Does Gastroesophageal Reflux Disease Increase the Risk of Sepsis and Its 28-day Mortality? A Causal Study Using a Mendelian Randomization Approach.

BACKGROUND: Gastroesophageal reflux disease (GERD) is a prevalent gastrointestinal disorder. Recent studies indicate that GERD may exert systemic effects, potentially elevating the risk of severe infections, including sepsis. Nevertheless, the causal relationship between GERD and sepsis, as well as sepsis-related 28-day mortality, remains uncertain. AIM: The aim of this study is to investigate the causal relationship between GERD and the risk of sepsis, including 28-day mortality of sepsis. METHODS: This study utilized a two-sample Mendelian Randomization (MR) approach to analyze data from publicly available genome-wide association studies (GWAS) databases ( https://gwas.mrcieu.ac.uk/ ). The analysis comprised 129,080 cases and 473,524 controls for GERD; 11,643 patients and 474,841 controls for sepsis; and 1,896 patients and 484,588 controls for 28-day mortality from sepsis. The objective was to evaluate the causal impact of GERD on the risk of sepsis and 28-day sepsis mortality. Genetic variation data pertinent to GERD were obtained from the most recent genome-wide association studies (GWAS). The primary analysis employed the Inverse Variance Weighted (IVW) method. Sensitivity and pleiotropy analyses were performed to validate the robustness of the findings. RESULTS: MR analysis revealed a notable link between genetically predicted GERD and increased sepsis risk (odds ratio [OR] 1.37, 95% confidence interval [CI] 1.24-1.52; p = 2.79 × 10-9). Moreover, GERD correlated with elevated 28-day mortality of sepsis (OR 1.44, 95% CI 1.11-1.85; p = 5.34 × 10-3). These results remained consistent throughout various sensitivity analyses, indicating their resilience against potential pleiotropy and other biases. CONCLUSION: This study indicates that genetic predisposition to GERD may be linked to an elevated risk of sepsis and its associated 28-day mortality. However, the study does not establish a direct causal relationship for GERD itself, nor does it assess the impact of GERD treatment. Further research is needed to explore the underlying mechanisms and potential therapeutic interventions involved.

Mortality, Reoperation, and Hospital Stay Within 90 Days of Primary and Secondary Antireflux Surgery in a Population-Based Multinational Study.

BACKGROUND & AIMS: Absolute rates and risk factors of short-term outcomes after antireflux surgery remain largely unknown. We aimed to clarify absolute risks and risk factors for poor 90-day outcomes of primary laparoscopic and secondary antireflux surgery. METHODS: This population-based cohort study included patients who had primary laparoscopic or secondary antireflux surgery in the 5 Nordic countries in 2000-2018. In addition to absolute rates, we analyzed age, sex, comorbidity, hospital volume, and calendar period in relation to all-cause 90-day mortality (main outcome), 90-day reoperation, and prolonged hospital stay (≥2 days over median stay). Multivariable logistic regression provided odds ratios (ORs) with 95% confidence intervals (95% CI), adjusted for confounders. RESULTS: Among 26,193 patients who underwent primary laparoscopic antireflux surgery, postoperative 90-day mortality and 90-day reoperation rates were 0.13% (n = 35) and 3.0% (n = 750), respectively. The corresponding rates after secondary antireflux surgery (n = 1 618) were 0.19% (n = 3) and 6.2% (n = 94). Higher age (56-80 years vs 18-42 years: OR, 2.66; 95% CI 1.03-6.85) and comorbidity (Charlson Comorbidity Index ≥2 vs 0: OR, 6.25; 95% CI 2.42-16.14) increased risk of 90-day mortality after primary surgery, and higher hospital volume suggested a decreased risk (highest vs lowest tertile: OR, 0.58; 95% CI, 0.22-1.57). Comorbidity increased the risk of 90-day reoperation. Higher age and comorbidity increased risk of prolonged hospital stay after both primary and secondary surgery. Higher annual hospital volume decreased the risk of prolonged hospital stay after primary surgery (highest vs lowest tertile: OR, 0.74; 95% CI, 0.67-0.80). CONCLUSION: These findings suggest that laparoscopic antireflux surgery has an overall favorable safety profile in the treatment of gastroesophageal reflux disease, particularly in younger patients without severe comorbidity who undergo surgery at high-volume centers.

Wide Area Transepithelial Sampling with Computer-Assisted Analysis (WATS3D) Is Cost-Effective in Barrett's Esophagus Screening.

