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Introduction: Postoperative complications following major surgery have been shown to be associated with reduced health-related quality of life (HRQL), and severe complications may have profound negative effects. This study aimed to examine whether long-term HRQL differs with the occurrence and severity of complications in a European multicenter prospective dataset of patients following esophagectomy for cancer. Methods: Disease-free patients following esophagectomy for cancer between 2010 and 2016 from the LASER study were included. Patients completed the LASER, EORTC QLQ-C30 and EORTC QLQ-OG25 questionnaires >1 year following treatment. Long-term HRQL was compared between patients with and without postoperative complications, subgroup analysis was performed for severity of complications (no, minor [Clavien-Dindo I-II], severe [Clavien-Dindo ≥ III]), using univariable and multivariable regression. Results: 645 patients were included: 283 patients with no, 207 with minor and 155 with severe complications. Significantly more dyspnea (QLQ-C30) was reported by patients with compared to patients without complications (differenceinmeans 6.3). In subgroup analysis, patients with severe complications reported more dyspnea (difference in means 8.3) than patients with no complications. None of the differences were clinically relevant (difference in means ≥ 10 points). LASER-based low mood (OR2.3) was statistically different for minor versus severe complications. Conclusion: Comparable HRQL was found in patients with and without postoperative complications following esophagectomy for cancer, after a mean follow-up of 4.4 years. Furthermore, patients with different levels of severity of complications had comparable HRQL. The level of HRQL in esophageal cancer patients are more likely explained by the impact of the complex procedure of the esophagectomy itself.

To determine the impact of surveillance on recurrence pattern, treatment, survival and health-related quality-of-life (HRQL) following curative-intent resection for esophageal cancer.Although therapies for recurrent esophageal cancer may impact survival and HRQL, surveillance protocols after primary curative treatment are varied and inconsistent, reflecting a lack of evidence.European iNvestigation of SUrveillance after Resection for Esophageal cancer was an international multicenter study of consecutive patients undergoing surgery for esophageal and esophagogastric junction cancers (2009-2015) across 20 centers (NCT03461341). Intensive surveillance (IS) was defined as annual computed tomography for 3 years postoperatively. The primary outcome measure was overall survival (OS), secondary outcomes included treatment, disease-specific survival, recurrence pattern, and HRQL. Multivariable linear, logistic, and Cox proportional hazards regression analyses were performed.Four thousand six hundred eighty-two patients were studied (72.6% adenocarcinoma, 69.1% neoadjuvant therapy, 45.5% IS). At median followup 60 months, 47.5% developed recurrence, oligometastatic in 39%. IS was associated with reduced symptomatic recurrence (OR 0.17 [0.12-0.25]) and increased tumor-directed therapy (OR 2.09 [1.58-2.77]). After adjusting for confounders, no OS benefit was observed among all patients (HR 1.01 [0.89-1.13]), but OS was improved following IS for those who underwent surgery alone (HR 0.60 [0.47-0.78]) and those with lower pathological (y)pT stages (Tis-2, HR 0.72 [0.58-0.89]). IS was associated with greater anxiety ( P =0.016), but similar overall HRQL.IS was associated with improved oncologic outcome in select cohorts, specifically patients with early-stage disease at presentation or favorable pathological stage post neoadjuvant therapy. This may inform guideline development, and enhance shared decision-making, at a time when therapeutic options for recurrence are expanding.

Esophageal adenocarcinoma (EAC) is associated with visceral obesity (VO). Non-alcoholic fatty liver disease (NAFLD) is common within this phenotype; however, its incidence and clinical significance in EAC have not been studied.A total of 559 patients with hepatic stetatosis (HS) defined by unenhanced CT were enrolled. In a sub-study, in 140 consecutive patients a liver biopsy was taken intraoperatively to study HS and non-alcoholic steatohepatitis (NASH). Postoperative complications were defined as per the Esophageal Complications Consensus Group (ECCG). Liver biochemistry was measured peri-operatively, with an ALT 5 defined as acute liver injury (ALI). Mann-Whitney U test or Fisher's exact test was utilized and the Kaplan-Meier method for survival.42% (n = 234/559) of patients had CT-defined HS. HS was associated with VO in 56% of cases, metabolic syndrome (Met S) in 37% and type 2 diabetes in 25%, compared with 44, 21, and 15% in non-HS patients (p 0.01). Pathologic HS was present in 32% (45/140) and graded as mild, moderate, and severe in 73, 24, and 3%, respectively, with NASH reported in 16% and indefinite/borderline NASH in 42% of HS cases. Postoperative ALI was similar (p = 0.88) in both HS (10%) and non-HS cohorts (11%). Operative complication severity was similar in both cohorts. 5-yr survival was 53% (HS) vs 50% (p = 0.890).This study establishes for the first time the incidence and clinical impact of NAFLD in EAC patients undergoing surgery and highlights no major impact on oncologic outcomes, nor in the severity of complications.

Background Data on the long-term symptom burden in patients surviving oesophageal cancer surgery are scarce. The aim of this study was to identify the most prevalent symptoms and their interactions with health-related quality of life. Methods This was a cross-sectional cohort study of patients who underwent oesophageal cancer surgery in 20 European centres between 2010 and 2016. Patients had to be disease-free for at least 1 year. They were asked to complete a 28-symptom questionnaire at a single time point, at least 1 year after surgery. Principal component analysis was used to assess for clustering and association of symptoms. Risk factors associated with the development of severe symptoms were identified by multivariable logistic regression models. Results Of 1081 invited patients, 876 (81.0 per cent) responded. Symptoms in the preceding 6 months associated with previous surgery were experienced by 586 patients (66.9 per cent). The most common severe symptoms included reduced energy or activity tolerance (30.7 per cent), feeling of early fullness after eating (30.0 per cent), tiredness (28.7 per cent), and heartburn/acid or bile regurgitation (19.6 per cent). Clustering analysis showed that symptoms clustered into six domains: lethargy, musculoskeletal pain, dumping, lower gastrointestinal symptoms, regurgitation/reflux, and swallowing/conduit problems; the latter two were the most closely associated. Surgical approach, neoadjuvant therapy, patient age, and sex were factors associated with severe symptoms. Conclusion A long-term symptom burden is common after oesophageal cancer surgery.

Oncotype DX™ (ODX) score estimates prognosis and predicts breast cancer recurrence. It also individualizes patient adjuvant chemotherapy prescription in breast cancer. This assay relies on genetic and molecular markers; the clinicopathological phenotype of which are tested routinely. The aim of this study was determine whether clinicopathological and immunohistochemical information predicts ODX recurrence score (RS). Secondly, to assess the impact on adjuvant chemotherapy (AC) and oncological outcome of ODX testing in patients in a European tertiary referral center. Estrogen receptor positive (ER+), human epidermal growth factor receptor-2 negative (HER2-), lymph node negative (LN-), and female breast cancer patients with ODX testing performed between 2007 and 2015 were categorized into low- (11), intermediate- (11-25), and high-risk (25) groups. Clinicopathological and immunohistochemical correlates of RS were determined. Predictors of RS were assessed using binary logistic regression. Oncological outcome was assessed using Kaplan-Meier and Cox regression analyses. ODX was performed in 400 consecutive ER+LN- patients. Median follow-up was 74.1 months (3.0-144.4). Low grade (odds ratio [OR]:2.39; 95% confidence interval [CI]:1.04-5.51, p = 0.041) independently predicted low ODX, while high grade (OR:2.04; 95% CI: 1.19-3.49, p = 0.009) and reduced progesterone receptor (PgR) expression (OR: 2.57, 95% CI: 1.42-4.65, p = 0.002) independently predicted high ODX. Omission of AC in intermediate- (p = 0.159) and high-risk (p = 0.702) groups did not negatively impact survival. In conclusion, tumor grade independently predicts low and high RS, while PgR negativity predicts high RS. ODX reduced AC prescription without compromising oncological outcome.

