Malate-aspartate shuttle promotes l-lactate oxidation in mitochondria.

Metabolism in cancer cells is rewired to generate sufficient energy equivalents and anabolic precursors to support high proliferative activity. Within the context of these competing drives aerobic glycolysis is inefficient for the cancer cellular energy economy. Therefore, many cancer types, including colon cancer, reprogram mitochondria-dependent processes to fulfill their elevated energy demands. Elevated glycolysis underlying the Warburg effect is an established signature of cancer metabolism. However, there are a growing number of studies that show that mitochondria remain highly oxidative under glycolytic conditions. We hypothesized that activities of glycolysis and oxidative phosphorylation are coordinated to maintain redox compartmentalization. We investigated the role of mitochondria-associated malate-aspartate and lactate shuttles in colon cancer cells as potential regulators that couple aerobic glycolysis and oxidative phosphorylation. We demonstrated that the malate-aspartate shuttle exerts control over NAD+ /NADH homeostasis to maintain activity of mitochondrial lactate dehydrogenase and to enable aerobic oxidation of glycolytic l-lactate in mitochondria. The elevated glycolysis in cancer cells is proposed to be one of the mechanisms acquired to accelerate oxidative phosphorylation.

How Soon Should Patients With Colon Cancer Undergo Definitive Resection?

BACKGROUND: Timing of surgery has been shown to affect outcomes in many forms of cancer, but definitive national data do not exist to determine the effect of time to surgery on survival in colon cancer. OBJECTIVE: This study aimed to determine whether a delay in definitive surgery in colon cancer significantly affects survival. DATA SOURCES: A retrospective cohort study using 2 independent population-based databases, The Surveillance, Epidemiology, and End Results Medicare-linked database and the National Cancer Database, was performed. STUDY SELECTION: All patients had American Joint Committee on Cancer stage 1 through 3 colon cancer. Patients were more than 18 years of age in the National Cancer Database cohort and older than 66 years of age in the Medicare cohort. Patients had a minimum of 3 years of follow-up. MAIN OUTCOME MEASURES: The main outcome was overall survival as a function of time between diagnosis and surgery in 4 intervals (1-2, 3-4, 5-6, >6 weeks). RESULTS: The Medicare cohort demonstrated an adjusted 5-year survival of 8% to 14% higher in patients with a surgical delay between 3 and 6 weeks, with significantly lower hazard ratios in that interval. The National Cancer Database cohort demonstrated an adjusted 5-year survival of 9% to 16% higher in patients with surgery 3 to 6 weeks after diagnosis, with comparatively similar improvements in survival hazard. LIMITATIONS: Because this was a retrospective study of administrative databases, with Medicare data limited to billing data, the causality of outcomes must be interpreted with caution. CONCLUSIONS: The ideal timing of definitive resection in colon cancer is between 3 and 6 weeks after initial diagnosis. All efforts should be made for patients to obtain definitive surgery within this interval to achieve a modest but significant improvement in overall survival. See Video Abstract at http://links.lww.com/DCR/B76. ¿CUÁNDO DEBEN SOMETERSE LOS PACIENTES CON CÁNCER DE COLON A UNA RESECCIÓN DEFINITIVA?: Se ha demostrado que el momento de la cirugía afecta los resultados en muchas formas de cáncer, pero no existen datos nacionales definitivos para determinar el efecto del tiempo hasta la cirugía en la supervivencia en el cáncer de colon.Determinar si un retraso en la cirugía definitiva en el cáncer de colon afecta significativamente la supervivencia.Un estudio de cohorte retrospectivo que utiliza dos bases de datos independientes basadas en la población; Se realizó la base de datos vinculada a la vigilancia, la epidemiología y los resultados finales y la base de datos nacional del cáncer.Pacientes con cáncer de colon en estadíos 1 a 3 del Comité Estadounidense Conjunto sobre el Cáncer. Los pacientes tenían más de 18 años en la cohorte de la National Cancer Database y más de 66 años en la cohorte de Medicare. Los pacientes tuvieron un mínimo de 3 años de seguimiento.El resultado principal fue la supervivencia general en función del tiempo entre el diagnóstico y la cirugía en 4 intervalos (1-2, 3-4, 5-6, y mas de 6 semanas).La cohorte de Medicare demostró una supervivencia ajustada de 5 años de 8 a 14% más en pacientes con un retraso quirúrgico entre 3 a 6 semanas, con razones de riesgo significativamente más bajas en ese intervalo. La cohorte de la National Cancer Database demostró una supervivencia ajustada a 5 años de 9 a 16% más en pacientes con cirugía de 3 a 6 semanas después del diagnóstico, con mejoras comparativamente similares en el riesgo de supervivencia.Dado que este fue un estudio retrospectivo de bases de datos administrativas, con datos de Medicare limitados a datos de facturación, la causalidad de los resultados debe interpretarse con precaución.El momento ideal para la resección definitiva en el cáncer de colon es entre tres y seis semanas después del diagnóstico inicial. Se deben hacer todos los esfuerzos para que los pacientes obtengan una cirugía definitiva dentro de este intervalo para lograr una mejora modesta pero significativa en la supervivencia general. Consulte Video Resumen en http://links.lww.com/DCR/B76.

