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Colin J Ireland,1 Andrea L Gordon,2 Sarah K Thompson,3 David I Watson,4 David C Whiteman,5 Richard L Reed,6 Adrian Esterman1,7 1School of Nursing and Midwifery, Division of Health Sciences, University of South Australia, Adelaide, SA, Australia; 2School of Pharmacy and Medical Science, Division of Health Sciences, University of South Australia, Adelaide, SA, Australia; 3Discipline of Surgery, University of Adelaide, Adelaide, SA, Australia; 4Department of Surgery, Flinders University, Bedford Park, SA, Australia; 5Population Health Department, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia; 6Discipline of General Practice, Flinders University, Bedford Park, SA, Australia; 7Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD, Australia Background: Esophageal adenocarcinoma is a disease that has a high mortality rate, the only known precursor being Barrett’s esophagus (BE). While screening for BE is not cost-effective at the population level, targeted screening might be beneficial. We have developed a risk prediction model to identify people with BE, and here we present the external validation of this model. Materials and methods: A cohort study was undertaken to validate a risk prediction model for BE. Individuals with endoscopy and histopathology proven BE completed a questionnaire containing variables previously identified as risk factors for this condition. Their responses were combined with data from a population sample for analysis. Risk scores were derived for each participant. Overall performance of the risk prediction model in terms of calibration and discrimination was assessed. Results: Scores from 95 individuals with BE and 636 individuals from the general population were analyzed. The Brier score was 0.118, suggesting reasonable overall performance. The area under the receiver operating characteristic was 0.83 (95% CI 0.78–0.87). The Hosmer–Lemeshow statistic was p=0.14. Minimizing false positives and false negatives, the model achieved a sensitivity of 74% and a specificity of 73%. Conclusion: This study has validated a risk prediction model for BE that has a higher sensitivity than previous models. Keywords: Barrett’s esophagus, risk prediction model, screening, validation

Introduction: Gastroesophageal reflux is common, and when medical therapy is ineffective, alternative treatments should be considered. Nissen fundoplication controls reflux but can be followed by side effects such as dysphagia and flatulence. To improve outcomes, modifications have been advocated., Areas Covered: Modifications to Nissen fundoplication and newer procedures for gastroesophageal reflux aim to improve overall outcome. Randomized controlled trials (RCTs) and long-term outcomes from large cohorts are prioritized to consider the optimal procedure for reflux and hiatus hernia., Expert Opinion: Fundoplication is an effective treatment for gastroesophageal reflux, with success rates of >80% reported at 18-20-year follow-up. RCTs confirm that Nissen fundoplication delivers better reflux control than medication. However, some patients are troubled by side effects. Anterior and posterior partial fundoplication variants have been proposed as procedures that offer equally good reflux control, but fewer side effects, and RCTs have confirmed this with follow-up to 20 years. Which partial fundoplication is better is debated. Alternative laparoscopic or endoscopic approaches require expensive implants or equipment and deliver less reliable reflux control than partial fundoplication. Currently, level I evidence confirms that laparoscopic partial fundoplication delivers the optimal outcome in fit patients with reflux that is not well controlled by medication.

Background and Aim: The first step towards developing a screening strategy for Barrett's esophagus (BE) is the identification of individuals in the community. Currently available tools include endoscopy, less-invasive non-endoscopic devices, and non-invasive risk stratification models. We evaluated the cost of potential strategies for identification of BE as a first step towards screening., Methods: Two hypothetical cohorts of the general population aged ≥ 50 years with BE prevalence rates of 1.9% and 6.8% were modeled. Four potential screening tools were evaluated: (i) risk stratification based on non-weighted clinical factors according to US/European guidelines, (ii) weighted risk stratification using algorithmic models, (iii) less-invasive devices such as Cytosponge + trefoil factor 3 (TFF3), and (iv) endoscopy. Using a decision-analytic model, the cost per BE case identified and the cost-effectiveness were compared for six potential BE screening strategies based on combinations of the four screening tools; (i) + (iv), (ii) + (iv), (iii) + (iv), (i) + (iii) + (iv), (ii) + (iii) + (iv), and only (iv)., Results: The cost per BE case identified was lowest for the weighted risk stratification followed by Cytosponge-TFF3 then endoscopy strategy at both 1.9% and 6.8% BE prevalences (US$9282 and US$3406, respectively) although it was sensitive to the cost of less-invasive devices. This strategy was also most cost-effective for a BE prevalence of 1.9%. At BE prevalence of 6.8%, the Cytosponge-TFF3 followed by endoscopy strategy was most cost-effective., Conclusions: Incorporating weighted risk stratification and less-invasive devices such as Cytosponge-TFF3 into BE screening strategies has a potential to cost-effectively identify BE in the community although device cost and the community prevalence of BE will impact the optimal strategy., (© 2024 The Author(s). Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Some patients with gastroesophageal reflux (GERD) experience extraesophageal symptoms, which are considered due to laryngopharyngeal reflux (LPR). Most studies evaluating fundoplication for LPR report outcomes from individuals who also have typical esophageal GERD symptoms. Information is limited for patients with LPR but no GERD symptoms. To determine whether LPR patients benefit from fundoplication outcomes were determined for individuals with LPR ± GERD and also those without LPR., Methods: Patients undergoing fundoplication from 1997 to 2015 were identified and divided into three symptom groups: LPR only, LPR and GERD, and GERD only. Heartburn, dysphagia, and satisfaction were assessed using 0-10 analog scores and compared at short (1-2 years) and later (5 years) follow-up., Results: 2204 patients underwent fundoplication. 24 patients had LPR only, 130 patients had LPR and GERD, and matched to 1319 patients with GERD only. At 1-2 years follow-up, the LPR only group had lower satisfaction scores than those with GERD symptoms (± concurrent LPR) (7.00 ± 3.49 vs. 8.41 ± 2.42, p = 0.019, and mean ± s.d.). At 1-2 years, 68.1% of the LPR only group had a good outcome (satisfaction score: 7-10) versus 84.6% with LPR and GERD and 84.1% with GERD only., Conclusion: At 1-2 years follow-up, patients with LPR only were less satisfied following fundoplication compared with patients with typical GERD (±LPR). However, some patients with LPR only did benefit and might be considered for surgery if appropriately counseled. Outcomes were similar for patients with LPR and typical GERD and those with only typical symptoms., (© 2024 International Society of Surgery/Société Internationale de Chirurgie (ISS/SIC).)

