Surgery remains the cornerstone in the multidisciplinary treatment of colon and rectal cancer. Many diagnostic, technical, and adjuvant therapies are known to impact the immediate and long-term oncologic results. Guidelines for appropriate cancer-specific management of colorectal cancer should be adhered to so as to optimize the oncologic outcomes. Similarly, patient-specific surgical outcomes are also linked to many systems-based factors, such as appropriate use of perioperative antibiotics, venous thromboembolism prophylaxis, and avoidance of surgical complications.
Key points
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Technical factors impact short-term and long-term outcomes following colorectal cancer surgery. These include appropriate vascular ligation and lymph node harvest, adequate bowel and radial margins, and technical precision within the correct surgical planes.
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Many systems-based factors also affect patient outcomes following colorectal cancer surgery.
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Systems for the appropriate use of venous thromboembolism prophylaxis and perioperative antibiotics have been designed and should be closely adhered to for optimal outcomes.
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Postoperative complications have implications for immediate as well as long-term oncologic outcomes. Attempts should be made to avoid complications where possible and to quickly diagnose and treat them when they do occur.
Introduction
Surgical resection remains the primary treatment modality for colon and rectal cancer. Short-term and long-term patient outcomes are influenced by a multitude of factors following colorectal cancer surgery. This review discusses technical and systems-based factors that have been shown to affect outcomes in the management of patients with colon and rectal cancer.
Introduction
Surgical resection remains the primary treatment modality for colon and rectal cancer. Short-term and long-term patient outcomes are influenced by a multitude of factors following colorectal cancer surgery. This review discusses technical and systems-based factors that have been shown to affect outcomes in the management of patients with colon and rectal cancer.
Technical quality factors in colorectal cancer surgery
Colon Cancer
Lymphadenectomy and vessel ligation
The length of bowel removed is based on the blood supply that drains the tumor-bearing segment of the colon. It is recommended that the proximal and distal margins are a minimum of 5 cm each. There is no survival advantage to removing additional colon beyond that required after vessel ligation. The mesentery to the affected segment should be removed en bloc, incorporating the major feeding vessel(s) and the dependent lymphatic-bearing region. Any malignant-appearing lymph nodes (LNs) outside of the boundaries of this envelope of tissue should also be resected if possible. Standard ligation at the origin of the feeding vessel is recommended by the American Society of Colon and Rectal Surgeons because most studies find no survival benefit with high ligation of the feeding vessel. However, at least one large study has suggested that there is an advantage for overall survival and recurrence rate when high vascular ligation is performed in Dukes B and C tumors of the colon and rectum.
There is abundant evidence suggesting that survival improves with increasing LN harvest. A minimum of 12 LNs should be identified and evaluated from the resected colon cancer specimen to allow for accurate staging. The College of American Pathologists suggests that if fewer than 12 LNs are initially identified, additional procedures (such as fat-clearing techniques) should be performed. Patients with N0 disease status but fewer than 12 LNs examined are considered high-risk stage II disease and should be considered for adjuvant chemotherapy.
En bloc resection for T4 lesions
Contiguous structures to which the tumor has adhered or invaded should be removed en bloc with the colon. Inflammatory-appearing adhesions between the tumor and other structures are often malignant, and this cannot be differentiated visually. Poeze and colleagues found that patients with T4 disease who underwent en bloc resection of all involved organs had similar survival outcomes to those with T3 disease.
Synchronous cancers
Approximately 5% of patients with a new diagnosis of colon cancer will have a synchronous lesion within the remaining colon/rectum. There is no difference in outcomes between an extended colectomy and 2 separate segmental resections.
Prophylactic oophorectomy
The ovaries should be examined at the time of colon resection and removed if suspicious for metastatic disease. There is no clear benefit to removal of normal-appearing ovaries, and prophylactic oophorectomy is not currently recommended.
Laparoscopy
There is an abundance of level I evidence from 4 large multicenter randomized trials consistently showing that laparoscopic colectomy for cancer is associated with equivalent rates of perioperative morbidity and mortality as open colectomy. The same trial groups have reported long-term oncologic outcomes and found no differences in survival and recurrence rates. Surgeons with training in laparoscopy should offer a minimally invasive approach to patients with colon cancer and no contraindications to laparoscopy.
Adjuvant chemotherapy
Patients with stage III colon cancer should be considered for adjuvant chemotherapy. Multiple large randomized trials have demonstrated a survival benefit in this patient population. The current standard therapy is oxaliplatin with fluoropyrimidine and leucovorin (FOLFOX). Data for stage II colon cancer are mixed, but adjuvant chemotherapy should also be considered for patients with high-risk features in the setting of a clinical trial (T4, perforation, lymphovascular involvement, perineural invasion, poorly differentiated histology, fewer than 12 LNs resected).
