Quantifying Perioperative Risks for Antireflux and Hiatus Hernia Surgery: A Multicenter Cohort Study of 4301 Patients.

OBJECTIVE: Using a comprehensive Australian cohort, we quantified the incidence and determined the independent predictors of intraoperative and postoperative complications associated with antireflux and hiatus hernia surgeries. In addition, we performed an in-depth analysis to understand the complication profiles associated with each independent risk factor. BACKGROUND: Predicting perioperative risks for fundoplication and hiatus hernia repair will inform treatment decision-making, hospital resource allocation, and benchmarking. However, available risk calculators do not account for hernia anatomy or technical aspects of surgery in estimating perioperative risk. METHODS: Retrospective analysis of all elective antireflux and hiatus hernia surgeries in 36 Australian hospitals over 10 years. Hierarchical multivariate logistic regression analyses were performed to determine the independent predictors of intraoperative and postoperative complications accounting for patient, surgical, anatomic, and perioperative factors. RESULTS: A total of 4301 surgeries were analyzed. Of these, 1569 (36.5%) were large/giant hernias and 292 (6.8%) were revisional procedures. The incidence rates of intraoperative and postoperative complications were 12.6% and 13.3%, respectively. The Charlson Comorbidity Index, hernia size, revisional surgery, and baseline anticoagulant usage independently predicted both intraoperative and postoperative complications. These risk factors were associated with their own complication profiles. Finally, using risk matrices, we visualized the cumulative impact of these 4 risk factors on the development of intraoperative, overall postoperative, and major postoperative complications. CONCLUSIONS: This study has improved our understanding of perioperative morbidity associated with antireflux and hiatus hernia surgery. Our findings group patients along a spectrum of perioperative risks that inform care at an individual and institutional level.

Assessment of laparoscopic fundoplication with endoscopy: room for improvement.

INTRODUCTION: Gastroesophageal reflux disease affects a significant portion of the Australian and world population. Minimally invasive laparoscopic fundoplication is a highly effective treatment in appropriately selected patients, with a 90% satisfaction rate. However, up to 5% will undergo revisional surgery. Endoscopy is an important investigation in the evaluation of persistent or new symptoms after fundoplication. Our study sought to evaluate the inter-rater reliability and variability in assessing fundoplication with endoscopy. METHODS: Upper gastrointestinal (UGI) surgeons and gastroenterologists were invited to join the cohort study through their professional membership with two societies based in Australia. Participants completed a two part 25-item multiple choice questionnaire, involving the analysis of ten static endoscopic images post-fundoplication. RESULTS: A total of 101 participants were included in the study (64 UGI surgeons and 37 gastroenterologists). Over 95% of participants were consultant level, working in non-rural tertiary hospitals. Total accuracy for all 10 cases combined was 76% for UGI surgeons and 69.9% for gastroenterologists. In three of the 10 cases, UGI surgeons performed significantly better than gastroenterologists (p < 0.05). When assessing performance across each of the 4 questions for each case, UGI surgeons were more accurate than gastroenterologists in describing the integrity of the wrap (p = 0.014). Inter-rater reliability was low across both groups for most domains (kappa < 1). CONCLUSION: Our study confirms low inter-rater reliability between endoscopists and large variations in reporting. UGI surgeons performed better than gastroenterologists in certain cases, usually when describing the integrity of the fundoplication. Our study provides further support for the use of a standardized reporting system in post-fundoplication patients.

Quality of life following repair of large hiatal hernia is not influenced by the use of mesh-Longer-term follow-up from a randomized trial.