BACKGROUND: Wide area transepithelial sampling with three-dimensional computer-assisted analysis (WATS3D) is an adjunct to the standard random 4-quadrant forceps biopsies (FB, "Seattle protocol") that significantly increases the detection of Barrett's esophagus (BE) and associated neoplasia in patients undergoing screening or surveillance. AIMS: To examine the cost-effectiveness of adding WATS3D to the Seattle protocol in screening patients for BE. METHODS: A decision analytic model was used to compare the effectiveness and cost-effectiveness of two alternative BE screening strategies in chronic gastroesophageal reflux disease patients: FB with and without WATS3D. The reference case was a 60-year-old white male with gastroesophageal reflux disease (GERD). Effectiveness was measured by the number needed to screen to avert one cancer and one cancer-related death, and quality-adjusted life years (QALYs). Cost was measured in 2019 US$, and the incremental cost-effectiveness ratio (ICER) was measured in $/QALY using thresholds for cost-effectiveness of $100,000/QALY and $150,000/QALY. Cost was measured in 2019 US$. Cost and QALYs were discounted at 3% per year. RESULTS: Between 320 and 337 people would need to be screened with WATS3D in addition to FB to avert one additional cancer, and 328-367 people to avert one cancer-related death. Screening with WATS3D costs an additional $1219 and produced an additional 0.017 QALYs, for an ICER of $71,395/QALY. All one-way sensitivity analyses resulted in ICERs under $84,000/QALY. CONCLUSIONS: Screening for BE in 60-year-old white male GERD patients is more cost-effective when WATS3D is used adjunctively to the Seattle protocol than with the Seattle protocol alone.

Reoperation after antireflux surgery: a population-based cohort study.

BACKGROUND: Antireflux surgery for gastro-oesophageal reflux disease (GORD) and/or hiatal hernia is effective. Between 10 and 20 per cent of patients undergo reoperation for recurrent symptoms. Most studies are undertaken in a single centre and possibly underestimate the rate of reoperation. The aim of this nationwide population-based cohort study was to investigate long-term reoperation rates after antireflux surgery. METHODS: This study included patients who underwent antireflux surgery between 2000 and 2017 in Denmark, and were registered in the Danish nationwide health registries. Reoperation rates were calculated for 1, 5, 10 and 15 years after the primary antireflux operation for GORD and/or hiatal hernia. Duration of hospital stay, 30- and 90-day mortality and morbidity, and use of endoscopic pneumatic dilatation were assessed. RESULTS: This study included a total of 4258 antireflux procedures performed in 3717 patients. Some 3252 patients had only primary antireflux surgery and 465 patients underwent reoperation. The 1-, 5-, 10- and 15-year rates of repeat antireflux surgery were 3·1, 9·3, 11·7 and 12·8 per cent respectively. Thirty- and 90-day mortality rates were similar for primary surgery (0·4 and 0·6 per cent respectively) and reoperations. The complication rate was higher for repeat antireflux surgery (7·0 and 8·3 per cent at 30 and 90 days respectively) than primary operation (3·4 and 4·8 per cent). A total of 391 patients (10·5 per cent of all patients) underwent endoscopic dilatation after primary antireflux surgery, of whom 95 (24·3 per cent) had repeat antireflux surgery. CONCLUSION: In this population-based study in Denmark, the reoperation rate 15 years after antireflux surgery was 12·8 per cent. Reoperations were associated with more complications.

ANTECEDENTES: La cirugía antirreflujo es efectiva en el tratamiento de la enfermedad por reflujo gastroesofágico (gastro-oesophageal reflux disease, GORD) y/o de la hernia de hiato. Entre el 10% y el 20% de los pacientes tienen que ser reoperados por recidiva de los síntomas. La mayoría de los estudios son unicéntricos, lo que posiblemente infravalora la tasa de reintervenciones. El objetivo de este estudio de cohortes de base poblacional nacional fue investigar las tasas de reintervenciones a largo plazo tras la cirugía antirreflujo. MÉTODOS: Este estudio incluyó pacientes sometidos a cirugía antirreflujo entre 2000 y 2017 en Dinamarca y que fueron registrados en los registros nacionales de salud daneses. Se calcularon las tasas de reintervención para 1, 5, 10 y 15 años tras la operación antirreflujo primaria por GORD y/o hernia de hiato. Se evaluaron la duración de la estancia hospitalaria, la morbilidad y mortalidad a 30 y 90 días, y el uso de dilatación neumática endoscópica. RESULTADOS: Este estudio incluyó un total de 4.258 procedimientos antirreflujo efectuados en 3.717 pacientes. Unos 3.252 pacientes fueron sometidos únicamente a cirugía antirreflujo primaria y 465 pacientes a una reintervención. Las tasas de cirugía antirreflujo de revisión a 1, 5, 10 y 15 años fueron del 3,1%, 9,3%, 11,7% y 12,9%, respectivamente. La mortalidad a los 30 y 90 días fue similar cuando se comparó cirugía primaria y reintervenciones (mortalidad a 30 días 0,4% y 90 días 0,6% versus 0% y 0,4%, respectivamente). La tasa de complicaciones fue más elevada para la cirugía antirreflujo de revisión en comparación con la cirugía primaria: tasa de complicaciones a los 30 días 7,0%, 90 días 8,3% versus 30 días 3,4% y 90 días 4,8%, respectivamente. Un total de 391 pacientes (10,5% de todos los pacientes) fueron sometidos a dilatación endoscópica tras la cirugía antirreflujo primaria y 95 de 391 pacientes (24,3%) precisaron cirugía antirreflujo de revisión. CONCLUSIÓN: En este estudio de base poblacional en Dinamarca, la tasa de reintervención a los 15 años tras cirugía antirreflujo fue del 12,9%. Las reintervenciones se asociaron con más complicaciones.