Purpose: Post-operative urinary retention (POUR) is a well-recognised complication of inguinal hernia repair (IHR). The magnitude of the problem is unclear, and contradictory evidence surrounds postulated risk factors. POUR risks patient distress, catheter-complications and a financial and logistical burden to services. Separately, in the field of IHR, there has been a lack of research into patients’ perceptions of surgical ‘success’. Our aim is to perform a two-phase, multi-centre prospective study to: Assess the rate, risk factors and impact related to POUR post IH repair. Develop and validate a patient reported outcome measure (PROM) for inguinal hernia repair. Methods: RETAINER I: We propose a 24-week prospective study with voluntary international participation in 4 week blocks. All patients undergoing elective IH repair (minimally-invasive/open) will be eligible. Standardised data collection will include patient and perioperative factors. Primary outcome will be development of POUR, defined as the need for insertion of a urinary catheter as determined by the treating clinician. Secondary outcomes will be identification of factors predisposing to POUR and the impact of POUR. RETAINER II: A patient reported outcome measure will be developed using representative patient focus groups for item generation, from which an initial questionnaire will be developed and piloted. Validity, reliability, sensitivity and reproducibility will be assessed using the QQ-10 and standard psychometric methodology. Conclusions: Using an international multicentre collaborative approach will produce the necessary volume of patients, whilst capturing inter-centre variability, to accurately reflect POUR rates and allow analysis of risk factors. This patient pool will provide an excellent opportunity to develop a PROM using appropriate qualitative methodology. Highlights: RETAINER I & II Protocols RETAINER (RETention of urine After INguinal hernia Elective Repair) I is a prospective, multicentre, international observational study. RETAINER I aims to explore the incidence of and risk factors for urinary retention following elective inguinal hernia repair. Urinary retention following inguinal hernia repair has a marked impact on patients and creates a significant financial and logistical burden for hospital services. RETAINER II is a prospective, qualitative study, recruiting patients to guide the creation of a patient-reported outcome measure (PROM) for elective inguinal hernia repair.

Background Recurrence-free patients after esophageal cancer surgery face long-term nutritional consequences, occurring in the context of an exaggerated postprandial gut hormone response. Acute gut hormone suppression influences brain reward signaling and eating behavior. This study aimed to suppress gut hormone secretion and characterize reward responses and eating behavior among postesophagectomy patients with unintentional weight loss. Methods This pilot study prospectively studied postoperative patients with 10% or greater body weight loss (BWL) beyond 1 year who were candidates for clinical treatment with long-acting octreotide (LAR). Before and after 4 weeks of treatment, gut hormone secretion, food cue reactivity (functional magnetic resonance imaging), eating motivation (progressive ratio task), ad libitum food intake, body composition, and symptom burden were assessed. Results Eight patients (7 male, age: mean ± SD 62.8 ± 9.4 years, postoperative BWL: 15.5 ± 5.8%) participated. Octreotide LAR did not significantly suppress total postprandial plasma glucagon-like peptide-1 response at 4 weeks (P = .08). Postprandial symptom burden improved after treatment (Sigstad score median [range]: 12 [2-28] vs 8 [3-18], P = .04) but weight remained stable (pre: 68.6 ± 12.8 kg vs post: 69.2 ± 13.4 kg, P = .13). There was no significant change in brain reward system responses, during evaluation of high-energy or low-energy food pictures, nor their appeal rating. Moreover, treatment did not alter motivation to eat (P = .41) nor ad libitum food intake(P = .46). Conclusion The protocol used made it feasible to characterize the gut-brain axis and eating behavior in this cohort. Inadequate suppression of gut hormone responses 4 weeks after octreotide LAR administration may explain the lack of gut-brain pathway alterations. A higher dose or shorter interdose interval may be required to optimize the intervention.

OBJECTIVE The aim of this study was to propose and test a novel adverse pathology classification in AEG. BACKGROUND Recent scientific advances show genomic and molecular concordance across all AEG types, suggesting a rationale for a biologic classification. We tested a 3-dimension adverse pathology classification across the entire junction and per Siewert anatomic subtype. METHODS Of 1625 patients with AEG, 650 underwent radical surgery, 55% post-neoadjuvant therapy (NeoT). Adverse features defined a priori were poor differentiation (PD), lymphatic invasion (LI), vascular invasion (VI), and perineural invasion (PN), with 3 groupings: 0 (no adverse feature), 1 to 2, and 3 to 4. Multivariable logistic and Cox proportional hazards regression were applied. RESULTS For adverse pathology, 31%, 46%, and 23% had 0, 1 to 2, and 3 to 4, respectively. Fifty percent of cases were AEG I, 25% AEG II, and 25% AEG III. Median survival was not reached, 49 and 17 months for 0, 1 to 2, and 3 to 4 adverse pathology, respectively (P < 0.001), and 76, 51, and 34 months for AEG I, II, and III, respectively (P < 0.001); AEG I was significantly (P< 0.001) associated with lower c (y)pT and c (y)pN stages, and LI, VI, PN, and PD (poor vs other). The pathology model was significant for survival along with (y)pT and (y)pN, and predicted response to chemotherapy and chemoradiation irrespective of anatomic subtype (P < 0.001). CONCLUSION A novel classification using standard pathology as proxy for poor biology is associated with survival and response to therapy. This effect is observed across the entire AEG spectrum, highlighting how biology should be aligned with anatomy in the modern paradigm of AEG management and design of clinical trials.

The uptake of robotic surgery is rapidly increasing worldwide across surgical specialties. However, there is currently a much higher use of robotic surgery in the United States of America (USA) compared to the United Kingdom (UK) and Ireland. Reduced exposure to robotic surgery in training may lead to longer learning curves and worse patient outcomes. We aimed to identify whether any difference exists in exposure to robotic surgery during general surgical training between trainees in the USA, UK and Ireland. Over a 15-week period from September 2021, a survey was distributed through the professional networks of the research team. Participants were USA, UK or Irish trainees who were part of a formal general surgical training curriculum. 116 survey responses were received. US trainees (n = 34) had all had robotic simulator experience, compared to only 37.93% of UK (n = 58) and 75.00% of Irish (n = 24) trainees (p 0.00001). 91.18% of US trainees had performed 15 or more cases as the console surgeon, compared to only 3.44% of UK and 16.67% of Irish trainees (p 0.00001). Fifty UK trainees (86.21%) and 22 Irish trainees (91.67%) compared to 12 US trainees (35.29%) do not think they have had adequate robotics training (p 0.00001). Surgical trainees in the USA have had significantly more exposure to training in robotic surgery than their UK and Irish counterparts.

The attenuation of diabetic kidney disease (DKD) by metabolic surgery is enhanced by pharmacotherapy promoting renal fatty acid oxidation (FAO). Using the Zucker Diabetic Fatty and Zucker Diabetic Sprague Dawley rat models of DKD, we conducted studies to determine if these effects could be replicated with a non-invasive bariatric mimetic intervention. Metabolic control and renal injury were compared in rats undergoing a dietary restriction plus medical therapy protocol (DMT; fenofibrate, liraglutide, metformin, ramipril, and rosuvastatin) and ad libitum-fed controls. The global renal cortical transcriptome and urinary 1H-NMR metabolomic profiles were also compared. Kidney cell type-specific and medication-specific transcriptomic responses were explored through in silico deconvolution. Transcriptomic and metabolomic correlates of improvements in kidney structure were defined using a molecular morphometric approach. The DMT protocol led to ∼20% weight loss, normalized metabolic parameters and was associated with reductions in indices of glomerular and proximal tubular injury. The transcriptomic response to DMT was dominated by changes in fenofibrate- and peroxisome proliferator-activated receptor-α (PPARα)-governed peroxisomal and mitochondrial FAO transcripts localizing to the proximal tubule. DMT induced urinary excretion of PPARα-regulated metabolites involved in nicotinamide metabolism and reversed DKD-associated changes in the urinary excretion of tricarboxylic acid (TCA) cycle intermediates. FAO transcripts and urinary nicotinamide and TCA cycle metabolites were moderately to strongly correlated with improvements in glomerular and proximal tubular injury. Weight loss plus pharmacological PPARα agonism is a promising means of attenuating DKD.

Objective To identify the most prevalent symptoms and those with greatest impact upon health-related quality of life (HRQOL) among esophageal cancer survivors. Background Long-term symptom burden after esophagectomy, and associations with HRQOL, are poorly understood. Patients and methods Between 2010 and 2016, patients from 20 European Centers who underwent esophageal cancer surgery, and were disease-free at least 1 year postoperatively were asked to complete LASER, EORTC-QLQ-C30, and QLQ-OG25 questionnaires. Specific symptom questionnaire items that were associated with poor HRQOL as identified by EORTC QLQ-C30 and QLQ-OG25 were identified by multivariable regression analysis and combined to form a tool. Results A total of 876 of 1081 invited patients responded to the questionnaire, giving a response rate of 81%. Of these, 66.9% stated in the last 6 months they had symptoms associated with their esophagectomy. Ongoing weight loss was reported by 10.4% of patients, and only 13.8% returned to work with the same activities.Three LASER symptoms were correlated with poor HRQOL on multivariable analysis; pain on scars on chest (odds ratio (OR) 1.27; 95% CI 0.97-1.65), low mood (OR 1.42; 95% CI 1.15-1.77) and reduced energy or activity tolerance (OR 1.37; 95% CI 1.18-1.59). The areas under the curves for the development and validation datasets were 0.81 ± 0.02 and 0.82 ± 0.09 respectively. Conclusion Two-thirds of patients experience significant symptoms more than 1 year after surgery. The 3 key symptoms associated with poor HRQOL identified in this study should be further validated, and could be used in clinical practice to identify patients who require increased support.

