
|(Transverse colon resection)||Transverse colon (including both flexures)||Midcolic artery|
|Splenic flexure||Extended left hemicolectomy||Right flexure to rectosigmoid colon (sigmoid, beginning of rectum)||Midcolic artery, left colic artery, inferior mesenteric artery||5|
|Descending colon||Left hemicolectomy||Left flexure to sigmoid colon (beginning of rectum)||Inferior mesenteric artery, left branch of midcolic artery||5|
|Sigmoid colon||Rectosigmoid resection||Descending colon to rectum||Superior hemorrhoidal artery, inferior mesenteric artery||5|
Intraoperative Surgical Technique
For all left-sided colonic resections, it is advisable to place the patient in a modified lithotomy position, which gives access to the anus (eg, for a stapled anastomosis) and allows an assistant or the surgeon to stand between the legs for retraction or an excellent view to mobilize the splenic flexure, respectively. The same positioning obviously also can be used for all other colon resections, but a supine position usually is sufficient and faster. Laparoscopic procedures typically require the operating table to be tilted and moved to steep Trendelenburg's position; appropriate fixation and securing of the patient is therefore mandatory.
For an open procedure, the peritoneal cavity is most commonly entered through a midline laparotomy incision. For a proctocolectomy, we usually recommend the use of an infraumbilical incision in order to provide good exposure for the pelvic dissection. For a more proximal segmental colon resection, however, an equally short but higher midline incision may be more convenient. In addition, a transverse incision or even a subcostal incision may give excellent exposure for a right hemicolectomy.
For a laparoscopic procedure, a first camera trocar is placed in either Veress needle or in open Hasson technique. The site should be chosen such that additional working ports can be placed along a circle with the target in the center.
After the peritoneal cavity is entered (open or laparoscopically), the abdomen is explored systematically to determine the resectability of the tumor. Special attention is addressed to the presence of distant metastases in the liver, peritoneal carcinomatosis, or additional synchronous lesions throughout the large intestine. Other accessible organ systems are assessed equally, for example the gallbladder and the female reproductive organs.
The surgical technique has been standardized for three segments: right colon, left colon, and rectosigmoid. Depending on the extent of the resection eventually needed in an individual patient, the technique for those segments may be combined (see Table 36-14). With a detailed description of the maximal resection, that is, an open total colectomy/proctocolectomy, all information about the individual steps necessary to perform any colorectal resection of lesser extent will therefore be provided.
The same steps should be achieved with laparoscopic resections; however, depending on the surgeon's preference and skills, a medial-to-lateral mobilization of the colon (ie, starting at the feeding vascular stalks before moving to the retroperitoneal attachments) supports the autoretraction of the colon throughout the critical steps.
On careful exploration of the abdomen, mobilization of the colon starts on the right side. Use of a mobile (eg, Richardson retractor) instead of a fixed (eg, Balfour or Bookwalter retractor) abdominal wall retractor in this first phase will allow a more flexible and unidirectional exposure according to rapidly changing needs. The small bowel is eviscerated from the abdomen and moved to the left. The abdominal wall is retracted to the right side while exerting countertraction on the cecum and ascending colon. A small incision is made at the exposed white line of Toldt to enter the retroperitoneum. Elevating the ascending colon from the retroperitoneal structures, the peritoneum is divided along the lateral gutter from the terminal ileum to the hepatic flexure. On the right side, the ureter is at fairly low risk and routinely falls away; however, special care is needed to avoid damage to the third part of the duodenum. The mobilization is facilitated by firm traction placed on the colon and the surgeon's left hand inserted into the retroperitoneum as a guide to divide along the peritoneal reflection. Because of the limited view around the hepatic flexure and the presence of small vessels at this level, transsection of the peritoneum with cautery is often advisable.