Endoscopy for gastroesophageal reflux disease and survival in esophageal adenocarcinoma.

Gastroesophageal reflux disease (GERD) is a risk factor of esophageal adenocarcinoma (EAC) and the most common indication for upper gastrointestinal endoscopy. Yet, whether GERD or endoscopy practice influence survival in EAC is largely unknown and was assessed in our study.This nationwide cohort study included all Swedish residents diagnosed with EAC in 1997-2013 with follow-up to 2018. Exposures were history of GERD and endoscopies prior to EAC. The main outcome was EAC-specific 5-year mortality. Multivariable Cox regression provided hazard ratios (HRs) with 95% confidence intervals (CIs) adjusted for potential confounders. Among 6,600 EAC patients (79.3% males, median age 70 years) followed for 9,138 person-years, 440 (6.7%) had GERD and 592 (9.0%) had ≥1 endoscopy before EAC diagnosis. GERD was associated with a decreased risk of mortality (adjusted HR 0.71, 95% CI 0.64-0.80), which was only slightly attenuated by adjustment for prior endoscopies (HR 0.79, 95% CI 0.70-0.90), and further adjustments also for tumor stage and surgical resection (HR 0.74, 95% CI 0.62-0.89). Compared to EAC patients without prior endoscopy, mortality was unchanged in GERD patients having undergone 1 or 2 endoscopies before EAC diagnosis (HR 1.02, 95% CI 0.80-1.31, for 1 endoscopy; HR 0.90, 95% CI 0.63-1.30, for 2 endoscopies), while the mortality was decreased in patients with ≥3 endoscopies (HR 0.55, 95% CI 0.36-0.85). Our study indicates that GERD may be associated with a better prognosis in the event of EAC; however, the use of endoscopy screening has a limited impact on survival unless performed very frequently.

Impact of Abdominal Visceral Adiposity on Adult Asthma Symptoms.

BACKGROUND: Previous studies have shown the association of anthropometric measures with poor asthma symptoms, especially among women. However, the potential influence of visceral adiposity on asthma symptoms has not been investigated well. OBJECTIVE: In this study, we have evaluated whether visceral adiposity is related to poor adult asthma symptoms independent of anthropometric measures and sex. If this relationship presented, we investigated whether it is explained by influence on pulmonary functions and/or obesity-related comorbidities. METHODS: We analyzed data from 206 subjects with asthma from Japan. In addition to anthropometric measures (body mass index and waist circumference), abdominal visceral and subcutaneous fat were assessed by computed tomography scan. Quality of life was assessed using the Japanese version of the Asthma Quality of Life Questionnaire. RESULTS: All obesity indices had inverse association with reduced asthma quality of life among females. However, only the visceral fat area showed a statistical inverse association with Asthma Quality of Life Questionnaire in males. Only abdominal visceral fat was associated with higher gastroesophageal reflux disease and depression scores. Although all obesity indices showed inverse association with functional residual capacity, only visceral fat area had a significant inverse association with FEV1 % predicted, independent of other obesity indices. CONCLUSIONS: Regardless of sex, abdominal visceral fat was associated with reduced asthma quality of life independent of other obesity indices, and this may be explained by the impact of abdominal visceral fat on reduced FEV1 % predicted and higher risk for gastroesophageal reflux disease and depression. Therefore, visceral adiposity may have more clinical influence than any other obesity indices on asthma symptoms.