Background Nutritional optimisation is an essential component of prehabilitation and enhanced recovery for patients with oesophageal and gastric cancer, but may be associated with increased burden of inpatient care. The aim of this study was to determine risk factors associated with complications and unplanned hospital attendance among patients treated with home enteral nutrition. Methods Consecutive patients with oesophageal or gastric cancer commencing home enteral nutrition from March 2020-June 2021 were prospectively studied. The primary outcome measure was the incidence of complications associated with home enteral feeding requiring unplanned hospital attendance. Univariable and multivariable linear and logistic regression were used to determine factors independently associated with enteral feeding associated morbidity and healthcare utilisation. Results 70 patients were studied (27% pre neoadjuvant therapy, 63% postoperative; 19% gastrostomy, 81% jejunostomy). Tube complications requiring unplanned hospital attendance occurred in 33% of patients (25% gastrostomy, 38% jejunostomy, P = 0.405), most commonly dislodgement (15%), fixation problem (13%), and blockage (6%). Small bowel obstruction was rare (1.4%). Inpatient length of stay (LOS) following feeding tube placement and training was 5.1±2.4 days (gastrostomy: 5.5±2.7, jejunostomy: 4.4±1.9 days, P = 0.074). 17 unplanned hospital visits among nine patients (13.0%) occurred with a cumulative LOS of 71 inpatient days. On multivariable analysis patients undergoing neoadjuvant therapy were at the greatest risk of overall enteral feeding tube morbidity (OR19.34 [3.29–113.56], P = 0.001), dislodgement (OR19.09 [2.35-155.11], P = 0.006) and unplanned hospital attendance (P Conclusions Unplanned hospital attendance is common among patients undergoing supplemental home enteral nutrition during treatment for oesophagogastric cancer. Fixation problems and dislodgement account for the majority of presentations, and are more common among older patients and those undergoing neoadjuvant therapy. Pragmatic strategies to optimise tube fixation and minimise the need for unplanned hospital visits among patients receiving home enteral nutrition are urgently needed.

Introduction An arteriovenous malformation (AVM) is defined as an abnormal connection between arteries and veins, bypassing the capillary system. AVM of the breast is a rare clinical entity, with limited evidence to guide management. We present the case of a congenital AVM of the breast in an otherwise healthy woman, with an interesting presenting complaint. Case Description A 38-year-old female presented with a ‘buzzing’ sensation and mastalgia in her left breast. Examination revealed a visible pulsatile linear abnormality with a bruit on auscultation. Duplex ultrasonography demonstrated mixing of the arterial and venous flow, consistent with an AVM. Operative management entailed ultrasound guided identification, ligation and excision of all aneurysmal segments. Histopathologic evaluation demonstrated an AVM with no malignant features. At one year postoperatively, the patient reported complete symptom resolution. Literature review identified nine case reports, including two cases of congenital breast AVM, both treated surgically. Seven cases of iatrogenic AVM were identified, with diagnosis based on duplex ultrasonography and management by surgical ligation in all except one, which resolved spontaneously. Conclusions ongenital AVM of the breast is a rare clinical entity. Diagnosis can be established using duplex ultrasonography, while CT and MRI may be useful for preoperative planning. Endovascular management alone is associated with high recurrence rates and surgical excision is the favoured approach where technically feasible without major aesthetic or functional compromise.

The ECCG developed a standardized platform for reporting operative complications, with consensus definitions, and DUCA adopted these definitions and have reported a comparison against these benchmarks. The aim of this study was to report five year complications data using the standardized definitions of the Esophageal Complications Consensus Group (ECCG), and to compare with published ECCG benchmark studies from the collaborative group and from the Dutch Upper Gastrointestinal Cancer Audit (DUCA). Methods All patients undergoing multimodal therapy or surgery with curative intent from 2014 to 2018 inclusive were studied. All data were recorded prospectively and maintained internally as well as entered onto a secure online database (Esodata.org) from 2015. Statistical analysis was performed using SPSS® (version 18.0). Results 219 patients (mean age 67; 77% male) underwent open resection, 66.6% via transthoracic en bloc resection. 30-day and 90-day mortality were 0.0 and 0.9%, respectively. The anastomotic leak rate was 5.4%, and chyle leak 5.4%. Pneumonia was recorded in 18.2%, respiratory failure 10.9%, and ARDS in 2.7%. Atrial dysrhythmia occurred in 22.8%, recurrent nerve injury 3.1%, and delirium in 5.0%. Compared with both ECCG and DUCA, where MIE constituted 47% and 86% of surgical approaches, respectively, overall complications were similar in this open series, as was complications severity, however anastomotic leak rate were several-fold less, and mortality rates were lower. Conclusion In this unselected consecutive series and comparative audit with benchmark averages from the ECCG and DUCA publication, a low mortality and anastomotic leak rate were the key differential findings. Although not risk-stratified or directly matched, the severity of complications from this ‘open’ series is consistent with series containing large numbers of total or hybrid MIE, highlighting a need to adhere to these strictly defined definitions in further prospective research and randomized studies.

BackgroundThe Rehabilitation Strategies Following Esophagogastric cancer (ReStOre) randomized control trial demonstrated a significant improvement in cardiorespiratory fitness of esophagogastric cancer survivors. This follow-up, exploratory study analyzed the biological effect of exercise intervention on levels of 55 serum proteins, encompassing mediators of angiogenesis, inflammation, and vascular injury, from participants on the ReStOre trial.MethodsPatients >6 months disease free from esophagogastric cancer were randomized to usual care or the 12-week ReStOre program (exercise training, dietary counselling, and multidisciplinary education). Serum was collected at baseline (T0), post-intervention (T1), and at 3-month follow up (T2). Serum biomarkers were quantified by enzyme-linked immunosorbent assay (ELISA).ResultsThirty-seven patients participated in this study; 17 in the control arm and 20 in the intervention arm. Exercise intervention resulted in significant alterations in the level of expression of serum IP-10 (mean difference (MD): 38.02 (95% CI: 0.69 to 75.35)), IL-27 (MD: 249.48 (95% CI: 22.43 to 476.53)), and the vascular injury biomarkers, ICAM-1 (MD: 1.05 (95% CI: 1.07 to 1.66)), and VCAM-1 (MD: 1.51 (95% CI: 1.04 to 2.14)) at T1. A significant increase in eotaxin-3 (MD: 2.59 (95% CI: 0.23 to 4.96)), IL-15 (MD: 0.27 (95% CI: 0 to 0.54)) and decrease in bFGF (MD: 1.62 (95% CI: -2.99 to 0.26)) expression was observed between control and intervention cohorts at T2 (pConclusionsExercise intervention significantly altered the expression of a number of serum biomarkers in disease-free patients who had prior treatment for esophagogastric cancer.ImpactExercise rehabilitation causes a significant biological effect on serum biomarkers in esophagogastric cancer survivors.Clinical Trial RegistrationClinicalTrials.gov (NCT03314311).

Although established and emerging therapies for recurrent esophageal cancer (EC) may impact on survival and health related quality of life (HR-QL), surveillance protocols after the primary curative treatment of EC are varied and inconsistent, reflecting a limited evidence-base to guide an optimum approach. Specifically, whether advantages exist for an intensive surveillance protocol is unknown and was the focus of this study. Methods ENSURE was an international multicentre observational study of consecutive patients undergoing surgery with curative intent for esophageal and junctional cancers (2009–2015) across 20 European and North American centers (NCT03461341). Intensive surveillance (IS) was defined as routine annual CT/PET-CT during the first three postoperative years, and compared with standard surveillance (SS) with investigation as clinically indicated. The primary outcome measure was overall survival (OS), secondary outcomes included treatment, disease-specific survival (DSS), disease-free survival (DFS), recurrence pattern, and HR-QL. Multivariable linear, logistic and Cox proportional hazards regression analyses were performed to determine the independent impact of surveillance on oncologic outcomes and HR-QL. Results 4,682 patients were studied, 45.5% underwent IS. At median follow-up of 60 months, 47.5% developed recurrence; oligometastatic in 39% of cases, with 31% receiving best supportive care, 60% chemotherapy and/or radiation, and 8% surgical resection. IS was associated with reduced symptomatic recurrence (OR0.17 [0.12–0.25]), increased tumor-directed therapy (OR2.09 [1.58–2.77]), and improved OS (HR0.90 [0.82–0.98], 5-year OS 47.9 ± 1.2% versus 43.2 ± 1.1%). On multivariable analysis, significantly improved OS with IS was maintained for patients who underwent surgery alone (HR0.60 [0.47–0.78]) and in those with lower pathological (y)pT stages (Tis-2, HR0.72 [0.58–0.89]). IS was associated with greater anxiety (P = 0.016), but similar overall HR-QL. Conclusion These data suggest that IS may improve oncologic outcomes, particularly in patients with early stage disease at presentation or with a favorable pathological stage post induction therapy. This may be relevant to guideline development and provide a framework and rationale for RCTs. It may also inform shared decision-making with patients at a time where therapeutic options for recurrence are expanding.

