Preoperative Chemoradiotherapy vs Chemotherapy for Adenocarcinoma of the Esophagogastric Junction: A Network Meta-Analysis.

Importance: The prognosis of patients with adenocarcinoma of the esophagus and esophagogastric junction (AEG) is poor. From current evidence, it remains unclear to what extent preoperative chemoradiotherapy (CRT) or preoperative and/or perioperative chemotherapy achieve better outcomes than surgery alone. Objective: To assess the association of preoperative CRT and preoperative and/or perioperative chemotherapy in patients with AEG with overall survival and other outcomes. Data Sources: Literature search in PubMed, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, ClinicalTrials.gov, and International Clinical Trials Registry Platform was performed from inception to April 21, 2023. Study Selection: Two blinded reviewers screened for randomized clinical trials comparing preoperative CRT plus surgery with preoperative and/or perioperative chemotherapy plus surgery, 1 intervention with surgery alone, or all 3 treatments. Only data from participants with AEG were included from trials that encompassed mixed histology or gastric cancer. Among 2768 initially identified studies, 17 (0.6%) met the selection criteria. Data Extraction and Synthesis: The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines were followed for extracting data and assessing data quality by 2 independent extractors. A bayesian network meta-analysis was conducted using the 2-stage approach. Main Outcomes and Measures: Overall and disease-free survival, postoperative morbidity, and mortality. Results: The analyses included 2549 patients (2206 [86.5%] male; mean [SD] age, 61.0 [9.4] years) from 17 trials (conducted from 1989-2016). Both preoperative CRT plus surgery (hazard ratio [HR], 0.75 [95% credible interval (CrI), 0.62-0.90]; 3-year difference, 105 deaths per 1000 patients) and preoperative and/or perioperative chemotherapy plus surgery (HR, 0.78 [95% CrI, 0.64-0.91]; 3-year difference, 90 deaths per 1000 patients) showed longer overall survival than surgery alone. Comparing the 2 modalities yielded similar overall survival (HR, 1.04 [95% CrI], 0.83-1.28]; 3-year difference, 15 deaths per 1000 patients fewer for CRT). Similarly, disease-free survival was longer for both modalities compared with surgery alone. Postoperative morbidity was more frequent after CRT plus surgery (odds ratio [OR], 2.94 [95% CrI, 1.01-8.59]) than surgery alone. Postoperative mortality was not significantly more frequent after CRT plus surgery than surgery alone (OR, 2.50 [95% CrI, 0.66-10.56]) or after chemotherapy plus surgery than CRT plus surgery (OR, 0.44 [95% CrI, 0.08-2.00]). Conclusions and Relevance: In this meta-analysis of patients with AEG, both preoperative CRT and preoperative and/or perioperative chemotherapy were associated with longer survival without relevant differences between the 2 modalities. Thus, either of the 2 treatments may be recommended to patients.

Graded operative autonomy in emergency appendectomy mirrors case-complexity: surgical training insights from the SnapAppy prospective observational study.

INTRODUCTION: Surgical skill, a summation of acquired wisdom, deliberate practice and experience, has been linked to improved patient outcomes. Graded mentored exposure to pathologies and operative techniques is a cornerstone of surgical training. Appendectomy is one of the first procedures surgical trainees perform independently. We hypothesize that, given the embedded training ethos in surgery, coupled with the steep learning curve required to achieve trainer-recognition of independent competency, 'real-world' clinical outcomes following appendectomy for the treatment of acute appendicitis are operator agnostic. The principle of graded autonomy matches trainees with clinical conditions that they can manage independently, and increased complexity drives attending input or assumption of the technical aspects of care, and therefore, one cannot detect an impact of operator experience on outcomes. MATERIALS AND METHODS: This study is a subgroup analysis of the SnapAppy international time-bound prospective observational cohort study (ClinicalTrials.gov Trial #NCT04365491), including all consecutive patients aged ≥ 15 who underwent appendectomy for appendicitis during a three-month period in 2020-2021. Patient- and surgeon-specific variables, as well as 90-day postoperative outcomes, were collected. Patients were grouped based on operating surgeon experience (trainee only, trainee with direct attending supervision, attending only). Poisson and quantile regression models were used to (adjusted for patient-associated confounders) assess the relationship between surgical experience and postoperative complications or hospital length of stay (hLOS), respectively, adjusted for patient-associated confounders. The primary outcome of interest was any complications within 90 days. RESULTS: A total of 4,347 patients from 71 centers in 14 countries were included. Patients operated on by trainees were younger (Median (IQR) 33 [24-46] vs 38 [26-55] years, p < 0.001), had lower ASA classifications (ASA ≥ 3: 6.6% vs 11.6%, p < 0.001) and fewer comorbidities compared to those operated on by attendings. Additionally, trainees operated alone on fewer patients with appendiceal perforation (AAST severity grade ≥ 3: 8.7% vs 15.6%, p < 0.001). Regression analyses revealed no association between operator experience and complications (IRR 1.03 95%CI 0.83-1.28 for trainee vs attending; IRR 1.13 95%CI 0.89-1.42 for supervised trainee vs attending) or hLOS. CONCLUSION: The linkage of case complexity with operator experience within the context of graduated autonomy is a central tenet of surgical training. Either subconsciously, or by design, patients operated on by trainees were younger, fitter and with earlier stage disease. At least in part, these explain why clinical outcomes following appendectomy do not differ depending on the experience of the operating surgeon.