Condyloma Acuminatum, Anal Intraepithelial Neoplasia, and Anal Cancer in the Setting of HIV: Do We Really Understand the Risk?

BACKGROUND: The gold standard for surveillance of patients with anal lesions is unclear. OBJECTIVE: The aim of this study was to stratify patients for risk of progression of disease and to determine appropriate intervals for surveillance of patients with anal disease. DESIGN: This was a retrospective chart review for patients treated for anal lesions between 2007 and 2014. Only patients with ≥1 year of follow-up from index evaluation, pathology, documented physical examination, and anoscopy findings were included for analysis. SETTINGS: The study was conducted at an urban university hospital. PATIENTS: HIV-positive patients with anal lesions treated with excision and fulguration were included. MAIN OUTCOME MEASURES: Recurrence of anal lesions, progression of disease, and progression to cancer were measured. RESULTS: Ninety-one patients met inclusion criteria. The mean age was 41.6 years, and mean follow-up was 38.6 months (range, 11.0-106.0 mo). On initial pathology, 8 patients (8.8%) had a diagnosis of condyloma acuminatum without dysplasia, 20 patients (22%) had anal intraepithelial neoplasia I, 32 (35.2%) had anal intraepithelial neoplasia II, and 31 (34.1%) had anal intraepithelial neoplasia III. Sixty-nine patients (75.8%) had repeat procedures. Seven (87.5%) of 8 patients with condyloma and 6 (30%) of 20 patients with anal intraepithelial neoplasia I progressed to high-grade lesions. Five (15.6%) of 32 patients progressed from anal intraepithelial neoplasia II to III, and 2 patients with anal intraepithelial neoplasia III (6.5%) developed squamous cell carcinoma (2.3% for the entire cohort). LIMITATIONS: This was a single institution study. High-resolution anoscopy was not used. CONCLUSIONS: All of the HIV-positive patients with condyloma or anal intraepithelial neoplasia, regardless of the presence of dysplasia, should be surveyed at equivalent 3-month time intervals, because their risk of progression of disease is high. Video Abstract at http://links.lww.com/DCR/A389.

Body mass index predicts operative time in elective colorectal procedures.

BACKGROUND: Obesity currently affects more than a third of the United States population and is associated with increased surgical complications. Compared to all other subspecialties, colorectal surgery is the most affected by the increasing trend in obese surgical patients. Operative time has been found to have the greatest impact on hospital costs and physician workload. This study was conducted to determine whether obesity has a direct impact on operative time in elective colorectal procedures using a high-powered, nationally representative patient sample. METHODS: A retrospective analysis was conducted on 45,362 patients who underwent open and laparoscopic ileocolic resections, partial colectomies, and low pelvic anastomoses using American College of Surgeons National Surgical Quality Improvement Program data from 2005-2009. Operative time was the main outcome variable, whereas body mass index (BMI) was the main independent variable. BMI was divided into three classes as follows: normal (<25), overweight and/or obese (25-35), and morbidly obese (>35). A univariate linear model was used to analyze the relationship while controlling for confounding factors such as demographics and preoperative conditions. Statistical significance was established at P ≤ 0.05. RESULTS: Morbidly obese patients were found to have longer operative times than did normal patients across each individual colorectal procedure (P < 0.001), ranging from a mean difference of 17.8 min for open ileocolic resections to 56.6 min for laparoscopic low pelvic anastomoses with colostomies. CONCLUSIONS: BMI, as an objective measure of obesity, is a direct, statistically significant independent predictor of operative time across elective colorectal procedures.

