Long-term oncologic outcomes for simultaneous resection of synchronous metastatic liver and primary colorectal cancer.

BACKGROUND: Twenty-five percent of patients with colorectal cancer present with simultaneous liver metastasis. Complete resection is the only potential curative treatment. Due to improvements in operative and perioperative management, simultaneous liver and colon resections are an accepted procedure at specialized centers for selected patients. Nevertheless, little is known about the long-term, oncologic results of simultaneous operative procedures compared with those of staged operations. METHODS: Patients with colorectal cancer and simultaneous liver metastases presenting for complete resection at a tertiary cancer center were identified. Patients who received the primary colon resection at an outside institution were excluded from analysis. RESULTS: Between 1984 and 2008, 429 patients underwent operative treatment for colorectal cancer with simultaneous liver metastasis. Of these, 320 (75%) had simultaneous resection and 109 had staged resection. There was no difference in the distribution of primary tumor locations between the 2 groups. Mean size of the hepatic metastases was significantly greater in the staged group (median 4 cm vs 2.5 cm; P < .01). Neither disease-free nor overall survival differed significantly between the 2 treatment strategies. The extent of the liver procedure (more than 3 segments) was identified as a risk factor for decreased disease-free and overall survival (both P < .01). CONCLUSION: Simultaneous liver and colorectal resections for metastatic colorectal cancer are associated with similar long-term cancer outcome compared with staged procedures.

Patient expectations of functional outcomes after rectal cancer surgery: a qualitative study.

BACKGROUND: Rectal cancer patients' expectations of health and function may affect their disease- and treatment-related experience, but how patients form expectations of postsurgery function has received little study. OBJECTIVE: We used a qualitative approach to explore patient expectations of outcomes related to bowel function after sphincter-preserving surgery for rectal cancer. DESIGN: This was a cohort study of patients who were about to undergo sphincter-preserving surgery for rectal cancer. SETTINGS: The study was conducted through individual telephone interviews with participants. PATIENTS: Twenty-six patients (14 men and 12 women) with clinical TNM stage I to III disease were enrolled. MAIN OUTCOME MEASURES: The semistructured interview script contained open-ended questions on patient expectations of postoperative bowel function and its perceived impact on daily function and life. Two researchers analyzed the interview transcripts for emergent themes using a grounded theory approach. RESULTS: Participant expectations of bowel function reflected 3 major themes: 1) information sources, 2) personal attitudes, and 3) expected outcomes. The expected outcomes theme contained references to specific symptoms and participants' descriptions of the certainty, importance, and imminence of expected outcomes. Despite multiple information sources and attempts at maintaining a positive personal attitude, participants expressed much uncertainty about their long-term bowel function. They were more focused on what they considered more important and imminent concerns about being cancer free and getting through surgery. LIMITATIONS: This study was limited by context in terms of the timing of interviews (relative to the treatment course). The transferability to other contexts requires further study. CONCLUSIONS: Patient expectations of long-term functional outcomes cannot be considered outside of the overall context of the cancer experience and the relative importance and imminence of cancer- and treatment-related events. Recognizing the complexities of the expectation formation process offers opportunities to develop strategies to enhance patient education and appropriately manage expectations, attend to immediate and long-term concerns, and support patients through the treatment and recovery process.

A phase II, randomized, controlled trial of acupuncture for reduction of Postcolectomy Ileus.

PURPOSE: Postoperative ileus (POI) prolongs hospital stay and increases risk of postoperative complications. We conducted a randomized, sham-controlled trial to evaluate whether acupuncture reduces POI more effectively than sham acupuncture. METHODS: Colon cancer patients undergoing elective colectomy were randomized to receive 30 min of true or sham acupuncture twice daily during their first 3 postoperative days. GI-3 (the later of the following two events: time that the patient first tolerated solid food, AND time that the patient first passed flatus OR a bowel movement) and GI-2 (the later of the following two events: time patient first tolerated solid food AND time patient first passed a bowel movement) were determined. Pain, nausea, vomiting, and use of pain medications were evaluated daily for the first 3 postoperative days. RESULTS: Ninety patients were randomized. Eighty-one received the allocated intervention: 39 in the true acupuncture group and 42 in the sham acupuncture group, all evaluated for the primary endpoint. The mean time to GI-3 was 149 h [standard deviation (SD) 71 h] and 146 (SD 62 h) after surgery for the acupuncture group and the sham acupuncture group (difference between means -2 h; 95 % confidence interval -31, 26; p = 0.9). No significant differences were found between groups for secondary endpoints. CONCLUSIONS: True acupuncture as provided in this study did not reduce POI more significantly than sham acupuncture. The study was limited by a standard deviation much larger than expected, suggesting that a study with a larger sample size might be required.