Clinical and Laboratory Characteristics and Mortality in Korean Patients with Systemic Sclerosis: A Nationwide Multicenter Retrospective Cohort Study.

OBJECTIVE: We aimed to investigate demographic and clinical features and predictors of mortality in Korean patients with systemic sclerosis (SSc). METHODS: We performed a retrospective multicenter medical chart review in Korean patients diagnosed with SSc from 1986 to 2016 at 11 university hospitals representing each geographic area of Korea. SSc patients were defined according to the American College of Rheumatology preliminary classification criteria and subtyped as limited cutaneous (lcSSc) or diffuse cutaneous (dcSSc) SSc. RESULTS: We enrolled 751 patients (female, 86.7%; mean age at diagnosis, 48.9 yrs). The most common organ involvement was interstitial lung disease (52.7%), followed by gastroesophageal reflux disease (32.9%) and pulmonary arterial hypertension (13.6%). Patients with lcSSc were more common than those with dcSSc (64.8 vs 35.2%), whereas anti-Scl-70 and anticentromere antibody positivity were identified in 302 (42.5%) and 175 (25.5%) patients, respectively. In the 46 (6.1%) patients who developed a malignancy, lung cancer (23.9%) was the most common diagnosis, followed by gastric (13%) and breast cancer (13%). During the study period, 57 (7.6%) patients died, and the 5- and 10-year survival rates were 94% and 87%, respectively. Increased age at diagnosis, cardiovascular involvement, and anti-Scl-70 antibody positivity were significant predictors of death. CONCLUSION: Clinical manifestations and survival rates in Korean SSc patients are similar to those of other populations. However, the prevalence of anti-Scl-70 antibody is higher in Korean SSc patients compared with whites, while the prevalence of anticentromere antibody is lower.

Clinicopathology and Survival in Patients with Gastroesophageal Reflux After Radical Surgery of Proximal Gastric Cancer.

BACKGROUND: Gastroesophageal reflux (GR) after radical resection of proximal gastric cancer (PGC) may influence survival; however, few studies have investigated survival in PGC patients who develop GR following radical resection. This study aimed to correlate the occurrence of GR after proximal gastrectomy (PG) and total gastrectomy (TG) with clinicopathological factors and long-term survival. METHODS: The PGC patient cohort was retrospectively grouped as follows: postoperative patients with and without GR (NGR). Clinicopathological characteristics and survival data were compared between the two groups. RESULTS: A total of 88 patients who underwent PG (53%) experienced postoperative GR; however, only 30 patients who underwent TG (14%) experienced GR (P = 0.000). The incidence of GR was significantly associated with surgical procedure (P < 0.01), tumor size (P < 0.01), infiltration depth (P < 0.01), lymph node metastasis (P = 0.018), postoperative distant metastasis (P < 0.01) and recurrence (P = 0.001). The 5-year overall survival of the GR group was significantly worse than that of the NGR group (39.3 vs. 46.5%, respectively; P = 0.046). The PG and TG groups had significantly different 5-year overall survival (45.2 vs. 50.9%, respectively; P = 0.047), and multivariate analysis revealed GR as an independent risk factor associated with poor overall survival. CONCLUSIONS: Patients who experienced GR after radical resection for PGC were more likely to develop recurrence and metastasis, leading to shorter survival. TG for PGC was associated with a more favorable 5-year overall survival than was PG. Thus, TG should be performed for PGC patients with tumors larger than 5 cm, T3/T4 disease or lymph node metastasis to improve their long-term survival.

All-cause and cancer-specific mortality in GORD in a population-based cohort study (the HUNT study).

OBJECTIVE: Gastro-oesophageal reflux is a public health concern which could have associated oesophageal complications, including adenocarcinoma, and possibly also head-and-neck and lung cancers. The aim of this study was to test the hypothesis that reflux increases all-cause and cancer-specific mortalities in an unselected cohort. DESIGN: The Nord-Trøndelag health study (HUNT), a Norwegian population-based cohort study, was used to identify individuals with and without reflux in 1995-1997 and 2006-2008, with follow-up until 2014. All-cause mortality and cancer-specific mortality were assessed from the Norwegian Cause of Death Registry and Cancer Registry. Multivariable Cox regression was used to calculate HRs with 95% CIs for mortality with adjustments for potential confounders. RESULTS: We included 4758 participants with severe reflux symptoms and 51 381 participants without reflux symptoms, contributing 60 323 and 747 239 person-years at risk, respectively. Severe reflux was not associated with all-cause mortality, overall cancer-specific mortality or mortality in cancer of the head-and-neck or lung. However, for men with severe reflux a sixfold increase in oesophageal adenocarcinoma-specific mortality was found (HR 6.09, 95% CI 2.33 to 15.93) and the mortality rate was 0.27 per 1000 person-years. For women, the corresponding mortality was not significantly increased (HR 3.68, 95% CI 0.88 to 15.27) and the mortality rate was 0.05 per 1000 person-years. CONCLUSIONS: Individuals with severe reflux symptoms do not seem to have increased all-cause mortality or overall cancer-specific mortality. Although the absolute risk is small, individuals with severe reflux symptoms have a clearly increased oesophageal adenocarcinoma-specific mortality.

