Responsiveness and convergent validity of QLU-C10D and EQ-5D-3L in assessing short-term quality of life following esophagectomy.

AIM: This study assessed the responsiveness and convergent validity of two preference-based measures; the newly developed cancer-specific EORTC Quality of Life Utility Measure-Core 10 dimensions (QLU-C10D) relative to the generic three-level version of the EuroQol 5 dimensions (EQ-5D-3L) in evaluating short-term health related quality of life (HRQoL) outcomes after esophagectomy. METHODS: Participants were enrolled in a multicentre randomised controlled trial to determine the impact of preoperative and postoperative immunonutrition versus standard nutrition in patients with esophageal cancer. HRQoL was assessed seven days before and 42 days after esophagectomy. Standardized Response Mean and Effect Size were calculated to assess responsiveness. Ceiling effects for each dimension were calculated as the proportion of the best level responses for that dimension at follow-up/post-operatively. Convergent validity was assessed using Spearman's correlation and the level of agreement was explored using Bland-Altman plots. RESULTS: Data from 164 respondents (mean age: 63 years, 81% male) were analysed. HRQoL significantly reduced on both measures with large effect sizes (> 0.80), and a greater mean difference (0.29 compared to 0.16) on QLU-C10D. Both measures had ceiling effects (> 15%) on all dimensions at baseline. Following esophagectomy, ceiling effects were observed with self-care (86%), mobility (67%), anxiety/depression (55%) and pain/discomfort (19%) dimensions on EQ-5D-3L. For QLU-C10D ceiling effects were observed with emotional function (53%), physical function (16%), nausea (35%), sleep (31%), bowel problems (21%) and pain (20%). A strong correlation (r = 0.71) was observed between EQ-5D-3L anxiety and QLU-C10D emotional function dimensions. Good agreement (3.7% observations outside the limits of agreement) was observed between the utility scores. CONCLUSION: The QLU-C10D is comparable to the more widely applied generic EQ-5D-3L, however, QLU-C10D was more sensitive to short-term utility changes following esophagectomy. Cognisant of requirements by policy makers to apply generic utility measures in cost effectiveness studies, the disease-specific QLU-C10D should be used alongside the generic measures like EQ-5D-3L. TRIAL REGISTRATION: The trial was registered with the Australian New Zealand Clinical Trial Registry (ACTRN12611000178943) on the 15th of February 2011.

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

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

Long-term Efficacy of Laparoscopic Antireflux Surgery on Regression of Barrett's Esophagus Using BRAVO Wireless pH Monitoring: A Prospective Clinical Cohort Study.

OBJECTIVE: To assess the long-term efficacy of antireflux surgery on Barrett's esophagus (BE) using BRAVO wireless pH monitoring. BACKGROUND: BE is associated with chronic gastroesophageal reflux and esophageal cancer. Till date, studies have failed to demonstrate that preventing gastroesophageal reflux with antireflux surgery halts the progression of BE, often because of difficulties in objectively proving an effective antireflux barrier. METHODS: Since 1991, all patients undergoing antireflux surgery across 2 hospital sites have been followed in a prospective database. Patients with BE and at least 5 years follow up after antireflux surgery were identified. All patients completed a clinical outcome questionnaire and underwent endoscopic assessment and histological evaluation of their BE. Fourty-eight hours pH monitoring was then performed with the wireless BRAVO system. RESULTS: A total of 50 patients (40 males:10 females) were included in the study, with an average follow up of 11.9 years. Approximately, 92% (46/50) reported their outcome of surgery as "excellent" or "good" and 86% (43/50) reported "none" or "mild" symptoms. Histological regression of BE was seen in 41% (20/49). Lower esophageal acid exposure (percentage time pH < 4) was significantly greater in those with no pathological regression (P = 0.008). Moreover, 64% (32/50) showed endoscopic reduction in the length of BE. Acid exposure was also significantly less in the group showing endoscopic reduction of BE (%time pH < 4, 0.2 vs 3.6, P = 0.007). CONCLUSIONS: Antireflux surgery is safe and effective in patients with Barrett's esophagus. An intact fundoplication, as assessed with BRAVO wireless pH monitoring, suggests that antireflux surgery may halt the progression of Barrett's esophagus, and this might reduce the risk of cancer development.