Rectal Cancer
Staging
Patients with a new diagnosis of rectal cancer should undergo local tumor staging with an endorectal ultrasound or a dedicated magnetic resonance imaging (MRI) study in an effort to define the depth of tumor penetration through the bowel wall, as well as potential regional LN involvement. MRI also offers the ability to estimate the circumferential resection margin (CRM). Patients should also undergo staging studies to rule out metastatic disease to the most common sites of metastasis (liver and lung).
Neoadjuvant chemoradiation
Neoadjuvant therapy in the form of external beam radiation and administration of fluoropyrimidine chemotherapy is the standard of care for locally advanced (T3–4, N positive) middle and low rectal tumors. In the United States, the radiation is generally given over a 5-week period with approximately 25 fractions followed by surgery 6 to 12 weeks after the completion of radiation. Short-course radiotherapy with only 5 fractions in 5 days followed by surgery within 7 days is also used with similar outcomes. Neoadjuvant radiotherapy is preferred over postoperative radiotherapy. No differences in disease-free or overall survival have been established. Radiotherapy plus total mesorectal excision (TME) is associated with improved local recurrence rates compared with TME alone.
Local excision
Local excision has historically been offered to patients who are considered to be too frail to undergo resection. In fit patients, resection of the tumor-bearing rectum and draining LNs is the standard of care. Local excision of a rectal cancer may be considered for patients with T1 lesions in the absence of high-risk histologic features and detectable LN involvement. The National Cancer Comprehensive Network guidelines maintain that when the following features are present, patients can be offered local excision: T1 lesion, well-differentiated or moderately differentiated histology, absence of lymphovascular invasion, absence of perineural invasion, tumor smaller than 3 cm in diameter, and tumor occupies less than one-third the circumference of the rectal lumen. Local recurrence following transanal excision is 8% to 13% in published studies.
Vascular ligation
There is no definite oncologic advantage to high ligation of the inferior mesenteric artery except when apical LNs are clinically positive. In a systematic review, Titu and colleagues found that high tie was associated with an increased LN harvest. High ligation of the inferior mesenteric artery as well as the associated vein does allow for significant “lengthening” of the left colon mesentery, facilitating very low colorectal anastomoses.
Total mesorectal excision
Heald was one of the first surgeons to broadcast the importance of a precisely dissected, nonblunt TME. Multiple studies have demonstrated that TME is superior to intra-mesorectal dissection for oncologic outcomes, morbidity, and postoperative function. Hida and colleagues described spread of tumor deposits/LNs within the mesorectum extending at least 4 cm distal to the mucosal border of an upper rectal cancer. This evidence led to the current recommendation that all mid and lower rectal tumors be treated with a complete mesorectal excision and all upper rectal cancers be treated with a minimum of a 5-cm mesorectal margin. Martling and colleagues showed that a national training program for TME in Sweden resulted in increased sphincter-sparing resections, decreased local recurrence, and improved survival following rectal cancer surgery. The quality of the TME specimen is also under scrutiny. Quirke and colleagues showed that the plane of dissection outside the mesorectum versus within the mesorectal fascia is an independent predictor of local recurrence.
Margins
Historically, 5-cm distal margins were required for all rectal cancers. In the modern era, a 2-cm distal margin is suggested to be adequate for middle and low rectal cancers combined with a TME. Several investigators have shown that a distal margin of 1 cm for very low rectal cancers following neoadjuvant chemoradiotherapy does not affect local recurrence or disease-free survival.
The radial margin or CRM is also important. This has been shown to be an independent predictor of recurrence and survival. A CRM of 1 mm or less is associated with a higher local recurrence rate and decreased overall survival, and a CRM of 2 mm is a predictor of local recurrence.
Lymphadenectomy
The recommended extent of lymphadenectomy in the absence of extensive nodal involvement is as described previously in this article with ligation of the superior hemorrhoidal artery and mesorectal excision. Mekenkamp and colleagues suggest that at least 8 LNs are necessary to accurately assign a nodal stage of N0 for rectal cancer. Clinically positive LNs at the base of the inferior mesenteric artery or in the lateral pelvic compartment should be removed if possible. Routine extended lateral pelvic LN dissection has not been shown to offer a survival benefit and is associated with a higher incidence of urinary and sexual dysfunction than TME alone. Fujita and colleagues are conducting a randomized trial comparing TME alone with TME plus lateral LN dissection. Although the oncologic results are pending, they have reported a higher incidence of clinically significant bleeding and longer operative times in the group undergoing extended lymphadenectomy.