Cohort profile: the Nordic Antireflux Surgery Cohort (NordASCo).

PURPOSE: To describe a newly created all-Nordic cohort of patients with gastro-oesophageal reflux disease (GORD), entitled the Nordic Antireflux Surgery Cohort (NordASCo), which will be used to compare participants having undergone antireflux surgery with those who have not regarding risk of cancers, other diseases and mortality. PARTICIPANTS: Included were individuals with a GORD diagnosis recorded in any of the nationwide patient registries in the Nordic countries (Denmark, Finland, Iceland, Norway and Sweden) in 1964-2014 (with various start and end years in different countries). Data regarding cancer, other diseases and mortality were retrieved from the nationwide registries for cancer, patients and causes of death, respectively. FINDINGS TO DATE: The NordASCo includes 945 153 individuals with a diagnosis of GORD. Of these, 48 433 (5.1%) have undergone primary antireflux surgery. Median age at primary antireflux surgery ranged from 47 to 52 years in the different countries. The coding practices of GORD seem to have differed between the Nordic countries. FUTURE PLANS: The NordASCo will initially be used to analyse the risk of developing known or potential GORD-related cancers, that is, tumours of the oesophagus, stomach, larynx, pharynx and lung, and to evaluate the mortality in the short-term and long-term perspectives. Additionally, the cohort will be used to evaluate the risk of non-malignant respiratory conditions that might be caused by aspiration of gastric contents.

The risk of mortality following secondary fundoplication in a population-based cohort study.

BACKGROUND: Mortality following laparoscopic fundoplication has been found to be negligible. However, some patients require secondary fundoplication, and the risk of mortality following such procedure is scarcely studied. METHODS: This nationwide Swedish population-based cohort study included all patients undergoing secondary fundoplication following primary laparoscopic fundoplication in 1997 to 2013, regardless of indication. Primary outcome was mortality within 90 days of surgery, and secondary outcome was postoperative length of hospital stay. RESULTS: A total of 9,765 patients underwent primary laparoscopic fundoplication, 540 (5.5%) patients underwent secondary fundoplication. About 382 (70.7%) were conducted laparoscopically, and 158 (29.3%) were conducted with an open technique. No deaths occurred within 90 days of the secondary fundoplication. Median length of stay was longer following secondary fundoplication (4.8 days, interquartile range 1.0 to 5.0 days), compared to primary laparoscopic fundoplication (2.5 days, interquartile range 1.0 to 3.0 days). CONCLUSIONS: This population-based cohort study indicates that secondary fundoplication following primary laparoscopic fundoplication is a safe procedure. The longer hospital stay following secondary fundoplication compared to primary laparoscopic fundoplication is likely explained by the higher rate of open surgical approach.

Outcome Evaluation of Laparoscopic and Open Nissen Fundoplication in Children-A Systematic Review and Meta-Analysis.

Our aim was to estimate the efficacy of laparoscopic and open Nissen fundoplication (ONF) in the treatment of gastroesophageal reflux disease (GERD) in children. An electronic systematic review of the published literature was conducted in Cochrane Library, MEDLINE (PubMed), and EmBase in October 2015 in English and without time restrictions. The participants, interventions, and comparisons in the clinical question translated directly into eligibility criteria for study inclusion and exclusion. Study information extraction and methodological quality assessments were accomplished by two reviewers independently. Methodological quality was assessed by using the "Criteria for judging risk of bias in the 'Risk of bias' assessment tool." Odds ratio (OR) with 95 per cent confidence interval was computed as summary statistics. Fixed-effects model was used and a pooled OR was calculated with the Mantel-Haenszel method initially. If the studies were heterogeneous, then the DerSimonian and Laird random effects model was used for meta-analysis. Outcome indices included mortality of patients, recurrence of GERD, reoperation of GERD, patients with complications, length of postoperative hospital stay, and surgery duration of laparoscopic Nissen fundoplication (LNF) and ONF. Statistical analyses were carried out by using Review Manager 5.2. The duration of follow-up varied between two days and four years. Children operated with LNF had a higher recurrence rate of GERD than those undergoing ONF. The pooled OR of LNF versus ONF was 2.98 (95% confidence interval = 1.29-6.87) while the heterogeneity was I2 = 47 per cent and P = 0.13. Statistical analysis showed that there was no significant difference for mortality, reoperation, and complication. The mean duration of surgery was significantly longer in the LNF than the ONF group while the results of length of postoperative hospital stay remained inconformity. In this meta-analysis, children operated with LNF had a higher recurrence rate of GERD than those undergoing ONF. Meanwhile, when considering the outcomes of mortality, reoperation, and complications, there was no significant difference. The mean duration of surgery was significantly longer in the LNF than the ONF group while no consistent conclusion of length of postoperative hospital stay was found.

