Summary Background Patients with locally advanced rectal cancer who achieve a pathological complete response to neoadjuvant chemoradiation have an improved prognosis. The need for surgery in these patients has been questioned, but the proportion of patients achieving a pathological complete response is small. We aimed to assess whether adding cycles of mFOLFOX6 between chemoradiation and surgery increased the proportion of patients achieving a pathological complete response. Methods We did a phase 2, non-randomised trial consisting of four sequential study groups of patients with stage II–III locally advanced rectal cancer at 17 institutions in the USA and Canada. All patients received chemoradiation (fluorouracil 225 mg/m2 per day by continuous infusion throughout radiotherapy, and 45.0 Gy in 25 fractions, 5 days per week for 5 weeks, followed by a minimum boost of 5.4 Gy). Patients in group 1 had total mesorectal excision 6–8 weeks after chemoradiation. Patients in groups 2–4 received two, four, or six cycles of mFOLFOX6, respectively, between chemoradiation and total mesorectal excision. Each cycle of mFOLFOX6 consisted of racemic leucovorin 200 mg/m2 or 400 mg/m2, according to the discretion of the treating investigator, oxaliplatin 85 mg/m2 in a 2-h infusion, bolus fluorouracil 400 mg/m2 on day 1, and a 46-h infusion of fluorouracil 2400 mg/m2. The primary endpoint was the proportion of patients who achieved a pathological complete response, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00335816. Findings Between March 24, 2004, and Nov 16, 2012, 292 patients were registered, 259 of whom (60 in group 1, 67 in group 2, 67 in group 3, and 65 in group 4) met criteria for analysis. 11 (18%, 95% CI 10–30) of 60 patients in group 1, 17 (25%, 16–37) of 67 in group 2, 20 (30%, 19–42) of 67 in group 3, and 25 (38%, 27–51) of 65 in group 4 achieved a pathological complete response (p=0.0036). Study group was independently associated with pathological complete response (group 4 compared with group 1 odds ratio 3.49, 95% CI 1.39–8.75; p=0.011). In group 2, two (3%) of 67 patients had grade 3 adverse events associated with the neoadjuvant administration of mFOLFOX6 and one (1%) had a grade 4 adverse event; in group 3, 12 (18%) of 67 patients had grade 3 adverse events; in group 4, 18 (28%) of 65 patients had grade 3 adverse events and five (8%) had grade 4 adverse events. The most common grade 3 or higher adverse events associated with the neoadjuvant administration of mFOLFOX6 across groups 2-4 were neutropenia (five in group 3 and six in group 4) and lymphopenia (three in group 3 and four in group 4). Across all study groups, 25 grade 3 or worse surgery-related complications occurred (ten in group 1, five in group 2, three in group 3, and seven in group 4); the most common were pelvic abscesses (seven patients) and anastomotic leaks (seven patients). Interpretation Delivery of mFOLFOX6 after chemoradiation and before total mesorectal excision has the potential to in...

PURPOSE Prospective data on the efficacy of a watch-and-wait strategy to achieve organ preservation in patients with locally advanced rectal cancer treated with total neoadjuvant therapy are limited. METHODS In this prospective, randomized phase II trial, we assessed the outcomes of 324 patients with stage II or III rectal adenocarcinoma treated with induction chemotherapy followed by chemoradiotherapy (INCT-CRT) or chemoradiotherapy followed by consolidation chemotherapy (CRT-CNCT) and either total mesorectal excision (TME) or watch-and-wait on the basis of tumor response. Patients in both groups received 4 months of infusional fluorouracil-leucovorin-oxaliplatin or capecitabine-oxaliplatin and 5,000 to 5,600 cGy of radiation combined with either continuous infusion fluorouracil or capecitabine during radiotherapy. The trial was designed as two stand-alone studies with disease-free survival (DFS) as the primary end point for both groups, with a comparison to a null hypothesis on the basis of historical data. The secondary end point was TME-free survival. RESULTS Median follow-up was 3 years. Three-year DFS was 76% (95% CI, 69 to 84) for the INCT-CRT group and 76% (95% CI, 69 to 83) for the CRT-CNCT group, in line with the 3-year DFS rate (75%) observed historically. Three-year TME-free survival was 41% (95% CI, 33 to 50) in the INCT-CRT group and 53% (95% CI, 45 to 62) in the CRT-CNCT group. No differences were found between groups in local recurrence-free survival, distant metastasis-free survival, or overall survival. Patients who underwent TME after restaging and patients who underwent TME after regrowth had similar DFS rates. CONCLUSION Organ preservation is achievable in half of the patients with rectal cancer treated with total neoadjuvant therapy, without an apparent detriment in survival, compared with historical controls treated with chemoradiotherapy, TME, and postoperative chemotherapy.

