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Abstract: Background: A national initiative in Ireland in 2000 defined 13 designated Units to provide care for symptomatic breast cancer, and resources, including an ability to develop audit programmes, were provided. In the absence of a national audit of breast cancer outcomes, the aim of this study is to provide a detailed report of one Unit''s subsequent experience, in particular comparing process and outcome data with international norms and benchmarks, and to infer on the likely impact of the national initiative. Methods: A 5-year prospective audit of patients presenting to the Symptomatic Breast Clinic from 2001 to 2005 was conducted. All cancer diagnoses were discussed at the Breast Multidisciplinary Conference, and all clincopathological treatment details and follow-up information were entered by a full-time data manager. Overall survival was calculated using the Kaplan–Meier method. Results: Eight hundred and thirty-nine patients were diagnosed through the clinic, 18 (2%) Stage 0, 169 (20%) Stage I, 380 (45%) Stage II, 142 (17%) Stage III, and 123 (15%) Stage IV. At a median follow-up of 35 months the overall 5-year survival was 71%, with 100%, 91%, 83%, 72%, and 11% survival for Stages 0–IV, respectively, and disease-specific survival of 82%. Conclusions: The process and outcome data are consistent with international benchmarks. These data from one designated centre support the national initiatives in Ireland to restructure breast services. [Copyright &y& Elsevier]

AbstractPurposeMethodResultConclusionThe impact of long-term aerodigestive symptoms following oesophageal cancer surgery is still not well understood. This study aimed to qualitatively understand the long-term impact of aerodigestive symptoms on quality of life in adults post-oesophagectomy.Participants who received curative transhiatal/transthoracic surgery for oesophageal cancer in Ireland’s National Oesophageal Cancer Centre were invited to attend semi-structured interviews. Surgery had to be completed at least 12 months prior. Reflexive thematic analysis was conducted.Forty participants were interviewed individually face-to-face. Four key themes were identified: (a) isolation, reflecting the reported solitude experienced by oesophageal cancer survivors when attempting to manage their ongoing aerodigestive symptoms; (b) fear, including fear of choking and fear that dysphagia symptoms may indicate recurrence of oesophageal cancer; (c) altered work capacity, caused by ongoing aerodigestive symptoms; and (d) avoidance of social situations involving food, due to the pain, discomfort, and embarrassment caused by these symptoms.Oesophageal cancer treatment can be lifesaving, however, such medical interventions can result in distressing physiological aerodigestive symptoms throughout survivorship, which can significantly impact quality of life. Our findings indicate a need for greater community support to manage aerodigestive symptoms and reduce the impact these have on quality of life. [ABSTRACT FROM AUTHOR]

Abstract: Recent evidence links obesity with the rising incidence of oesophageal adenocarcinoma. In Ireland between 1995 and 2004 the incidence of oesophageal adenocarcinoma increased by 38%, and this coincided with a 67% increase in the prevalence of obesity. In this study, a prospective case-control study was undertaken in 760 patients presenting to a tertiary centre between 1994 and 2004 diagnosed with cancer of the oesophagus, gastric cardia or stomach. Data were compared with 893 healthy controls. Multivariate logistic regression models were used to calculate the odds ratio (OR) of developing either cancer type according to quartiles of body mass index (BMI). Based on pre-illness BMI, 82% of patients who developed adenocarcinoma of the oesophagus were either overweight or obese compared with 59% of the healthy control population (P <0.001). A dose-dependent relationship existed between BMI and oesophageal adenocarcinoma in males. The adjusted odds ratio was 4.3 (95% CI: 2.3–7.9) among males in the highest BMI quartile compared with males in the lowest quartile (P <0.001 for trend). Using common cut-off points for BMI, the OR of adenocarcinoma of the lower oesophagus was 11.3 times higher (95% CI: 3.5–36.4) for individuals with a BMI >30kg/m2 versus individuals with a BMI <22kg/m2 (P <0.001 for trend). For adenocarcinoma of the gastric cardia, males in the top quartile of BMI had an OR of 3.5 (95% CI: 1.3–9.4) compared with the lowest quartile (P =0.03 for trend). A significant (P <0.001) inverse relationship between BMI and oesophageal SCC was observed. The odds ratio for adenocarcinoma of the oesophagus, the oesophago-gastric junction and gastric cardia rose significantly with increasing BMI. For tumours of the lower oesophagus, obesity increased the risk 10.9-fold. The increased risk is significant in males only. [Copyright &y& Elsevier]