Whole-mount pathologic analysis of rectal cancer following neoadjuvant therapy: implications of margin status on long-term oncologic outcome.

OBJECTIVE: Extent of distal resection margins in rectal cancer surgery remains controversial. We set out to determine the long-term oncologic impact of resection margins in patients with locally advanced rectal cancer using a comprehensive pathologic whole-mount section analysis. BACKGROUND: It has been demonstrated that there is minimal disease beyond the gross tumor margin after neoadjuvant combined modality therapy (CMT) for rectal cancer. Although this suggests that close resection margins may be used for sphincter preservation, the long-term oncologic impact of this approach is unclear. METHODS: We prospectively enrolled 103 patients with locally advanced rectal cancer after neoadjuvant CMT. Whole-mount pathologic analysis was performed, and clinicopathologic variables were correlated with disease-specific survival (DSS). RESULT: : Sphincter preservation was achieved in 80% of patients, and the median distal margin was 2 cm (0.1 to 10 cm). There were 22 patients (21%) with distal margins 1 cm or less and no patient had a positive distal margin. Median radial margin was 1 cm and 4 patients (4%) had a margin of 1 mm or less. Viable distal intramural tumor spread was found in 3 patients (2.7%) and in all cases was limited to 1 cm or less from the gross tumor edge. At a median follow-up of 68 months, 5-year DSS was 86% and 1 patient experienced a local recurrence. Factors predictive of worse DSS included advanced tumor (T) and nodal (N) stage, tumor progression on neoadjuvant CMT, lack of a complete pathologic response, tumor location of 5 cm or less from the anal verge, and neurovascular invasion. The extent of the distal and radial margins of resection was not associated with DSS. CONCLUSIONS: These results suggest that carefully selected patients with locally advanced rectal cancers who undergo neoadjuvant CMT can achieve excellent local control and DSS with a sphincter-sparing rectal resection and a margin distal clearance of 1 cm.

Pulmonary recurrence predominates after combined modality therapy for rectal cancer: an original retrospective study.

OBJECTIVE: To characterize patterns of recurrence in locally advanced rectal cancer treated with combined modality therapy (CMT): neoadjuvant chemoradiation + total mesorectal excision + adjuvant chemotherapy. METHODS: A total of 593 consecutive rectal cancer patients (1998 to 2007) with locally advanced (stage II/III) disease (noted on endorectal ultrasound or magnetic resonance imaging) who received CMT were analyzed for patterns of recurrence. RESULTS: After median 44-month follow-up (interquartile range, 25 to 64 months), 119 patients (20%) recurred: 105 distant, 7 local, 7 local and distant, and 112 distant-only recurrence. Ninety-three (78%) had single-organ recurrence, and 26 (22%) had multiple-organ recurrence. The most common site of distant recurrence was lung (69% of all patients with distant relapse); 20% had liver recurrence. Fourteen patients (2.4%) recurred locally. Pulmonary metastases were most commonly identified by computed tomographic scan versus abnormal positron emission tomographic (PET) scan or carcinoembryonic antigen (CEA). Risk factors associated with pulmonary recurrence were the following: pathologic stage, tumor distance from anal verge, lymphovascular or perineural invasion. Five-year freedom from pulmonary recurrence for patients with 0, 1, 2, or 3 risk factors was 99%, 90%, 61%, and 42%, respectively. Thirty of 59 patents with pulmonary recurrence underwent lung metastasectomy; 3-year freedom from recurrence was 37%. CONCLUSIONS: Unlike colon cancer, which most frequently recurs in the liver, locally advanced rectal cancer treated with CMT relapses most frequently in the lung. Pulmonary metastasis was associated with advanced pathologic stage, low-lying tumor, lymphovascular invasion, or perineural invasion. Confirmation of pulmonary metastasis usually requires serial imaging because metastases are often small when initially detected, well below the resolution of PET, and not necessarily associated with elevated CEA. Individualized risk-based surveillance strategies are recommended in this patient population.