Quality and outcomes of synchronous two-team Ivor-Lewis oesophagectomy: Revisiting a variant technique.

BACKGROUND AND OBJECTIVES: In 1975, a modification of popular two-stage Ivor-Lewis oesophagectomy was published with synchronous resection in chest and abdomen. As data on this technique are rare and inconsistent, we aimed to investigate safety, feasibility, and outcome of this approach. METHODS: Outcome of 201 patients undergoing synchronous oesophagectomy from 2000 to 2013 was analysed retrospectively. Two groups (early: 2000-2006; late: 2007-2013) were analysed to allow comparison of outcome over time. RESULTS: Patients in the later period had fewer respiratory comorbidities (P = 0.010), median blood loss decreased significantly over time while lymph node yield increased (P < 0.001). Overall complications occurred in 58.9 (early) versus 51.7% (late) of patients (P = 0.320), anastomotic leaks in 14.3 versus 6.7% (P = 0.112), respiratory complications in 48.2 versus 34.8% (P = 0.063). Thirty-day/90-day mortality was 2.7% versus 3.4, respectively, 8.1% versus 6.8% (P ≤ 0.793). Long-term survival was better in the later cohort (P = 0.004). CONCLUSIONS: Our data of 201 patients over a period of 14 years suggests that this technique is a quick, feasible, safe, and reasonable alternative to standard two-stage Ivor-Lewis oesophagectomy. Quality of this approach and ultimate outcomes have improved over time, with similar complication rates/outcomes to literature accepted standards for two-stage approach, especially in the later time period. J. Surg. Oncol. 2016;114:719-724. © 2016 Wiley Periodicals, Inc.

Laparoscopic repair of very large hiatus hernia with sutures versus absorbable mesh versus nonabsorbable mesh: a randomized controlled trial.

OBJECTIVE: Determine whether absorbable or nonabsorbable mesh in repair of large hiatus hernias reduces the risk of recurrence, compared with suture repair. BACKGROUND: Repair of large hiatus hernia is associated with radiological recurrence rates of up to 30%, and to improve outcomes mesh repair has been recommended. Previous trials have shown less short-term recurrence with mesh, but adverse outcomes limit mesh use. METHODS: Multicentre prospective double blind randomized controlled trial of 3 methods of repair: sutures versus absorbable mesh versus nonabsorbable mesh. Primary outcome-hernia recurrence assessed by barium meal radiology and endoscopy at 6 months. Secondary outcomes-clinical symptom scores at 1, 3, 6, and 12 months. RESULTS: A total of 126 patients enrolled: 43 sutures, 41 absorbable mesh, and 42 nonabsorbable mesh. Among them, 96.0% were followed up to 12 months, with objective follow-up data in 92.9%. A recurrent hernia (any size) was identified in 23.1% after suture repair, 30.8% after absorbable mesh, and 12.8% after nonabsorbable mesh (P = 0.161). Clinical outcomes were similar, except less heartburn at 3 and 6 months and less bloating at 12 months with nonabsorbable mesh; more heartburn at 3 months, odynophagia at 1 month, nausea at 3 and 12 months, wheezing at 6 months; and inability to belch at 12 months after absorbable mesh. The magnitudes of the clinical differences were small. CONCLUSIONS: No significant differences were seen for recurrent hiatus hernia, and the clinical differences were unlikely to be clinically significant. Overall outcomes after sutured repair were similar to mesh repair.

Preoperative factors predicting clinical outcome following laparoscopic fundoplication.