Introduction: The emergence of the novel coronavirus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and the coronavirus disease COVID-19 has impacted enormously on non-COVID-19-related hospital care. Curtailment of intensive care unit (ICU) access threatens complex surgery, particularly impacting on outcomes for time-sensitive cancer surgery. Oesophageal cancer surgery is a good example. This study explored the impact of the pandemic on process and short-term surgical outcomes, comparing the first wave of the pandemic from April to June in 2020 with the same period in 2019., Methods: Data from all four Irish oesophageal cancer centres were reviewed. All patients undergoing resection for oesophageal malignancy from 1 April to 30 June inclusive in 2020 and 2019 were included. Patient, disease, and peri-operative outcomes (including COVID-19 infection) were compared., Results: In 2020, 45 patients underwent oesophagectomy, and 53 in the equivalent period in 2019. There were no differences in patient demographics, co-morbidities, or use of neoadjuvant therapy. The median time to surgery from neoadjuvant therapy was 8 weeks in both 2020 and 2019. There were no significant differences in operative interventions between the two time periods. There was no difference in operative morbidity in 2020 and 2019 (28% vs 40%, p = 0.28). There was no in-hospital mortality in either period. No patient contracted COVID-19 in the perioperative period., Conclusions: Continuing surgical resection for oesophageal cancer was feasible and safe during the COVID-19 pandemic in Ireland. The national response to this threat was therefore successful by these criteria in the curative management of oesophageal cancer., (© 2021. Royal Academy of Medicine in Ireland.)

Background: Oesophageal cancer has a reputation for poor survival, and a relatively high risk of major postoperative morbidity and mortality. Encouragingly, a recent international cancer registry study reports a doubling of survival outcomes in Ireland over the last 20 years. This study focused on both oncologic and operative outcomes in patients treated with curative intent requiring surgery at a high-volume center., Methods: All patients undergoing surgery or multimodal therapy with curative intent from 2009 to 2018 were studied. All data was recorded prospectively and maintained internally. The period 2009-2013 was compared with 2014-2018 to monitor any change in trends., Results: Four hundred and seventy-five patients (adenocarcinoma 77%, mean age 65; 76% male; 64% neoadjuvant therapy) underwent open surgical resection, 54% via en bloc 2-stage, 19.8% en bloc 3-stage, and 26.5% by a transhiatal approach. New onset atrial fibrillation was the commonest index complication, in 108 (22.7%), 80 (18%) developed suspected pneumonia/respiratory tract infection, 20 (4.2%) an anastomotic leak, and 25 (5.2%) a chyle leak. The 90-day mortality rate was 1.2% and 0.8% at 30 days. The median survival was 77.17 months, with a 5-year survival of 56%., Conclusion: Consistent with registry data on population survival for oesophageal cancer, this study highlights markedly improved survival outcomes in patients treated curatively, reflecting international trends, as well as low mortality rates; however, cardiorespiratory complications remain significant.