Emerging data demonstrate long-term survival after salvage interventions for local or oligometastatic recurrence after planned curative resection for esophageal cancer, providing rationale for postoperative surveillance. However, the impact of intensive surveillance on oncologic outcome is unknown. This multicenter collaborative study aimed to characterize oncologic surveillance protocols across esophageal cancer centers internationally and determine the independent effect of intensive surveillance on oncologic outcome. Methods The ENSURE international multicenter study included consecutive patients who underwent surgery with curative intent for cTxNxM0 esophageal cancer from June 2009 to June 2015. Intensive surveillance was defined as use of cross-sectional imaging, at least annually, during the first three postoperative years. The estimated sample size of 4425 provided 90% power to detect a 5% increase in 5-year overall survival (OS, primary outcome measure). Secondary outcome measures included disease-free (DFS) and disease-specific survival (DSS), surveillance strategies, incidence of oligometastatic recurrence, treatment strategies, and HRQOL. The study was registered on ClinicalTrials.gov (NCT03461341). Results 4597 patients were included. The participating 27 centres undertook mean(SD) 52.3(17.1) esophageal cancer resections annually between 3.5 ± 1.3 attending surgeons. 37%, 11% and 19% centers utilized postoperative surveillance CT, PET-CT and endoscopy, respectively. Among all patients, intensive surveillance was associated with improved OS (HR0.92 [0.85–0.99]) but not DSS (HR0.93 [0.85–1.01]) or DFS (HR0.97 [0.90–1.04]), and on multivariable analysis, intensive surveillance did not provide oncologic benefit (OS HR1.10 [0.99–1.22], DSS HR1.12 [1.00–1.25]), but reduced observed DFS (HR1.19 [1.08–1.31]). Evaluating surveillance modalities, neither surveillance endoscopy nor laboratory tests improved oncologic outcome, however flexible nasolaryngoscopy was associated with improved OS (HR0.84 [0.69–1.0]). Conclusion ENSURE, the first study powered to assess the impact of postoperative surveillance protocols on oncologic outcome in esophageal cancer, demonstrated no overall survival benefit following intensive imaging surveillance, with reduced observed disease-free survival time. However, routine assessment for secondary aerodigestive malignancies may be of oncologic benefit. The present data do not support the use of intensive imaging surveillance among all patients following esophageal cancer surgery. Further reports detailing subgroup analyses and HRQOL impact are anticipated.

Visceral obesity, metabolic syndrome and non-alcoholic fatty liver disease (NAFLD) represent risk factors for esophageal adenocarcinoma (EAC). The prevalence of NAFLD, and its impact on the hepatic response to esophageal cancer surgery, has never been systematically evaluated, and was the focus of this study. Methods Consecutive patients (n = 547) treated with curative intent for esophageal cancer from 2007–2017 were studied. In an unselected subgroup (n = 138), liver biopsies were collected intraoperatively and assessed for NAFLD, defined as ≥5% macrovesicular steatosis. Postoperative complications were recorded prospectively, including Clavien-Dindo grade (CD) and comprehensive complications index (CCI). Liver function tests were monitored in the first postoperative week, with hepatocellular dysfunction defined as a transaminase rise ≥3-times the upper limit of normal. Multivariable logistic and Cox proportional hazards regression were utilised to determine independent predictors of operative and oncologic outcome. The study was registered on clinicaltrials.gov (NCT04152044). Results NAFLD was evident in 62 patients (47.7%) who had biopsies, with a mean (SD) score of 10.1(9.3)%. NAFLD was associated with metabolic syndrome (41.9 vs 25%, P = 0.04), obesity (44.1 vs 11.9%, P Conclusion A marker of metabolic dysregulation in obesity-associated carcinogenesis, NAFLD is prevalent among patients with esophageal cancer. Liver dysfunction post esophagectomy is common, and although temporary, is associated with worse oncologic outcomes. Baseline NAFLD did not incur an adverse long-term oncologic outcome.

Visceral obesity (VO) and metabolic syndrome (MetS) are risk factors for esophageal adenocarcinoma (EAC); however, their impact on operative and oncological outcomes is unclear. The aim of this study was to determine the incidence of VO and MetS among patients with EAC, and to assess their independent impact on operative and oncological outcomes. A total of 454 consecutive patients undergoing treatment with curative intent were studied. Total, subcutaneous, visceral fat area (VFA), and lean body mass (LBM) were measured by computed tomography pretreatment, with VO defined as VFA >163.8cm2 for men and 80.1cm2 for women. MetS was defined per the ATPIII definition. Multivariable logistic and Cox proportional hazards regression were utilized to determine independent predictors of oncologic and operative outcomes. A total of 227 patients (50.0%) had VO. A total of 134 (30%) overall had MetS, 44% in the VO cohort. VO was associated with Barrett’s esophagus (P = 0.002) and lower cT (P = 0.006) and cN stage (P = 0.011), and improved disease-specific (P = 0.021) and overall survival (P = 0.012). No survival benefit existed for patients with VO who also had MetS. For operative complications, neither VO nor MetS increased the severity of complications, or mortality. However, VO was significantly (P = 0.035) associated with anastomotic leak and pneumonia (P = 0.037). MetS alone did not increase complication risk. VO increases specific major operative complications with no increase in mortality. VO improved survival, mainly relating to earlier stage disease; however, co-existent MetS abrogated this benefit. These seemingly paradoxical outcomes highlight manageable and potentially targetable perioperative challenges in the context of an overall favorable oncologic vista.

Sarcopenia, myosteatosis and obesity in cancer may confer negative clinical outcomes, but their prevalence and impact among patients with retroperitoneal and trunk soft tissue sarcoma have not been systematically studied. The aim of this study was to determine body composition among patients with retroperitoneal and trunk sarcoma, and assess impact on operative and oncologic outcomes.Consecutive patients undergoing treatment with curative intent from 2009 to 2019 were studied. Subcutaneous fat area and visceral fat areas, intramuscular adipose, lean body mass and fat mass were determined at diagnosis by CT at L3. Univariable and multivariable linear, logistic and Cox proportional hazards regression were performed.95 patients (43.2% retroperitoneal, 48.4% trunk, 46.3% multivisceral resection) were studied. Visceral obesity was evident in 47.4%. Postoperative morbidity occurred in 25.9%, with preoperative radiotherapy (OR10.53 [95% CI 1.08-102.39], P = 0.042) and fat mass (OR1.41 [1.12-1.79], P = 0.004) independently predictive on multivariable analysis, while intramuscular adipose independently predicted inpatient LOS (P 0.001), wound infection (P = 0.024, OR1.20 [1.02-1.40]) and major postoperative morbidity (P = 0.027, OR1.15 [1.02-1.31]). Increasing fat mass, subcutaneous fat area and intramuscular adipose were associated with greater tumor size (all P 0.01), while intramuscular adipose predicted disease progression during neoadjuvant therapy (P = 0.024), and independently predicted disease specific survival (DSS) (P = 0.005, HR1.11 [1.03-1.20]) and overall survival (OS) on multivariable analysis (P 0.001, HR1.19 [1.08-1.31]).Visceral obesity is common in retroperitoneal and trunk sarcoma, and measures of adiposity are associated with adverse operative, but not oncologic outcomes. Myosteatosis is independently associated with postoperative morbidity and adverse oncologic outcomes. Body composition may represent a marker of risk among patients with retroperitoneal and trunk sarcoma.