As the right edge of the gastrocolic ligament is reached, it may be easier to complete the dissection of the hepatic flexure in retrograde direction. The abdominal wall retractor is moved quickly into the upper end of the incision in order to pull in a cephalad direction. The lesser sac is entered far to the left in an avascular portion of the omentum, and the greater omentum is divided inferior to the gastroepiploic vessels between clamps and ligatures. While the omentum may be preserved in benign diseases, its resection with the respective colon segment is part of an oncologic resection. Dissection of the gastrocolic ligament is carried out from the left to the right. Connective tissue attachments between the antrum, duodenum, and transverse mesocolon and the hepatic flexure are divided stepwise by a combination of blunt digital tunneling and sharp dissection using both hands. Care should be taken at this point to avoid dissecting too deeply into the retroperitoneum, where large blood vessels can be encountered. Once the mobilization has been completed around the hepatic flexure, the right colon and transverse colon are attached only to their vascular supply and are ready for resection. This would be used for any standard right hemicolectomy or the first part of an extended transverse colectomy. For total colectomy, mobilization of the whole colon commonly is continued before dividing the major vessels.
At this point, the abdominal wall retractor is moved to the left side of the abdomen, and traction is placed to expose the left portion of the colon. The dissection is initiated at the level of the sigmoid, where the white line of Toldt again is incised and the retroperitoneum entered. Once the areolar tissues are identified, a small sponge is taken, and with firm pressure against the sigmoid mesentery, the retroperitoneal tissues are bluntly reflected, and the left ureter is exposed. Only after the ureter has been clearly identified and moved out of the way is incision of the peritoneum continued into the pelvis for a short distance and up to the splenic flexure along the left gutter. The colon is reflected bluntly from the retroperitoneal tissues, and with firm traction the peritoneal incision is continued. Gentle traction on the transverse and descending colon will help to lower the splenic flexure until it can be visualized fully. A hand placed in the retroperitoneum will help to mobilize the splenic flexure, and under direct vision the peritoneum over the splenic flexure can be incised. Care must be taken at this point to protect the spleen from direct or traction injury. The final attachments of the splenocolic ligament that hold the splenic flexure are clamped and divided in appropriate tissue portions. Clamping and ligating this tissue are recommended because even small vessels retracting into the left upper quadrant can be a nuisance.
After completion of the first two parts, the colon is mobilized completely from its retroperitoneal attachments from the terminal ileum to the upper rectum. Elevation of the colon allows identification of all primary feeding vessels. In order to ligate the inferior mesenteric vessels, the surgeon is on the patient's left and the colon is reflected to the left. The attachments that run over the sacral promontory and up along the left gutter are incised, and a hand is used to dissect the tissues bluntly from behind the inferior mesenteric vessels. By identifying the inferior mesenteric vessels and making the window just under those, the hypogastric nerves going down into the pelvis are protected routinely. Sometimes, for example if there is concern about cancer in the rectum or if the patient is very obese, these structures need to be freed up more to elevate the nerves initially and later to dissect them out under direct vision. The avascular window around the origin of feeding vessels then is opened. In the case of the inferior mesenteric vessels, the left hand is placed behind the inferior mesenteric stalk, and the thumb and opposing index finger can clear a window of avascular tissue above it. Dissection of redundant adipose tissue around the vessels is carried out under direct vision, before the vessels are clamped. Before transsection and ligature of the vessels, the remote location of the ureter is confirmed once more. If the ureter is not identified properly before dividing the vascular pedicle, accidental dissection of the ureter can occur and requires a repair. If unrecognized intraoperatively, the ureter injury may result in a urinoma. In difficult cases (eg, repeat operation or recurrence), it is therefore advisable to place preoperative ureteral stents to allow better identification. The whole vascular stalk may be ligated with a double ligature or a suture ligature. Individual ligature of the artery and vein is optional and has not been shown to provide an advantage. For the reason mentioned earlier, it is recommended to ligate the vessels as proximally as possible, but from an oncologic standpoint a high ligation of the IMA does not provide any advantage in comparison with a low ligature distal to the origin of the left colic artery.232,233
The vascular dissection is then continued around the colonic mesentery. The avascular tissue can be divided sharply while clamping is applied to vessels when they are encountered. The vascular anatomy of the colon is quite variable. However, if one is truly in the retroperitoneum and ligating named vessels at their origin, the colon can be taken out with as few as three to four clamps. In particular, the inferior mesenteric, middle colic, and ileocolic vessels need to be ligated. The presence of additional right and left colic vessels sometimes requires the use of five or six clamps. By taking the vessels closer to their origin, that is, before they branch off into multiple subsegments, fewer clamps are necessary and the dissection proceeds more rapidly.