Impact of Clinician Linkage on Unequal Access to High-Volume Hospitals for Colorectal Cancer Surgery.

BACKGROUND: Understanding drivers of persistent surgical disparities remains an important area of cancer care delivery and policy. The degree to which clinician linkages contribute to disparities in access to quality colorectal cancer surgery is unknown. Using hospital surgical volume as a proxy for quality, the study team evaluated how clinician linkages impact access to colorectal cancer surgery at high-volume hospitals (HVHs). STUDY DESIGN: Maryland's Health Services Cost Review Commission was used to evaluate 6,909 patients who underwent colon or rectal cancer operations from 2013 to 2018. Two linkages based on patient sharing were examined separately for colon and rectal cancer surgery: (1) from primary care clinicians to specialists (gastroenterologist or medical oncologist) and (2) from specialists to surgeons (general or colorectal). A referral link was defined as 9 or more shared patients between 2 clinicians. Adjusted regression models examined associations between referral links and odds of receiving colon or rectal cancer operations at HVHs. RESULTS: The cohort included 5,645 colon and 1,264 rectal cancer patients across 52 hospitals. Every additional referral link between a primary care clinician and a specialist connected to a HVH was associated with a 12% and 14% increased likelihood of receiving colon (odds ratio [OR] 1.12, CI 1.07 to 1.17) and rectal (OR 1.14, CI 1.08 to 1.20]) cancer operations at a HVH, respectively. Every additional referral link between a specialist and a surgeon at a HVH was associated with at least a 25% increased likelihood of receiving colon (OR 1.28, CI 1.20 to 1.36) and rectal (OR 1.25, CI 1.15 to 1.36) cancer operation at a HVH. CONCLUSIONS: Patients of clinicians with linkages to HVHs are more likely to have their colorectal cancer operations at these hospitals. These findings suggest that policy interventions targeting clinician relationships are an important step in providing equitable surgical care.

Mitochondria membrane transformations in colon and prostate cancer and their biological implications.

Mitochondria have emerged as important determinants in cancer progression and malignancy. However, the role of mitochondrial membranes in cancer onset and progression has not been thoroughly investigated. This study compares the structural and functional properties of mitochondrial membranes in prostate and colon cancer cells in comparison to normal mitochondria, and possible therapeutic implications of these membrane changes. Specifically, isolation of cell mitochondria and preparation of inverted sub-mitochondrial particles (SMPs) illuminated significant cancer-induced modulations of membrane lipid compositions, fluidity, and activity of cytochrome c oxidase, one of the key mitochondrial enzymes. The experimental data further show that cancer-associated membrane transformations may account for mitochondria targeting by betulinic acid and resveratrol, known anti-cancer molecules. Overall, this study probes the relationship between cancer and mitochondrial membrane transformations, underlying a potential therapeutic significance for mitochondrial membrane targeting in cancer.

Mitochondrial responses to organelle-specific drug delivering nanoparticles composed of polypeptide and peptide complexes.

Aims: The mechanistic study of the drug carrier-target interactions of mitochondria-unique nanoparticles composed of polypeptide-peptide complexes (mPoP-NPs). Materials & methods: The isolated organelles were employed to address the direct effects of mPoP-NPs on dynamic structure and functional wellbeing of mitochondria. Mitochondria morphology, respiration, membrane potential, reactive oxygen species generation, were examined by confocal microscopy, flow cytometry and oxygraphy. Lonidamine-encapsulated formulation was assessed to evaluate the drug delivery capacity of the naive nanoparticles. Results: The mPoP-NPs do not alter mitochondria structure and performance upon docking to organelles, while successfully delivering drug that causes organelle dysfunction. Conclusion: The study gives insight into interactions of mPoP-NPs with mitochondria and provides substantial support for consideration of designed nanoparticles as biocompatible and efficient mitochondria-targeted platforms.

Reinstating Elective Surgeries in MedStar Health: A Roadmap for Healthcare Organizations.