Introduction Sarcopenia and obesity in cancer may confer negative outcomes, but their prevalence and impact on modern regimens for retroperitoneal sarcoma (RPS) have not been systematically studied. Sarcopaenia and obesity measurements by computed tomography (CT) measurements at L3 may be confounded by the disease process itself. The aim of this study is to determine feasibility in providing the prevalence of sarcopenia and visceral obesity in the management of RPS to assess their potential impact on operative and oncologic outcomes. Method Consecutive sample patients undergoing treatment for RPS from our database were retrospectively studied. Total, subcutaneous and visceral fat areas (VFA), myosteatosis, skeletal muscle index (SMI) lean body mass and fat mass were determined at diagnosis by CT. Sarcopenia will be defined by CT at L3 as SMI 163.8cm2 for men and >80.1cm2 for women. Result 40 consecutive patients, 21 [52.5%] female, 56.7±15.1 years, were studied. The most common histologic types were leiomyosarcoma (8 [20.0%]), dedifferentiated liposarcoma (7 [17.5%]), well differentiated liposarcoma (7 [17.5%]), myxoid liposarcoma (4 [10.0%]). Mean±SD body composition measures were: lean body mass, 50.4±12.0 kg; total fat mass, 27.2±8.6 kg; visceral fat area, 148.5±120.2 cm2; subcutaneous fat area, 222.2±20.4 cm2; myosteatosis, 8.9±7.3 cm2. Conclusion Assessment of body composition among patients with RPS is feasible. Analysis to identify the prevalence and significance of sarcopenia and visceral obesity and its relationship to operative and oncologic outcomes is ongoing. Take-home message Assessment of body composition in RPS is feasible and its effect on outcomes is under investigation

Introduction Sarcopenia in cancer may confer negative outcomes, but its prevalence and impact in the modern multimodal management of locally advanced breast cancer have not been systematically studied. Method Patients undergoing neoadjuvant therapy and surgery for locally advanced breast cancer between 2010 and 2015 were studied. Skeletal muscle index (SMI) and lean body mass (LBM) were determined. Sarcopenia was defined by computed tomography (CT) at L3 as SMI Result 258 patients were studied. Sarcopenia was present in 23.0%, 7.8% and 0.0% of patients with normal weight, overweight and obesity, respectively (P=0.001). Sarcopenia was not associated with baseline cT and cN stage, tumour grade, histologic type or receptor status. Patients with sarcopenia exhibited equivalent indices of neoadjuvant therapy response including ypT and ypN stage, pathologic complete response and Sataloff grade following surgical resection. Postoperatively, sarcopenia was not independently associated with comprehensive complications index (P=0.242), length of stay (P=0.716) or overall morbidity (P=0.365). However, on multivariable analysis, lower LBM independently predicted reduced invasive disease-free (P=0.049,HR0.93[95%CI0.87-1.00]) and overall (P=0.028,HR0.92[0.85-0.99]), but not disease-specific survival (P=0.070). Conclusion Consistent with a lack of association with baseline and post-treatment pathologic features, sarcopenia in locally advanced breast cancer is associated with reduced overall, but not disease-specific, survival. These data indicate that the prognostic impact of sarcopenia may be mediated by impaired performance status and increased non-cancer mortality. Take-home message Consistent with a lack of association with baseline and post-treatment pathologic features, sarcopenia in locally advanced breast cancer is associated with reduced overall, but not disease-specific, survival. These data indicate that the prognostic impact of sarcopenia may be mediated by impaired performance status and increased non-cancer mortality.

OBJECTIVE To determine the incidence, risk factors, and consequences of AKI in patients undergoing surgery for esophageal cancer. SUMMARY OF BACKGROUND DATA Esophageal cancer surgery is an exemplar of major operative trauma, with well-defined risks of respiratory, cardiac, anastomotic, and septic complications. However, there is a paucity of literature regarding AKI. METHODS Consecutive patients undergoing curative-intent surgery for esophageal cancer from 2011 to 2017 in 3 high-volume centers were studied. AKI was defined according to the AKI Network criteria. AKI occurred if, within 48 hours postoperatively, serum creatinine rose by 50% or by 0.3 mg/dL (26.5 μmol/L) from preoperative baseline. Complications were recorded prospectively. Multivariable logistic regression determined factors independently predictive of AKI. RESULTS A total of 1135 patients (24.7%:75.3% female:male, with a mean age of 64, a baseline BMI of 27 kg m, and dyslipidemia in 10.2%), underwent esophageal cancer surgery, 85% having an open thoracotomy. Overall in-hospital mortality was 2.1%. Postoperative AKI was observed in 208 (18.3%) patients, with AKI Network 1, 2, and 3 in 173 (15.2%), 28 (2.5%), and 7 (0.6%), respectively. Of these, 70.3% experienced improved renal function within 48 hours. Preoperative factors independently predictive of AKI were age [P = 0.027, odds ratio (OR) 1.02 (1.00-1.04)], male sex [P = 0.015, OR 1.77 (1.10-2.81)], BMI at diagnosis [P < 0.001, OR 1.10 (1.07-1.14)], and dyslipidemia [P = 0.002, OR 2.14 (1.34-3.44)]. Postoperatively, AKI was associated with atrial fibrillation (P = 0.013) and pneumonia (P = 0.005). Postoperative AKI did not impact survival outcomes. CONCLUSION AKI is common but mostly self-limiting after esophageal cancer surgery. It is associated with age, male sex, increased BMI, dyslipidemia, and postoperative morbidity.

Background The benefit of chemotherapy (NAC) for patients with ER/PR positive, HER2 negative breast cancer is unclear. Our aim was to determine factors associated with histopathologic response and oncologic outcome following NAC in this group. Methods Consecutive female patients undergoing neoadjuvant therapy and surgery for locally advanced Luminal A breast cancer between 2010 and 2015 were studied. Multivariable linear, logistic, and Cox regression analysis was undertaken. Results 114 patients were studied. Pathological complete response (pCR) was achieved in 7.9% of patients, ypN0 in 25.5%, and downstaging in 33.6%. However, 43.9% exhibited a Sataloff C-D response. Tumor grade independently predicted pCR (P = 0.039), while PR score predicted ypN0 (P = 0.017) and downstaging (P=0.029). 5-year invasive disease-free (iDFS) and overall survival (OS) were 68.5 ± 4.7% and 77.7 ± 4.3%, respectively. Conclusion After NAC for Luminal A breast cancer, pCR rates are low. Patients with high grade tumors with weak PR expression exhibit the most promising response rates.

Esophageal adenocarcinoma (EAC) is increasing exponentially year on year in Western civilisation, linked epidemiologically to GERD and obesity. It is characterized by a highly immunosuppressive tumour microenvironment (TME) and evasion of immune surveillance. A novel treatment option is upregulating immune mediated anti-tumour response via Immune Checkpoint Blockers (ICB). Methods The effects of immune checkpoint blockers were characterised in terms of proliferation, cytolysis and cancer cell viability. The basal expression of immune checkpoints (TIGIT, PD-1, PD-L1, PD-L2) and Damage Associated Molecular Patterns (Calreticulin, HMGB1) in EAC patients was profiled ex vivo using fresh tumor, blood and lymph-node tissue (n = 10) by flow cytometry. In an in-vitro study, T-lymphocytes were isolated and treated with Nivolumab, Pembrolizumab or Atezolizumab, activated and co-cultured for 48 hours with a panel of four esophageal cancer cell lines; OE33P, OE33R, FLO-1, FLO-1LM treated with 1.8Gy and 3.6Gy of radiation (Fig 1). Cytolysis was measured using a CCK8 assay.(n = 6). Results The expression of TIGIT, TIM-3, PD-1 and its ligands (PD-L1, PD-L2) were higher (p Conclusion Fractionated radiation can enhance immunologic function. In combination with ICB, this symbiotic relationship enhances the cytotoxic potential of T lymphocytes with conventional dosing, however, with hypofractionation, this signifies true immunogenicity, and as such this provides a basis for advocating for potential combination strategies with ICB in the multimodal treatment of EAC.

The human microbiota, the collection of microbes that inhabit the human body, is increasingly recognized as playing a role in human health. A seminal example of this relationship is Helicobacter pylori and gastric cancer oncogenesis. The decline in H.pylori prevalence and non-cardia gastric cancer incidence have coincided with the rise in oesophageal adenocarcinoma (OAC) incidence. We sought to explore the relationship between the gastric and oesophageal microbiome and OAC oncogenesis. Methods This study aimed to explore changes in the microbiome associated with oesophageal adenocarcinoma and its precancerous and inflammatory states by performing 16S rRNA gene amplicon sequencing on DNA extracted from oesophago-gastric biopsies from patients with normal oesophageal mucosa, reflux oesophagitis, Barrett’s oesophagus with and without dysplasia, locally advanced but resectable oesophageal adenocarcinoma, and incurable metatstatic oesophageal adenocarcinoma (See Table 1). We dissected ecological differences between sample site and clinical classification using a variety of approaches including examining differentially abundant taxa and inferred metabolic pathways, alpha diversity and beta-diversity. Results There was no statistically significant difference in beta diversity with respect to biopsy location. Alpha diversity was reduced in gastric biopsies compare to oesophageal biopsies. A small but significant shift was noted in beta diversity (Bray–Curtis Dissimilarity) with respect to clinical classification in biopsies derived from the gastroesophageal junction (GEJ) and stomach. Fusobacterium nucleatum was found to overrepresented in oesophageal biopsies derived from diseased groups relative to the healthy controls. Several taxa assigned to the genus Prevotella were depleted in biopsies of individuals with metastatic OAC compared to all other groups. Conclusion Community structure was shifted in samples derived from the GEJ, the epicentre of OAC oncogenesis. Fusobacterium plays a role in cancer development and progression through a number of mechanisms including increasing cell proliferation, immune cell infiltration and chemoresistance. Fusobacterium can cause upregulation of MicroRNA-21, a microRNA upregulated in OAC.