Once the vessels have been ligated, the bowel may be divided by means of cutting linear stapling devices at the previously determined levels. In patients with an underlying disease (eg, ulcerative colitis or FAP), the dissection at this point would be continued as a total mesorectal excision down into the pelvis to the pelvic floor (see respective chapters). It is strongly recommended to have the specimen assessed macroscopically to verify the pathology. Tumor in the resection margin means an inadequate cancer operation requiring a re-resection. Intraoperative frozen sections of the resection margins should be requested whenever there is any doubt about the completeness of the resection.
After the resection has been completed, either the bowel ends can be reanastomosed or the proximal end may be brought out as an ostomy. Prerequisites for a successful anastomosis are meticulous technique, well-vascularized and healthy appearing tissues, apposition of bowel ends without any tension, and good nutritional status of the patient with an albumin level greater than 3.0 mg/dL. Constructing an anastomosis under tension and/or with poor blood supply increases the risk of an anastomotic leak that may cause an infection and sepsis. A protective diverting ostomy does not prevent the leak as such but should diminish the life-threatening complications of an anastomotic leak. While a stapled functional end-to-end anastomosis between the ileum and the colon (ie, an enterocolonic anastomosis) is reasonable, this type of anastomosis may potentially be less desirable between two colon segments (ie, a colocolonic anastomosis) because it can result in an iatrogenic giant diverticulum that may interfere with the propulsion of formed stool or impede the performance of a surveillance colonoscopy. Performing an end-to-end anastomosis, either hand-sewn or by means of a circular stapler, will avoid these problems. An ileocolonic anastomosis in most instances can be performed in an unprepared bowel, whereas a colocolonic anastomosis on the left side traditionally requires pre- or intraoperative reduction in the stool load unless a colostomy was performed. As mentioned previously, this view has come under scrutiny.
Placement of drains is more often a matter of personal preference than of scientific objectiveness.234–236 Most bowel anastomoses, even colocolonic anastomoses, do not need to be drained. The use of drains generally may be recommended when a pelvic dissection and anastomosis have been performed and accumulation of fluid and blood in the dependent areas around the anastomosis should be avoided. Whether prospective, but underpowered, studies are sufficient evidence to effectuate a change in this practice needs to be determined.237,238
Laparotomy versus Laparoscopy.
Laparoscopic colon surgery has a clearly established place in the management of both benign and malignant colon diseases. In many specialized centers, it is even regarded the first-line approach unless patient-specific factors suggest otherwise. The path to a nearly unanimous endorsement of the technique at least for right-sided, left-sided, and sigmoid resections for colon cancer started in the early 1990s,239 moved from palliative resections to institutional case series in curative intent, and culminated in several prospective randomized trials throughout the world,240–245 the first large-scale trial being a multicenter study by the NCI.241 This study, which enrolled 872 patients with stages I–III colon cancer, confirmed that there was a moderate quality-of-life benefit for the laparoscopic approach246 but otherwise no difference in oncological outcome and survival between the laparoscopic and open-resection groups.241 Subsequently, two large-scale European prospective multicenter trials (ie, the COLOR [COlon cancer Laparoscopic or Open Resection] trial with 1248 and the CLASICC [Conventional versus Laparoscopic-Assisted Surgery In Colorectal Cancer] trial with 794 patients) have confirmed similar results.247,248 This equality of the study results offered the unique opportunity for both opponents and proponents of the laparoscopic approach to justify their personal preference for either the open or laparoscopic technique depending on their background and skills. In contrast to one early report of a high incidence of port-site recurrences, it has become clear subsequently that with appropriate surgical technique, the incidence is in the range of 0.8–1.3% and, on a stage-by-stage comparison, not higher than wound implants after open surgery.