Surgery and high-dose-rate intraoperative radiation therapy for recurrent squamous-cell carcinoma of the anal canal.

BACKGROUND: Locoregionally recurrent squamous-cell carcinoma of the anal canal is managed with salvage surgery. High-dose-rate intraoperative radiation therapy has been used in selected patients with this disease to reduce the risk of local recurrence. OBJECTIVE: The aim of this article is to present our institutional experience with this technique. DESIGN: Medical records of 14 patients with locoregionally recurrent squamous-cell carcinoma of the anal canal who underwent this technique between 1992 and 2007 were reviewed. SETTING: The study was conducted at an academic cancer center. PATIENTS: The median age was 45 years (range, 36-77), and 13 of the patients were women. All had prior radiation with or without chemotherapy. INTERVENTIONS: The surgical procedures included abdominoperineal resection with or without sacrectomy (n = 8), low anterior resection (n = 2), and pelvic exenteration (n = 4). The median radiation dose was 1500 cGy (range, 1500-1750). All cases of radiographic invasion of adjacent structures correctly predicted pathologic invasion. There was pathologic invasion into adjacent structures in 11 cases (79%), and adherence to the sacrum without invasion in 2 cases (14%). Surgical margins were positive (n = 6), close (<1 mm) (n = 3), and negative (n = 5). RESULTS: The median follow-up from our technique was 17 months (range, 5-145). Subsequent recurrence occurred in 11 cases, at a median of 8 months from treatment. Two-year actuarial control was 7.1%, and the overall survival was 21.4%. Acute toxicities included wound-healing complications (n = 6); gastrointestinal obstruction (n = 5); neurogenic bladder (n = 1); ureteral stricture (n = 3); and peripheral neuropathy (n = 2). LIMITATIONS: This is a small retrospective series in which the meaningful analysis of associations between clinical variables and outcomes was not possible. CONCLUSION: Salvage surgery with high-dose-rate intraoperative radiation therapy did not appear to be associated with a locoregional control or survival benefit in this series. The addition of high-dose-rate intraoperative radiation therapy to salvage surgery is insufficient to compensate for positive surgical margins. Preoperative imaging should be used to aid in patient selection to identify those patients in whom negative margins can be obtained and to aid in the determination of appropriate salvage surgery.

Management of patients with malignant bowel obstruction and stage IV colorectal cancer.

BACKGROUND: Malignant bowel obstruction (MBO), a serious problem in stage IV colorectal cancer (CRC) patients, remains poorly understood. Optimal management requires realistic assessment of treatment goals. This study's purpose is to characterize outcomes following palliative intervention for MBO in the setting of metastatic CRC. STUDY DESIGN: Retrospective review of a prospective palliative database identified 141 patients undergoing surgical (OR; n = 96) or endoscopic (GI; n = 45) procedures for symptoms of MBO. RESULTS: Median patient age was 58 years, median follow-up 7 months. Most (63%) had multiple sites of metastases. Computed tomography (CT) scan findings of carcinomatosis (p = 0.002), ascites (p = 0.05), and multifocal obstruction with carcinomatosis and ascites (p = 0.03) significantly predicted the need for percutaneous or open gastrostomy tube, or stoma. Procedure-associated morbidity for 81 patients with small bowel obstruction (SBO) was 37%; 7% developed an enterocutaneous fistula/anastomotic leak. Thirty-day mortality was 6%. Most (84%) patients were palliated successfully; some received additional chemotherapy (38%) or surgery (12%). Procedure-associated morbidity for 60 patients with large bowel obstruction (LBO) was 25%; 11 patients (18%) required other procedures for stent failure, with one death at 30 days. Symptom resolution was >97%. Patients with LBO had improved symptom resolution, shorter length of stay (LOS), and longer median survival than patients with SBO. CONCLUSIONS: Patients with MBO and stage IV CRC were successfully palliated with GI or OR procedures. Patients with CT-identified ascites, carcinomatosis, or multifocal obstruction were least likely to benefit from OR procedures. CT plays an important role in preoperative planning. Sound clinical judgment and improved understanding are required for optimal management of MBO.