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., (© The Author(s) 2024. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus.)

Purpose: Patients with gastroesophageal reflux disease often undergo a 24-hour pH test to confirm pathologic reflux before surgery. However, a negative pH test can occur in some individuals with reflux, and a case might still be made for antireflux surgery based on symptoms of reflux even in the absence of endoscopic esophagitis. The long-term outcomes in patients who underwent antireflux surgery despite negative preoperative test results were determined., Methods: Patients were selected from a prospective database. A total of 745 patients met the inclusion criteria, which included typical esophageal reflux symptoms, absence of a large hiatus hernia, preoperative 24-hour pH study performed, endoscopy, and postoperative symptom and satisfaction follow-up available at 5 years. Patients were divided into 3 groups based on 24-hour pH study and endoscopy results: negative pH and negative endoscopy (n = 65), negative pH and positive endoscopy (n = 72), and positive pH (n = 608). The negative pH and negative endoscopy group underwent surgery based on clinical assessment and typical esophageal reflux symptoms. Baseline and follow-up outcomes at 5 years were evaluated using 0 to 10 analog scores, which assessed heartburn, dysphagia, and satisfaction with the overall outcome. Data were analyzed to compare the groups., Results: The groups were well matched for demographics and preoperative symptom scores. At the median 5-year follow-up, clinical outcome scores were similar among the groups for heartburn, dysphagia, and overall satisfaction. The mean heartburn scores were 1.80 in the negative pH and negative endoscopy group, 1.88 in the negative pH and positive endoscopy group, and 1.91 in the positive pH group (P = .663). The mean satisfaction scores were high in all groups: 8.13, 7.31, and 7.72, respectively (P = .293)., Conclusion: No difference in clinical outcome scores was observed. The negative pH and negative endoscopy group had high satisfaction scores and low heartburn and dysphagia scores. Our findings support antireflux surgery in well-selected symptomatic patients with a negative preoperative pH test., (Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.)

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., (© 2024 The Authors. World Journal of Surgery published by John Wiley & Sons Ltd on behalf of International Society of Surgery/Société Internationale de Chirurgie (ISS/SIC).)

Objective: To explore the causes of the decrease in bladder cancer survival that has occurred over the past four decades., Methods: We extracted data from the South Australian Cancer Registry. Data from the period 1 January 1977 to 31 December 2020 were extracted to explore changes in incidence and survival among a total of 8356 patients diagnosed with ≥pT1 disease. Invasive bladder cancer was defined as ≥pT1 in this study., Results: Invasive bladder cancer age-standardized incidence decreased from 7.20 cases per 100 000 people in 1977 to 5.85 cases per 100 000 in 2020. The mean age at diagnosis increased from 68 years to 76 years. The crude incidence for patients aged 80 years and over increased by 3.3% per year (95% confidence interval [CI] 2.1 to 4.6). Overall survival decreased over the study period (hazard ratio [HR] 1.22 [95% CI 1.09 to 1.35]), however, survival increased after adjusting for age at diagnosis (HR 0.80 [95% CI 0.76 to 0.94]). Despite a decrease in non-bladder cancer-specific deaths in older people, there was no change in the bladder cancer-specific death rate in older people (HR 0.94 [95% CI 0.70 to 1.26]). Male sex was associated with higher survival (HR 0.87 [95% CI 0.83 to 0.92]), whereas socioeconomic advantage was not., Conclusions: Invasive bladder cancer survival has decreased over the past 40 years, with the age structure of the population being a significant contributing factor., Patient Summary: We looked at why bladder cancer survival is decreasing using a large cancer registry with information from 1977 to 2020. We found that people are now more likely to be diagnosed at an older age. Older people often live for a shorter time with bladder cancer compared to younger people. Bladder cancer survival has decreased because there are more older people with the disease than previously., (© 2024 The Authors. BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