IntroductionRoux-en-Y Gastric Bypass Surgery (RYGB) reduces albuminuria and the long-term incidence of end-stage renal disease in patients with obesity and diabetes. Preclinical modelling in experimental diabetic kidney disease (DKD) demonstrates that improvements in glomerular structure likely underpin these findings.Research Design & MethodsIn adult male Zucker Diabetic Fatty (ZDF) rats, we profiled the effect of RYGB on weight and metabolic control as well biochemical, structural and ultrastructural indices of diabetic renal injury. Furthermore, we sequenced the renal cortical transcriptome in these rats and used bioinformatic pathway analyses to characterise the transcriptional alterations governing the renal reparative response to RYGBResultsIn parallel with improvements in weight and metabolic control, RYGB reduced albuminuria, glomerulomegaly, podocyte stress, and podocyte foot process effacement. Pathway analysis of RYGB-induced transcriptomic changes in the renal cortex highlighted correction of disease-associated alterations in fibrosis, inflammation and biological oxidation pathways. RYGB reversed disease-associated changes in the expression of TGF-β superfamily genes that strongly correlated with improvements in structural measures of glomerulopathy.ConclusionsImproved glomerular structure in ZDF rats following RYGB is underpinned by pathway level changes, including interruption of the TGF-β driven pro-fibrotic programme. Our data provide an important layer of experimental support for clinical evidence demonstrating that RYGB arrests renal damage in patients with obesity and Type 2 Diabetes.KEY MESSAGESWhat is already known about this subject?RYGB is an effective treatment for obesity and type 2 diabetes and longitudinal cohort studies have demonstrated it’s albuminuria lowering effect and evidence of longer term reno-protection.Studies in pre-clinical models of diabetic kidney disease have described favourable changes in measures of renal structure and ultrastructure following RYGB.What are the new findings?The present study directly correlates structural and ultrastructural improvements in the ZDF rat kidney following RYGB with corrective shifts in the global renal transcriptome.Chronic renal remodelling responses in experimental DKD that are governed by TGF-β signalling are interrupted and reversed by RYGB.How might these results change the focus of research or clinical practice?These data will support further interrogation of RYGB specific shifts in the renal transcriptome with a view to identifying tractable targets for treatment response biomarkers and bariatric mimetic based diet and pharmacotherapy based interventions.

Summary Improved cure rates in esophageal cancer care have increased focus on health-related quality of life (HRQL) in survivorship. To optimize recovery after esophagectomy, particularly nutritional well-being, a personalized multidisciplinary survivorship clinic was established at this center. Assessments at 6 and 12 months postoperatively include validated European Organization for the Research and Treatment of Cancer (EORTC) symptom and health-related quality of life (HRQL) questionnaires, functional status review, anthropometry, and biochemical screening for micronutrient deficiencies. 75 patients, at a mean age of 63 years, 84% male, 85% with adenocarcinoma, and 73% receiving multimodal therapy were included. Mean preoperative body mass index (BMI) was 27.5 (4.3) kg m −2. 6- and 12-month assessments were completed by 66 (88%) and 37 (93%) recurrence-free patients, respectively. Mean body weight loss at 6 months was 8.5 ± 6.6% and at 12 months 8.8 ± 7.3%. Of the 12-month cohort, micronutrient deficiency was present in 27 (79.4%) preoperatively and 29 (80.6%) after 1 year (P = 0.727), most commonly iron deficiency (preoperative: 16 [43.2%] and postoperative: 17 [45.9%] patients, P = 0.100). 26 (70.3%) of these patients also had clinically significant dumping syndrome persisting to 12 months after surgery. We describe a novel follow-up support structure for esophageal cancer patients in the first year of survivorship. This may serve as an exemplar model with parallel application across oncological care.

Summary Esophagectomy causes postprandial symptoms associated with an exaggerated postprandial gut hormone response. This study aimed to compare the gastrointestinal transit time of patients 1 year after esophagectomy with unoperated controls, including its relation to satiety gut hormone release. In this cross-sectional study, consecutive, disease-free patients after esophagectomy with pyloroplasty were compared with unoperated control subjects to assess gastric emptying (GE) and cecal arrival time (CAT). Serial plasma samples were collected before, and for 300 minutes after, a mixed-meal challenge. Body composition was assessed, and symptom scores were calculated. Eleven patients 1 year post-esophagectomy (age: 62.6 ± 9.8, male: 82%) did not show a significantly different GE pattern compared with 10 control subjects (P = 0.245). Rather, patients could be categorized bimodally as exhibiting either rapid or slow GE relative to controls. Those with rapid GE trended toward a higher postprandial symptom burden (P = 0.084) without higher postprandial glucagon-like peptide-1 (GLP-1) secretion (P = 0.931). CAT was significantly shorter after esophagectomy (P = 0.043) but was not significantly associated with GE, GLP-1 secretion, or symptom burden. Neither early nutrient delivery to the proximal small intestine nor to the colon explains the exaggerated postprandial GLP-1 response after esophagectomy. GE varies significantly in these patients despite consistent pyloric management.

Summary The ECCG developed a standardized platform for reporting operative complications, with consensus definitions. The Dutch Upper Gastrointestinal Cancer Audit (DUCA) published a national comparison against these benchmarks. This study compares ECCG data from the Irish National Center (INC) with both published benchmark studies. All patients undergoing multimodal therapy or surgery with curative intent from 2014 to 2018 inclusive were studied, with data recorded prospectively and entered onto a secure online database (Esodata.org). 219 patients (mean age 67; 77% male) underwent open resection, 66.6% via transthoracic en bloc resection. 30-day and 90-day mortality were 0.0 and 0.9%,nrespectively. Anastomotic leak rate was 5.4%, pneumonia 18.2%, respiratory failure 10%, ARDS 2.7%, atrial dysrhythmia 22.8%, recurrent nerve injury 3%, and delirium in 5% of patients. Compared with both ECCG and DUCA, where MIE constituted 47 and 86% of surgical approaches, respectively, overall complications were similar, as were severity of complications; however, anastomotic leak rate was several-fold less, and mortality was significantly lower (P < 0.001). In this consecutive series and comparative audit with benchmark averages from the ECCG and DUCA publications, a low mortality and anastomotic leak rate were the key differential findings. Although not risk stratified, the severity of complications from this ‘open’ series is consistent with series containing large numbers of total or hybrid MIE, highlighting a need to adhere to these strictly defined definitions in further prospective research and randomized studies.

To prospectively characterize changes in body weight, satiety, and postprandial gut hormone profiles following esophagectomy.With improved oncologic outcomes in esophageal cancer, there is an increasing focus on functional status and health-related quality of life in survivorship. Early satiety and weight loss are common after esophagectomy, but the pathophysiology of these phenomena remains poorly understood.In this prospective study, consecutive patients undergoing esophagectomy with gastric conduit reconstruction were studied preoperatively and at 10 days, 6 weeks, and 3 months postoperatively. Glucagon-like peptide 1 (GLP-1) immunoreactivity of plasma collected immediately before and at 15, 30, 60, 90, 120, 150, and 180 minutes after a standardized 400-kcal mixed meal was determined. Gastrointestinal symptom scores were computed using European Organization for Research and Treatment of Cancer questionnaires.Body weight loss at 6 weeks and 3 months postoperatively among 13 patients undergoing esophagectomy was 11.1 ± 2.3% (P0.001) and 16.3 ± 2.2% (P0.0001), respectively. Early satiety (P = 0.043), gastrointestinal pain and discomfort (P = 0.01), altered taste (P= 0.006), and diarrhea (P= 0.038) scores increased at 3 months postoperatively. Area under the curve for the satiety gut hormone GLP-1 was significantly increased from 10 days postoperatively (2.4 ± 0.2-fold increase, P0.01), and GLP-1 peak increased 3.8 ± 0.6-, 4.7 ± 0.8-, and 4.4 ± 0.5-fold at 10 days, 6 weeks, and 3 months postoperatively (all P0.0001). Three months postoperatively, GLP-1 area under the curve was associated with early satiety (P = 0.0002, R = 0.74), eating symptoms (P = 0.007, R = 0.54), and trouble enjoying meals (P = 0.0004, R = 0.73).After esophagectomy, patients demonstrate an exaggerated postprandial satiety gut hormone response, which may mediate postoperative changes in satiety, body weight, and gastrointestinal quality of life.