Acid Gastroesophageal Reflux Disease and Apparent Life-Threatening Events: Simultaneous pH-metry and Cardiorespiratory Monitoring.

AIM: To investigate the prevalence and the characteristics of gastroesophageal reflux disease (GERD) in infants with apparent life threatening events (ALTE). MATERIALS AND METHODS: Infants with at least one episode of ALTE in absence of predisposing factors were included. All infants underwent a cardiorespiratory recording with simultaneous 24-hour pH-monitoring. Patients were divided into 3 groups according to the severity of GERD: A. Reflux Index (RI) <3%, B. RI = 3-7%, C. RI >7%. Monthly evaluations were performed and the anti-reflux therapy was maintained till normalization of monitoring and clinic. RESULTS: 41 infants were enrolled. GERD was found in 80% of patients (moderate in 54%, severe in 27%). A normalization of the cardiorespiratory tracks was recorded on average after 1 month for group A, 7 months for the group B and 9.5 months for group C. A significant difference was registered between group A and both group B and C (P < 0.0001), as well as between the group B and C (P < 0.05). CONCLUSION: GERD influences significantly the time of normalization of the cardiorespiratory monitoring in infants with ALTE. GERD diagnosis and treatment are mandatory in these patients.

Trajectories of endoscopic Barrett esophagus: Chronological changes in a community-based cohort.

AIM: To elucidate longitudinal changes of an endoscopic Barrett esophagus (BE), especially of short segment endoscopic BE (SSBE). METHODS: This study comprised 779 patients who underwent two or more endoscopies between January 2009 and December 2015. The intervals between the first and the last endoscopy were at least 6 mo. The diagnosis of endoscopic BE was based on the criteria proposed by the Japan Esophageal Society and was classified as long segment (LSBE) and SSBE, the latter being further divided into partial and circumferential types. The potential background factors that were deemed to affect BE change included age, gender, antacid therapy use, gastroesophageal reflux disease-suggested symptoms, esophagitis, and hiatus hernia. Time trends of a new appearance and complete regression were investigated by Kaplan-Meier curves. The factors that may affect appearance and complete regression were investigated by χ(2) and Student-t tests, and multivariable Cox regression analysis. RESULTS: Incidences of SSBE and LSBE were respectively 21.7% and 0%, with a mean age of 68 years. Complete regression of SSBE was observed in 61.5% of initial SSBE patients, while 12.1% of initially disease free patients experienced an appearance of SSBE. Complete regressions and appearances of BE occurred constantly over time, accounting for 80% and 17% of 5-year cumulative rates. No LSBE development from SSBE was observed. A hiatus hernia was the only significant factor that facilitated BE development (P = 0.03) or hampered (P = 0.007) BE regression. CONCLUSION: Both appearances and complete regressions of SSBE occurred over time. A hiatus hernia was the only significant factor affecting the BE story.

Hiatal hernia on thoracic computed tomography in pulmonary fibrosis.

Gastro-oesophageal reflux has long been suspected of implication in the genesis and progression of idiopathic pulmonary fibrosis (IPF). We hypothesised that hiatal hernia may be more frequent in IPF than in other interstitial lung disease (ILD), and that hiatal hernia may be associated with more severe clinical characteristics in IPF.We retrospectively compared the prevalence of hiatal hernia on computed tomographic (CT) scans in 79 patients with IPF and 103 patients with other ILD (17 scleroderma, 54 other connective tissue diseases and 32 chronic hypersensitivity pneumonitis). In the IPF group, we compared the clinical, biological, functional, CT scan characteristics and mortality of patients with hiatal hernia (n=42) and without hiatal hernia (n=37).The prevalence of hiatal hernia on CT scan at IPF diagnosis was 53%, similar to ILD associated with scleroderma, but significantly higher than in the two other ILD groups. The size of the hiatal hernia was not linked to either fibrosis CT scan scores, or reduction in lung function in any group. Mortality from respiratory causes was significantly higher among IPF patients with hiatal hernia than among those without hiatal hernia (p=0.009).Hiatal hernia might have a specific role in IPF genesis, possibly due to pathological gastro-oesophageal reflux.