Recurrence rates and prognostic factors in ypN0 rectal cancer after neoadjuvant chemoradiation and total mesorectal excision.

BACKGROUND: Neoadjuvant chemoradiation followed by surgery and adjuvant chemotherapy is typically recommended for patients with locally advanced rectal cancer. Patients with pathologically node-negative tumors have an improved prognosis, but recurrence patterns and independent prognostic factors in these patients have been incompletely characterized. METHODS: Using a retrospective cohort study design, we included all rectal cancer patients treated with neoadjuvant chemoradiation and curative surgery from 1993 through 2003, who had ypN0 tumors. We characterized recurrence rates and patterns in patients not treated with adjuvant chemotherapy. Secondarily, we compared them to patients who did receive adjuvant treatment and assessed for independent prognostic factors, using univariate and multivariable survival analyses. RESULTS: Overall, 324 ypN0 patients (ypT0: n = 73; ypT1-2: n = 130; ypT3-4: n = 120) were followed for a median of 5.8 years. The risk of recurrence was associated with pathologic stage-2.7% ypT0, 12.3% ypT1-2, 24.2%ypT3-4. Five-year recurrence-free survival in patients who did not receive adjuvant treatment was 100% (ypT0), 84.4% (ypT1-2) and 75% (ypT3-4). There was no significant difference in 5-year recurrence-free survival between patients who did and did not receive adjuvant treatment. In multivariable analysis, pathologic stage was the factor most strongly associated with recurrence (hazard ratio 3.6 for ypT3-4 vs. ypT0-2, 95% confidence interval 1.9-6.7, P < 0.0001). CONCLUSIONS: The recurrence rates for selected patients with ypT0-2N0 rectal cancer after neoadjuvant chemoradiation and total mesorectal excision are low. Although standard practice remains completion of planned postoperative adjuvant chemotherapy for all patients undergoing chemoradiation, these data suggest prospective trials may be warranted to measure the benefit of adjuvant chemotherapy in favorable subgroups, such as ypT0-2N0.

Evaluation of ¹8F-FDG-PET for early detection of suboptimal response of rectal cancer to preoperative chemoradiotherapy: a prospective analysis.

BACKGROUND: Early identification of inadequate response to preoperative chemoradiotherapy (CRT) may spare rectal cancer patients the toxicity of ineffective treatment. We prospectively evaluated tumor response with (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) early in the course of preoperative CRT. METHODS: A total of 27 prospectively accrued patients with locally advanced rectal cancer (T(3-4)/N(1)) received preoperative CRT (5040 cGy + 5FU-based chemotherapy). Patients underwent PET scanning before and 8-14 days after commencement of CRT. Scans were interpreted using 3 standard parameters: SUV(max), SUV(avg), and total lesion glycolysis (TLG) as well as an investigational parameter: visual response score (VRS). Percent pathologic response was quantified as a continuous variable. All PET parameters were correlated with pathology. Pathologic complete/near-complete response was defined as ≥95% tumor destruction, suboptimal response as <95%. Statistical analysis was performed using the Wilcoxon rank sum test and receiver operating characteristic (ROC) curve analysis. RESULTS: Of the 27 patients, 11 (41%) had pathologic complete/near-complete response; 16 (59%) had suboptimal response. SUV(max), SUV(avg), and TLG did not discriminate between responders and nonresponders. Visual response score (VRS) was statistically significantly higher for complete/near-complete responders than for suboptimal responders (65 vs. 33%, P = 0.02). Suboptimal responders were identified with 94% sensitivity and 78% accuracy using a VRS cut-off of 50%. CONCLUSIONS: In this pilot study, FDG-PET at 8-14 days after the beginning of preoperative CRT was unsuccessful at predicting pathological response with enough accuracy to justify an early change in therapy.

Significance of acellular mucin pools in rectal carcinoma after neoadjuvant chemoradiotherapy.