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Peri-operative SARS-CoV-2 infection increases postoperative mortality. The aim of this study was to determine the optimal duration of planned delay before surgery in patients who have had SARS-CoV-2 infection. This international, multicentre, prospective cohort study included patients undergoing elective or emergency surgery during October 2020. Surgical patients with pre-operative SARS-CoV-2 infection were compared with those without previous SARS-CoV-2 infection. The primary outcome measure was 30-day postoperative mortality. Logistic regression models were used to calculate adjusted 30-day mortality rates stratified by time from diagnosis of SARS-CoV-2 infection to surgery. Among 140,231 patients (116 countries), 3127 patients (2.2%) had a pre-operative SARS-CoV-2 diagnosis. Adjusted 30-day mortality in patients without SARS-CoV-2 infection was 1.5% (95%CI 1.4-1.5). In patients with a pre-operative SARS-CoV-2 diagnosis, mortality was increased in patients having surgery within 0-2 weeks, 3-4 weeks and 5-6 weeks of the diagnosis (odds ratio (95%CI) 4.1 (3.3-4.8), 3.9 (2.6-5.1) and 3.6 (2.0-5.2), respectively). Surgery performed ≥ 7 weeks after SARS-CoV-2 diagnosis was associated with a similar mortality risk to baseline (odds ratio (95%CI) 1.5 (0.9-2.1)). After a ≥ 7 week delay in undertaking surgery following SARS-CoV-2 infection, patients with ongoing symptoms had a higher mortality than patients whose symptoms had resolved or who had been asymptomatic (6.0% (95%CI 3.2-8.7) vs. 2.4% (95%CI 1.4-3.4) vs. 1.3% (95%CI 0.6-2.0), respectively). Where possible, surgery should be delayed for at least 7 weeks following SARS-CoV-2 infection. Patients with ongoing symptoms ≥ 7 weeks from diagnosis may benefit from further delay.

PURPOSE: This study was designed to estimate the prevalence of, and identify risk factors associated with, fecal incontinence in racially diverse females older than aged 40 years. METHODS: The Reproductive Risks for Incontinence Study at Kaiser is a population-based study of 2,109 randomly selected middle-aged and older females (average age, 56 years). Fecal incontinence, determined by self-report, was categorized by frequency. Females reported the level of bother of fecal incontinence and their general quality of life. Potential risk factors were assessed by self-report, interview, physical examination, and record review. Multivariate logistic regression analysis was used to determine the independent association between selected risk factors and the primary outcome of any reported fecal incontinence in the past year. RESULTS: Fecal incontinence in the past year was reported by 24 percent of females (3.4 percent monthly, 1.9 percent weekly, and 0.2 percent daily). Greater frequency of fecal incontinence was associated with decreased quality of life (Medical Outcome Short Form-36 Mental Component Scale score, P = 0.01), and increased bother (P < 0.001) with 45 percent of females with fecal incontinence in the past year and 100 percent of females with daily fecal incontinence reporting moderate or great bother. In multivariate analysis, the prevalence of fecal incontinence in the past year increased significantly [odds ratio per 5 kg/m 2 (95 percent confidence interval)] zwith obesity [1.2 (1.1-1.3)], chronic obstructive pulmonary disease [1.9 (1.3-2.9)], irritable bowel syndrome [2.4 (1.7-3.4)], urinary incontinence [2.1 (1.7-2.6)], and colectomy [1.9 (1.1-3.1)]. Latina females were less likely to report fecal incontinence than white females [0.6 (0.4-0.9)]. CONCLUSIONS: Fecal incontinence, a common problem for females, is associated with

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BACKGROUND: Indocyanine green fluoroscopy has been shown to improve anastomotic leak rates in early phase trials. OBJECTIVE:We hypothesized that the use of fluoroscopy to ensure anastomotic perfusion may decrease anastomotic leak after low anterior resection. DESIGN:We performed a 1:1 randomized controlled parallel study. Recruitment of 450 to 1000 patients was planned over 2 years. SETTINGS:This was a multicenter trial.

Constipation is a common problem and affects between 2% and 28% of the general population. It is thought to affect more women than men. The severity of constipation is variable and it can be an acute or chronic condition. Often, it requires frequent interventions that may produce mixed or even unsatisfactory results. Knowledge of potentially gender- and age-related differences in constipation would be useful to clinicians to help them identify high-risk patients. In addition, researchers might use this information to design both descriptive and intervention studies. This article reviews the evidence from the studies on gender and age differences in prevalence of constipation, gender differences in the prevalence and characteristics of constipation, and age differences in the prevalence and characteristics of constipation. The available literature suggests that the prevalence of constipation is consistently higher in women than in men. However, evidence of gender differences in the characteristics of constipation is inconsistent. Prevalence rates appear to increase gradually after the age of 50 years, with the largest increase after the age of 70 years. The literature is both sparse and inconsistent in its description of age differences in the characteristics of constipation. This lack of research is a significant issue given the magnitude of this problem in the older adult population. Research is needed on gender and age differences in the symptoms of constipation, and how covariates impact the prevalence and severity of constipation in the elderly.