BACKGROUND: Antireflux surgery is effective for the treatment of gastroesophageal reflux, but not all patients benefit equally from it. The challenge is to identify the patients who will ultimately benefit from antireflux surgery. The aim of this study was to identify preoperative factors that predict clinical outcome after antireflux surgery, with special interest in the influence of socioeconomic factors. METHODS: Preoperative clinical and socioeconomic data from 1,650 patients who were to undergo laparoscopic fundoplication were collected prospectively. Clinical outcome measures (persistent heartburn, dysphagia, satisfaction) were assessed at short-term (1 year) and longer-term (≥ 3 years) follow-up. RESULTS: At early follow-up, male gender (relative risk [RR] 1.091, p < 0.001) and the presence of a hiatus hernia (RR 1.065, p = 0.002) were independently associated with less heartburn. Male gender was also associated with higher overall satisfaction (RR 1.046, p = 0.034). An association was found between postoperative dysphagia and age (RR 0.988, p = 0.007) and the absence of a hiatus hernia (RR 0.767, p = 0.001). At longer-term follow-up, only male gender (RR 1.125, p < 0.001) was an independent prognostic factor for heartburn control. Male gender (RR 0.761, p = 0.001), the presence of a hiatus hernia (RR 0.823, p = 0.014), and cerebrovascular comorbidities (RR 1.306, p = 0.019) were independent prognosticators for dysphagia at longer-term follow-up. A hiatus hernia was the only factor associated with better overall satisfaction. Socioeconomic factors did not influence any clinical outcomes at short- and longer-term follow-up. CONCLUSION: Male gender and hiatus hernia are associated with a better clinical outcome following laparoscopic fundoplication, whereas socioeconomic status does not influence outcome.

Virtual adjunctive gut-directed hypnotherapy for people with Crohn's disease: A randomized controlled pilot and feasibility trial.

BACKGROUND: Gut-directed hypnotherapy appears to be a promising adjunctive treatment for people with Crohn's disease. The primary objective of this pilot trial was to evaluate feasibility and acceptability of virtually delivered hypnotherapy to determine the parameters for a future definitive trial. METHODS: This prospective, single-site, randomized controlled pilot and feasibility trial compared a 7-week course of virtually delivered adjunctive gut-directed hypnotherapy to standard medical treatment only for adults with Crohn's disease. Primary outcomes were study feasibility and intervention acceptability. Secondary outcomes were objective disease activity and patient-reported outcomes. Assessments took place at five time-points: baseline, post-intervention, and follow-up three-, six-, and 12-months post-intervention. KEY RESULTS: Recruitment took place between July 2020 and August 2021 at a tertiary hospital. Recruitment was initially slow and subsequently expanded to community settings. Thirty-seven participants were enrolled in the trial: 95% were retained at post-intervention and 76% at 12-months. Completion of online assessments was high (97-100% across all time-points) whilst objective data collection was low (34-44%). Most intervention participants completed all hypnotherapy sessions (88%) and reported being extremely satisfied (73%), despite 60% experiencing technical issues. CONCLUSION & INFERENCES: Virtually delivered hypnotherapy was acceptable to participants. Certain aspects of the trial including online assessment were feasible, while recruitment and objective data collection were challenges. Undertaking a future definitive trial will require broader recruitment scope and significant funding for widespread objective data collection. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ANZCTR#1260000348954.

The influence on outcome of indications for antireflux surgery.

BACKGROUND: Patients with gastroesophageal reflux referred for fundoplication present with different symptom patterns. Previous studies have not analyzed the clinical outcome after fundoplication in patients stratified according to symptom patterns. METHODS: Five hundred eighteen patients undergoing laparoscopic fundoplication were stratified according to reflux symptom patterns: group 1, regurgitation; group 2, poorly controlled reflux; group 3, regurgitation and poor reflux control (combination of 1 and 2); and group 4, symptoms well controlled but patient does not want to continue taking medication. Clinical outcomes (heartburn control, dysphagia, satisfaction) were assessed prospectively using a standardized questionnaire at early (6 months to 2 years) and late (3-5 years) follow-up intervals. RESULTS: Preoperative demographic data for the four groups were similar, except for age and the frequency of esophagitis (patients in group 4 were younger and more likely to have esophagitis). Perioperative morbidity was similar for the four groups. Eighty-seven percent of the overall study group was satisfied at early follow-up and 88% at late follow-up. Early clinical outcomes were similar for all subgroups, except dysphagia scores were higher in early follow-up in groups 1 and 3 (P = 0.001). At late clinical follow-up, there were no significant differences in clinical outcome between any groups. CONCLUSIONS: At early follow-up (6 months to 2 years), patients who had reported regurgitation as the primary indication for surgery had a less favorable clinical outcome for the side effect dysphagia. However, at later follow-up, the type of preoperative reflux symptoms did not influence the clinical outcome.