The presence of mucin pools lacking neoplastic epithelium ("acellular" mucin) in resection specimens of rectal carcinoma after neoadjuvant chemoradiotherapy (CRT) is a well-recognized phenomenon. The current recommendation by the College of American Pathologists is to regard acellular mucin as a type of treatment response and not as residual tumor. However, data-based evidence for or against such an approach is incomplete. In this study, we systematically analyzed the pattern and significance of mucin pools in 108 consecutive, prospectively collected resection specimens from patients who had uT3-4 and/or uN1 rectal cancer and were treated with preoperative long-course CRT. The 108 patients, 39 female and 69 male, had a median age of 58.5 years. With every tumor entirely examined in whole-mount sections, mucin pools were identified in 33 cases (33 of 108, 31%); in 16 (15%) they were all acellular. The mucin pools were focal (10% to 50% of the entire lesion) in 25 cases and extensive (>50%) in 8 cases. Mucin pools were also noted in the lymph nodes in 6 cases (6%); 3 of these were entirely acellular. Five cases had mucin pools in both the primary site and the lymph nodes. When acellular mucin was considered as "no residual tumor," the complete pathologic response rate for the entire cohort was 22% (24 of 108). The pathologic stage of the residual tumor (ypT) was 0 or 1 for 27 cases (25%) and 2 to 4 for 81 cases. The pathologic stage of nodal disease (ypN) was 0 for 83 (77%) and 1 or 2 for 25 cases. When acellular mucin was considered as "residual tumor," the complete pathologic response rate dropped to 17%; ypT was upstaged in 10 tumors and ypN was upstaged in 2 tumors. With a median follow-up of 31 months, the 3-year recurrence-free survival (RFS) was 73% for the entire group. Advanced pathologic response and low pathologic stage of the residual tumor (determined based on the depth of only viable tumor cells) correlated significantly with better RFS. However, the correlation between pathologic response and RFS became insignificant when acellular mucin pools were considered as residual tumor. Neither the presence of mucin pools nor their extent or cellularity had an impact on RFS. Furthermore, none of the 12 patients whose ypT or ypN was upstaged by acellular mucin had recurrent disease (3-y RFS of 100%). Thus, our results suggest that mucin pools in rectal carcinoma after neoadjuvant CRT do not have a significant impact on patient outcome, supporting the College of American Pathologists recommendation that only viable tumor cells, not acellular mucin, are to be interpreted as residual disease in the tumor pathologic staging.

A predictive model for lymph node yield in colon cancer resection specimens.

OBJECTIVE: To develop a predictive model of lymph node yield in a series of colon cancer resection specimens with detailed anatomic and surgical technique data. BACKGROUND: Lymph node yield in colon resection specimens has been associated with accuracy of staging and cancer outcomes. We hypothesized that lymph node yield is associated with multiple factors including patient, tumor,and surgical variables. METHODS: The pathology specimens from 152 elective colon neoplasm resections were prepared so that the lymph nodes were separated according to their anatomic relationship to the vascular pedicles and to the tumor. Prior to dissection, the specimen was measured. A linear regression analysis of a priori identified predictors and confounders of lymph node quantity was performed. Potential predictors in the model were age, gender, tumor stage, size, location,and differentiation, presence of lymphovascular or perineural invasion,mucinous histology, number of vascular pedicles, and use of endoscopic tattoo. Potential confounders were American Society of Anesthesiologists class, body mass index, count of lymph node metastasis, and specimen length. RESULTS: Tumor size, tumor location, number of resected pedicles, and use of tattoo had a significant linear or quadratic relationship with lymph node yield when controlling other variables. 23% of the variation in lymph node count was explained by the 15 variables in the model. A model with the 4 significant variables explained 19% of the variation. CONCLUSION: Multiple tumor and surgical factors are associated with lymph node yields in colon specimens. A standard minimum of lymph nodes may not be applicable to all colon cancer resections.

Impact of a temporary stoma on the quality of life of rectal cancer patients undergoing treatment.