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., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

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., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Up to 70% of people diagnosed with upper gastrointestinal (GI) tract or hepato-pancreato-biliary (HPB) cancers experience substantial reductions in quality of life (QoL), including high distress levels, pain, fatigue, sleep disturbances, weight loss and difficulty swallowing. With few advocacy groups and support systems for adults with upper GI or HPB cancers (i.e. pancreas, liver, stomach, bile duct and oesophageal) and their carers, online supportive care programs may represent an alternate cost-effective mechanism to support this patient group and carers. iCare is a self-directed, interactive, online program that provides information, resources, and psychological packages to patients and their carers from the treatment phase of their condition. The inception and development of iCare has been driven by consumers, advocacy groups, government and health professionals. The aims of this study are to determine the feasibility and acceptability of iCare, examine preliminary efficacy on health-related QoL and carer burden at 3- and 6-months post enrolment, and the potential cost-effectiveness of iCare, from health and societal perspectives, for both patients and carers., Methods and Analysis: A Phase II randomised controlled trial. Overall, 162 people with newly diagnosed upper GI or HPB cancers and 162 carers will be recruited via the Upper GI Cancer Registry, online advertisements, or hospital clinics. Patients and carers will be randomly allocated (1:1) to the iCare program or usual care. Participant assessments will be at enrolment, 3- and 6-months later. The primary outcomes are i) feasibility, measured by eligibility, recruitment, response and attrition rates, and ii) acceptability, measured by engagement with iCare (frequency of logins, time spent using iCare, and use of features over the intervention period). Secondary outcomes are patient changes in QoL and unmet needs, and carer burden, unmet needs and QoL. Linear mixed models will be fitted to obtain preliminary estimates of efficacy and variability for secondary outcomes. The economic analysis will include a cost-consequences analysis where all outcomes will be compared with costs., Discussion: iCare provides a potential model of supportive care to improve QoL, unmet needs and burden of disease among people living with upper GI or HPB cancers and their carers., Australian and New Zealand Clinical Trials Registry: ACTRN12623001185651. This protocol reflects Version #1 26 April 2023., (© 2024. The Author(s).)

Background: New evidence has emerged since latest guidelines on the management of paraesophageal hernia, and guideline development methodology has evolved. Members of the European Association for Endoscopic Surgery have prioritized the management of paraesophageal hernia to be addressed by pertinent recommendations., Objective: To develop evidence-informed clinical practice recommendations on paraesophageal hernias, through evidence synthesis and a structured evidence-to-decision framework by an interdisciplinary panel of stakeholders., Methods: We performed three systematic reviews, and we summarized and appraised the certainty of the evidence using the GRADE methodology. A panel of general and upper gastrointestinal surgeons, gastroenterologists and a patient advocate discussed the evidence in the context of benefits and harms, the certainty of the evidence, acceptability, feasibility, equity, cost and use of resources, moderated by a Guidelines International Network-certified master guideline developer and chair. We developed the recommendations in a consensus meeting, followed by a modified Delphi survey., Results: The panel suggests surgery over conservative management for asymptomatic/minimally symptomatic paraesophageal hernias (conditional recommendation), and recommends conservative management over surgery for asymptomatic/minimally symptomatic paraesophageal hernias in frail patients (strong recommendation). Further, the panel suggests mesh over sutures for hiatal closure in paraesophageal hernia repair, fundoplication over gastropexy in elective paraesophageal hernia repair, and gastropexy over fundoplication in patients who have cardiopulmonary instability and require emergency paraesophageal hernia repair (conditional recommendation). A strong recommendation means that the proposed course of action is appropriate for the vast majority of patients. A conditional recommendation means that most patients would opt for the proposed course of action, and joint decision-making of the surgeon and the patient is required. Accompanying evidence summaries and evidence-to-decision frameworks should be read when using the recommendations. This guideline applies to adult patients with moderate to large paraesophageal hernias type II to IV with at least 50% of the stomach herniated to the thoracic cavity. The full guideline with user-friendly decision aids is available in https://app.magicapp.org/#/guideline/j7q7Gn ., Conclusion: An interdisciplinary panel provides recommendations on key topics on the management of paraesophageal hernias using highest methodological standards and following a transparent process., Guideline Registration Number: PREPARE-2023CN018., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Nausea is a common and unpleasant sensation for which current therapies such as serotonin (5-HT 3 ) antagonists are often ineffective, while also conferring a risk of potential adverse events. Isopropyl alcohol (IPA) has been proposed as a treatment for nausea. We aimed to compare IPA with 5-HT 3 antagonists for the treatment of nausea across all clinical settings., Methods: MEDLINE, EMBASE, PubMed, CENTRAL and CINAHL were searched from inception to 17 July 2023 for randomised controlled trials (RCTs) comparing inhaled IPA and a 5-HT 3 antagonist for treatment of nausea. Severity and duration of nausea, rescue antiemetic use, adverse events and patient satisfaction were the outcomes sought. Risk of bias (RoB) was assessed using Cochrane RoB 2. Random-effects model was used for meta-analysis. Combination of meta-analyses and narrative review was used to synthesise findings. The evidence was appraised using GRADE., Results: From 1242 records, 4 RCTs were included with 382 participants. Participants receiving IPA had a significantly lower mean time to 50% reduction in nausea (MD - 20.06; 95% CI - 26.26, - 13.85). Nausea score reduction at 30 min was significantly greater in the IPA group (MD 21.47; 95% CI 15.47, 27.47). IPA led to significantly reduced requirement for rescue antiemetics (OR 0.60; 95% CI 0.37, 0.95; p = 0.03). IPA led to no significant difference in patient satisfaction when compared with a 5-HT 3 antagonist. The overall GRADE assessment of evidence quality ranged from very low to low., Conclusion: IPA may provide rapid, effective relief of nausea when compared with 5-HT 3 antagonists., (© 2023. The Author(s).)