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

Barrett's esophagus (BE) is the main pathological precursor of esophageal adenocarcinoma (EAC). Progression to high-grade dysplasia (HGD) or EAC from nondysplastic BE (NDBE), low-grade dysplasia (LGD) and indefinite for dysplasia (IND) varies widely between population-based studies and specialized centers for many reasons, principally the rigor of the biopsy protocol and the accuracy of pathologic definition. In the Republic of Ireland, a multicenter prospective registry and bioresource (RIBBON) was established in 2011 involving six academic medical centers, and this paper represents the first report from this network. A detailed clinical, endoscopic and pathologic database registered 3,557 patients. BE was defined strictly by both endoscopic evidence of Barrett's epithelium and the presence of specialized intestinal metaplasia (SIM). A prospective web-based database was used to gather information with initial and follow-up data abstracted by a data manager at each site. A total of 2,244 patients, 1,925 with no dysplasia, were included with complete follow-up. The median age at diagnosis was 60.5 with a 2.1:1 male to female ratio and a median follow-up time of 2.7 years (IQR 1.19-4.04), and 6609.25 person years. In this time period, 125 (5.57%) progressed to HGD/EAC, with 74 (3.3%) after 1 year of follow-up and 38 (1.69%) developed EAC, with 20 (0.89%) beyond 1 year. The overall incidence of HGD/EAC was 1.89% per year; 1.16% if the first year is excluded. The risk of progression to EAC alone overall was 0.57% per year, 0.31% excluding the first year, and 0.21% in the 1,925 patients who had SIM alone at diagnosis. Low-grade dysplasia (LGD) progressed to HGD/EAC in 31% of patients, a progression rate of 12.96% per year, 6.71% with the first year excluded. In a national collaboration of academic centers in Ireland, the progression rate for NDBE was similar to recent population studies. Almost one in two who progressed was evident within 1 year. Crucially, LGD diagnosed and confirmed by specialist gastrointestinal pathologists represents truly high-risk disease, highlighting the importance of expertise in diagnosis and management, and providing indirect support for ablative therapies in this context., (© The Author(s) 2020. 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.)

Objective: To study malabsorption and malnutrition after curative resection of esophageal and gastric cancer., Design: Prospective cohort study., Background: Improved cure rates for esophageal and gastric cancer have increased focus on health-related quality of life (HR-QL) in survivorship. Although malnutrition is well described in long-term follow-up, and gastrointestinal symptoms are common, data on gut and pancreatic-related malabsorption are scant., Methods: Disease-free patients at least 18 months after esophageal or gastric oncologic resections represented the study cohort. A modified Gastrointestinal Symptom Rating Scale questionnaire was completed, and weight, fecal elastase (FE), albumin, vitamins, and micronutrients measured preoperatively and at 1, 6, and 18 to 24 months postoperatively. Small intestinal bacterial overgrowth (SIBO) and changes in body composition were also evaluated postoperatively., Results: At a median follow-up of 23 months, 45 of 66 patients in a consecutive series were disease-free. Mean weight (78 ± 19 vs 67 ± 16 kg), body mass index (27 ± 5 vs 24 ± 5 kg/m), Vitamin A (1.7 ± 0.6 vs 1.2 ± 0.4 umol/L), and Vitamin E (28 ± 7 vs 20 ± 7 umol/L) were significantly decreased (P < 0.01) at last follow-up compared with preoperatively. Malabsorption was evident in 73% of patients, of whom 44% had FE < 200 μg/g and 38% had evidence of SIBO. Total body fat-free mass (175 ± 96 vs 84 ± 71, P < 0.001) and skeletal muscle index (44 ± 8 vs 39 ± 8, P = 0.007) were significantly decreased at 18 to 24 months., Conclusions: Malabsorption and malnutrition are prevalent in survivorship of esophageal and stomach cancer. This may be underappreciated, and both gut and pancreatic insufficiency represent modifiable targets in the interdisciplinary approach to recovery of HR-QL.