INTRODUCTION: The use of prosthetic mesh in laparoscopic repair of large hiatus hernias remains controversial. Clinical and quality of life outcomes from a randomized controlled trial of mesh versus suture repair previously showed few differences at early follow-up. This study evaluated longer-term quality of life outcomes from that trial. METHODS: A prospective, multicentre, double blind randomized controlled trial assessed three methods of repair for large hiatus hernias: sutures-only versus absorbable mesh versus non-absorbable mesh. Quality of life was assessed using the Short-Form 36 (SF-36) questionnaire which was completed preoperatively and then at 3, 6, 12 months following surgery and annually thereafter. SF-36 outcomes were compared across the three repair techniques at longer-term follow-up (3-6 years), and to earlier baseline and 12-month outcomes. RESULTS: 126 patients were randomized; 43-suture-only, 41-absorbable mesh and 42-non-absorbable mesh. Questionnaires were completed by 118 patients preoperatively, 115 at 12 months and 98 at longer-term follow-up (median 5 years). There were no significant differences between the repair techniques for the subscale and composite scores at longer-term follow-up. The mental component score improved significantly after surgery and was sustained across follow-up for all techniques. The physical component score also improved significantly but was lower at longer-term follow-up compared to the 12-month follow up in both mesh groups. CONCLUSION: Surgical repair of large hiatus hernias provides sustained long-term improvement in quality of life. The addition of mesh does not improve quality of life. TRIAL REGISTRATION: This trial is registered with the Australia and New Zealand Clinical Trials Registry ACTRN12605000725662.

Mucosal impedance as a diagnostic tool for gastroesophageal reflux disease: an update for clinicians.

Mucosal impedance is a marker of esophageal mucosal integrity and a novel technique for assessing esophageal function and pathology. This article highlights its development and clinical application for gastroesophageal reflux disease (GERD), Barrett's esophagus, and eosinophilic esophagitis. A narrative review of key publications describing the development and use of mucosal impedance in clinical practice was conducted. A low mean nocturnal baseline impedance (MNBI) has been shown to be an independent predictor of response to anti-reflux therapy. MNBI predicts medication-responsive heartburn better than distal esophageal acid exposure time. Patients with equivocal evidence of GERD using conventional methods, with a low MNBI, had an improvement in symptoms following the initiation of PPI therapy compared to those with a normal MNBI. A similar trend was seen in a post fundoplication cohort. Strong clinical utility for the use of mucosal impedance in assessing eosinophilic esophagitis has been repeatedly demonstrated; however, there is minimal direction for application in Barrett's esophagus. The authors conclude that mucosal impedance has potential clinical utility for the assessment and diagnosis of GERD, particularly when conventional investigations have yielded equivocal results.

Understanding Potentially Preventable Mortality Following Oesophago-Gastric Cancer Surgery: Analysis of a National Audit of Surgical Mortality.

INTRODUCTION: At a national level, understanding preventable mortality after oesophago-gastric cancer surgery can direct quality-improvement efforts. Accordingly, utilizing the Australian and New Zealand Audit of Surgical Mortality (ANZASM), we aimed to: (1) determine the causes of death following oesophago-gastric cancer resections in Australia, (2) quantify the proportion of potentially preventable deaths, and (3) identify clinical management issues contributing to preventable mortality. METHODS: All in-hospital mortalities following oesophago-gastric cancer surgery from 1 January 2010 to 31 December 2020 were analysed using ANZASM data. Potentially preventable and non-preventable cases were compared. Thematic analysis with a data-driven approach was used to classify clinical management issues. RESULTS: Overall, 636 complications and 123 clinical management issues were identified in 105 mortalities. The most common causes of death were cardio-respiratory in aetiology. Forty-nine (46.7%) deaths were potentially preventable. These cases were characterized by higher rates of sepsis (59.2% vs 33.9%, p = 0.011), multiorgan dysfunction syndrome (40.8% vs 25.0%, p = 0.042), re-operation (63.3% vs 41.1%, p = 0.031) and other complications compared with non-preventable mortality. Potentially preventable mortalities also had more clinical management issues per patient [median (IQR): 2 (1-3) vs 0 (0-1), p < 0.001), which adversely impacted preoperative (30.6% vs 7.1%, p = 0.002), intraoperative (18.4% vs 5.4%, p = 0.037) and postoperative (51.0% vs 17.9%, p < 0.001) care. Thematic analysis highlighted recurrent areas of deficiency with preoperative, intraoperative and postoperative patient management. CONCLUSIONS: Almost 50% of deaths following oesophago-gastric cancer resections were potentially preventable. These were characterized by higher complication rates and clinical management issues. We highlight recurrent themes in patient management to improve future quality of care.

Para-conduit diaphragmatic hernia following esophagectomy-the new price of minimally invasive surgery?