Large hiatus hernias with a significant paraesophageal component (types II-IV) have a range of insidious symptoms. Management of symptomatic hernias includes conservative treatment or surgery. Currently, there is no paraesophageal hernia disease-specific symptom questionnaire. As a result, many clinicians rely on the health-related quality of life questionnaires designed for gastro-esophageal reflux disease (GORD) to assess patients with hiatal hernias pre- and postoperatively. In view of this, a paraesophageal hernia symptom tool (POST) was designed. This POST questionnaire now requires validation and assessment of clinical utility. Twenty-one international sites will recruit patients with paraesophageal hernias to complete a series of questionnaires over a five-year period. There will be two cohorts of patients-patients with paraesophageal hernias undergoing surgery and patients managed conservatively. Patients are required to complete a validated GORD-HRQL, POST questionnaire, and satisfaction questionnaire preoperatively. Surgical cohorts will also complete questionnaires postoperatively at 4-6 weeks, 6 months, 12 months, and then annually for a total of 5 years. Conservatively managed patients will repeat questionnaires at 1 year. The first set of results will be released after 1 year with complete data published after a 5-year follow-up. The main results of the study will be patient's acceptance of the POST tool, clinical utility of the tool, assessment of the threshold for surgery, and patient symptom response to surgery. The study will validate the POST questionnaire and identify the relevance of the questionnaire in routine management of paraesophageal hernias., (© The Author(s) 2023. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Revisional antireflux surgery, including hiatus hernia repair, is increasingly common. Mesh-augmented hiatal closure at the time of index operation is controversial but commonly performed. Although a meta-analysis of randomized data has demonstrated no additional benefit of routine mesh placement, it is unclear whether this practice results in harm, particularly at the time of revisional antireflux surgery. We determined whether pre-existing mesh at the hiatus increases morbidity during and after revisional antireflux surgery., Methods: Analysis of prospectively-maintained databases of all elective revisional antireflux surgery cases in 36 hospitals across Australia took place over 10 years. Intraoperative and postoperative outcomes of patients with and without prior hiatal mesh were compared. Propensity score-matched analysis was used to validate primary findings., Results: A total of 346 revisional cases (35 with pre-existing mesh) were analyzed. The 2 groups had comparable baseline characteristics. In total, 77 (22.2%) patients had 148 intraoperative adverse events. Pre-existing mesh was associated with a higher risk of intraoperative complications (48.6% vs 22.5%, odds ratio 3.25, 95% confidence interval 1.63-6.38, P = .002), secondary to bleeding, and lacerations to pleura, lung, and liver. Overall, 63 (18.2%) patients developed postoperative complications. Pre-existing mesh was associated with increased postoperative morbidity (37.1% vs 16.1%, odds ratio 3.09, 95% confidence interval 1.50-6.43, P = .005), particularly due to bleeding and respiratory complications. Importantly, pre-existing mesh independently predicted the occurrence of intraoperative and postoperative complications., Conclusion: Prior hiatal mesh significantly increases morbidity during and after revisional antireflux surgery. Given that revisional surgery is increasingly being performed, our findings discourage routine mesh use during primary antireflux surgery., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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., (© 2023. The Author(s).)

Oesophageal adenocarcinoma is a poor prognosis cancer and the molecular features underpinning response to treatment remain unclear. We investigate whole genome, transcriptomic and methylation data from 115 oesophageal adenocarcinoma patients mostly from the DOCTOR phase II clinical trial (Australian New Zealand Clinical Trials Registry-ACTRN12609000665235), with exploratory analysis pre-specified in the study protocol of the trial. We report genomic features associated with poorer overall survival, such as the APOBEC mutational and RS3-like rearrangement signatures. We also show that positron emission tomography non-responders have more sub-clonal genomic copy number alterations. Transcriptomic analysis categorises patients into four immune clusters correlated with survival. The immune suppressed cluster is associated with worse survival, enriched with myeloid-derived cells, and an epithelial-mesenchymal transition signature. The immune hot cluster is associated with better survival, enriched with lymphocytes, myeloid-derived cells, and an immune signature including CCL5, CD8A, and NKG7. The immune clusters highlight patients who may respond to immunotherapy and thus may guide future clinical trials., (© 2023. The Author(s).)