For the laparoscopic procedure, about three to five trocars are inserted. Lacking the tactile sensation of open procedures, tattooing of the target lesion should generally be performed prior to the surgery. The colon should be mobilized to the same extent as during open surgery, but it may be advantageous to start with the vascular pedicle rather than with the retroperitoneal attachments. The technical equipment to perform an intracorporeal resection and anastomosis is available, but it is questionable whether there is any advantage to this because at some point an incision must be made anyway to retrieve the specimen. In the laparoscopically assisted technique, the segment, once it has been mobilized to the required extent, therefore is exteriorized through a small sleeve-protected abdominal incision, and an extra-abdominal resection and anastomoses are performed. The bowels are returned into the abdomen, the fascia is closed, and the pneumoperitoneum may be reinstalled to inspect the peritoneal cavity again. To facilitate complex resections, some surgeons use hand-assisted laparoscopic surgery (HALS) to combine tactile sensation with a minimally invasive approach.
Sentinel Lymph Node Mapping.
Although the interest in lymphatic mapping and sentinel lymph nodes has been derived from favorable experiences in breast cancer and melanoma, most recent data do not support the value of this technique for colon cancer. In particular, analysis of the recent intergroup study 0114 demonstrated a lack of correlation in an alarming 54% of the patients.249 Sentinel lymph node mapping not only may be misleading and therefore not useful in the management of colorectal cancer, but there also is simply no need for this technique in colon resections because the lymphadenectomy—in contrast to breast and melanoma surgery—is not associated with any morbidity.
Special Circumstances in Emergency Surgery
Approximately 20% of patients with colon cancer present as an emergency requiring an urgent operation for a tumor-related complication (eg, bowel obstruction, perforation, or massive bleeding).250 Morbidity and mortality are significantly higher than under elective conditions. Contributing factors are the lack of a mechanical bowel preparation and the patient's impaired overall status, which typically is characterized by dehydration, third spacing of fluids, anemia, a deranged metabolism with electrolyte imbalances, and possible sepsis. The risks for wound and intra-abdominal infections and anastomotic leakages are three to six times higher.251
Sixteen percent of patients with colon cancer present with a bowel obstruction and complain of colicky abdominal pain, abdominal distension, vomiting, constipation, and, occasionally, paradoxical diarrhea. Imaging studies (abdominal x-ray or CT scan) characteristically demonstrate the features of a large or small bowel obstruction depending on how proximal in the colon the obstruction is located and whether the ileocecal valve is competent. Attention should be paid to the diameter of the cecum, which presents a risk of cecal perforation if the diameter reaches 12 cm or more. Urgent intervention is required in such circumstances to prevent cecal perforation. The most important differential diagnosis is pseudo-obstruction (Ogilvie's syndrome), which is seen as a result of various medical conditions and may mimic the features of bowel obstruction. Every patient therefore should have a rigid proctoscopy, followed by a water-soluble contrast enema, which should visualize only the colon up to the site of obstruction but not beyond the stenosis because the hyperosmolar nature of the contrast material can result in an increase in the intraluminal volume and trigger a perforation.
If the level of obstruction in the colon is proximal enough, a resection with primary enterocolonic anastomosis, for example right hemicolectomy, extended right hemicolectomy, or subtotal colectomy, may be carried out. If the tumor is located on the left side of the colon, adjustments to the surgical approach are necessary because the stool load proximal to the obstruction is of concern for a colocolonic anastomosis and because that segment of the colon could not be cleared before the operation. Synchronous lesions, which in the setting of an obstructing lesion may occur in up to 15%, may be missed and necessitate further intervention in the future. Strategies then include either (1) a subtotal colectomy, (2) an on-table lavage with segmental colon resection, intraoperative colonoscopy, and primary anastomosis, or (3) performance of a two- or even three-stage procedure instead of the elective one-stage approach. Historically, obstructed left-sided tumors were treated with a three-stage approach starting with a defunctioning loop colostomy, followed by resection and anastomosis and last by closure of the defunctioning stoma. The Hartmann procedure, the classic example among several two-stage procedures, consists of a discontinuous rectosigmoid resection with creation of a terminal colostomy and a blind rectal stump in the first stage, followed by a colostomy takedown and reanastomosis in a second operation.
More recently, there has been a trend toward attempting to relieve the acute obstruction at the tumor-bearing segment by colonoscopic insertion of a self-expanding metallic stent. Successful decompression of the prestenotic colon converts the emergency situation into an elective setting, allowing for stabilization of the patient and performance of bowel preparation. The risk of a colonic perforation during stent placement is relatively low but acceptable because an emergency operation would be necessary anyway if the stent could not be placed successfully. Several nonrandomized, noncontrolled case series have demonstrated that colonic stenting for acute obstruction is safe and highly successful.252–255 A proximal diversion hence may be avoided with this procedure.