BACKGROUND: Data from randomized controlled trials support use of a diverting stoma in rectal cancer patients with low anastomoses, but there is little data on how this impacts patient quality of life (QOL). This study prospectively evaluates QOL in stage I-III rectal cancer patients undergoing sphincter-preserving surgery (SPS) with a temporary diverting stoma. MATERIALS AND METHODS: Patents were identified from a prospective single-institution study of stage I-III rectal cancer patients undergoing SPS. Patients completed the EORTC C30/CR38 QOL scale preoperatively, at stoma closure, and at 6 months. The Stoma Quality of Life (SQOL) was administered at stoma closure. Subscales of the EORTC hypothesized to be affected by a diverting stoma were identified a priori. Longitudinal trends were analyzed using repeated measures ANOVA. Frequencies for responses on specific SQOL items were tabulated, and correlations between SQOL subscales and EORTC Global QOL assessed with Pearson correlation coefficient. RESULTS: Global QOL was reportedly good (mean score 70.2) and did not change with a temporary stoma (P = .83). Physical (P = .33), role (P = .07), and social function (P = .48) were also stable. Decreased body image was observed (P = .03). Stoma-related difficulties identified by the SQOL included sexual activity (53%), leakage (39%), discomfort in clothing (34%), concerns regarding privacy to empty pouch (32%), and feeling unattractive (31%). "Overall satisfaction with life," Work/social function (P < .001), sexuality/body image (P = .01), and stoma function (P = .01) subscales of the SQOL correlated strongly with the EORTC Global QOL score (P < .001). CONCLUSION: In this longitudinal study of QOL in rectal cancer patients with a temporary stoma, Global QOL was good despite significant stoma-related difficulties. Use of alternative research methodology is necessary to provide insight into why this contradiction exists.

Close distal margin and rectal cancer recurrence after sphincter-preserving rectal resection.

PURPOSE: Negative surgical margins are important for local control of rectal cancer treated with sphincter-preserving surgery. However, the association of rectal cancer recurrence with close distal margin is not well established. METHODS: Data were extracted from a prospective database of patients collected between 1991 and 2003. Included were 627 patients who underwent curative low anterior resection with total mesorectal excision for rectal cancer 2 to 12 cm from the anal verge. Three hundred ninety-nine patients received neoadjuvant therapy, 65 received postoperative adjuvant therapy alone, and 163 were treated with surgery alone. Median follow-up was 5.8 years. RESULTS: On multivariable analysis, overall recurrence was associated with pathologic stage, lymphovascular invasion, and distal margin. Mucosal recurrence was uncommon; only 16 events were recorded, and of those only 8 were at the initial site of isolated tumor recurrence; 7 of the 8 were surgically salvaged. On univariable analysis, mucosal recurrence was associated with close distal margin (5 vs 2% at 5 y) and lymphovascular invasion (7 vs 2%). Pelvic recurrence, other than isolated mucosal recurrence, was associated with distal location (6 vs 4% at 5 y) and lymphovascular invasion (11 vs 4%). Distal margin as a continuous variable was associated with overall recurrence (excluding isolated mucosal recurrence). CONCLUSIONS: Close distal resection margin identifies patients with increased risk of mucosal and overall cancer recurrence. Although neither causality nor a minimally acceptable margin length can be defined, the data support the importance of achieving a clear distal resection margin in the surgical management of rectal cancer.

Effects of obesity in rectal cancer surgery.

BACKGROUND: Increased local recurrence after total mesorectal excision (TME) in obese rectal cancer patients has been attributed to technical difficulties associated with adiposity. In this study, we evaluate whether higher body mass index (BMI) compromises surgical resection in patients with locally advanced, mid-to-low rectal cancer after neoadjuvant therapy, adversely affecting long-term oncologic outcomes. STUDY DESIGN: Five-hundred and ninety-six patients with uT3/4 and/or uN1 rectal adenocarcinoma were treated from 1998 to 2007 with neoadjuvant therapy, followed by radical resection using TME. Outcomes were analyzed according to BMI: obese (BMI >or=30) and nonobese (BMI <30). Median follow-up was 39 months. RESULTS: In all, 26.7% of patients were obese. The rate for positive circumferential margin in nonobese was 4.9% versus 2.5% in obese (p = 0.21). The sphincter-sparing rate in nonobese was 79.5% versus 80.5% in obese (p = 0.77). Five-year overall survival for nonobese was 84% versus 90% for obese (p = 0.92). Five-year disease-free survival for nonobese was 76% versus 73% for obese (p = 0.75). Operative time was longer in obese than nonobese; 4.3 versus 3.7 hours, respectively (p < 0.01). Length of stay was longer in obese than nonobese; 8 versus 7 days, respectively (p < 0.01). Similar results were obtained in analysis stratified by gender. CONCLUSIONS: After neoadjuvant therapy for mid-to-low rectal cancer, higher BMI did not compromise sphincter preservation or complete resection or negatively affect long-term outcomes. These findings might be related to the fact that resection was performed in a specialty center with dedicated oncologic surgeons. However, higher BMI was associated with longer operative time, indicating a more technically demanding procedure and longer hospital stay.