Serum outperforms plasma in small extracellular vesicle microRNA biomarker studies of adenocarcinoma of the esophagus.

BACKGROUND: Circulating microRNAs (miRNAs) are potential biomarkers for many diseases. However, they can originate from non-disease specific sources, such as blood cells, and compromise the investigations for miRNA biomarkers. While small extracellular vesicles (sEVs) have been suggested to provide a purer source of circulating miRNAs for biomarkers discovery, the most suitable blood sample for sEV miRNA biomarker studies has not been defined. AIM: To compare the miRNA profiles between matched serum and plasma sEV preparations to determine their suitability for biomarker studies. METHODS: Matched serum and plasma samples were obtained from 10 healthy controls and 10 patients with esophageal adenocarcinoma. sEV isolates were prepared from serum and plasma using ExoQuickTM and quantified using NanoSight. RNA was extracted from sEV preparations with the miRNeasy Serum/Plasma kit and profiled using the Taqman Openarray qPCR. The overall miRNA content and the expression of specific miRNAs of reported vesicular and non-vesicular origins were compared between serum and plasma sEV preparations. The diagnostic performance of a previously identified multi-miRNA biomarker panel for esophageal adenocarcinoma was also compared. RESULTS: The overall miRNA content was higher in plasma sEV preparations (480 miRNAs) and contained 97.5% of the miRNAs found in the serum sEV preparations (412 miRNAs).The expression of commonly expressed miRNAs was highly correlated (Spearman's R = 0.87, P < 0.0001) between the plasma and serum sEV preparations, but was consistently higher in the plasma sEV preparations. Specific blood-cell miRNAs (hsa-miR-223-3p, hsa-miR-451a, miR-19b-3p, hsa-miR-17-5p, hsa-miR-30b-5p, hsa-miR-106a-5p, hsa-miR-150-5p and hsa-miR-92a-3p) were expressed at 2.7 to 9.6 fold higher levels in the plasma sEV preparations compared to serum sEV preparations (P < 0.05). In plasma sEV preparations, the percentage of protein-associated miRNAs expressed at relatively higher levels (Ct 20-25) was greater than serum sEV preparations (50% vs 31%). While the percentage of vesicle-associated miRNAs expressed at relatively higher levels was greater in the serum sEV preparations than plasma sEV preparations (70% vs 44%). A 5-miRNA biomarker panel produced a higher cross validated accuracy for discriminating patients with esophageal adenocarcinoma from healthy controls using serum sEV preparations compared with plasma sEV preparations (AUROC 0.80 vs 0.54, P < 0.05). CONCLUSION: Although plasma sEV preparations contained more miRNAs than serum sEV preparations, they also contained more miRNAs from non-vesicle origins. Serum appears to be more suitable than plasma for sEV miRNAs biomarkers studies.

Circulating Serum Exosomal miRNAs As Potential Biomarkers for Esophageal Adenocarcinoma.

BACKGROUND: The poor prognosis and rising incidence of esophageal adenocarcinoma highlight the need for improved detection methods. The potential for circulating microRNAs (miRNAs) as biomarkers in other cancers has been shown, but circulating miRNAs have not been well characterized in esophageal adenocarcinoma. We investigated whether circulating exosomal miRNAs have potential to discriminate individuals with esophageal adenocarcinoma from healthy controls and non-dysplastic Barrett's esophagus. METHODS: Seven hundred fifty-eight miRNAs were profiled in serum circulating exosomes from a cohort of 19 healthy controls, 10 individuals with Barrett's esophagus, and 18 individuals with locally advanced esophageal adenocarcinoma. MiRNA expression was assessed using all possible permutations of miRNA ratios per individual. Four hundred eight miRNA ratios were differentially expressed in individuals with cancer compared to controls and Barrett's esophagus (Mann-Whitney U test, P < 0.05). The 179/408 ratios discriminated esophageal adenocarcinoma from healthy controls and Barrett's esophagus (linear regression, P < 0.05; area under receiver operating characteristic (ROC) > 0.7, P < 0.05). A multi-biomarker panel (RNU6-1/miR-16-5p, miR-25-3p/miR-320a, let-7e-5p/miR-15b-5p, miR-30a-5p/miR-324-5p, miR-17-5p/miR-194-5p) demonstrated enhanced specificity and sensitivity (area under ROC = 0.99, 95% CI 0.96-1.0) over single miRNA ratios to distinguish esophageal adenocarcinoma from controls and Barrett's esophagus. CONCLUSIONS: This study highlights the potential for serum exosomal miRNAs as biomarkers for the detection of esophageal adenocarcinoma.