Technique for abdominoperineal resection
Positive CRMs, local recurrence, and bowel perforations are more common for abdominoperineal resection (APR) than for sphincter-saving techniques, and survival is lower. Porter and colleagues described an inadvertent perforation rate of 24% in their series of APRs for rectal cancer. Inadvertent perforation was associated with an increased recurrence rate and decreased survival. Others have published similar findings. This has led to a call for change in APR to a cylindrical, extralevator technique. This dissection may be facilitated by placing the patient in the prone jack-knife position for the perianal phase.
Laparoscopy
Randomized trials have shown short-term equivalence between the laparoscopic and open techniques for proctectomy. Lymph node harvest is equivalent, and the rate of positive CRM is also similar for the 2 techniques.
Data are limited regarding the oncologic outcomes following laparoscopy for rectal cancer. Multiple trials are ongoing, and currently the laparoscopic technique is advised only by surgeons with advanced laparoscopy expertise in the setting of a clinical trial.
System quality factors in colorectal cancer surgery
As previously discussed, there are a number of diagnostic, therapeutic, and technical factors that influence the oncologic outcomes for patients with colorectal cancer. These can be considered the cancer-specific quality factors. However, quality cancer surgical care is not completely defined by purely oncologic issues. Numerous surgical system issues influence the surgical outcome of the patient with colorectal cancer. Many of these system quality elements are the same for patients undergoing colorectal surgery for benign conditions. However, patients with colorectal cancer may have a worse prognosis if there are adverse outcomes related to failure to follow best practice. In this section, we review some of the major surgical quality process measures, antibiotic use, and venous thromboprophylaxis. Furthermore, we will review the impact of system factors on complications and oncologic outcomes.
Appropriate prophylactic antibiotic use
The rapid development and wide distribution of antibiotics during the latter half of the twentieth century led to dramatic antibiotic use in surgical patients. The indiscriminate use of antibiotics in surgery was first noted in the late 1970s when nearly 50% of hospital antibiotic use was related to surgical prophylaxis. The role of prophylactic antibiotics is to obtain therapeutic tissue levels of antibiotics effective against the most common types of organisms encountered during the operative procedure. For colorectal surgery, that would include antibiotic coverage for skin organisms as well as aerobic and anaerobic intestinal flora.
During the 1980s, numerous studies reported that the optimal timing of administration of prophylactic antibiotics was within 60 minutes of incision. These studies also demonstrated that prolonged antibiotic use after surgery had no benefit. Although these basic principles of prophylactic antibiotic use were generally adopted nationwide, the antibiotic choices for colorectal surgery were extremely variable and this led to marked differences in surgical site infections (SSIs) within and between institutions complicating the ability to determine a best practice.
To address this wide variation in surgical antibiotic prophylaxis, an attempt was made to study the impact of a standardized regimen of antibiotic selection, timing of administration, and duration of use. A large population-based study was funded by the Centers for Medicare and Medicaid Services (CMS) and conducted in 56 hospitals in Washington State. Using standardized antibiotic protocols and additional elements, SSIs in the participating hospitals were reduced by 27% from an overall of 2.3% to 1.7% after 1 year. The results of this study launched the first series of national surgical quality process measures that have evolved into the CMS Surgical Care Improvement Program (SCIP). Although instituted as national best practices, there have been follow-up analyses in large population studies that have not observed the same reduction in SSIs. However, looking at specifically colorectal surgery, selecting the appropriate antibiotics, with proper administration, including re-dosing and discontinuing them early, have all been associated with a reduction in SSI.
The goal of antibiotic prophylaxis is to have therapeutic antibiotic tissue levels while the wound is open not only at the time of incision but also at closure. This is important for colorectal surgery because of the extended duration of colorectal operations. An additional concern in antibiotic prophylaxis is the increasing size of our patients. Duration of operation and patient size influence how prophylactic antibiotics should be dosed and re-dosed. These essential elements are not considered in the national SCIP quality performance measures. However, the importance of appropriate dosing and re-dosing is reflected in the recent surgical prophylaxis guidelines from the major infectious disease, surgical, and pharmacy societies; the guidelines emphasize weight-based dosing within 60 minutes before skin incision and weight-based re-dosing for cases lasting 3 hours or longer, in addition to appropriate antibiotic selection. Re-dosing is especially important for the most commonly used colorectal surgery prophylactic cephalosporin, cefazolin.
The cause of SSIs in colorectal patients is complex and multifactorial. Certainly, appropriate antibiotic use in the perioperative period will not prevent an SSI. Practices that have successfully demonstrated sustainable reductions in colorectal SSIs have implemented a number of standardized protocols addressing many of the contributing factors to SSIs. However, all of these “SSI reduction bundles” closely follow the national antibiotic prophylaxis guidelines for colorectal surgery.