Background:Multiple studies demonstrate an albuminuria-lowering impact of Roux-en-Y gastric bypass surgery, but neither evaluation of its penetrance across different baseline levels of albuminuria nor its association with alterations in podocyte phenotype has previously been reported.Methods:We profiled changes in body weight, glycaemic control and urinary albumin excretion following Roux-en-Y gastric bypass surgery in 105 patients with type 2 diabetes, albuminuria of varying degrees of severity and classified as being at moderate or high risk of chronic kidney disease progression according to the Kidney Disease: Improving Global Outcomes 2012 criteria. In parallel pre-clinical studies, the impact of Roux-en-Y gastric bypass surgery on markers of podocyte injury was assessed in the Zucker diabetic fatty rat model of diabetic kidney disease.Results:At 12- to 18-month post-operative follow-up in patients at moderate or high risk of chronic kidney disease, significant reductions in albuminuria were observed across all tertiles of baseline albumin–creatinine ratio, with remission of albuminuria occurring in 78% of patients. Relative to sham-operated control animals, weight loss and improvements in glycaemia following Roux-en-Y gastric bypass surgery in Zucker diabetic fatty rats were paralleled by normalisation of glomerular tuft-size, reductions in podocyte expression of desmin, and preservation of podocyte foot process morphology.Conclusion:Improvements in podocyte differentiation likely underpin the reductions in albuminuria observed following Roux-en-Y gastric bypass surgery.

Aim Long-term functional outcomes and the associations to health-related quality of life (HRQOL) after esophagectomy is largely unknown. LASER is a multi-center European study aimed to identify the most prevalent symptoms, and those with the greatest impact upon HRQOL among patients surviving more than one-year after esophagectomy for cancer, and to develop a clinically relevant symptom-based tool to measure HRQOL. Background & Methods Between 2010 and 2016, patients from 20 European Centers who underwent esophagectomy for esophageal cancer, and were disease-free at least one year postoperatively were invited to complete the LASER questionnaire, EORTC-QLQ30 and OG25. Specific symptom questionnaire items that were associated with a poor HRQOL as identified by EORTC-QLQC30 and OG25 were identified by multivariable linear and logistic regression analysis and combined to form a tool, which was tested using receiver operating characteristics curve analysis. Results A total of 876 of 1081 invited patients responded to the questionnaire, giving a response rate of 81%. Of these, 66.9% stated in the last 6 months they had had symptoms associated with their esophagectomy and 52.4% of patients had sought medical treatment for their symptoms. Ongoing weight loss was reported by 10.4% of patients while 32.4% were struggling to maintain their body weight, and 18.8% of patients required supplemental oral nutrition. Only 13.8% of patients had returned to work with the same activities as before. Three LASER symptoms in multivariate analysis were correlated with poor HRQOL; pain on scars on chest (Odds ratio (OR) 1.27; 95% CI 0.97-1.65), low mood (OR 1.42; 95% CI 1.15-1.77) and reduced energy or activity tolerance (OR 1.37; 95% CI 1.18-1.59). The areas under the curves for the development and validation datasets were 0.81±0.02 and 0.82±0.09 respectively. Conclusions Two-thirds of patients experience symptoms related to their esophagectomy more than one year after surgery. The three key symptoms associated with poor HRQOL identified in this study should be further validated, and could be used in clinical practice to identify patients who require increased long-term term support.

Background Oesophagectomy remains the only curative intervention for oesophageal cancer, with defined nutritional and health-related quality of life (HR-QOL) consequences. It follows therefore that there is a significant risk of decline in physical wellbeing with oesophagectomy however this has been inadequately quantified. This study prospectively examines change in physical functioning and habitual physical activity participation, from pre-surgery through 6-months post-oesophagectomy. Methods Patients scheduled for oesophagectomy with curative intent were recruited. Key domains of physical functioning including exercise tolerance (six-minute walk test (6MWT)) and muscle strength (hand-grip strength), and habitual physical activity participation, including sedentary behaviour (accelerometry) were measured pre-surgery (T0) and repeated at 1-month (T1) and 6-months (T2) post-surgery. HR-QOL was measured using the EORTC-QOL C30. Results Thirty-six participants were studied (mean age 62.4 (8.8) years, n = 26 male, n = 26 transthoracic oesophagectomy). Mean 6MWT distance decreased significantly from T0 to T1 (p = 0.006) and returned to T0 levels between T1 and T2 (p

Background: The impact of cardiorespiratory comorbidity on operative outcomes after esophagectomy remains controversial. This study investigated the effect of cardiorespiratory comorbidity on postoperative complications for patients treated for esophageal or gastroesophageal junction cancer. Patients and Methods: A European multicenter cohort study from five high-volume esophageal cancer centers including patients treated between 2010 and 2017 was conducted. The effect of cardiorespiratory comorbidity and respiratory function upon postoperative outcomes was assessed. Results: In total 1590 patients from five centers were included; 274 (17.2%) had respiratory comorbidity, and 468 (29.4%) had cardiac comorbidity. Respiratory comorbidity was associated with increased risk of overall postoperative complications, anastomotic leak, pulmonary complications, pneumonia, increased Clavien–Dindo score, and critical care and hospital length of stay. After neoadjuvant chemoradiotherapy, respiratory comorbidity was associated with increased risk of anastomotic leak [odds ratio (OR) 1.83, 95% confidence interval (CI) 1.11–3.04], pneumonia (OR 1.65, 95% CI 1.10–2.47), and any pulmonary complication (OR 1.52, 95% CI 1.04–2.22), an effect which was not observed following neoadjuvant chemotherapy or surgery alone. Cardiac comorbidity was associated with increased risk of cardiovascular and pulmonary complications, respiratory failure, and Clavien–Dindo score ≥ IIIa. Among all patients, forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio > 70% was associated with reduced risk of overall postoperative complications, cardiovascular complications, atrial fibrillation, pulmonary complications, and pneumonia. Conclusions: The results of this study suggest that cardiorespiratory comorbidity and impaired pulmonary function are associated with increased risk of postoperative complications after esophagectomy performed in high-volume European centers. Given the observed interaction with neoadjuvant approach, these data indicate a potentially modifiable index of perioperative risk.

4032 Background: Although established and emerging therapies for recurrent esophageal cancer (EC) may impact on survival and health related quality of life (HRQL), surveillance protocols after the primary curative treatment of EC are varied and inconsistent, reflecting a limited evidence-base to guide an optimum approach. Specifically, whether advantages exist for an intensive surveillance protocol is unknown and was the focus of this study. Methods: European iNvestigation of SUrveillance after Resection for Esophageal cancer (ENSURE) is an international multicenter retrospective observational study of consecutive patients undergoing surgery with curative intent for esophageal and gastroesophageal junction cancers (2009 – 2015) across 20 European and North American cancer centers (NCT03461341). Intensive surveillance (IS) was defined as routine annual CT/PET-CT along with clinical assessment during the first three postoperative years, and compared with standard surveillance (SS) with investigation as clinically indicated. The primary outcome measure was overall survival (OS), secondary outcomes included treatment administered, disease-specific survival (DSS), disease-free survival (DFS), recurrence pattern, and HRQL. Multivariable linear, logistic and Cox proportional hazards regression analyses were performed to determine the independent impact of surveillance on oncologic outcomes and HRQL. Results: 4,682 patients were studied (72.6% adenocarcinoma, 69.1% neoadjuvant therapy). 45.5% underwent IS. At a median follow-up of 60 months, 47.5% developed disease recurrence. Oligometastatic recurrence occurred in 39% of cases, with 31% receiving best supportive care, 60% chemotherapy and/or radiation, and 8% surgical resection. IS was associated with reduced symptomatic recurrence (odds ratio [OR] 0.17 [0.12–0.25]), increased tumor-directed therapy (OR 2.09 [1.58–2.77]), and improved OS (HR 0.90 [0.82–0.98], 5-year OS 47.9±1.2% versus 43.2±1.1%). After adjusting for confounders, significantly improved overall survival with IS was maintained for patients who underwent surgery alone as initial therapy (HR 0.60 [0.47–0.78]) and in those with lower pathological (y)pT stages (Tis-2, HR 0.72 [0.58–0.89]). IS was associated with greater anxiety ( P= 0.016), but similar overall HRQL. Conclusions: These data suggest that IS may improve oncologic outcomes, particularly in patients with early stage disease at presentation or with a favorable pathological stage post induction therapy. This may be relevant to guideline development and provide a framework and rationale for RCTs. It may also inform shared decision-making with patients at a time where therapeutic options for recurrence are expanding.