The Accuracy of Point-of-Care Ultrasound (POCUS) in Acute Gallbladder Disease.

There is increasing recognition that point-of-care ultrasound (POCUS), performed by the clinician at the bedside, can be a natural extension of the clinical examination-the modern abdominal "stethoscope" and provides an opportunity to expedite the care pathway for patients with acute gallbladder disease. The primary aims of this study were to benchmark the accuracy of surgeon-performed POCUS in suspected acute gallbladder disease against standard radiology or pathology reports and to compare time to POCUS diagnosis with time to definitive imaging. This prospective single-arm observational cohort study was conducted in four hospitals in Ireland, Italy, and Portugal to assess the accuracy of POCUS against standard radiology in patients with suspected acute biliary disease (ClinicalTrials.govIdentifier: NCT02682368). The findings of surgeon-performed POCUS were compared with those on definitive imaging or surgery. Of 100 patients recruited, 89 were suitable for comparative analysis, comparing POCUS with radiological findings in 84 patients and with surgical/histological findings in five. The overall global accuracy of POCUS was 88.7% (95% CI, 80.3-94.4%), with a sensitivity of 94.7% (95% CI, 85.3-98.9%), a specificity of 78.1% (95% CI, 60.03-90.7%), a positive likelihood ratio (LR+) of 4.33 and negative likelihood ratio (LR) of 0.07. The mean time from POCUS to the final radiological report was 11.9 h (range 0.06-54.9). In five patients admitted directly to surgery, the mean time between POCUS and incision was 2.30 h (range 1.5-5), which was significantly shorter than the mean time to formal radiology report. Sixteen patients were discharged from the emergency department, of whom nine did not need follow-up. Our study is one of the very few to demonstrate a high concordance between surgeon-performed POCUS of patients without a priori radiologic diagnosis of gallstone disease and shows that the expedited diagnosis afforded by POCUS can be reliably leveraged to deliver earlier definitive care for patients with acute gallbladder pathology, as the general surgeon skilled in POCUS is uniquely positioned to integrate it into their bedside assessment.

Surgical Trainee Experience with Open Cholecystectomy and the Dunning-Kruger Effect.

BACKGROUND: Laparoscopic cholecystectomy has become the standard approach to gallbladder surgery, but open cholecystectomy retains a role in complex cases. AIMS: The aim of this study was to evaluate exposure of senior trainees in general surgery to open cholecystectomy and their experience and confidence in independent performance. METHODS: General surgical trainees on a higher surgical training programme from surgical training years 5 (ST 5) to 8 (ST8) were invited to partake in an online anonymous survey. Data pertaining to case numbers, whether supervised or independently performed and level of comfort were collated and analyzed. RESULTS: Twenty-six of 40 trainees responded (65%). Twenty-one (81%) had performed over 40 laparoscopic cholecystectomies with their trainer either scrubbed or un-scrubbed in theatre. As to open cholecystectomy experience, 12 trainees had assisted in 5 or fewer cases and only 3 assisted in over 20; 17 (65%) had performed 2 or fewer cases whilst assisted by their trainer while 24 of 26 trainees (92%) had no independent experience of open cholecystectomy. However, 16 felt they would be "somewhat comfortable" and 2 reported feeling "very comfortable" while only 8 reported they were "not comfortable" converting to open cholecystectomy. CONCLUSIONS: This study confirms a steep decline in training opportunities in open cholecystectomy, but also raises concern about a Dunning-Kruger effect as, despite this lack of experience, the majority felt "somewhat comfortable" or "very comfortable" in converting to open surgery. Trainees need first to be familiar with safer alternatives to conversion. Surgical trainers need to consider the assessment of confidence as well as competence as an endpoint of trainee evaluation.