Pre-lung transplant measures of reflux on impedance are superior to pH testing alone in predicting early allograft injury.

AIM: To evaluate pre-lung transplant acid reflux on pH-testing vs corresponding bolus reflux on multichannel intraluminal impedance (MII) to predict early allograft injury. METHODS: This was a retrospective cohort study of lung transplant recipients who underwent pre-transplant combined MII-pH-testing at a tertiary care center from January 2007 to November 2012. Patients with pre-transplant fundoplication were excluded. Time-to-event analysis was performed using a Cox proportional hazards model to assess associations between measures of reflux on MII-pH testing and early allograft injury. Area under the receiver operating characteristic (ROC) curve (c-statistic) of the Cox model was calculated to assess the predictive value of each reflux parameter for early allograft injury. Six pH-testing parameters and their corresponding MII measures were specified a priori. The pH parameters were upright, recumbent, and overall acid reflux exposure; elevated acid reflux exposure; total acid reflux episodes; and acid clearance time. The corresponding MII measures were upright, recumbent, and overall bolus reflux exposure; elevated bolus reflux exposure; total bolus reflux episodes; and bolus clearance time. RESULTS: Thirty-two subjects (47% men, mean age: 55 years old) met the inclusion criteria of the study. Idiopathic pulmonary fibrosis (46.9%) represented the most common pulmonary diagnosis leading to transplantation. Baseline demographics, pre-transplant cardiopulmonary function, number of lungs transplanted (unilateral vs bilateral), and post-transplant proton pump inhibitor use were similar between reflux severity groups. The area under the ROC curve, or c-statistic, of each acid reflux parameter on pre-transplant pH-testing was lower than its bolus reflux counterpart on MII in the prediction of early allograft injury. In addition, the development of early allograft injury was significantly associated with three pre-transplant MII measures of bolus reflux: overall reflux exposure (HR = 1.18, 95%CI: 1.01-1.36, P = 0.03), recumbent reflux exposure (HR = 1.25, 95%CI: 1.04-1.50, P = 0.01) and bolus clearance (HR = 1.09, 95%CI: 1.01-1.17, P = 0.02), but not with any pH-testing parameter measuring acid reflux alone. CONCLUSION: Pre-transplant MII measures of bolus reflux perform better than their pH-testing counterparts in predicting early allograft injury post-lung transplantation.

A Single Institution's First 100 Patients Undergoing Laparoscopic Anti-Reflux Fundoplications: Where Are They 20 Years Later?

Although anti-reflux surgery has been used liberally over the past decades for the treatment of gastroesophageal reflux disease (GERD), few studies report follow-up after 10 years. This study was undertaken to report follow-up on 100 consecutive GERD patients up to 22 years after utilizing a laparoscopic fundoplication. Hundred consecutive patients undergoing laparoscopic fundoplication for GERD were prospectively followed beginning in 1992. The frequency and severity of symptoms before and after laparoscopic fundoplication were scored on a Likert scale (1 = never/none to 10 = always/very bothersome). Median data are reported. Of the 100 patients who underwent laparoscopic fundoplication for their GERD, nine were reoperations. Twenty-six patients are deceased on average 11 years after their fundoplications. Seventy-four patients are alive, with 27 patients, actively followed for 19 years after their fundoplications. At most recent follow-up, patients experienced long-term amelioration of symptom frequency and severity after fundoplication (e.g., heartburn frequency = 8-2, severity = 8-1; P < 0.01 for each). Eighty-four per cent of patients rated their symptom frequency as less than once per month. Eighty-eight per cent of patients were satisfied with their postoperative results, and 95 per cent of patients confirmed they would have the operation again knowing what they know now. Long-term follow-up documents high patient satisfaction and durable symptomatic relief up to two decades after laparoscopic fundoplication for GERD. Patients should seek this operation not only for symptomatic relief, but to mitigate the deleterious effects of long-term acid exposure and anti-acid therapy.

Gastric Acid suppression is associated with decreased erlotinib efficacy in non-small-cell lung cancer.