Introduction: Coronavirus disease 2019 (COVID-19) infections have strained hospital resources worldwide. As a result, many facilities have suspended elective operations and ambulatory procedures. As the incidence of new cases of COVID-19 decreases, hospitals will need policies and algorithms to facilitate safe and orderly return of normal activities. We describe the recommendations of a task force established in a multi-institutional healthcare system for resumption of elective operative and ambulatory procedures applicable to all hospitals and service lines. Methods: MedStar Health created a multidisciplinary task force to develop guidelines for resumption of elective surgeries/procedures. The primary focus areas included the establishment of a governance structure at each healthcare facility, prioritization of elective cases, preoperative severe acute respiratory syndrome coronavirus 2 testing, and an assessment of the needs and availability of staff, personal protective equipment, and other essential resources. Results: Each hospital president was tasked with establishing a local perioperative leadership team answering directly to them and granted the authority to prioritize elective surgery and ambulatory procedures. An elective surgery algorithm was established using a simplified Medically Necessary Time Sensitive score, with multiple steps requiring a "go/no-go" assessment based on local resources. In addition, mandatory preoperative COVID testing policies were developed and operationalized. Conclusions: Even when the COVID pandemic has passed, hospitals and surgical centers will require COVID screening and testing, case prioritization, and supply chain management to provide care essential to the surgical patient while protecting their safety and that of staff. Our guidelines consider these factors and are applicable to both tertiary academic medical centers and smaller community facilities.

Cardiolipin mediates curcumin interactions with mitochondrial membranes.

Curcumin, the main molecular ingredient of the turmeric spice, has been reported to exhibit therapeutic properties for varied diseases and pathological conditions. While curcumin appears to trigger multiple signaling pathways, the precise mechanisms accounting for its therapeutic activity have not been deciphered. Here we show that curcumin exhibits significant interactions with cardiolipin (CL), a lipid exclusively residing in the mitochondrial membrane. Specifically, we found that curcumin affected the structures and dynamics of CL-containing biomimetic and biological mitochondrial membranes. Application of several biophysical techniques reveals the CL-promoted association and internalization of curcumin into lipid bilayers. In parallel, curcumin association with CL containing bilayers increased their fluidity and reduced lipid ordering. These findings suggest that membrane modifications mediated by CL interactions may play a role in the therapeutic functions of curcumin, and that the inner mitochondrial membrane in general might constitute a potential drug target.

Rectal procidentia: diagnosis and management.

Rectal prolapse or procidentia is a common condition with detrimental effects on continence and social function. One of the most devastating complications for patients suffering from this disorder is fecal incontinence. The psychologic trauma these patients experience can be debilitating. This article provides an overview of rectal procidentia, including a review of the symptomatic presentation, etiology, classification, diagnosis, and treatment.

Nursing home status is an independent risk factor for adverse 30-day postoperative outcomes after common, nonemergent inpatient procedures.

BACKGROUND: Nursing home residents undergoing surgery have a higher rate of postoperative adverse outcomes than nonnursing home patients. This study seeks to determine what contribution nursing home status makes to theses occurrences, independent of comorbid conditions. METHODS: Using the American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) database, the 30-day postoperative outcomes of the 5 commonest nonemergent inpatient procedures performed on nursing home residents were compared with those in nonnursing home residents using logistic regression analysis. RESULTS: Nursing home status was found to be an independent risk factor for septic complications in all procedures, for blood transfusion requirement after lower leg amputation, for pneumonia and stroke/cerebrovascular accident after thromboendarterectomy, and for mortality after partial colectomy with primary anastomosis. CONCLUSIONS: These data suggest that, in addition to serving as a surrogate indicator of health status and current morbidity, residence in a nursing home makes an independent contribution to adverse postoperative outcomes.

Incidentally discovered low-grade appendiceal mucinous neoplasm: a precursor to pseudomyxoma peritonei.

Appendiceal mucoceles (AMs) infrequently arise from an underlying malignancy. Treatment has progressed toward a less aggressive approach over time; they can be managed by appendectomy-only unless pathology reveals malignancy. The ultimate goal of management is to prevent AM rupture, avoiding the syndrome of pseudomyxoma peritonei.

Patient-specific risk factors are predictive for postoperative adverse events in colorectal surgery: an American College of Surgeons National Surgical Quality Improvement Program-based analysis.