A 50-year-old man presented to the emergency department with a 1-day history of severe epigastric pain, vomiting and fever. He had a background of alcohol excess and smoking. The patient was tachycardic and febrile with an elevated white blood cell count and C reactive protein. CT demonstrated extensive upper abdominal free fluid, without free air, with a large cystic lesion arising from the greater curvature of the stomach, and a second smaller cystic lesion arising from the posterior aspect of the gastric fundus. The patient was managed with nasogastric drainage, parenteral nutrition, intravenous antibiotics and proton pump inhibitors, and CT-guided abdominal drainage, with resolution of sepsis, and further outpatient care was transferred to our unit. Follow-up endoscopy demonstrated a diverticulum arising from the posterior aspect of the gastric fundus, with normal mucosa throughout the remaining stomach, while CT showed an additional cystic lesion arising from the greater curvature, with thickening of the adjacent gastric wall consistent with a gastric duplication cyst (GDC). Laparoscopy confirmed a small diverticulum at the fundus, and a large GDC anteriorly with associated omental adhesions consistent with prior perforation—two wedge resections were performed. Histology demonstrated no evidence of malignancy or ectopic mucosa. The patient recovered uneventfully and remained free from recurrent symptoms at 6 weeks postoperatively. GDC is a rare entity, which may be associated with ectopic mucosa, malignant transformation and upper gastrointestinal perforation. No previous report describes the coexistence of a GDC and gastric diverticulum. Herein we describe the investigation and management of this condition, and review the associated peer-reviewed literature.

Risk factors for advanced airway intervention among patients with dentofacial infection (DFI) are poorly understood. The appropriate delivery of clinical care to this patient group raises challenging anaesthetic service provision issues. The purpose of this study was to identify factors which may predict a requirement for an awake fibre optic intubation (AFOI) technique for airway management in this patient population.A retrospective analysis of data for consecutive patients admitted with DFI were analysed at the OralMaxillofacial department at St James's Hospital, Dublin from July 2014-July 2015 was carried out. Receiver operating characteristic analysis determined optimal cut-off values predictive of AFOI, and multivariate logistic regression determined independent risk factors for AFOI.One hundred and twenty-five patients (64 male, 61 female) were admitted with DFI. The mean age was 35.9 years (range 16-91). AFOI was carried out in 58 (67.4%) patients who required GA. Increasing age was associated with an increase likelihood of AFOI (P = 0.047 95% CI 1.07(1.00-1.14). Reduced mouth opening was significantly associated with requirement for AFOI (28.8 ± 8.6 vs. 14.8 ± 8.6 mm, P 0.0001). On receiver operating characteristic (ROC) analysis, mouth opening predicted requirement for AFOI with 87% accuracy (AUC 0.87 [95% CI 0.80-0.95], P 0.0001). Using a cut-off value of 16.5 mm predicted subsequent AFOI with 96.7% (95% CI 78.1-100.0%) specificity and 65.6% (95% CI 51.4-77.8%) sensitivity. Initial C-reactive protein (CRP) was significantly associated with requirement for AFOI (60.1 ± 40.0 vs. 121.3 ± 89.8, P = 0.002). A CRP value of over 110 mg/L predicted subsequent AFOI with 95.8% (95% CI 78.9-100.0%) specificity.Increasing age, reduced mouth opening 16.5 mm, and an increased serum admission CRP 100 mg/L on admission significantly increase the requirement for AFOI on multivariate and univariate regression analysis. The availability of anaesthetists experienced in AFOI is essential for safe management of these patients.

It remains controversial whether neoadjuvant chemoradiation (nCRT) for oesophageal cancer influences operative morbidity, in particular pulmonary, and quality of life. This study combined clinical outcome data with systematic evaluation of pulmonary physiology to determine the impact of nCRT on pulmonary physiology and clinical outcomes in locally advanced oesophageal cancer.Consecutive patients treated between 2010 and 2016 were included. Three-dimensional conformal radiation was standard, with a lung dose-volume histogram of V20 less than 25 per cent, and total radiation between 40 and 41·4 Gy. Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and diffusion capacity for carbon monoxide (DLCO) were assessed at baseline and 1 month after nCRT. Radiation-induced lung injury (grade 2 or greater), comprehensive complications index (CCI) and pulmonary complications were monitored prospectively. Health-related quality of life was assessed among disease-free patients in survivorship.Some 228 patients were studied. Comparing pulmonary physiology values before with those after nCRT, FEV1 decreased from mean(s.d.) 96·8(17·7) to 91·5(20·4) per cent (-3·6(10·6) per cent; P 0·001), FVC from 104·9(15·6) to 98·1(19·8) per cent (-3·2(11·9) per cent; P = 0·005) and DLCO from 97·6(20·7) to 82·2(20·4) per cent (-14·8(14·0) per cent; P 0·001). Five patients (2·2 per cent) developed radiation-induced lung injury precluding surgical resection. Smoking (P = 0·005) and increased age (P 0·001) independently predicted percentage change in DLCO. Carboplatin and paclitaxel with 41·4 Gy resulted in a greater DLCO decline than cisplatin and 5-fluorouracil with 40 Gy (P = 0·001). On multivariable analysis, post-treatment DLCO predicted CCI (P = 0·006), respiratory failure (P = 0·020) and reduced physical function in survivorship (P = 0·047).These data indicate that modern nCRT alters pulmonary physiology, in particular diffusion capacity, which is linked to short- and longer-term clinical consequences, highlighting a potentially modifiable index of risk.El tema de si en el cáncer de esófago la quimiorradioterapia neoadyuvante (neoadjuvant chemoradiation, nCRT) repercute sobre la morbilidad postoperatoria, especialmente sobre la morbilidad pulmonar y la calidad de vida de los pacientes que sobreviven sigue siendo controvertido. Este estudio combina datos sobre resultados clínicos con una evaluación sistemática de la fisiología pulmonar para determinar el impacto de la nCRT sobre la fisiología pulmonar y los resultados clínicos en el cáncer de esófago localmente avanzado. MÉTODOS: Se incluyeron pacientes consecutivos tratados entre 2010-2016. La radioterapia conformal 3D fue la estándar, con un histograma dosis-volumen del pulmón V2025% y radiación entre 40-41,4 Gy. Se evaluaron el volumen espiratorio forzado (forced expiratory volume, FEV1), la capacidad vital forzada (forced vital capacity, FVC) y la capacidad de difusión del monóxido de carbono (diffusion capacity for carbon monoxide, DLCO) al inicio y un mes tras la nCRT. La lesión pulmonar inducida por la radioterapia (EORTC grado ≥ 2), el índice de complicaciones integral (comprehensive complications index, CCI), grado de Clavien-Dindo, y complicaciones pulmonares fueron analizadas de manera prospectiva. Se evaluó la calidad de vida relacionada con la salud entre los pacientes supervivientes libres de enfermedad (EORTC QLQ-C30, OG25, OES18).Se estudiaron un total de 228 pacientes. Al comparar los valores de la fisiología pulmonar antes y después de la nCRT respectivamente, la FEV1 disminuyó de 96,8 ± 17,7% a 91,5 ± 20,4% (-3,6 ± 10,6%, P = 0,0002), la FVC de 104,9 ± 15,6 a 98,1 ± 19,8% (-3,2 ± 11,9%, P = 0,005) y la DLCO de 97,6 ± 20,7 a 82,2 ± 20,4% (-14,8 ± 14,0%, P0,0001). Cinco pacientes (2,2%) desarrollaron lesión pulmonar relacionada con la radioterapia impidiendo la resección quirúrgica. Los factores predictores independientes de %ΔDLCO fueron el hábito tabáquico (P = 0,005) y la edad avanzada (P0,001). El tratamiento con carboplatino/paclitaxel/41,4Gy determinó un mayor descenso de la DLCO en comparación con cisplatino/5-fluorouracilo/40Gy (P = 0,001). En el análisis multivariable, la DLCO tras el tratamiento fue una variable predictora de CCI (P = 0,006), fracaso respiratorio/intubación prolongada (P = 0,020) y reducción de la función física en los supervivientes (P = 0,047). CONCLUSIÓN: Estos datos indican que la moderna nCRT altera la fisiología pulmonar, especialmente la difusión pulmonar, con consecuencias clínicas a corto y largo plazo. La DLCO podría constituir un factor de riesgo potencialmente modificable.