Gastroesophageal Mucosal Injury after Cholecystectomy: An Indication for Surveillance?

BACKGROUND: Cholecystectomy alters bile release dynamics from pulsatile meal-stimulated to continuous, and results in retrograde duodeno-gastric bile reflux (DGR). Bile is implicated in mucosal injury after gastric surgery, but whether cholecystectomy causes esophagogastric mucosal inflammation, therefore increasing the risk of metaplasia, is unclear. STUDY DESIGN: This study examined whether cholecystectomy-induced DGR promotes chronic inflammatory mucosal changes of the stomach and/or the esophagogastric junction (EGJ). Four groups of patients were studied and compared with controls. A group of patients was studied before and 1 year after cholecystectomy; 2 further groups were studied long-term post-cholecystectomy (LTPC) at 5 to 10 years and 10 to 20 years. All underwent abdominal ultrasound and upper gastrointestinal endoscopy with gastric antral and EGJ biopsies, noting the presence of gastric bile pooling. Biopsy specimens were stained for Ki67 and p53 overexpression, and the bile reflux index (BRI) was calculated. RESULTS: At endoscopy, bile pooling was observed in 9 of 26 (34.6%) controls, in 8 of 25 (32%) patients pre-cholecystectomy, in 15 of 25 (60%) 1 year post-cholecystectomy patients (p = 0.047), and 23 of 29 (79.3%) LTPC patients (p = 0.001). Bile reflux index positivity at the EGJ increased from 19% of controls through 41% of LTPC patients (p = 0.032). Ki67 was overexpressed at the EGJ in 19% of controls, but in 62% of LTPC patients (p = 0.044); p53 was overexpressed at the EGJ in 19% of controls compared with 66% of LTPC patients (p = 0.001). CONCLUSIONS: Duodeno-gastric bile reflux was more common in patients with gallstones than in controls, and its incidence doubled after cholecystectomy. This was associated with inflammatory changes in the gastric antrum and the EGJ, evident in most LTPC patients. Ki67 and p53 overexpression at the EGJ suggests cellular damage attributable to chronic bile exposure post-cholecystectomy, increasing the likelihood of dysplasia. Further studies are required to determine whether DGR-mediated esophageal mucosal injury is reversible or avoidable, and whether surveillance endoscopy is indicated after cholecystectomy.

Does impaired gallbladder function contribute to the development of Barrett's esophagus and esophageal adenocarcinoma?

INTRODUCTION: Esophageal adenocarcinoma is aetiologically associated with gastro-esophageal reflux, but the mechanisms responsible for the metaplasia-dysplasia sequence are unknown. Bile components are implicated. Impaired gallbladder function may contribute to duodenogastric reflux (DGR) and harmful GERD. AIMS: This study aims to compare gallbladder function in patients with Barrett's esophagus, adenocarcinoma, and controls. METHODS: Three groups of patients, all free of gallstone disease, were studied. Group 1: (n = 15) were normal controls. Group 2: (n = 15) were patients with >3-cm-long segment of Barrett's esophagus. Group 3: (n = 15) were patients with esophageal adenocarcinoma. Using real-time ultrasonography unit, gallbladder volume was measured in subjects following a 10-h fast. Ejection fraction was calculated before and after standard liquid meal and compared between the groups. RESULTS: The mean percentage reduction in gallbladder volume was 50% at 40 min in the adenocarcinoma group compared with 72.4% in the control group (p < 0.001). At 60 min, gallbladder filling had recommenced in the control group to 64.1% of fasting volume while continuing to empty with further reduction to 63% in the Barrett's group and to 50.6% (p = 0.008) in the adenocarcinoma group. The mean gallbladder ejection fraction decreased progressively from controls to Barrett's to adenocarcinoma and was significantly lower in Barrett's group (60.9%; p = 0.019) and adenocarcinoma group (47.9%; p < 0.001) compared with normal controls (70.9%). CONCLUSION: Gallbladder function is progressively impaired in Barrett's esophagus and adenocarcinoma. Gallbladder malfunction increases duodenogastric reflux, exposing the lower esophagus to an altered chemical milieu which, in turn, may have a role in promoting metaplasia-dysplasia-neoplasia sequence in the lower esophageal mucosa.