Cancer is a leading cause of global morbidity and mortality, accounting for 250 Disability-Adjusted Life Years and 10 million deaths in 2019. Minimising unwarranted variation and ensuring appropriate cost-effective treatment across primary and tertiary care to improve health outcomes is a key health priority. There are few studies that have used linked data to explore healthcare utilisation prior to diagnosis in addition to post-diagnosis patterns of care. This protocol outlines the aims of the DaLECC project and key methodological features of the linked dataset. The primary aim of this project is to explore predictors of variations in pre- and post-cancer diagnosis care, and to explore the economic and health impact of any variation. The cohort of patients includes all South Australian residents diagnosed with cancer between 2011 and 2020, who were recorded on the South Australian Cancer Registry. These cancer registry records are being linked with state and national healthcare databases to capture health service utilisation and costs for a minimum of one-year prior to diagnosis and to a maximum of 10 years post-diagnosis. Healthcare utilisation includes state databases for inpatient separations and emergency department presentations and national databases for Medicare services and pharmaceuticals. Our results will identify barriers to timely receipt of care, estimate the impact of variations in the use of health care, and provide evidence to support interventions to improve health outcomes to inform national and local decisions to enhance the access and uptake of health care services.

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., (© The Author(s) 2023. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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.

Background: Breast reduction surgery has been shown to be the most effective treatment for symptomatic breast hypertrophy in women. However, existing studies have been limited to a relatively short-term follow-up. This study aimed to assess the long-term outcomes following breast reduction surgery., Methods: This is a prospective cohort study of women aged 18 years and above who underwent breast reduction surgery over a 12-year period. Participants completed a series of patient-reported outcome measures, including the Short Form-36 (SF-36), BREAST-Q reduction module, Multidimensional Body-Self Relations Questionnaire (MBSRQ), and study-specific questions preoperatively, 12 months postoperatively, and at a long-term follow-up of up to 12 years postoperatively., Results: Long-term outcome data were obtained from 103 participants. The median follow-up time following surgery was 6.0 years, range 3-12 years. The mean SF-36 scores remained stable and significantly higher than baseline over time, with no significant differences found in all eight subscales or summary scales. BREAST-Q scores remained significantly higher than baseline in all four scales. MBSRQ scores for appearance evaluation, health evaluation, and body areas satisfaction score remained significantly higher than scores reported preoperatively; in contrast, scores for appearance and health orientation and self-classified weight were significantly lower. Compared with normative data, long-term outcome scores remained stable and at levels equivalent or beyond population norms., Conclusions: This study demonstrated that patients continue to report a high level of satisfaction and improved health-related quality of life in the longer term following breast reduction surgery., Competing Interests: Conflict of interest statement None., (Copyright © 2023 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Background: Oesophageal cancer is the eighth most common cancer and sixth leading cause of cancer-related mortality worldwide. Salvage oesophagectomies are associated with an increased risk of mortality, although recent data suggests that long-term survival rates following salvage oesophagectomy are similar to planned oesophagectomy. The aim was therefore to meta-analyse outcomes for patients undergoing salvage versus planned oesophagectomies to assess the differences in short-term mortality and long-term survival., Methods: A systematic review of Medline, Scopus, Web of Science and PubMed was performed to identify relevant studies. Data were extracted and compared by meta-analysis, using odds ratio and mean differences with 95% confidence intervals., Results: Nineteen studies meeting inclusion criteria were included in the meta-analysis, which compared patients in the planned oesophagectomy group (n = 23 555) to patients in the salvage oesophagectomy group (n = 2227). There were significant differences between the groups in terms of rates of postoperative mortality (5.7% salvage oesophagectomy versus 3.1% planned oesophagectomy, P = 0.0004), anastomotic leak (20.6% salvage oesophagectomy versus 14.5% planned oesophagectomy, P < 0.00001), pulmonary complications (37.1% salvage oesophagectomy versus 24.2% planned oesophagectomy, P < 0.0001) and R0 margin (87.6% salvage oesophagectomy versus 91.3% planned oesophagectomy, P < 0.0001). There was no statistical difference between long-term survival rates at 5 years with 39.2% for salvage and 42.6% for planned oesophagectomy (P = 0.28)., Conclusions: Salvage oesophagectomies do offer a meaningful chance of long-term survival (at 5 years) for select patients with oesophageal cancer, but the elevated risk of post-operative complications and mortality following salvage oesophagectomy should be recognized., (© 2022 Royal Australasian College of Surgeons.)