Outcomes for trainees vs experienced surgeons undertaking laparoscopic antireflux surgery - is equipoise achieved?

BACKGROUND: There is a learning curve associated with laparoscopic antireflux surgery which has an impact on patient outcomes. It is unclear, however, whether this can be eliminated by supervision of early cases by experienced surgeons. The aim of this study was to evaluate the impact of training under supervision on outcomes for laparoscopic fundoplication. METHOD: Patients undergoing primary laparoscopic antireflux surgery from 1995 to 2009 were identified from a prospective database. Patients were classified according to whether they were operated on by an experienced consultant or supervised trainee, and sub-categorised according to the presence of a very large hiatus hernia. A standardised questionnaire was used to assess outcomes for heartburn, dysphagia and satisfaction at 1 and 5 years follow-up. Outcomes for the study groups were compared. RESULTS: One thousand seven hundred and ten patients underwent surgery; 1,112 were operated on by consultants and 598 by trainees. The peri-operative complication rate was not different between the groups, although in patients operated on by trainees, there were increased rates of endoscopic dilatation (9 vs. 5 % p = 0.014) and re-operation (9 vs. 6 %, p = 0.031), and a lower satisfaction rate (76 vs. 82 %, p = 0.044) within 5 years of surgery. All other outcomes were similar for trainees vs. consultants. CONCLUSION: The learning curve for laparoscopic fundoplication had a small, but statistically significant, impact on patient outcomes, with slightly lesser outcomes when surgery was undertaken by trainees, even when supervised by experienced surgeons. Although the differences were not large, they raise questions about equipoise and highlight ethical dilemmas with teaching new generations of surgeons.

Anterior 90° partial vs Nissen fundoplication--5 year follow-up of a single-centre randomised trial.

INTRODUCTION: Nissen fundoplication can be followed by side effects, and this has driven modifications, including partial fundoplications. We previously reported early outcomes from a randomised trial of Nissen vs anterior 90° partial fundoplication. This paper reports 5-year follow-up outcomes to determine whether anterior 90° fundoplication achieves a satisfactory longer-term outcome. METHODS: From February 1999 to August 2003, 79 patients were randomised to Nissen vs anterior 90° fundoplication. Patients were followed yearly using a standardized clinical questionnaire which included symptom scores to assess heartburn, dysphagia, other post-fundoplication side effects and overall satisfaction with the outcome. Five-year clinical outcomes were analysed. RESULTS: Seventy-four patients were available for follow-up at 5 years. There were no significant differences for heartburn or satisfaction, although more patients used antisecretory medication after anterior 90° fundoplication (29.7 vs 8.1 %). Dysphagia was greater after Nissen fundoplication when measured by an analogue score for solid food and a composite dysphagia score. Symptoms of bloating were more common following Nissen fundoplication (80.0 vs 32.4 %), and less patients could eat a normal diet (78.4 vs 94.6 %). Re-operation was undertaken in four patients after Nissen fundoplication (dysphagia, three; hiatus hernia, one) vs three after anterior 90° fundoplication (recurrent reflux, three). CONCLUSIONS: At 5 years, anterior 90° partial fundoplication was associated with less side effects, offset by greater use of antisecretory medication. Reflux symptoms and overall satisfaction were similar to Nissen fundoplication. Laparoscopic anterior 90° partial fundoplication is an effective treatment for gastro-esophageal reflux.