Colonic perforation secondary to a tumor occurs in two different settings. Either a transmural tumor perforates itself, or the proximal colon becomes overdistended, particularly in the case of a competent ileocecal valve. Both conditions may result in diffuse fecal peritonitis with significant morbidity and mortality. In addition, the tumor perforation results in spillage of tumor cells and thus has to be considered a stage IV tumor. Surgical management is indicated in every case and requires not only addressing the site of colonic perforation but also removing the tumor in an oncologically correct fashion.250 The same tactical principles described in the preceding section apply.
Massive Colonic Bleeding.
Massive bleeding from a colonic tumor is a relatively rare complication. The general algorithms for the workup and management of lower gastrointestinal bleedings apply, but, most commonly, the bleeding site can be easily identified. If the bleeding is minor or self-limited, the standard workup can be performed. If the patient is or remains unstable and requires repeated transfusions, surgical management is indicated.
Management of Advanced Disease
Locally Advanced Disease.
It has been estimated that approximately 15% of colonic tumors will be adherent to adjacent organs.256 With locally advanced colon tumors, it is still possible to achieve cure if the surgeon is prepared to resect involved adjacent organs. Unfortunately, it is often impossible to distinguish between malignant and inflammatory adhesions, but at least 40% of these adhesions are expected to harbor malignant cells. The surgeon therefore has to consider them malignant until proven otherwise and perform an en bloc resection to achieve a tumor-free margin.257
At the time of presentation, 20% of patients with colorectal cancer have stage IV disease. Distant metastasis, particularly liver and lung, is a major cause of death in patients with colorectal carcinoma. However, patients with asymptomatic liver metastases may have a statistically natural life expectancy of several months up to almost 2 years without any treatment. Chemotherapy and surgical metastasectomy in selected patients may improve disease-free and overall survival substantially, resulting in a cure rate of 30%.258 In the case of potentially resectable metastases, resection of the colonic primary tumor therefore should be performed in an oncologic fashion.
Inoperable Disseminated Disease.
In patients with unresectable metastatic disease, the surgical treatment goal is to provide palliation and to prevent predictable complications. In contrast to the oncologically defined standard resections, a limited segmental wedge resection of the colon is acceptable in this setting. In particular, tumors located in the sigmoid colon or in the cecum and ascending colon are suitable for a laparoscopic or laparoscopically assisted resection because these segments can be mobilized easily to a sufficient extent to ensure a safe anastomosis. If a tumor in a patient with metastatic disease is too advanced locally to be resected safely (eg, infiltration of other organs), palliation may be achieved by creating an internal bypass or a proximal diversion.
Postoperative fast-track management after a colorectal resection has become very straightforward and routine. The immediate postoperative monitoring of vital signs, fluids, and electrolytes, as well as adequate pain control, is not different from any other major surgery. However, there has been an increased emphasis on epidural pain management, early mobilization and regular spirometry exercises, avoidance of tubes and drains (eg, nasogastric tubes), and early resumption of oral intake no later than on the first or second postoperative day with advancement to a regular diet as tolerated. Daily assessment of the abdomen and bowel activity is crucial, including careful auscultation and palpation of the abdomen to assess bowel sounds or peritoneal signs. Unless soaking, a wound dressing may be left in place until the second postoperative day or even for 5–10 days if an occlusive transparent dressing is used. The incision has to be checked daily for the presence of induration, hematoma, redness, dehiscence, or discharge of fluids (eg, pus, hematoma, or serosanguineous fluid). Large amounts of serous fluids draining from the wound should not be mistaken for a seroma but indicate a fascial dehiscence until proven otherwise. The average length of stay after colorectal resections depends on the patient's constitution but generally is in the range between 5 and 7 days for an open standard procedure, and 2 and 5 days for a laparoscopic approach. Before discharge, further tumor treatment should have been addressed with the patient. Adjuvant chemotherapy (and rarely radiation therapy) typically are not initiated before 3–4 weeks after surgery and may be delayed if infectious complications or anastomotic leaks occur.