Randomized clinical trials in rectal and anal cancers.

This article reviews randomized clinical trials (RCTs) published between April 2001 and November 2008 on the management of patients with rectal cancer. In total, the authors reviewed 78 RCTs on therapy for rectal cancer. Of these, five met the authors' criteria for level 1a evidence. The article discusses the major RCTs and relevant findings that have impacted clinical management most and includes most but not all RCTs on therapy for rectal cancer published during this period.

Definition and grading of anastomotic leakage following anterior resection of the rectum: a proposal by the International Study Group of Rectal Cancer.

BACKGROUND: Anastomotic leakage represents a major complication after anterior resection of the rectum. The incidence of anastomotic leakage varies considerably among clinical studies in part owing to the lack of a standardized definition of this complication. The aim of the present article was to propose a definition and severity grading of anastomotic leakage after anterior rectal resection. METHODS: After a literature review a consensus definition and severity grading of anastomotic leakage was developed within the International Study Group of Rectal Cancer. RESULTS: Anastomotic leakage should be defined as a defect of the intestinal wall at the anastomotic site (including suture and staple lines of neorectal reservoirs) leading to a communication between the intra- and extraluminal compartments. Severity of anastomotic leakage should be graded according to the impact on clinical management. Grade A anastomotic leakage results in no change in patients' management, whereas grade B leakage requires active therapeutic intervention but is manageable without re-laparotomy. Grade C anastomotic leakage requires re-laparotomy. CONCLUSION: The proposed definition and clinical grading is applicable easily in the setting of clinical studies. It should be applied in future reports to facilitate valid comparison of the results of different studies.

Immunohistochemistry as first-line screening for detecting colorectal cancer patients at risk for hereditary nonpolyposis colorectal cancer syndrome: a 2-antibody panel may be as predictive as a 4-antibody panel.

The utility of immunohistochemical detection of DNA mismatch repair proteins in screening colorectal cancer for hereditary nonpolyposis colorectal cancer (HNPCC) is being widely investigated. Currently, in both research and clinical settings, a 4-antibody panel that includes the 4 most commonly affected proteins (MLH1, MSH2, MSH6, and PMS2) is being used generally. On the basis of the biochemical properties of these proteins, we hypothesized that a 2-antibody panel, comprising MSH6 and PMS2, would be sufficient to detect abnormalities in all 4 proteins. We tested this hypothesis on a series of 232 colorectal carcinoma samples derived from 2 patient cohorts: (1) a prospectively accrued series of patients who were judged to carry a higher-than-average risk for HNPCC based on the revised Bethesda guidelines (n=190); and (2) a retrospective series of patients who were 40 years of age or younger (n=42). Immunohistochemical stains were regarded as negative (protein lost), when there was no nuclear labeling in tumor cells (with positive internal control). Overall, 70 of the 232 tumors demonstrated loss of at least one protein. The most common abnormality was concurrent loss of MLH1 and PMS2 (observed in 17% of the cases), followed by concurrent loss of MSH2 and MSH6 (6%). All MLH1 and MSH2-abnormal cases were also abnormal for PMS2 and MSH6, respectively, whereas 9 of 50 (18%) PMS2 and 6 of 20 (30%) MSH6-abnormal cases showed only isolated loss of PMS2 or MSH6 (with normal staining for MLH1 and MSH2). As such, our findings provide evidence that a 2-antibody panel (PMS2 and MSH6) is as effective as the current 4-antibody panel in detecting DNA mismatch repair protein abnormalities. Such a cost-effective approach carries significant implication, as immunohistochemistry is being widely used as first-line screening for HNPCC.

Treatment for patients with rectal cancer and a clinical complete response to neoadjuvant therapy: a decision analysis.