Esophageal Cancer is the seventh commonest cancer worldwide with poor overall survival. Significant morbidity related to open esophagectomy has driven practice toward hybrid, totally minimally invasive and robotic procedures. With the increase in minimally invasive approaches, it has been suggested that there might be an increased incidence of subsequent para-conduit diaphragmatic hernia. To assess the incidence, modifiable risk factors and association with operative approach of this emerging complication, we evaluated outcomes following esophagectomy from two Australian Centers. Prospectively collected databases were examined to identify patients who developed versus did not develop a para-conduit hernia. Patient characteristics, disease factors, treatment factors, operative and post-operative factors were compared for these two groups. A total of 24 of 297 patients who underwent esophagectomy were diagnosed with a symptomatic para-conduit diaphragmatic hernia (8.1%). The significant risk factor for hernia was a minimally invasive abdominal approach (70.8% vs. 35.5%; P = 0.004, odds ratio = 12.876, 95% CI 2.214-74.89). Minimally invasive thoracic approaches were not associated with increased risk. Minimally invasive abdominal approaches to esophagectomy doubled the risk of developing a para-conduit diaphragmatic hernia. Effective operative solutions to address this complication are required.

A Method for Increasing the Robustness of Stable Feature Selection for Biomarker Discovery in Molecular Medicine Developed Using Serum Small Extracellular Vesicle Associated miRNAs and the Barrett's Oesophagus Disease Spectrum.

The biomarker development field within molecular medicine remains limited by the methods that are available for building predictive models. We developed an efficient method for conservatively estimating confidence intervals for the cross validation-derived prediction errors of biomarker models. This new method was investigated for its ability to improve the capacity of our previously developed method, StaVarSel, for selecting stable biomarkers. Compared with the standard cross validation method, StaVarSel markedly improved the estimated generalisable predictive capacity of serum miRNA biomarkers for the detection of disease states that are at increased risk of progressing to oesophageal adenocarcinoma. The incorporation of our new method for conservatively estimating confidence intervals into StaVarSel resulted in the selection of less complex models with increased stability and improved or similar predictive capacities. The methods developed in this study have the potential to improve progress from biomarker discovery to biomarker driven translational research.

Sutured Versus Mesh-augmented Hiatus Hernia Repair: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: This meta-analysis systematically reviewed published randomized control trials comparing sutured versus mesh-augmented hiatus hernia (HH) repair. Our primary endpoint was HH recurrence at short- and long-term follow-up. Secondary endpoints were: surgical complications, operative times, dysphagia and quality of life. SUMMARY BACKGROUND DATA: Repair of large HHs is increasingly being performed. However, there is no consensus for the optimal technique for hiatal closure between sutured versus mesh-augmented (absorbable or nonabsorbable) repair. METHODS: A systematic review of Medline, Scopus (which encompassed Embase), Cochrane Central Register of Controlled Trials, Web of Science, and PubMed was performed to identify relevant studies comparing mesh-augmented versus sutured HH repair. Data were extracted and compared by meta-analysis, using odds ratio and mean differences with 95% confidence intervals. RESULTS: Seven randomized control trials were found which compared mesh-augmented (nonabsorbable mesh: n = 296; absorbable mesh: n = 92) with sutured repair (n = 347). There were no significant differences for short-term hernia recurrence (defined as 6-12 months, 10.1% mesh vs 15.5% sutured, P = 0.22), long-term hernia recurrence (defined as 3-5 years, 30.7% mesh vs 31.3% sutured, P = 0.69), functional outcomes and patient satisfaction. The only statistically significant difference was that the mesh repair required a longer operation time (P = 0.05, OR 2.33, 95% confidence interval 0.03-24.69). CONCLUSIONS: Mesh repair for HH does not offer any advantage over sutured hiatal closure. As both techniques deliver good and comparable clinical outcomes, a suture only technique is still an appropriate approach.

Randomized Trial of Laparoscopic Nissen Versus Anterior 180 Degree Partial Fundoplication - Late Clinical Outcomes at 15 to 20 years.