Objective: Modern series from high-volume esophageal centers report an approximate 40% 5-year survival in patients treated with curative intent and postoperative mortality rates of less than 4%. An objective analysis of factors that underpin current benchmarks within high-volume centers has not been performed., Methods: Three time periods were studied, 1990 to 1998 (period 1), 1999 to 2003 (period 2), and 2004 to 2008 (period 3), in which 471, 254, and 342 patients, respectively, with esophageal cancer were treated with curative intent. All data were prospectively recorded, and staging, pathology, treatment, operative, and oncologic outcomes were compared., Results: Five-year disease-specific survival was 28%, 35%, and 44%, and in-hospital postoperative mortality was 6.7%, 4.4%, and 1.7% for periods 1 to 3, respectively (P < .001). Period 3, compared with periods 1 and 2, respectively, was associated with significantly (P < .001) more early tumors (17% vs 4% and 6%), higher nodal yields (median 22 vs 11 and 18), and a higher R0 rate in surgically treated patients (81% vs 73% and 75%). The use of multimodal therapy increased (P < .05) across time periods. By multivariate analysis, age, T stage, N stage, vascular invasion, R status, and time period were significantly (P < .0001) associated with outcome., Conclusions: Improved survival with localized esophageal cancer in the modern era may reflect an increase of early tumors and optimized staging. Important surgical and pathologic standards, including a higher R0 resection rate and nodal yields, and lower postoperative mortality, were also observed., (Copyright © 2012 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Background: Gastric neuroendocrine tumours (NETs) are increasingly recognised, and management decisions may be difficult due to an incomplete understanding of aetiology, natural history and optimum therapy. This article presents a current understanding based on recent advances in epidemiology, classification, molecular profiling, and treatment., Methods: Relevant medical literature was identified from searches of PubMed and references cited in appropriate articles identified. Selection of articles was based on peer review, journal and relevance., Results: Gastric NETs may be divided into three clinical prognostic groups: type I is associated with autoimmune atrophic gastritis and hypergastrinaemia, type II is associated with Zollinger-Ellison syndrome, and type III lesions are gastrin-independent, have the greatest metastatic potential and poorest prognosis. There has been an increased frequency of gastric NETs reported. Management approaches have evolved in parallel with advances in endoscopic staging and surgery, as well as improved understanding of the biology and natural history of NETs., Conclusions: Gastric NETs present a spectrum of activity from indolent tumours to metastatic malignancy. Treatment decisions for patients must be individualised and are best managed by a multidisciplinary team approach. The current evidence base is limited to small series and efforts to treat patients within clinical networks of expertise are warranted., (Copyright © 2012 S. Karger AG, Basel.)

Background: Transthoracic esophagectomy (TTE) with lymphadenectomy represents the gold standard of operative approaches to esophageal cancer. The TTE procedure carries significant operative risk, particularly in patients with co-morbidities, and the possible oncologic benefit of a mediastinal lymph node dissection in certain subgroups of patients with esophageal cancer is controversial. Transhiatal esophagectomy (THE), which avoids a thoracotomy, may reduce morbidity and mortality below levels seen with TTE, and there is no proof from randomized studies of any oncologic inferiority to TTE in patients with early tumors. Accordingly, the selective use of THE has increased in our high-volume center in recent years, and this study audits that experience over the last decade, Methods: Between 2000 and 2009 inclusive, 584 patients were treated surgically with curative intent. The standard operative approach in our unit is en bloc TTE, and THE represents 5.5% overall, and 11.1% in the second 5-year period (2004-2009), compared with 2% previously. The present study details the selection of these cases (n = 32) treated with THE and their outcomes, as well as the outcomes in the TTE (n = 438) group, Result: Transhiatal esophagectomy was used for early stage carcinoma (n = 18) and for patients of advanced age who also had co-morbidities (n = 14). Patients undergoing THE were significantly older (68.46 versus 63.07 years of age; p = 0.002), and were at higher operative risk based on ASA grade (grade 3: 53.1% versus 17.3%; p < 0.001), compared with TTE patients. The THE cohort also included more patients with early cancers compared with the TTE cohort (56.3% versus 17.6%; p < 0.001). There were no differences in R0 resection rates for patients with early tumors or advanced co-morbidity. Nodal yields were lower in THE patients (p = 0.005). The overall complication rate was lower in the THE group (31.6% versus 44.2%; p = 0.021), and there were no postoperative deaths in the transhiatal group, whereas the in-hospital mortality rate for the TTE group was 3% (p < 0.001). Disease-specific survival was equivalent with each approach., Conclusions: Transhiatal esophagectomy has a role in a pragmatic individualized approach to esophageal cancer. As an alternative to a standardized en bloc transthoracic esophagectomy, the transhiatal approach may be suitable for patients with predicted node-negative cancers or those with resectable disease who are not candidates for TTE because of co-morbidity.