Background: Recent studies have shown that radiation-induced pelvic toxicity often requires urological consultation. However, the 10-year incidence of genitourinary toxicity following intensity-modulated radiotherapy (IMRT) amongst patients with localised prostate cancer remains unclear. Hence, we conducted a systematic review and meta-analysis to determine the incidence of late genitourinary toxicity relying on Radiation Therapy Oncology Group (RTOG) and Common Terminology Criteria for Adverse Events (CTCAE) grade as well as the incidence of specific genitourinary toxicity. Secondary objectives involved quantifing the number of studies reporting 120-month follow-up endpoints, time to event analysis, predictive factors or economic evaluation., Methods: Articles published from January 2008 to December 2021 describing prospective studies were systematically searched in MEDLINE, EMBASE and Cochrane (PROSPERO protocol CRD42019133320). Quality assessment was performed by use of the Cochrane Risk of Bias 2 Tool for RCTs and the Newcastle Ottowa Scale for non-RCTs. Meta-analysis was performed on the 60-month incidence of RTOG and CTCAE Grade ≥2 genitourinary toxicity, haematuria, urinary retention and urinary incontinence., Results: We screened 4721 studies and six studies met our inclusion criteria. All included studies involved normofractionation, three included a hypofractionation comparator arm and none involved nodal irradiation. The pooled 60-month cumulative incidence of RTOG and CTCAE Grade ≥2 genitourinary toxicity were 17% (95% CI: 5-20%, n = 678) and 33% (95% CI: 27-38%, n = 153), respectively. The pooled 60-month cumulative incidence of Haematuria was 5% (95% CI: -4-14%, n = 48), Urinary incontinence 12% (95% CI: 6-18%, n = 194), Urinary retention 24% (95% CI: 9-40%, n = 10). One study reported time to event analyses, one reported predictive factors, no studies reported economic analysis or 120-month toxicity. There was considerable heterogeneity amongst the studies., Conclusion: There are few high-quality studies reporting 60-month toxicity rates after IMRT. Conservative estimates of 60-month toxicity rates are high and there is need for longer follow-up and consistent toxicity reporting standards., (© 2022. Crown.)

Objective: To determine whether early (before skin closure) versus postoperative chemoprophylaxis affects the incidence of venous thromboembolism (VTE) and bleeding following major abdominal surgery, in a high thromboembolic risk population., Background: Major abdominal surgery incurs both VTE and bleeding risks. Patients with high preoperative VTE risk derive the most benefit from chemoprophylaxis, but carry an increased risk of bleeding. The optimal window for chemoprophylaxis in the perioperative period, whereby both VTE and bleeding risks are minimized, is unknown., Methods: Analysis of pooled data from 5 multicenter studies including only high thromboembolic risk (Caprini score >4) patients. Clinical VTE was defined as radiographically proven symptomatic disease <30 days postsurgery. Major bleeding was defined as the need for blood transfusion, reintervention, or >20 g/L fall in hemoglobin., Results: From 5501 cases, chemoprophylaxis was initiated early in 1752 (31.8%) patients and postoperatively in 3749 (68.2%) patients. Baseline characteristics were similar between study groups. The incidence of clinical VTE was not associated with chemoprophylaxis timing [early 0.7% vs. postop 0.7%, odds ratio (OR): 1.11, 95% confidence interval (CI): 0.60-2.15, P =0.730]. Contrastingly, compared with postoperative chemoprophylaxis, early usage increased the risk of all bleeding (5.1% vs. 2.6%, OR: 2.04, 95% CI: 1.52-2.73, P <0.001) major bleeding (3.6% vs. 1.8%, OR: 1.99, 95% CI: 1.40-2.81, P <0.001), and reintervention (2.0% vs. 1.0%, OR: 2.10, 95% CI: 1.32-3.35, P =0.003). Early chemoprophylaxis independently predicted postoperative bleeding (OR: 1.71, 95% CI: 1.25-2.34, P <0.001), but not VTE., Conclusions: In high VTE risk patients undergoing major abdominal surgery, chemoprophylaxis commenced postoperatively reduces bleeding risk without affecting clinical VTE risk., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: There is currently a lack of evidence-based guidelines regarding surveillance for recurrence after esophageal and gastric (OG) cancer surgical resection, and which symptoms should prompt endoscopic or radiological investigations for recurrence. The aim of this study was to develop a core symptom set using a modified Delphi consensus process that should guide clinicians to carry out investigations to look for suspected recurrent OG cancer in previously asymptomatic patients., Methods: A web-based survey of 42 questions was sent to surgeons performing OG cancer resections at high volume centers. The first section evaluated the structure of follow-up and the second, determinants of follow-up. Two rounds of a modified Delphi consensus process and a further consensus workshop were used to determine symptoms warranting further investigations. Symptoms with a 75% consensus agreement as suggestive of recurrent cancer were included in the core symptom set., Results: 27 surgeons completed the questionnaires. A total of 70.3% of centers reported standardized surveillance protocols, whereas 3.7% of surgeons did not undertake any surveillance in asymptomatic patients after OG cancer resection. In asymptomatic patients, 40.1% and 25.9% of centers performed routine imaging and endoscopy, respectively. The core set that reached consensus, consisted of eight symptoms that warranted further investigations included; dysphagia to solid food, dysphagia to liquids, vomiting, abdominal pain, chest pain, regurgitation of foods, unexpected weight loss and progressive hoarseness of voice., Conclusion: There is global variation in monitoring patients after OG cancer resection. Eight symptoms were identified by the consensus process as important in prompting radiological or endoscopic investigation for suspected recurrent malignancy. Further randomized controlled trials are necessary to link surveillance strategies to survival outcomes and evaluate prognostic value., (© The Author(s) 2022. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus.)