OBJECTIVE: To determine very late clinical outcomes at up to 20 years follow-up from a randomized controlled trial of Nissen versus anterior 180-degree partial fundoplication. SUMMARY BACKGROUND DATA: Nissen fundoplication for gastroesophageal reflux can be followed by troublesome side effects. To address this, partial fundoplications have been proposed. Previously reports from a randomized controlled trial of Nissen versus anterior 180-degree partial fundoplication at up to 10 years follow-up showed good outcomes for both procedures. METHODS: One hundred seven participants were randomized to Nissen versus anterior 180-degree partial fundoplication. Fifteen to 20 year follow-up data was available for 79 (41 Nissen, 38 anterior). Outcome was assessed using a standardized questionnaire with 0 to 10 analog scores and yes/no questions to determine reflux symptoms, side-effects, and satisfaction with surgery. RESULTS: After anterior fundoplication heartburn (mean score 3.2 vs 1.4, P = .001) and proton pump inhibitor use (41.7% vs 17.1%, P = .023) were higher, offset by less dysphagia for solids (mean score 1.8 vs 3.3, P = .015), and better ability to belch (84.2% vs 65.9%, P = .030). Measures of overall outcome were similar for both groups (mean satisfaction score 8.4 vs 8.0, P = .444; 86.8% vs 90.2% satisfied with outcome). Six participants underwent revision after anterior fundoplication (Nissen conversion for reflux - 6), and 7 underwent revision after Nissen fundoplication (Nissen to partial fundoplication for dysphagia - 5; redo Nissen for reflux - 1; paraesophageal hernia -1). CONCLUSIONS: At 15 to 20 years follow-up Nissen and anterior 180-degree partial fundoplication achieved similar success, but with trade-offs between better reflux control versus more side-effects after Nissen fundoplication.

Routine Esophagograms After Hiatus Hernia Repair Minimizes Reoperative Morbidity: A Multicenter Comparative Cohort Study.

OBJECTIVE: Determine the utility of routine esophagograms after hiatus hernia repair and its impact on patient outcomes. BACKGROUND: Hiatus hernia repairs are common. Early complications such asre-herniation, esophageal obstruction and perforation, although infrequent, incur significant morbidity. Whether routine postoperative esophagograms enable early recognition of these complications, expedite surgical management, reduce reoperative morbidity, and improve functional outcomes are unclear. METHODS: Analysis of a prospectively-maintained database of hiatus hernia repairs in 14 hospitals, and review of esophagograms in this cohort. Results: A total of 1829 hiatus hernias were repaired. Of these, 1571 (85.9%) patients underwent a postoperative esophagogram. Overall, 1 in 48 esophagograms resulted in an early (<14 days) reoperation, which was undertaken in 44 (2.4%) patients. Compared to those without an esophagogram, patients who received this test before reoperation (n = 37) had a shorter time to diagnosis (2.4 vs 3.9 days, P = 0.041) and treatment (2.4 vs 4.3 days, P = 0.037) of their complications. This was associated with lower rates of open surgery (10.8% vs 42.9%, P = 0.034), gastric resection (0.0% vs 28.6%, P = 0.022), postoperative morbidity (13.5% vs 85.7%, P < 0.001), unplanned intensive care admission (16.2% vs 85.7%, P < 0.001), and decreased length-of-stay (7.3 vs 18.3 days, P = 0.009). Furthermore, we identified less intraoperative and postoperative complications, and superior functional outcomes at 1-year follow-up in patients who underwent early reoperations for an esophagogram-detected asymptomatic re-herniation than those who needed surgery for late symptomatic recurrences. CONCLUSIONS: Postoperative esophagograms decrease the morbidity associated with early and late reoperations, and should be considered for routine use after hiatus hernia surgery.

Partial Fundoplication is Effective Treatment for Female Patients with Gastroesophageal Reflux and Scleroderma: A Multicenter Comparative Cohort Study.

BACKGROUND: Patients with scleroderma often suffer from dysphagia and gastroesophageal reflux disease (GERD). Partial fundoplication is a validated anti-reflux procedure for GERD but may worsen dysphagia in scleroderma patients. Its utility in these patients is unknown. Here, we evaluate the efficacy and acceptability of partial fundoplication for the treatment of medically refractory GERD in patients with scleroderma. METHODS: Analysis of a prospectively maintained database of patients who underwent fundoplication across 14 hospitals between 1991 and 2019. Perioperative outcomes, reintervention rates, heartburn, dysphagia, and patient satisfaction were assessed at 3 months, 1- and 3-years post-surgery. RESULTS: A total of 17 patients with scleroderma were propensity score matched to 526 non-scleroderma controls. All underwent a partial fundoplication. Perioperative outcomes including complication rate, length of stay, and need for reoperation were similar between the two groups. Compared to baseline, both groups reported significantly improved heartburn at 3 months, 1- and 3-years following partial fundoplication. Surgery was equally effective at controlling heartburn across all follow-up timepoints in patients with or without scleroderma. Dysphagia to solids was more common in patients with scleroderma than controls at 3-months post-surgery, but was not significantly different to controls at 1- and 3-year follow-up. Satisfaction scores were high and comparable between both groups across all postoperative timepoints, with 100% of patients with scleroderma reporting that their initial choice to undergo surgery was correct. CONCLUSIONS: Partial fundoplication controls reflux and is associated with a transient period of dysphagia to solids in patients with scleroderma. This approach is safe, effective and acceptable for patients with scleroderma and medically refractory GERD.