BACKGROUND: Pay-for-performance measures incorporate surgical site infection rates into reimbursement algorithms without accounting for patient-specific risk factors predictive for surgical site infections and other adverse postoperative outcomes. METHODS: Using American College of Surgeons National Surgical Quality Improvement Program data of 67,445 colorectal patients, multivariable logistic regression was performed to determine independent risk factors associated with various measures of adverse postoperative outcomes. RESULTS: Notable patient-specific factors included (number of models containing predictor variable; range of odds ratios [ORs] from all models): American Society of Anesthesiologists class 3, 4, or 5 (7 of 7 models; OR 1.25 to 1.74), open procedures (7 of 7 models; OR .51 to 4.37), increased body mass index (6 of 7 models; OR 1.15 to 2.19), history of COPD (6 of 7 models; OR 1.19 to 1.64), smoking (6 of 7 models; OR 1.15 to 1.61), wound class 3 or 4 (6 of 7 models; OR 1.22 to 1.56), sepsis (6 of 7 models; OR 1.14 to 1.89), corticosteroid administration (5 of 7 models; OR 1.11 to 2.24), and operation duration more than 3 hours (5 of 7 models; OR 1.41 to 1.76). CONCLUSIONS: These findings may be used to pre-emptively identify colorectal surgery patients at increased risk of experiencing adverse outcomes.

Ischemic jejunal stricture following endovascular abdominal aortic aneurysm repair -- a case report.

Endograft repair has rapidly become an alternative to conventional open repair of abdominal aortic aneurysms. Various trials continue to show decreased morbidity when compared to open repair. However, as with any new procedure, complications specifically related to this technique are being described. Herein, we report a case of an isolated ischemic jejunal stricture presenting as a small-bowel obstruction secondary to cholesterol emboli following endograft repair of an abdominal aortic aneurysms.

Unique risks for mortality in patients with end-stage renal disease undergoing nonemergent colorectal surgery.

BACKGROUND: The aim of this study was to identify unique risk factors for mortality in patients with end-stage renal disease undergoing nonemergent colorectal surgery. METHODS: A multivariate logistic regression model predicting 30-day mortality was constructed for patients with end-stage renal disease undergoing nonemergent colorectal procedures. Data were obtained from the National Surgical Quality Improvement Program (2005-2010). RESULTS: Among the 394 patients analyzed, those with serum creatinine levels >7.5 mg/dL had .07 times the adjusted mortality risk of those with levels <3.5 mg/dL. For colorectal surgery patients, the average serum creatinine level was 5.52 ± 2.6 mg/dL, and mortality was 13% (n = 50). CONCLUSIONS: High serum creatinine was associated with a lower risk for mortality in patients with end-stage renal disease, even though creatinine is often considered a risk factor for surgery. These results show how variables from a patient-centered subpopulation can differ in meaning from the general population.

Optimizing single port surgery: a case report and review of technique in colon resection.

BACKGROUND: Minimally invasive colon surgery was first described in the early 1990s, decreasing the morbidity compared with open procedures. Recently, single port laparoscopy has emerged, with reports of applications to colon surgery. Although feasible, many new technical challenges exist. METHODS: An optimal operative technique for colon resection entirely through the umbilicus, using a robot and a GelPort is described. RESULTS: The robotic advantages of visualization and articulation minimize the disadvantages of single incision surgery. Programming the robotic arms in reverse decreases instrument clashing. In addition, the GelPort allows for trocar spacing and freedom of placement while providing a wound protector for specimen extraction. CONCLUSIONS: As single port surgery develops, disadvantages must be overcome. Using a combination of the robot and GelPort, these disadvantages are addressed and minimized.

Management of radiotherapy induced rectourethral fistula.

PURPOSE: An increasing number of men are being treated with BT or a combination of external beam radiation therapy and BT for localized prostate cancer. Although uncommon, the most severe complication following these procedures is RUF. We reviewed our recent experience with RUF following radiotherapy for prostate cancer to clarify treatment in these patients. MATERIALS AND METHODS: We recently treated 22 men with RUF following primary radiotherapy for adenocarcinoma of the prostate in 21 and adjuvant external beam radiation therapy following radical prostatectomy in 1. Time from the last radiation treatment to fistula presentation was 6 months to 20 years. RESULTS: Four patients underwent proctectomy with permanent fecal and urinary diversion. RUF repair in 5 patients was performed with preservation of fecal or urinary function. Six patients were candidates for reconstruction with preservation of urinary and rectal function, including 5 who underwent proctectomy, staged colo-anal pull-through and BMG repair of the urethral defect. The additional patient underwent primary closure of the rectum, BMG repair of the urethra and gracilis muscle interposition. Successful fistula closure was achieved in the 9 patients who underwent urethral reconstruction. All 8 candidates for rectal reconstruction showed radiological and clinical bowel integrity postoperatively with 2 awaiting final diverting stoma closure. CONCLUSIONS: With the increasing use of prostate BT the number of patients with severe rectal injury will likely continue to increase. Radiotherapy induced RUF carries significant morbidity and most patients are treated initially with fecal and urinary diversion. In properly selected patients good outcomes can be expected following repair using BMG for the urethral defect along with colo-anal pull-through or primary rectal repair and gracilis muscle interposition.