PURPOSE: A clinical complete response to neoadjuvant therapy occurs in a subset of patients with rectal cancer. Management of these patients is controversial and tension exists between the recurrence risk with observation, and the impact of surgery on quality-of-life. Therefore, the objective was to develop a decision-analytic model to evaluate the relative benefits of surgery vs. observation in rectal cancer patients who achieve clinical complete response after neoadjuvant chemoradiation. METHODS: Clinically relevant inputs and events, including the ability to identify complete responders, likelihood of relapse and of salvage surgery after relapse, and utilities for each health state, were simulated by use of a Markov state-transition model. Transition probabilities and health-state utilities were derived from the literature and expert consensus. One-way and two-way sensitivity analyses were performed to assess the robustness of model results to assumptions. The primary outcome was quality-adjusted life expectancy. RESULTS: In the base-case analysis, the quality-adjusted life expectancy with surgery exceeded observation (5.63 vs. 5.34 quality-adjusted life-years). Sensitivity analysis demonstrated that observation was preferred to surgery if the ability to correctly identify patients with true complete responses exceeded 58 percent, if quality-of-life after surgery was poor (utility <0.81), or if the relative reduction in recurrence risk with surgery was <43 percent when compared with observation. CONCLUSIONS: Our model outlines the issues associated with surgery vs. observation, and suggests that surgery is beneficial for the average patient with rectal cancer with a clinical complete response after neoadjuvant therapy. Current limitations in the clinical assessment of patient response to chemoradiation constitute an important factor influencing our results, and therefore warrant further investigation.

Outcome of primary tumor in patients with synchronous stage IV colorectal cancer receiving combination chemotherapy without surgery as initial treatment.

PURPOSE: The purpose of this study was to describe the frequency of interventions necessary to palliate the intact primary tumor in patients who present with synchronous, stage IV colorectal cancer (CRC) and who receive up-front modern combination chemotherapy without prophylactic surgery. PATIENTS AND METHODS: By using a prospective institutional database, we identified 233 consecutive patients from 2000 through 2006 with synchronous metastatic CRC and an unresected primary tumor who received oxaliplatin- or irinotecan-based, triple-drug chemotherapy (infusional fluorouracil, leucovorin, and oxaliplatin; bolus fluorouracil, leucovorin, and irinotecan; or fluorouracil, leucovorin, and irinotecan) with or without bevacizumab as their initial treatment. The incidence of subsequent use of surgery, radiotherapy, and/or endoluminal stenting to manage primary tumor complications was recorded. RESULTS: Of 233 patients, 217 (93%) never required surgical palliation of their primary tumor. Sixteen patients (7%) required emergent surgery for primary tumor obstruction or perforation, 10 patients (4%) required nonoperative intervention (ie, stent or radiotherapy), and 213 (89%) never required any direct symptomatic management for their intact primary tumor. Of those 213 patients, 47 patients (20%) ultimately underwent elective colon resection at the time of metastasectomy, and eight patients (3%) underwent this resection during laparotomy for hepatic artery infusion pump placement. Use of bevacizumab, location of the primary tumor in the rectum, and metastatic disease burden were not associated with increased intervention rate. CONCLUSION: Most patients with synchronous, stage IV CRC who receive up-front modern combination chemotherapy never require palliative surgery for their intact primary tumor. These data support the use of chemotherapy, without routine prophylactic resection, as the appropriate standard practice for patients with neither obstructed nor hemorrhaging primary colorectal tumors in the setting of metastatic disease.

Feasibility of ex vivo FDG PET of the colon.

To facilitate future direct correlations between fluorine 18 fluorodeoxyglucose (FDG)-avid colonic lesions and immunohistochemical assay findings, the authors tested the feasibility of ex vivo FDG positron emission tomography (PET) of the colon resected from humans. In this institutional review board-approved, HIPAA-compliant study, the authors, after obtaining informed patient consent, injected FDG intraoperatively in five patients with neoplasms and imaged their resected colons approximately 3 hours later. The colon could be imaged during this fairly limited time interval, and polyps and cancers could be identified. No biologic tissue degradation occurred. The authors concluded that ex vivo FDG PET of the colon is feasible and, when combined with careful histologic and immunohistochemical analyses, may serve as a research tool to determine the mechanisms of the normal colonic uptake of FDG and the localization of FDG in polyps and cancers.