Background: Health-related quality of life (HRQL) has been studied extensively during the first year following esophagectomy, but little is known about HRQL in long-term survivors. The aim of this study was to investigate HRQL in patients alive at least 1 year after surgical resection for esophageal cancer using validated European Organisation for Research and Treatment of Cancer (EORTC) quality of life (QOL) questionnaires (QLQ)., Methods: Eligible patients, without known disease recurrence and at least 1 year after esophagectomy, were identified from a prospectively maintained database. Patients completed general (QLQ-C30) and esophageal cancer-specific (QLQ-OES18, OG25) questionnaires. A numeric score (0-100) was computed in each conceptual area and compared with validated cancer (n = 1031) and age-matched (n = 7802) healthy populations using two-tailed unpaired t-tests. A cohort of 80 patients had pretreatment scores recorded., Results: Altogether, 132 of 156 eligible patients (84%) completed the self-rated questionnaire, 105 (67.3%) were men, and the mean age was 62 years (range 29-84 years). The mean time since esophagectomy was 70.3 months (12-299 months). Global health status was significantly reduced at least 1 year after esophagectomy (mean ± SD score 48.4 ± 18.6) when compared with patients with esophageal cancer prior to treatment (55.6 ± 24.1) and the general population (71.2 ± 22.4) (p < 0.0001). In a prospective cohort of eighty patients, symptoms related to swallowing difficulty, reflux, pain, and coughing significantly decreased in the long term (p < 0.0001). The degree of subjective swallowing dysfunction was highly correlated with a poor QOL (Spearman's ρ = 0.508, p < 0.01)., Conclusions: Global health status remains significantly reduced in long-term survivors after esophagectomy compared with population controls, and swallowing dysfunction is highly associated with this compromised QOL.

Background & Aims: Alcohol consumption may increase gastroesophageal reflux symptoms, cause damage to the esophageal mucosa, and/or promote carcinogenesis. However, reports about the association between alcohol and reflux esophagitis, Barrett's esophagus, and esophageal adenocarcinoma are conflicting., Methods: Information relating to alcohol consumption, at age 21 and 5 years before the interview date, was collected from 230 reflux esophagitis, 224 Barrett's esophagus, and 227 esophageal adenocarcinoma patients and 260 frequency-matched population controls. Logistic regression analyses were used to compare alcohol consumption in the 3 case groups to controls with adjustment for potential confounders., Results: Population controls reporting gastroesophageal reflux symptoms were less likely than controls without symptoms to drink alcohol 5 years before the interview date (odds ratio [OR], 0.44, 0.20-0.99). No associations were observed between total alcohol consumption 5 years before the interview date and reflux esophagitis, Barrett's esophagus, or esophageal adenocarcinoma (OR, 1.26, 0.78-2.05; OR, 0.72, 0.43-1.21; and OR, 0.75, 0.46-1.22, respectively). Wine was inversely associated with reflux esophagitis (OR, 0.45, 0.27-0.75). Total alcohol consumption at age 21 years was significantly associated with reflux esophagitis (OR, 2.24, 1.35-3.74) but not with Barrett's esophagus or esophageal adenocarcinoma (OR, 1.06, 0.63-1.79 and OR, 1.27, 0.77-2.10, respectively)., Conclusions: Alcohol consumption in early adulthood may lead to the development of reflux esophagitis. More recent alcohol consumption does not appear to confer any increased risk of reflux esophagitis, Barrett's esophagus, or esophageal adenocarcinoma. In fact, wine consumption may reduce the risk of these 3 esophageal disorders.