Pharyngeal Pouch Surgery in Octo- and Nonagenarians is Safe and Effective: A Multicentre Comparative Cohort Study.

BACKGROUND: Surgery is the only effective treatment strategy for a symptomatic pharyngeal pouch. However, octo- and nonagenarians are often denied referral to a surgeon because of perceived increased risks. Here, we compare the outcomes of pharyngeal pouch surgery in octo- and nonagenarians with patients under 80 years-of-age and determine the factors which predict post-operative complications and improvement in swallowing. METHODS: Analysis of a prospectively maintained database of patients who underwent pharyngeal pouch surgery across seven hospitals over 15 years. RESULTS: In total, 113 patients (≥80 years-of-age: 27, <80 years-of-age: 86) underwent endoscopic or open pharyngeal pouch surgery. Despite more comorbidities and a longer hospital stay (median: one extra day), patients ≥80 years-of-age had comparable operative time, complication profile, intensive care admission, emergency reoperation, and revisional pouch surgery as their younger counterparts. Furthermore, the severity of complications was not significantly different between the two age cohorts. No surgical mortality was recorded. Multivariate analysis demonstrated that diverticulectomy combined with cricopharyngeal myotomy independently predicted higher rates of complications (OR: 4.53, 95% CI: 1.43-14.33, p = 0.010), but also greater symptomatic improvement (OR: 4.36, 95% CI: 1.50-12.67, p = 0.007). Importantly, a greater proportion of octo- and nonagenarians experienced improved swallowing than patients <80 years-of-age (96.3% vs. 74.4%, p = 0.013). Moreover, advanced age was not predictive of post-operative complications on multivariate analysis. CONCLUSIONS: Pharyngeal pouch surgery in octo- and nonagenarians is safe and effective. Surgical correction in this age group alleviates symptoms and improves quality-of-life for most patients. These patients should not be denied surgery on the basis of advanced age alone.

Health-Related Quality of Life Associated with Barrett's Esophagus and Cancer.

BACKGROUND: Research assessing health-related quality of life (HRQoL) which can be applied to economic evaluation in Barrett's esophagus (BE) and esophageal cancer is limited. This study derived health state utilities for various 'stages' of BE and Cancer. METHODS: A cross-sectional survey was conducted, including patients with non-dysplastic BE, low-grade dysplasia, high-grade dysplasia, or esophageal adenocarcinoma. HRQoL was assessed using generic instruments-EQ-5D-5L and SF-36, and a cancer-specific instrument-EORTC QLQ-C30. Outcomes were compared for health states following different treatments. Correlations and agreements for the three instruments were investigated using Spearman's correlation coefficient (r) and intraclass correlation coefficient (ICC). RESULTS: A total of 97 respondents (80% male, mean age 68 years) returned questionnaires. The mean (standard deviation) health state utilities for the total sample were 0.79 (0.24) for the EQ-5D-5L, 0.57 (0.29) for the SF-6D (derived from SF-36) and 0.73 (0.20) for the QLU-C10D (derived from EORTC QLQ-C30). There were strong correlations (r > 0.80) and absolute agreement (except EQ-5D-5L and SF-6D with an ICC of 0.69) among the three instruments. No significant differences were observed for different stages of BE or interventions. However, following surgery for cancer patients reported better psychological well-being than those under surveillance or following endoscopic treatments. CONCLUSION: HRQoL for BE surveillance and following cancer treatment was similar. Esophagectomy was associated with better psychological functioning, and this might be attributed to a reduction in the perceived risk of cancer. The correlation between the EORTC QLU-C10D and the other health state utility instruments supports the validity of this new instrument.