Purpose: The risk of treatment-related toxicity is important for patients with localised prostate cancer to consider when deciding between treatment options. We developed a model to predict hospitalisation for radiation-induced genitourinary toxicity based on patient characteristics., Methods: The prospective South Australian Prostate Cancer Clinical Outcomes registry was used to identify men with localised prostate cancer who underwent curative intent external beam radiotherapy (EBRT) between 1998 and 2019. Multivariable Cox proportional regression was performed. Model discrimination, calibration, internal validation and utility were assessed using C-statistics and area under ROC, calibration plots, bootstrapping, and decision curve analysis, respectively., Results: There were 3,243 patients treated with EBRT included, of which 644 (20%) patients had a treated-related admission. In multivariable analysis, diabetes (HR 1.35, 95% CI 1.13-1.60, p < 0.001), smoking (HR 1.78, 95% CI 1.40-2.12, p < 0.001), and bladder outlet obstruction (BOO) without transurethral resection of prostate (TURP) (HR 7.49, 95% CI 6.18-9.08 p < 0.001) followed by BOO with TURP (HR 4.96, 95% CI 4.10-5.99 p < 0.001) were strong independent predictors of hospitalisation (censor-adjusted c-statistic = 0.80). The model was well-calibrated (AUC = 0.76). The global proportional hazards were met. In internal validation through bootstrapping, the model was reasonably discriminate at five (AUC 0.75) years after radiotherapy., Conclusions: This is the first study to develop a predictive model for genitourinary toxicity requiring hospitalisation amongst men with prostate cancer treated with EBRT. Patients with localised prostate cancer and concurrent BOO may benefit from TURP before EBRT., (© 2022. Crown.)

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., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: There are several options for the surgical management of GERD in adults. Previous guidelines and systematic reviews have compared the effects of total fundoplication versus pooled effects of different techniques of partial fundoplication., Objective: To develop evidence-informed, trustworthy, pertinent recommendations on the use of total, posterior partial and anterior partial fundoplications for the management of GERD in adults., Methods: We performed an update systematic review, network meta-analysis, and evidence appraisal using the GRADE and the Confidence in Network Meta-Analysis methodologies. An international, multidisciplinary panel of surgeons, gastroenterologists, and a patient representative reached unanimous consensus through an evidence-to-decision framework to select among multiple interventions, and a Delphi process to formulate the recommendation. The project was developed in an online authoring and publication platform (MAGICapp), and was overseen by an external auditor., Results: We suggest posterior partial fundoplication over total posterior or anterior 90° fundoplication in adult patients with GERD. We suggest anterior >90° fundoplication as an alternative, although relevant comparative evidence is limited (weak recommendation). The guideline, with recommendations, evidence summaries and decision aids in user friendly formats can also be accessed in MAGICapp: https://app.magicapp.org/#/guideline/j20X4n., Conclusion: This rapid guideline was developed in line with highest methodological standards and provides evidence-informed recommendations on the surgical management of GERD. It provides user-friendly decision aids to inform healthcare professionals' and patients' decision making., (© 2022 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Purpose: Studies of genitourinary toxicity following radiotherapy for prostate cancer are mainly from high volume single institutions and the incidence and burden of treatment remain uncertain. Hence we determine the cumulative incidence of treatment-related genitourinary toxicity in patients with localised prostate cancer treated with primary external beam radiotherapy (EBRT) at a state population level., Methods: We analysed data from a prospective population-based cohort, including hospital admission and cancer registry data, for men with localised prostate cancer who underwent primary EBRT without nodal irradiation between 1998 and 2019 in South Australia. The 10-year cumulative incidence of genitourinary toxicity requiring hospitalisation or procedures was determined. Clinical predictors of toxicity and the volume of admissions, non-operative, minor operative and major operative procedures were determined., Results: All the included patients (n = 3350) had EBRT, with a median (IQR) of 74 Gy (70-78) in 37 fractions (35-39). The 10-year cumulative incidence of was 28.4% (95% CI 26.3-30.6) with a total of 2545 hospital admissions, including 1040 (41%) emergency and 1893 (74%) readmissions. The 10-year cumulative incidence of patients in this cohort requiring a urological operative procedure was 18% (95% CI 16.1-19.9), with a total of 106 (4.2%) non-operative, 1044 (41%) minor operative and 57 (2.2%) major operative urological procedures., Conclusions: Genitourinary toxicity after radiotherapy for prostate cancer is common. Although there continue to be advancements in radiotherapy techniques, patients and physicians should be aware of the risk of late toxicity when considering EBRT., (© 2022. Crown.)

Aims: Gastric cancer with peritoneal involvement has a poor prognosis. Intraperitoneal (IP) paclitaxel has shown promising results in these patients. However, this approach has only been studied in the Asian population, and in combination with S-1. We investigated the maximum tolerated dose of IP paclitaxel, with a standard chemotherapy combination, in the Australian population., Methods: The study of the population included metastatic human epidermal growth factor receptor 2 (HER2) negative gastric adenocarcinoma with peritoneal involvement. Treatment included six 21-day cycles of cisplatin (80 mg/m 2 IV, day 1) plus capecitabine (1000 mg/m 2 PO BD, days 1-14) plus IP paclitaxel (days 1 and 8). IP paclitaxel doses for cohort 1-3 were 10, 20, and 30 mg/m 2 , respectively, in a 3 + 3 standard dose-escalation design., Results: Fifteen patients were enrolled of which 6 were female and the median age was 63. Two patients developed dose-limiting toxicities. No grade 4/5 toxicities were recorded. The maximum tolerated dose was not reached. Therefore, as defined by the study protocol, the recommended phase-2 dose for IP paclitaxel was determined to be 30 mg/m 2 . The 12-month survival rate was 46.7%, and the median survival was 11.5 months (interquartile range [IQR]: 15.3-6.9)., Conclusions: IP paclitaxel is safe in combination with cisplatin and capecitabine and the recommended phase-2 dose is 30 mg/m 2 ., (© 2021 John Wiley & Sons Australia, Ltd.)

