Luiz Felipe de Campos-Lobato

Predictive factors of pathologic complete response after neoadjuvant chemoradiation for rectal cancer.

Objective:This study evaluates factors associated with a pathologic complete response (pCR) after neoadjuvant chemoradiation for rectal cancer. Summary Background Data:Approximately 20% of rectal cancer patients undergoing neoadjuvant chemoradiation achieve pCR, which has been associated with decreased local recurrence and improved recurrence-free survival. Means of predicting pCR remain incompletely defined. Methods:A total of 306 consecutive patients with stage II or stage III rectal cancer who underwent neoadjuvant chemoradiation then surgery between 1997 and 2007 were identified from a single-institution. Sixty-four patients with concurrent inflammatory bowel disease, hereditary colorectal cancer, other malignancy, urgent surgery, incomplete chemoradiation, or insufficient data were excluded. All patients received neoadjuvant 5-FU-based chemotherapy and external beam radiation. Histologic response was categorized as pCR or not-pCR, which defined the 2 study cohorts. Variables were analyzed by univariate and multivariate analysis with pCR as the dependent variable. Fisher exact test, &khgr;2, Wilcoxon rank-sum, and logistic regression were used for analysis. P < 0.05 was considered statistically significant. Results:Of the total patients, 242 were studied, including 58 (24%) that achieved pCR. The 2 groups were statistically similar in terms of age, gender, body mass index, tumor differentiation, radiation dose, and pretreatment stage. On multivariate analysis, an interval ≥8 weeks between treatment completion and surgical resection was significantly associated with a higher rate of pCR, which correlated with decreased local recurrence and improved overall survival. Conclusion:Despite traditional beliefs that certain patient and tumor factors influence pCR, an extended interval between completion of neoadjuvant therapy and surgery was the single most important determinant in achieving a pCR.

Downstaging after chemoradiotherapy for locally advanced rectal cancer: is there more (tumor) than meets the eye?

PURPOSE: Preoperative chemoradiotherapy can lead to pathologic complete response of rectal cancer. This study was designed to determine the relationship between postchemoradiotherapy pathologic T stage (ypT stage) and nodal metastases and to evaluate whether pathologic complete response of the primary tumor results in sterilization of mesorectal lymph nodes. METHODS: Clinicopathological data from 1997 to 2007 of a prospectively maintained colorectal cancer database were examined. Inclusion criteria were patients with extraperitoneal rectal cancer who underwent preoperative chemoradiotherapy and subsequent radical resection. Statistical analysis was performed by use of Kruskall-Wallis and Wilcoxon rank-sum tests. RESULTS: Two hundred forty-two patients were identified (73.1% male, median age, 57 y (range, 36–85 y)). Data regarding preoperative chemoradiotherapy were available for 177 patients (73.1%). The median dose of radiotherapy was 5040 cGy (3060–6100 cGy). The mean preoperative radiotherapy dose and interval between chemoradiotherapy and surgery are similar when stratified by ypT stage (P = .55 and P = .72, respectively). Low anterior resection was performed in 174 patients (71.6%), and the remainder underwent abdominoperineal resection. A mural pathologic complete response was achieved in 62 patients (25.6%). In this pathologic complete-response group, positive lymph nodes were found in 2 patients (3.2%). The rate of metastatic lymph nodes increased as ypT stage increased (ypT1 = 11.1%, ypT2 = 29.2%, ypT3 = 37.3%). CONCLUSION: Patients with a mural pathologic complete response have a low rate of positive lymph nodes. These findings may have implications for the management strategies of these patients, including the use of local resection or a watch-and-wait policy. When the response to chemoradiotherapy is not complete, radical surgery should remain the treatment based on high rates of lymph node involvement.

Prone or lithotomy positioning during an abdominoperineal resection for rectal cancer results in comparable oncologic outcomes.

BACKGROUND: There is debate whether performing the perineal part of the abdominoperineal resection in a prone position in comparison with a lithotomy position optimizes circumferential resection margins and, subsequently, cancer outcomes. OBJECTIVE: The aim of this study was to compare outcomes of patients undergoing abdominoperineal in a prone vs a lithotomy position. DESIGN: A single-center, prospectively maintained colorectal cancer database was queried for patients with stages I to III rectal cancer undergoing abdominoperineal resection in a prone vs a lithotomy position from 1997 to 2007. Patients were compared with respect to demographics, tumor and treatment characteristics, perioperative morbidity, and oncologic outcomes. Oncologic outcomes were adjusted for age, ASA class, tumor stage, and use of adjuvant treatments. &khgr;2, Fisher exact probability test, Wilcoxon rank-sum test, Kaplan-Meier estimates, log-rank sum test, and Cox regression models were used for the analysis. P < .05 was considered significant. RESULTS: The query returned 168 patients (81 prone and 87 lithotomy), with a median age of 63 (interquartile range, 52–74) years and a median follow-up of 42 (interquartile range, 23–69) months. Prone and lithotomy patients were not statistically different regarding demographics, tumor stage, rates of R0 resection, number of harvested nodes, perioperative morbidity, follow-up time, and oncologic outcomes. CONCLUSIONS: Surgical positioning during the perineal part of the abdominoperineal resection does not affect perioperative morbidity or oncologic outcomes and should be left to the surgeons discretion.