The role of rehabilitation in patients undergoing oesophagectomy for cancer and pre-malignant disease: A qualitative exploration of the views of patients, carers and healthcare providers.

OBJECTIVE: Oesophagectomy for cancer is associated with significant morbidity and mortality, and reduced quality of life. Structured rehabilitation potentially offers improved physical and psychological outcomes. We aimed to explore patient, carer and healthcare provider attitudes and preferences towards the role of rehabilitation. METHODS: We interviewed 15 patients who had undergone an oesophagectomy, 10 carers and 13 healthcare providers about perceived impacts of treatment; preferred components of a rehabilitation program; barriers/enablers of support provision; and participation in rehabilitation programs. Data were analysed using framework analysis. RESULTS: The overarching theme was "Getting back to normal." Diagnosis of disease signified a disruption to the normal trajectory of patients' lives and the post-treatment period was characterised as striving to return to normal. Patients and carers focused on rehabilitation needs post-treatment including dietary support, physiotherapy and healthcare provider support. Healthcare providers described rehabilitation as potentially beneficial from the pre-treatment phase and, along with carers, highlighted the importance of psychological support. Barriers included access to services, cost of service provision and appointment burden. CONCLUSION: A need for rehabilitation services was identified by healthcare providers from the point of diagnosis, rather than only after surgery. Implications include improved service provision by healthcare institutions for patients undergoing oesophagectomy.

Acceptable outcomes after fundoplication-different views are held by patients, GPs, and surgeons.

Antireflux surgery aims to improve quality of life. However, whether patients and clinicians agree on what this means, and what is an acceptable outcome following fundoplication, is unknown. This study used clinical scenarios pertinent to laparoscopic fundoplication for gastroesophageal reflux to define acceptable outcomes from the perspective of patients, surgeons, and general practitioners (GPs). Patients who had previously undergone a laparoscopic fundoplication, general practitioners, and esophagogastric surgeons were invited to rank 11 clinical scenarios of outcomes following laparoscopic fundoplication for acceptability. Clinicopathological and practice variables were collated for patients and clinicians, respectively. GPs and esophagogastric surgeons additionally were asked to estimate postfundoplication outcome probabilities. Descriptive and multivariate statistical analyses were undertaken to examine for associations with acceptability. Reponses were received from 331 patients (36.4% response rate), 93 GPs (13.4% response), and 60 surgeons (36.4% response). Bloating and inability to belch was less acceptable and dysphagia requiring intervention more acceptable to patients compared to clinicians. On regression analysis, female patients found bloating to be less acceptable (OR: 0.51 [95%CI: 0.29-0.91]; P = 0.022), but dysphagia more acceptable (OR: 1.93 [95%CI: 1.17-3.21]; P = 0.011). Postfundoplication estimation of reflux resolution was higher and that of bloating was lower for GPs compared to esophagogastric surgeons. Patients and clinicians have different appreciations of an acceptable outcome following antireflux surgery. Female patients are more concerned about wind-related side effects than male patients. The opposite holds true for dysphagia. Surgeons and GPs differ in their estimation of event probability for patient recovery following antireflux surgery, and this might explain their differing considerations of acceptable outcomes.

Randomized Trial of Division Versus Nondivision of Short Gastric Vessels During Nissen Fundoplication: 20-Year Outcomes.

OBJECTIVE: To evaluate late outcomes from a randomized trial of division versus no division of short gastric vessels during laparoscopic Nissen fundoplication at up to 20 years follow-up. BACKGROUND: Nissen fundoplication is an established procedure for the treatment of gastroesophageal reflux disease. Controversy about whether side effects such as dysphagia could be reduced by division of the short gastric vessels led to the establishment of a randomized trial in 1994. Early results showed equivalent reflux control and dysphagia, but more bloating after vessel division. METHODS: A total of 102 patients underwent a laparoscopic Nissen fundoplication between May 1994 and October 1995, and were randomized to short gastric vessel division (50) versus nondivision (52). Follow-up was obtained yearly to 20 years using a standardized questionnaire administered by a blinded investigator. Clinical outcomes at 20 years or most recent follow-up were determined. RESULTS: No significant differences for heartburn symptom and satisfaction scores or medication use were found between treatment groups. At 15 to 20 (mean 19.6) years follow-up, significant differences persisted for epigastric bloating: 26% versus 50% for nondivision versus division groups (P = 0.046). Heartburn symptom scores were low and not different for nondivision versus division groups (mean analog scores 1.4 vs 2.1/10, P = 0.152). Overall satisfaction after surgery was high in both groups (mean analog scores 8.1 vs 8.6/10, P = 0.989). CONCLUSIONS: Although laparoscopic Nissen fundoplication has durable efficacy for heartburn symptom control at up to 20 years follow-up, division of short-gastric vessels failed to confer any reduction in side effects, and was associated with persistent epigastric bloat symptoms at late follow-up in this trial.