Background: The aim of this study was to develop a symptom severity instrument (ParaOesophageal hernia SympTom (POST) tool) specific to para-oesophageal hernia (POH)., Methods: The POST tool was developed in four stages. The first was establishment of a Steering Committee. In the second stage, items were generated through a systematic review and online scoping survey of international experts. In the third stage, a three-round modified Delphi consensus process was conducted with a group of international experts who were asked to rate the importance of candidate items. An a priori threshold for inclusion was set at 80 per cent. The modified Delphi process culminated in a consensus meeting to develop the first iteration of the tool. In the final stage, two international patient workshops were held to assess the content validity and acceptability of the POST tool., Results: The systematic review and scoping survey generated 64 symptoms, refined to 20 for inclusion in the modified Delphi consensus process. Twenty-six global experts participated in the Delphi consensus process. Five symptoms reached consensus across two rounds: difficulty getting solid foods down, chest pain after meals, difficulty getting liquids down, shortness of breath only after meals, and an early feeling of fullness after eating. The subsequent patient workshops deemed these five symptoms to be relevant and suggested that reflux should be included; these were taken forward to create the final POST tool., Conclusion: The POST tool is the first instrument designed to capture POH-specific symptoms. It will allow clinicians to standardize reporting of symptoms of POH and evaluate the response to surgical intervention., (© The Author(s) 2022. Published by Oxford University Press on behalf of BJS Society Ltd. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Oesophageal adenocarcinoma is a rapidly increasing problem in which treatment options are limited. Previous studies have shown that oesophageal adenocarcinoma cells and tissues express oestrogen receptors (ERs) and show growth suppression and apoptosis in response to ER modulator agents such as tamoxifen. ERs are known to be expressed in a number of isoforms that act together to regulate cell growth and cell death. In this study, we used western blotting to profile the expression of ERα and ERβ isoforms, and expression of the oncologically related molecules p53, HER2, and EGFR, in a panel of oesophageal adenocarcinoma cell lines. The cytotoxicity of tamoxifen in the cell lines was determined with Annexin V-FITC flow cytometry, and correlations between cytotoxicity and receptor expression were assessed using Spearman's rank-order correlation. Oesophageal adenocarcinoma cell lines showed varying cytotoxicity in response to tamoxifen. The ER species ERα90, ERα50, and ERα46, as well as p53, were positively associated with a cytotoxic response. Conversely, ERα74, ERα70, and ERβ54 were associated with a lack of cytotoxic response. The ER species detected in oesophageal adenocarcinoma cells may work together to confer sensitivity to ER modulators in this disease, which could open up a new avenue for therapy in selected patients.

Objective: To assess the cost-effectiveness of breast reduction surgery for women with symptomatic breast hypertrophy in Australia., Design: Cost-utility analysis of data from a prospective cohort study., Setting, Participants: Adult women with symptomatic breast hypertrophy assessed for bilateral breast reduction at the Flinders Medical Centre, a public tertiary hospital in Adelaide, April 2007 - February 2018. The control group included women with breast hypertrophy who had not undergone surgery., Main Outcome Measures: Health care costs (for the surgical admission and other related hospital costs within 12 months of surgery) and SF-6D utility scores (measure of health-related quality of life) were used to calculate incremental costs per quality-adjusted life-year (QALY) gained over 12 months, extrapolated to a 10-year time horizon., Results: Of 251 women who underwent breast reduction, 209 completed the baseline and at least one post-operation assessment (83%; intervention group); 124 of 350 invited women waiting for breast reduction surgery completed the baseline and 12-month assessments (35%; control group). In the intervention group, the mean SF-6D utility score increased from 0.313 (SD, 0.263) at baseline to 0.626 (SD, 0.277) at 12 months; in the control group, it declined from 0.296 (SD, 0.267) to 0.270 (SD, 0.257). The mean QALY gain was consequently greater for the intervention group (adjusted difference, 1.519; 95% CI, 1.362-1.675). The mean hospital cost per patient was $11 857 (SD, $4322), and the incremental cost-effectiveness ratio (ICER) for the intervention was $7808 per QALY gained. The probability of breast reduction surgery being cost-effective was 100% at a willingness-to-pay threshold of $50 000 per QALY and 88% at $28 033 per QALY., Conclusions: Breast reduction surgery for women with symptomatic breast hypertrophy is cost-effective and should be available to women through the Australian public healthcare system., (© 2021 AMPCo Pty Ltd.)