Recurrence and Survival after Minimally Invasive and Open Esophagectomy for Esophageal Cancer - A Post Hoc Analysis of the Ensure Study.

OBJECTIVE: The aim of this study was to determine the impact of operative approach (open [OE], hybrid [HMIE] and total minimally invasive esophagectomy [TMIE]) on operative and oncologic outcomes for patients treated with curative intent for esophageal and junctional cancer. SUMMARY BACKGROUND DATA: The optimum oncologic surgical approach to esophageal and junctional cancer is unclear. METHODS: This secondary analysis of the European multicenter ENSURE study includes patients undergoing curative-intent esophagectomy for cancer between 2009-2015 across 20 high-volume centers. Primary endpoints were disease-free survival (DFS) and the incidence and location of disease recurrence. Secondary endpoints included among others R0 resection rate, lymph node yield and overall survival (OS). RESULTS: In total, 3,199 patients were included. Of these, 55% underwent OE, 17% HMIE and 29% TMIE. DFS was independently increased post TMIE (HR 0.86 [95% CI 0.76-0.98], P=0.022) compared with OE. Multivariable regression demonstrated no difference in absolute locoregional recurrence risk according to operative approach (HMIE vs. OE OR 0.79, P=0.257, TMIE vs. OE OR 0.84, P=0.243). The probability of systemic recurrence was independently increased post HMIE (OR 2.07, P=0.031), but not TMIE (OR 0.86, P=0.508). R0 resection rates (P=0.005) and nodal yield (P<0.001) were independently increased after TMIE, but not HMIE (P=0.424; P=0.512) compared with OE. OS was independently improved following both HMIE (HR 0.79, P=0.009) and TMIE (HR 0.82, P=0.003) as compared with OE. CONCLUSION: In this European multicenter study, TMIE was associated with improved surgical quality and DFS, while both TMIE and HMIE were associated with improved OS as compared with OE for esophageal cancer.

History and evidence for state of the art of lymphadenectomy in esophageal cancer surgery.

The current curative multimodal treatment of advanced esophageal cancers consists of neoadjuvant or perioperative chemo(radio)therapy followed by a radical surgical resection of the primary tumor and a 2- or 3-field lymphadenectomy. One of the most important predictors of long-term survival of esophageal cancer patients is lymph node involvement. The distribution pattern of lymph node metastases in esophageal cancer is unpredictable and depends on the primary tumor location, histology, T-stage and application of neoadjuvant or perioperative treatment. The optimal extent of the lymphadenectomy remains controversial; there is no global consensus on this topic yet. Some surgeons advocate an aggressive and extended lymph node dissection to remove occult metastatic disease, to optimize oncological outcomes. Others promote a more restricted lymphadenectomy, since the benefit of an extended lymphadenectomy, especially after neoadjuvant chemoradiotherapy, has not been clearly demonstrated, and morbidity may be reduced. In this review, we describe the development of lymphadenectomy, followed by a summary of current evidence for lymphadenectomy in esophageal cancer treatment.

The effect of anastomotic leakage on the incidence of recurrence after tri-modality therapy for esophageal adenocarcinomas.

BACKGROUND: Neoadjuvant chemoradiotherapy (nCRTx) reduces the incidence of recurrence, while anastomotic leakage has shown increase the risk of recurrence. The primary objective of this retrospective study was to investigate the incidence and pattern of recurrence and secondary median recurrence-free interval and post-recurrence survival in patients with and without anastomotic leakage after multimodal therapy for esophageal adenocarcinoma. METHODS: Patients with recurrence after multimodal therapy between 2010 and 2018 were included. RESULTS: Six hundred and eighteen patients were included, 91 (14.7%) had leakage and 278 (45.0%) recurrence. Patients with leakage did not develop recurrence more often (48.4%) than those without (44.4%, [p = 0.484]). Recurrence-free interval for patients with (n = 44) and without leakage (n = 234) was 39 and 52 weeks, respectively (p = 0.049). Post-recurrence survival was 11 and 16 weeks, respectively (p = 0.702). Specified by recurrence site, post-recurrence survival for loco-regional recurrences was 27 versus 33 weeks (p = 0.387) for patients with and without leakage, for distant 9 versus 13 (p = 0.999), and for combined 11 versus 18 weeks (p = 0.492). CONCLUSION AND DISCUSSION: No higher incidence of recurrent disease was observed in patients with anastomotic leakage, however it is associated with a shorter recurrence-free interval. This could have implications for surveillance, as early detection of recurrent disease could influence therapeutic options.

Osteoarthritis is associated with symptoms of common mental disorders among former elite athletes.

PURPOSE: The primary aim was to establish the association between osteoarthritis (OA) and the occurrence and comorbidity of symptoms of common mental disorders (CMD: distress, anxiety/depression, sleep disturbance, adverse alcohol use) in a group of former elite athletes (rugby, football, ice hockey, Gaelic sports and cricket). A secondary aim was to explore this association in the subgroups of sports. METHODS: Cross-sectional analysis was performed on the baseline questionnaires from five prospective cohort studies conducted between April 2014 and January 2016 in former elite athletes of rugby, football, ice hockey, Gaelic sports and cricket. The presence of OA (diagnosed by a medical professional) was examined with a single question, and symptoms of CMD were evaluated through multiple validated questionnaires (4DSQ, GHQ-12, PROMIS, AUDIT-C). RESULTS: There was a significant association between OA and symptoms of distress (OR 1.7, 95 % CI 1.2-2.6), sleep disturbance (OR 1.6, 95 % CI 1.1-2.3), adverse alcohol use (OR 1.8, 95 % CI 1.2-2.6) and a comorbidity of symptoms of CMD (OR 1.5, 95 % CI 1.0-2.1) in former elite athletes. CONCLUSION: OA might be a risk factor for developing symptoms of CMD in former elite athletes. The clinical relevance of this study is that an interdisciplinary approach to the clinical care and support of former elite athletes after their careers is advocated as the interaction between the physical and mental health issues occurring on the long term is complex. Monitoring OA among former elite athletes should be empowered while strategies to prevent symptoms worsening should be developed and implemented. The self-awareness, prevention and care of mental health problems that might occur after a professional sports career should also be addressed. LEVEL OF EVIDENCE: Level III.