BACKGROUND: Erlotinib is a key therapy for advanced NSCLC. Concurrent AS therapy with TKIs might reduce TKI plasma levels. Because of gastroesophageal reflux disease prevalence, this retrospective analysis was undertaken to determine if coadministering erlotinib with AS therapy affected NSCLC outcomes. PATIENTS AND METHODS: Records of advanced NSCLC patients who received erlotinib from 2007 to 2012 at a large, centralized, cancer institution were retrospectively reviewed. Pertinent demographic data were collected and concomitant AS treatment was defined as AS prescription dates overlapping with ≥ 20% of erlotinib treatment duration. Records of patients who received erlotinib for ≥ 1 week were analyzed for progression-free survival (PFS) and overall survival (OS). RESULTS: Stage IIIB/IV NSCLC patients (n = 544) were identified and 507 had adequate data for review. The median age was 64 years and 272 were female. Adenocarcinoma (n = 318; 64%) and squamous (n = 106; 21%) were predominant subtypes; 124 patients received concomitant AS therapy. In this unselected population, median PFS and OS in AS versus no AS groups were 1.4 versus 2.3 months (P < .001) and 12.9 versus 16.8 months (P = .003), respectively. Factoring sex, subtype, and performance status in multivariate Cox proportional hazards ratios for PFS and OS between AS and no AS groups were 1.83 (95% confidence interval [CI], 1.48-2.25) and 1.37 (95% CI, 1.11-1.69), respectively. CONCLUSION: This large population-based study suggests erlotinib efficacy might be linked with gastric pH and OS could be adversely affected. To our knowledge, this is the first study demonstrating a possible negative clinical effect of coadministration of erlotinib with AS therapy. Further prospective investigation is warranted.

Proton pump inhibitors and histamine 2 blockers are associated with improved overall survival in patients with head and neck squamous carcinoma.

It has been postulated that gastroesophageal reflux plays a role in the etiology of head and neck squamous cell carcinomas (HNSCC) and contributes to complications after surgery or during radiotherapy. Antacid medications are commonly used in patients with HNSCC for the management of acid reflux; however, their relationship with outcomes has not been well studied. Associations between histamine receptor-2 antagonists (H2RA) and proton pump inhibitors (PPI) use and treatment outcomes were determined in 596 patients with previously untreated HNSCC enrolled in our SPORE epidemiology program from 2003 to 2008 (median follow-up 55 months). Comprehensive clinical information was entered prospectively in our database. Risk strata were created on the basis of possible confounding prognostic variables (age, demographics, socioeconomics, tumor stage, primary site, smoking status, HPV16 status, and treatment modality); correlations within risk strata were analyzed in a multivariable model. Patients taking antacid medications had significantly better overall survival (OS; PPI alone: P < 0.001; H2RA alone, P = 0.0479; both PPI + H2RA, P = 0.0133). Using multivariable Cox models and adjusting for significant prognostic covariates, both PPIs and H2RAs used were significant prognostic factors for OS, but only H2RAs use for recurrence-free survival in HPV16-positive oropharyngeal patients. We found significant associations between the use of H2RAs and PPIs, alone or in combination, and various clinical characteristics. The findings in this large cohort study indicate that routine use of antacid medications may have significant therapeutic benefit in patients with HNSCC. The reasons for this association remain an active area of investigation and could lead to identification of new treatment and prevention approaches with agents that have minimal toxicities.

Gastroesophageal cancer: focus on epidemiology, classification, and staging.

Gastroesophageal cancer (GEC), comprising proximal esophagogastric junction (EGJ) and distal gastric cancer (GC), is a significant public health concern. The epidemiology of these tumors has significantly changed over the past several decades especially in developed countries. There is a recognized decrease in incidence and mortality of distal GC and an increase in incidence and mortality of proximal EGJ cancer. The changing epidemiology is thought to be mainly due to changing trends of risk factors such as lower incidence of Helicobacter pylori infection and increasing incidence of obesity and gastroesophageal reflux. Histologically, EGJ cancers are adenocarcinoma (AC), while distal esophagus may be squamous cell carcinoma (SCC) or AC. Distal GC is predominantly AC. Following anatomical and histological distinction, tumors are staged with endoscopic ultrasound (EUS), computerized tomography (CT), and often positron emission tomography (PET) with or without diagnostic laparoscopic and peritoneal washing. Accurate staging of tumors, with emphasis on excluding occult metastasis, is imperative to avoid unnecessary surgical resection. Therefore, it is crucial to understand how these tumors are classified, the associated epidemiology, and the current standards of staging prior to selecting the appropriate course of therapy. In this review we will discuss the epidemiology, classification, and staging of locally advanced GEC.