The overall perioperative mortality within 30 days of colorectal resections is between 3.5 and 6%,259 with less than 2% after elective but up to 20% after emergency operations. Complications of surgery may be of a general or surgery-specific nature and can be classified based on the time of their occurrence as either early (within the first 30 days) or late (after 30 days). Intraoperative complications like injury to relevant anatomic structures such as ureters, spleen, bowel, and duodenum are related to the surgical technique, to blurred anatomic landmarks and layers owing to the disease (eg, peritonitis or massive adhesions), or to the patient's habitus (eg, obesity). Early surgery-specific complications include bleeding, most frequently within the first few days of the resection, nonspecific infections, or infections related to an anastomotic dehiscence. Other more general complications in the early postoperative period (postoperative days 1–3) commonly are related to the cardiopulmonary system and include pulmonary problems (eg, atelectasis, pneumonia, aspiration, and pulmonary embolism) and cardiac events (eg, arrhythmia, myocardial ischemia, and dysfunction). Insufficient pain control has been recognized as an important factor promoting these conditions because it results in a poor respiratory effort by the patient and the inability to cough up sputum, leading to superficial respiration and suboptimal saturation. High fever in the 3 days therefore may be related to the development of an atelectasis rather than to an early infection.
Infectious complications usually occur after the third postoperative day and may be located either intra-abdominally, in the wound, in the urinary tract, or in the lungs. The primary workup therefore includes bacteriologic cultures and stains, blood and urine analysis, and a chest x-ray.
Abdominal complications consist of delayed return of upper and lower gastrointestinal function (also referred to as postoperative ileus), fascial dehiscence, and anastomotic breakdown. Clinical leaks occur in 1–2% of all colonic resections, but subclinical leaks are more frequent and may be seen incidentally on contrast studies in otherwise asymptomatic patients. A leak may present with insidious symptoms such as fever, tachycardia, abdominal distension, ileus, feces draining through a drain or the wound, or local and generalized peritonitis. Occasionally, a leak may present with sudden deterioration, generalized peritonitis, and septic shock as the result of a significant and rapid contamination of the peritoneal cavity. Owing to the heterogeneous symptoms, a leak should be suspected in any patient who is not progressing to the expected degree. Blood parameters such as white blood cell counts and C-reactive protein may be elevated but are nonspecific and difficult to distinguish from a normal postoperative reaction. After an abdominal operation, normal free air should be resorbed within 7–10 days.260 The presence of substantial free subdiaphragmatic air later in the course should therefore raise the index of suspicion for an anastomotic leak.
Imaging studies to define the presence of an anastomotic leak include a water-soluble contrast enema to visualize extravasation of the contrast material and/or a CT scan with oral, intravenous, and possibly rectal contrast material. Apart from antibiotic treatment, the management of an anastomotic leak depends on its presumed extent and the clinical presentation. A patient with generalized peritonitis requires a relaparotomy after appropriate resuscitation. Depending on its location, the anastomosis either should be taken down and the ends should be exteriorized or, in more favorable conditions, resected, and a new anastomosis performed with healthy-looking bowel ends, either with or without proximal diversion. A local repair alone carries a high risk of failure but may succeed in combination with drain placement and a proximal diverting ostomy. By the time of the reexploration, the prolonged peritonitis in some cases already may have transformed the bowel loops into rigid pipes that would not allow any mobilization for an ostomy or for a new anastomosis. In such a case, creation of a confined leak by means of a catheter enterostomy may be a desperate attempt for local control. A fecal fistula can be managed in a conservative manner if there is no evidence of generalized peritonitis or uncontrolled sepsis. Under favorable conditions, including good nutritional support and absence of a distal obstruction or disease of the involved bowel segment, the fistula may close spontaneously. The surrounding skin will need special care, and a stoma therapist will be helpful in this regard.