External validation of a nomogram predicting conditional survival after tri-modality treatment of esophageal cancer.

BACKGROUND: A conditional survival nomogram was developed at a single high-volume center to predict 5-year overall survival for esophageal cancer patients after neoadjuvant chemoradiation and esophagectomy. The aim of this study was to externally validate the nomogram in a cohort of patients with esophageal adeno- or squamous cell carcinoma from another high-volume center. METHODS: Consecutive patients with an esophageal adeno- or squamous cell carcinoma who had undergone esophagectomy after being treated with preoperative chemoradiation between 2004 and 2016 were selected from a prospectively maintained institutional database. The level of discrimination for prediction of 5-year overall survival was quantified by Harrell's C statistic. Calibration of the conditional survival nomogram was visualized by plotting predicted 5-year survival and observed 5-year survival for comparison. RESULTS: Of the 296 patients examined, the probability of 5-year overall survival directly after surgery was 45% and increased to 51%, 68%, 78%, and 89% for each additional year survived. The predicted 5-year overall survival differed from the observed survival, with a calibration slope of 0.54, 0.55, 0.59, 0.73, and 1.09 directly after surgery and 1, 2, 3, and 4 years of survival after surgery, respectively. The nomogram's discrimination level for 5-year survival was moderate, with a C statistic of 0.65 compared to the 0.70 reported in the original study. CONCLUSION: The nomogram model has moderate predictive discrimination and accuracy, supporting its applicability to external cohorts to predict conditional survival. Further validation studies should empirically assess the model for predictive performance.

Radiation with concurrent radiosensitizing capecitabine tablets and single-dose mitomycin-C for muscle-invasive bladder cancer: A convenient alternative to 5-fluorouracil.

BACKGROUND AND PURPOSE: Chemoradiation (CRT) with mitomycin-C (MMC) and 5-fluorouracil (5-FU) has been shown to be superior to radiation alone in patients with muscle-invasive bladder cancer (MIBC). MMC/capecitabine is an effective replacement for 5FU as a radiosensitizer in other malignancies but has not been studied in bladder cancer. We evaluated the outcomes of MIBC patients treated with concurrent radiation and MMC/capecitabine. MATERIALS AND METHODS: MIBC patients treated with CRT (60 Gy in 5 weeks with single-dose MMC and capecitabine orally twice daily) between 2014 and 2019 were identified. Acute (<90 days) and late toxicity were registered. Endpoints were clinical complete response (cCR) in the bladder assessed by cystoscopy 3 months after CRT, locoregional disease-free survival (LDFS) and the number of salvage cystectomies. RESULTS: We analysed 71 cT2-4aN0-2 M0 MIBC patients (median age 70 years). Twenty-one (30%) patients received neoadjuvant or induction chemotherapy and 14 (20%) patients underwent a pelvic lymph node dissection prior to CRT. All patients received the full dose of planned radiation. Seven (10%) patients experienced acute grade 3-4 toxicities and 2 (3%) patients experienced late grade 3-4 toxicities. Sixty-eight (96%) patients achieved cCR. Eight (11%) patients had a bladder recurrence, of whom 3 (4%) required salvage cystectomy. Two-year LDFS was 79% (95% CI: 68-88) at a median follow-up of 23 (95% CI: 17-28) months. CONCLUSION: Radiation with concurrent MMC/capecitabine is a well-tolerated bladder-sparing treatment. Severe toxicity is infrequent and locoregional tumor control and short-term disease free survival appear similar to previous studies with MMC/5FU.

The mental wellbeing of current and retired professional cricketers: an observational prospective cohort study.

OBJECTIVE: Scientific knowledge about symptoms of common mental disorders in professional cricket is non-existent. Consequently, the aims of the study were to determine the prevalence and the 6 months incidence of symptoms of common mental disorders (CMD: distress, anxiety/depression, sleep disturbance, adverse alcohol use) among current and former professional cricketers and to explore the association of potential stressors (significant injury, surgery, adverse life events, career dissatisfaction) and CMD. METHODS: An observational prospective cohort study with a follow-up period of 6 months was conducted among current and former professional cricketers from South Africa. Using validated questionnaires to assess symptoms of common mental disorders as well as several stressors, an electronic questionnaire was set up and distributed by the South African Cricketers Association (SACA). RESULTS: A total of 116 participants enrolled at baseline (overall response rate of 33%) and 76 of those participants completed the 6 month follow-up (follow up rate of 66%). The prevalence of symptoms of CMD in current professional cricketers was 38% for distress, 38% for sleep disturbance, 37% for anxiety/depression and 26% for adverse alcohol use. Among former professional cricketers, baseline prevalence as was 26% for distress, 24% for anxiety/depression, 21% for sleep disturbance and 22% for adverse alcohol use. Career dissatisfaction led to an increased risk of distress, anxiety/depression and sleep disturbance in current professional cricketers. Surgeries and adverse life events led to an increase in reported symptoms of distress and anxiety/depression in current professional cricketers. CONCLUSIONS: It was concluded that symptoms of CMD are prevalent in both current and former professional cricketers and the association with surgery, adverse life events and cricket career dissatisfaction may provide some insight into possible mechanisms.