Identification of microRNA Biomarkers of Response to Neoadjuvant Chemoradiotherapy in Esophageal Adenocarcinoma Using Next Generation Sequencing.

BACKGROUND: Clinical trials report improved overall survival following neoadjuvant chemoradiotherapy in patients undergoing surgery for esophageal adenocarcinoma, with a 10-15% survival improvement. MicroRNAs (miRNAs) are small noncoding RNAs that are known to direct the behavior of cancers, including response to treatment. We investigated the ability of miRNAs to predict outcomes after neoadjuvant chemoradiotherapy. METHODS: Endoscopic biopsies from esophageal adenocarcinomas were obtained before neoadjuvant chemoradiotherapy and esophagectomy. miRNA levels were measured in the biopsies using next generation sequencing and compared with pathological response in the surgical resection, and subsequent survival. miRNA ratios that predicted pathological response were identified by Lasso regression and leave-one-out cross-validation. Association between miRNA ratio candidates and relapse-free survival was assessed using Kaplan-Meier analysis. Cox regression and Harrell's C analyses were performed to assess the predictive performance of the miRNAs. RESULTS: Two miRNA ratios (miR-4521/miR-340-5p and miR-101-3p/miR-451a) that predicted the pathological response to neoadjuvant chemoradiotherapy were found to be associated with relapse-free survival. Pretreatment expression of these two miRNA ratios, pretreatment tumor differentiation, posttreatment AJCC histopathological tumor regression grading, and posttreatment tumor clearance/margins were significant factors associated with survival in Cox regression analysis. Multivariate analysis of the two ratios together with pretherapy factors resulted in a risk prediction accuracy of 85% (Harrell's C), which was comparable with the prediction accuracy of the AJCC treatment response grading (77%). CONCLUSIONS: miRNA-ratio biomarkers identified using next generation sequencing can be used to predict disease free survival following neoadjuvant chemoradiotherapy and esophagectomy in patients with esophageal adenocarcinoma.

Influence of tumor response and treatment schedule on the distribution of tumor recurrence in esophageal cancer patients treated with neoadjuvant chemoradiotherapy.

BACKGROUND AND OBJECTIVES: The impact of different neoadjuvant chemoradiotherapy (nCRT) schedules and pathologic complete response (pCR) on the distribution of recurrence is unclear in esophageal cancer (EC). We assessed the effect of pCR and nCRT schedule in EC. METHODS: Patients with T1N+/T2-4aN0-3/M0 EC treated in different centers, with either carboplatin/paclitaxel/41.4 Gy (CROSS: n = 134) or Cisplatin/5-fluorouracil/45-50.4 Gy (Cis/5FU: n = 88) followed by surgery were included. The effect of pCR on distribution and site-specific recurrence was determined for the CROSS group. After propensity score matching we compared the impact of both schedules (n = 63 each) on the recurrence pattern. RESULTS: Overall (P = 0.005) and disease-free survival (P = 0.002) were significantly longer after pCR (n = 24). The pattern of recurrence differed between pCR and non-pCR group (P = 0.001) for locoregional (0 vs 7; 6.4%), distant (5; 20.8% vs 36; 32.7%), and combined local and distant (0 vs 21; 19.1%), respectively. After pCR, less local and distant recurrences were seen (P = 0.008). With equal median time to recurrence, the distribution of metastases only differed for lung metastases (P = 0.029), with 15 (23.8%) in the CROSS group versus 6 (9.5%) following Cis/5FU. CONCLUSIONS: Patients with pCR have less local and distant recurrence. The nCRT regime had a minor influence on the site-specific distribution of recurrence.