Adjuvant Chemotherapy and Radiotherapy
The rationale for adjuvant chemotherapy is based on the fact that we are clearly not as successful with surgical treatment as we would like to be. 5-Fluorouracil (5-FU) was the first and most extensively evaluated drug for the treatment of colorectal cancer. Multiple studies had been completed without proof of value until Krook's study.261 Subsequently, a review of 29 randomized trails concluded that adjuvant chemotherapy for colon cancer resulted in a 5% improvement in survival.262 When studies using 5-FU–based regimens are analyzed, there is a 2.3–5.7% absolute improvement in 5-year overall survival. However, when just those at high risk of recurrence are treated, the improvement in survival in this group is closer to 30%. Patients with stage III colon cancer are recognized to be at high risk for recurrence, and administration of 5-FU/leucovorin (LV) for 6 months after surgery has proven to decrease recurrence and improve long-term survival.263 The combination treatment of 5-FU/LV for 6 months was proven to be equivalent in efficacy to 12 months, and the addition of levamisole to 5-FU/LV did not seem to add any benefit.264 Low-dose LV also was demonstrated to be equally efficacious as high-dose LV when used in combination with 5-FU. Thus the first-line standard of treatment from 1998 to 2000 was a combination of 5-FU and low-dose LV (folinic acid) given for 6 months on either a weekly schedule or 5 consecutive days every 4 weeks. At present, there is not enough evidence to recommend the routine use of adjuvant chemotherapy in stage II disease. Lenz and colleagues have demonstrated that molecular or genetic markers may better identify subgroups of patients who are likely to benefit from adjuvant chemotherapy.265,266,267
Several new agents, for example irinotecan (CPT-11)268,269 and oxaliplatin,270–272 have demonstrated significantly superior activity in combination with 5-FU/LV in the metastatic setting. Irinotecan/5-FU/LV (IFL)268 and oxaliplatin/5-FU/LV (FOLFOX) have been entered into randomized clinical trials against 5-FU/LV in resected stage III colon cancer.273 Both these studies prove that the new agents in association with 5-FU/LV were superior to 5-FU/LV alone. Because of these successes, IFL was approved as first-line chemotherapy in 2000. In 2005, 5-FU/LV with oxaliplatin (FOLFOX) was approved for adjuvant therapy and has evolved in most centers as the treatment of choice. The FOLFOX regime has been compared in a large randomized, controlled trial with IFL and irinotecan/oxaliplatin (IROX) in patients with previously untreated metastatic colorectal cancer.273 This study showed significantly superior results of the FOLFOX regime for all end points. The median time to progression observed for FOLFOX was 8.7 months, response rate was 45%, and the median survival time was 19.5 months. The FOLFOX regimen had significantly lower rates of severe nausea, vomiting, diarrhea, febrile neutropenia, and dehydration. Sensory neuropathy and neutropenia were common with the regimens containing oxaliplatin.
Capecitabine (Xeloda), an oral agent designed to generate 5-FU preferentially in tumor tissue, is an exciting new development with improved convenience. A randomized phase III study comparing oral capecitabine versus intravenous 5-FU/LV concluded that capecitabine demonstrated a statistically significantly greater response rate compared with 5-FU/LV (26 vs 17%; p < .002) and an equivalent time to progression and overall survival.274 This study demonstrated that capecitabine is a suitable alternative to IV 5-FU and perhaps a replacement in the future. There are currently phase II trails being conducted on capecitabine/oxaliplatin (CAPEOX) and capecitabine/irinotecan (CAPEIRI).275–279
Two of the most fascinating targets in the treatment of colorectal cancer are the epithelial growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) blockers.280,281 Agents that inhibit the EGFR or bind to VEGF have demonstrated clinical activity as single agents and in combination with chemotherapy in phases II and III clinical trials. The most promising of these agents are the monoclonal antibodies cetuximab, which blocks the binding of epithelial growth factor, and bevacizumab, which binds free VEGF.280,281 However, the benefit of cetuximab is limited to patients with a tumor bearing wild-type K-ras while tumors bearing mutated K-ras do not show any response.282,283 Both agents have proven benefit and seem to work best as first-line therapy for metastatic colorectal cancer. Introduction into the primary adjuvant treatment after curative resection of stages II and III tumors will remain a subject of future trials. We await future developments of these and other newer drugs and their impact in the fight against colorectal cancer.
Generally, radiotherapy does not play a primary role in the adjuvant treatment of colon cancer. However, it may be considered as a locoregional field radiation in selected locally advanced T4N0–N1 tumors.284–286