Venous thromboembolism prevention
Venous thromboembolism (VTE) is a frequent complication in patients with cancer. The risk of symptomatic VTE is 4 to 7 times higher than the general population seeking medical care and is increased with recent surgery. In patients with colorectal cancer, a VTE increases adjusted incremental health care cost by nearly fourfold during chemotherapy. In patients undergoing major abdominal surgery who do not receive thromboprophylaxis, the rate of VTE ranges between 15% and 30% with a rate of fatal pulmonary embolism of 1%. In an analysis of the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) dataset, the incidence of postoperative, symptomatic VTE is 22.0 per 1000 for colon cancer and 16.9 per 1000 for rectal cancer, compared with 13.2 per 1000 and 5.5 per 1000, respectively, for benign conditions. Interestingly, despite some initial reports that laparoscopic colectomy is associated with a lower incidence of VTE, in a meta-analysis of randomized controlled trials comparing laparoscopic with open colectomy in patients with cancer, there was no observed difference in VTE rates.
The recommended VTE prophylaxis for patients undergoing colorectal surgery is a combination of lower extremity intermittent pneumatic compression devices (IPC) with chemical prophylaxis. The recommended chemical prophylaxis is either unfractionated heparin administered 3 times a day or therapeutic low molecular weight heparin (LMWH). These therapies have been shown in patients with abdominal and pelvic malignancies to be equally efficacious with no difference in postoperative bleeding complications. Although a combination therapy including both mechanical and chemical prophylaxis is recommended for colorectal surgery patients, the key component is the chemical prophylaxis. In a randomized controlled trial of LMWH and IPC versus IPC alone in more than 1000 patients undergoing abdominal surgery, the combined use of LMWH and IPC reduced the VTE rate by nearly 70%.
Of course, the primary concern of VTE chemoprophylaxis is a possible increased risk of postoperative bleeding events. In the Enoxaparin and Cancer (ENOXACAN) trial comparing standard unfractionated heparin to LMWH there were similar rates of overall bleeding and major bleeding in both arms, about 17% and 3%, respectively. A systematic review of chemical VTE prophylaxis in patients participating in randomized controlled surgical oncology trials revealed a significant benefit compared with mechanical prophylaxis. The overall rate of bleeding complications that required discontinuation of chemical prophylaxis was 3%. In subsequent studies looking at only colorectal surgery patients, the associated bleeding rates, minor and major events, were in the 3% to 10% range. In a large population-based study of colorectal patients in hospitals that used chemoprophylaxis and those that used only mechanical prophylaxis, the chemoprophylaxis hospitals had significantly fewer symptomatic VTE complications and similar or lower bleeding complications. This finding has been demonstrated in additional studies. In the large Canadian randomized trial comparing the efficacy of low-dose unfractionated heparin with LMWH, the rates of bleeding requiring reoperation were 0.2% and 0.3%, respectively. The evidence clearly supports the use of VTE chemoprophylaxis in colorectal surgery patients in the perioperative hospitalization period and this has become a national quality process measure. There is increasing evidence that these patients may significantly benefit from continued VTE chemoprophylaxis after discharge from hospital.
In an analysis of more than 68,000 newly diagnosed patients with colorectal cancer in California, the incidence of VTE within 2 years of diagnosis was 3.1%. Most VTE events occurred within 6 months of diagnosis, more than 30% occurring within 2 months of operation. The presence of a VTE within the first year after diagnosis was a major predictor of death. With the increased use of laparoscopy and postoperative clinical pathways leading to decreased length of stay, the duration of VTE chemoprophylaxis is also decreasing. Increasingly, follow-up data are demonstrating that many VTE complications are being diagnosed after the patient leaves the hospital. According to the ACS-NSQIP data set, more than a third of all colorectal cancer VTE episodes are detected after discharge. Furthermore, the symptomatic patients with VTE diagnosed after discharge from the hospital as compared with those diagnosed in the immediate perioperative period are more likely to have a recurrent VTE in the year after their surgery. The relatively high rate of postdischarge VTE events and the significant morbidity associated with them has prompted investigation of longer VTE prophylaxis. The most recent Cochrane review on the subject of extended thromboprophylaxis after abdominal or pelvic surgery using LMWH concluded that use of prophylaxis for 4 weeks after surgery significantly reduced postdischarge events without an increase in bleeding complications. Prolonged postoperative VTE prophylaxis resulted in a significant reduction in postdischarge symptomatic VTEs from 1.7% to 0.2%, with no difference in associated postoperative bleeding events.
Related posts:
Controversies in Laparoscopy for Colon and Rectal Cancer
Current Practices and Challenges of Adjuvant Chemotherapy in Patients with Colorectal Cancer
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Current Controversies in Neoadjuvant Chemoradiation of Rectal Cancer
Functional Consequences of Colorectal Cancer Management
An Approach to the Newly Diagnosed Colorectal Cancer Patient with Synchronous Stage 4 Disease
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