Positive microscopic margins alter outcome in lymph node-negative cholangiocarcinoma when resection is combined with adjuvant radiotherapy.

PURPOSE: The purpose of this study was to evaluate the prognostic significance of positive microscopic margins in hilar cholangiocarcinoma in patients treated with resection and adjuvant radiotherapy. MATERIALS AND METHODS: Between January 1983 and December 1997, 65 patients were definitively diagnosed with hilar cholangiocarcinoma and treated at our institution. Twenty-eight patients underwent curative resection. Of these patients, 23 received adjuvant radiotherapy with an average dose of 53 Gy (both external beam radiotherapy and low-dose rate brachytherapy). Portals included the preoperative primary tumor bed site with a 3- to 5-cm margin, the porta hepatis, and celiac lymph nodes. The patients with lymph node-negative pathologic specimens were reviewed, and an analysis of microscopic margins and subsequent impact on survival was determined with the Kaplan-Meier method and Wilcoxon test. RESULTS: There were 16 patients who met inclusion criteria. There was no perioperative mortality. Seven patients had negative margins and 9 patients had positive microscopic margins. Median follow up was 55 months, and median survival was 24.5 months for the entire group. Median and 5-year survival were 21.5 months and 18.4% in the margin-negative group and 26 months and 15% in patients with positive margins (P = 0.45). These survival differences were not statistically significant. DISCUSSION: Positive microscopic margins in lymph node-negative, resected hilar cholangiocarcinoma may not represent a negative prognostic factor when resection is combined with postoperative radiotherapy in this cohort. Further prospective, randomized studies are required to fully elucidate the benefits of adjuvant radiotherapy.

Longer time interval between completion of neoadjuvant chemoradiation and surgical resection does not improve downstaging of rectal carcinoma.

PURPOSE: An interval of six to eight weeks between completion of preoperative chemoradiation therapy and surgical resection of advanced rectal cancer has been described. Our purpose was to determine whether a longer time interval between completion of therapy and resection increases tumor downstaging and affects perioperative morbidity. METHODS: Forty patients with advanced adenocarcinoma of the rectum underwent preoperative chemoradiation on a prospective trial with irinotecan (50 mg/m2), 5-fluorouracil (225 mg/m2), and concomitant external-beam radiation (45-54 Gy) followed by complete surgical resection of the tumor with total mesorectal excision. The time interval between completion of chemoradiation and surgical resection ranged from 28 to 97 days. The patients were divided into two groups with 33 eligible patients: Group A (4-week to 8-week time interval; 28-56 days) and Group B (10-week to 14-week interval; 67-97 days). Tumor downstaging was compared between these two groups. The number of patients downstaged by at least one T stage, those downstaged by at least one N stage, those with pathologic complete responses, and those with only residual microscopic tumor foci were compared. Postoperative length of stay, estimated blood loss, perioperative morbidity, and sphincter-sparing procedures were also compared. Chi-squared tests and Student's t-test were calculated. RESULTS: Group A had 19 patients, and Group B had 14 patients. Patient demographics were comparable. Mean age was 52 years, and 70 percent of patients were male. There were no deaths. There were no statistical differences in perioperative morbidity, with three anastomotic leaks in Group A. Tumors were downstaged in 58 percent of patients in Group A and 43 percent of those in Group B (P = 0.61). Nodal downstaging occurred in 78 percent of Group A and 67 percent of Group B (P = 0.9). The pathologic complete response rate was 21 percent in Group A and 14 percent in Group B (P = 0.97), and a residual microfocus of tumor was found in 33 percent of patients in Group A and 42 percent of those in Group B (P = 0.90). These differences were not statistically significant. CONCLUSIONS: Perioperative morbidity is not affected by longer intervals. A longer interval between completion of neoadjuvant chemoradiation and surgical resection may not increase the tumor response rate of advanced rectal cancer in this cohort.