Reflux of gastric contents can lead to development of reflux esophagitis and Barrett's esophagus. Barrett's esophagus is a risk factor for esophageal adenocarcinoma. Damage to DNA may lead to carcinogenesis but is repaired through activation of pathways involving polymorphic enzymes, including human 8-oxoguanine glycosylase 1 (hOGG1), X-ray repair cross-complementing 1 (XRCC1), and xeroderma pigmentosum group D (XPD). Of the single nucleotide polymorphisms identified in these genes, hOGG1 Ser 326 Cys, XRCC1 Arg 399 Gln, and XPD Lys 751 Gln are particularly common in Caucasians and have been associated with lower DNA repair capacity. Small studies have reported associations with XPD Lys 751 Gln and esophageal adenocarcinoma. XRCC1 Arg 399 Gln has been linked to Barrett's esophagus and reflux esophagitis. In a population-based case-control study, we examined associations of the hOGG1 Ser 326 Cys, XRCC1 Arg 399 Gln, and XPD Lys 751 Gln polymorphisms with risk of esophageal adenocarcinoma, Barrett's esophagus, and reflux esophagitis. Genomic DNA was extracted from blood samples collected from cases of esophageal adenocarcinoma (n = 210), Barrett's esophagus (n = 212), reflux esophagitis (n = 230), and normal population controls frequency matched for age and sex (n = 248). Polymorphisms were genotyped using TaqMan allelic discrimination assays. Odds ratios and 95% confidence intervals were obtained from logistic regression models adjusted for potential confounding factors. There were no statistically significant associations between these polymorphisms and risk of esophageal adenocarcinoma, Barrett's esophagus, or reflux esophagitis.

Background: The impact of antireflux surgery on outcome in Barrett's esophagus, in particular its effect on both the regression of metaplasia and the progression of metaplasia through dysplasia to adenocarcinoma, remains unclear. This long-term follow-up study evaluated clinical, endoscopic, histopathologic, and physiologic parameters in patients with Barrett's esophagus who underwent antireflux surgery in a specialist unit., Methods: Between 1985 and 2001, 58 patients with Barrett's esophagus (49 long-segment and 9 short-segment) underwent a Rossetti-Nissen fundoplication, 32 via open procedure and 26 laparoscopically. Symptomatic follow-up with a detailed questionnaire was available in 58 (100%) and follow-up endoscopy and histology in 57 (98%) patients, and 41 patients (71%) underwent preoperative and postoperative 24-hour pH monitoring., Results: At a median follow-up of 59 months, 52 patients (90%) had excellent symptom control, whereas 6 patients (10%) had significant recurrent symptoms and were on regular proton pump inhibitor medication. Seventeen of 41 patients having preoperative and postoperative pH monitoring (41%) had a persistent increase of acid reflux above normal. Thirty-five percent (20 of 57) of patients showed either partial or complete regression of Barrett's epithelium. Six of 8 patients with preoperative low-grade dysplasia showed evidence of regression. Dysplasia developed after surgery in 2 patients, and 2 patients developed adenocarcinoma at 4 and 7 years after surgery. All 4 of these patients had abnormal postoperative acid scores., Conclusions: Nissen fundoplication provides excellent long-lasting relief of symptoms in patients with Barrett's esophagus and may promote regression of metaplasia and dysplasia. Control of symptoms does not concord fully with abolition of acid reflux. Progression of Barrett's to dysplasia and tumor was only evident in patients with abnormal postoperative acid scores, suggesting that pH monitoring has an important role in the follow-up of surgically treated patients.