Abdominoperineal resection does not decrease quality of life in patients with low rectal cancer

PURPOSE: Issues related to body image and a permanent stoma after abdominoperineal resection may decrease quality of life in rectal cancer patients. However, specific problems associated with a low anastomosis may similarly affect quality of life for patients undergoing low anterior resection. The aim of this study was to compare quality of life of low rectal cancer patients after undergoing abdominoperineal resection versus low anterior resection. METHODS: Demographics, tumor and treatment characteristics, and prospectively collected preoperative quality-of-life data for patients undergoing low anterior resection or abdominoperineal resection for low rectal cancer between 1995 and 2009 were compared. Quality of life collected at specific time intervals was compared for the two groups, adjusting for age, body mass index, use of chemoradiation, and 30 days postoperative complications. The short-form-36 questionnaire was used to determine quality of life. RESULTS: The query returned 153 patients (abdominoperineal resection  =  68, low anterior resection  =  85) with a median follow-up of 24 (3-64) mo. The after abdominoperineal resection group had a higher mean age (63 ± 12 vs. 54 ± 12, p < 0.001) and more American Society of Anesthesiologists classification 3/4 patients (65 percent vs. 43 percent, p  =  0.03) than low anterior resection. Other demographics, tumor stage, use of chemoradiation, overall postoperative complication rates, and quality-of-life follow-up time were not statistically different in both groups. Patients undergoing abdominoperineal resection had a lower baseline short-form-36 mental component score than those undergoing low anterior resection. However, 6 mo after surgery this difference was no longer statistically significant and essentially disappeared at 36 mo after surgery. CONCLUSION: Patients undergoing abdominoperineal resection for low rectal cancer have a similar long-term quality of life as those undergoing low anterior resection. These findings can help clinicians to better counsel patients with low rectal cancer who are being considered for abdominoperineal resection.

Enterocutaneous fistula associated with malignancy and prior radiation therapy.

Enterocutaneous fistula (ECF) associated with cancer or radiation injury increases the complexity of normal management. Factors such as timing of additional adjuvant therapy or palliative care, technical considerations for operating on irradiated bowel, poor wound healing, increased risk of additional ECF, and decreased likelihood of spontaneous ECF closure all need to be considered in this scenario. Here the authors focus specifically on the management of ECF associated with cancer and/or radiation-induced injury to the bowel.

Old Women Body Balance: Does the Pelvic Organ Prolapse Matter?

Pelvic organ prolapse (POP) is a common condition in older women. We have observed that patients with advanced POP complain of body imbalance. The purpose of this study was to investigate impact of advanced POP on older womens body balance. Thirty-eight consecutive women were selected. Body balance was assessed by stabilometric measures (SM) and the Berg Balance Scale (BBS). Groups, nonadvanced versus advanced POP, were statistically similar on the BBS and all SM, but median center of pressure displacement speed (COPd-speed) was P = .04. A univariate analysis did not confirm any association between advanced POP and increased COPd-speed. Advanced POP may have no impact on older womens body balance.

Response to Letter to the Editor: Neoadjuvant Therapy for Rectal Cancer: The Impact of Longer Interval Between Chemoradiation and Surgery

To the Editors: We thank Dr. Huerta for his kind words and thoughtful comments on our recent article. He brings forth several key issues that remain among the top challenges in treating rectal cancer. We agree that it would obviously be paramount to identify which patients would achieve a pathologic complete response (pCR), but unfortunately this is not currently possible. Indeed, our group and others are currently investigating possible genetic markers to potentially identify which patients are most likely to achieve pCR, but only the future will tell. As Dr. Huerta states, the interval of 8 weeks for analysis in this study was chosen from our previous work which identified that waiting at least 8 weeks was independently associated with a higher percentage of patients achieving pCR. This was a nonrandomized, retrospective study and the exact interval that would be most effective remains undefined. A welldesigned trial is necessary to accurately address this matter and an ongoing NIH-sponsored multicenter prospective trial is enrolling approximately 250 rectal cancer patients into one of five different treatment groups based on an increasing interval between completion of neoadjuvant therapy and surgery. The intervals being examined are 6, 12, 16, 20, and 24 weeks and the study is expected to complete enrollment within this year. Patients in the longer interval treatment arms will receive chemotherapy during the waiting period. Results of this trial will answer some of the critical issues regarding intervals between neoadjuvant chemoradiation and surgery.