A systematic review of the perforated duodenal diverticula: lessons learned from the last decade.

BACKGROUND: The perforated duodenal diverticulum remains a rare clinical entity, the optimal management of which has not been well established. Historically, primary surgery has been the preferred treatment modality. This was called into question during the last decade, with the successful application of non-operative therapy in selected patients. The aim of this systematic review is to identify cases of perforated duodenal diverticula published over the past decade and to assess any subsequent evolution in treatment. METHODS: A systematic review of English and non-English articles reporting on perforated duodenal diverticula using MEDLINE (2008-2020) was performed. Only cases of perforated duodenal diverticula in adults (> 18 years) that reported on diagnosis and treatment were included. RESULTS: Some 328 studies were identified, of which 31 articles met the inclusion criteria. These studies included a total of 47 patients with perforated duodenal diverticula. This series suggests a trend towards conservative management with 34% (16/47) of patients managed non-operatively. In 31% (5/16) patients initially managed conservatively, a step-up approach to surgical intervention was required. CONCLUSION: Conservative treatment of perforated duodenal diverticula appears to be an acceptable and safe treatment strategy in stable patients without signs of peritonitis under careful observation. For patients who fail to respond to conservative treatment, a step-up approach to percutaneous drainage or surgery can be applied. If surgery is required, competence in techniques ranging from simple diverticulectomy to Roux-en-Y gastric diversion or even Whipple's procedure may be required depending on tissue friability and diverticular collar size.

Preemptive Endoluminal Vacuum Therapy to Reduce Morbidity After Minimally Invasive Ivor Lewis Esophagectomy: Including a Novel Grading System for Postoperative Endoscopic Assessment of GI-Anastomoses.

OBJECTIVE: Preemptive endoluminal vacuum therapy (pEVT) is a novel concept to reduce postoperative morbidity and has the potential to disrupt current treatment paradigms for patients undergoing esophagectomy. SUMMARY OF BACKGROUND DATA: Endoluminal vacuum therapy is an accepted treatment for AL after esophagectomy. METHODS: Retrospective analysis of patients undergoing minimally invasive Ivor Lewis esophagectomy with pEVT between 11/2017 and 10/2020. The sponge was removed endoscopically after 4-6 days, and anastomosis and gastric conduit were assessed according to a novel endoscopic grading system. Further management was customized according to endoscopic appearance and clinical course. Endpoints were postoperative morbidity and AL rate, defined according to the Clavien-Dindo (CD) and International Esodata Study Group classifications. RESULTS: PEVT was performed in 67 consecutive patients, 57 (85%) were high-risk patients with an ASA score >2, WHO/ECOG score >1, age >65 years, or BMI >29 kg/m2. Thirty patients experienced textbook outcome, and overall minor (≤CD IIIa) and major (≥CD IIIb) morbidity was 40.3% and 14.9% respectively. 30-day-mortality was 0%. Forty-nine patients (73%) had uneventful anastomotic healing after pEVT without further endoscopic treatment. The remaining 18 patients (27%) underwent prolonged EVT with uneventful anastomotic healing in 13 patients (19%), contained AL in 4 patients (6%), and 1 uncontained leakage (1.5%) in a case with proximal gastric conduit necrosis, resulting in an overall AL rate of 7.5%. CONCLUSIONS: PEVT is an innovative and safe procedure with a promising potential to reduce postoperative morbidity after minimally invasive Ivor Lewis esophagectomy and may be particularly valuable in highly comorbid cases.

KRAS G12C in advanced NSCLC: Prevalence, co-mutations, and testing.

KRAS is the most commonly mutated oncogene in advanced, non-squamous, non-small cell lung cancer (NSCLC) in Western countries. Of the various KRAS mutants, KRAS G12C is the most common variant (~40%), representing 10-13% of advanced non-squamous NSCLC. Recent regulatory approvals of the KRASG12C-selective inhibitors sotorasib and adagrasib for patients with advanced or metastatic NSCLC harboring KRASG12C have transformed KRAS into a druggable target. In this review, we explore the evolving role of KRAS from a prognostic to a predictive biomarker in advanced NSCLC, discussing KRAS G12C biology, real-world prevalence, clinical relevance of co-mutations, and approaches to molecular testing. Real-world evidence demonstrates significant geographic differences in KRAS G12C prevalence (8.9-19.5% in the US, 9.3-18.4% in Europe, 6.9-9.0% in Latin America, and 1.4-4.3% in Asia) in advanced NSCLC. Additionally, the body of clinical data pertaining to KRAS G12C co-mutations such as STK11, KEAP1, and TP53 is increasing. In real-world evidence, KRAS G12C-mutant NSCLC was associated with STK11, KEAP1, and TP53 co-mutations in 10.3-28.0%, 6.3-23.0%, and 17.8-50.0% of patients, respectively. Whilst sotorasib and adagrasib are currently approved for use in the second-line setting and beyond for patients with advanced/metastatic NSCLC, testing and reporting of the KRAS G12C variant should be included in routine biomarker testing prior to first-line therapy. KRAS G12C test results should be clearly documented in patients' health records for actionability at progression. Where available, next-generation sequencing is recommended to facilitate simultaneous testing of potentially actionable biomarkers in a single run to conserve tissue. Results from molecular testing should inform clinical decisions in treating patients with KRAS G12C-mutated advanced NSCLC.

Current surgical concepts for type III hiatal hernia: a survey among members of the Swiss Society of Visceral Surgery.

AIMS OF THE STUDY: Surgery for large hiatal hernias has greatly evolved over the last decade, but there is an ongoing controversy regarding many technical aspects, such as the use of meshes or the necessity to add a fundoplication. The purpose of this survey was to assess the current spectrum of surgical care for mixed axial and paraoesophageal hiatal hernias (type III hiatal hernia) in Switzerland. METHODS: In April 2020, we conducted a web-based survey comprising 25 questions on surgical management of type III hiatal hernia among members of the Swiss Society for Visceral Surgery. The survey focused exclusively on primary hernias in an elective setting. Responses were graded on a five-point Likert scale and analysed using descriptive statistics. Consensus was defined as agreement (agree or strongly agree) ≥75%. RESULTS: Forty-seven visceral surgeons with a median annual institutional caseload of 15 (interquartile range 10-30) type III hiatal hernia participated in the survey (response rate 15%). Agreement ≥75% was found for several basic technical steps (access via laparoscopy, hernia sac resection, preservation of vagus nerves, preservation of aberrant left hepatic artery, single-stitch posterior suture repair of hiatus with braided, non-resorbable material, complementary antireflux procedure). In contrast, consensus was not achieved for several important surgical details (mesh hiatoplasty, type of antireflux procedure, gastropexy, management of short oesophagus). A high percentage of participating surgeons experienced mesh related complications in their own or assigned patients: erosions (15% and 36%, respectively), stenoses (26% and 24%, respectively) and pericardial tamponades (9% and 15%, respectively). Nevertheless, hiatal reinforcement with mesh (in all or in selected cases) was reported by 91% of participants without consensus regarding mesh type, shape, placement and fixation technique. CONCLUSIONS: Apart from a few generally accepted technical steps, surgical management of type III hiatal hernia is highly variable amongst visceral surgeons in Switzerland. Although mesh-related complications appear to be common, most Swiss surgeons report routine mesh use for hiatal reinforcement.

Pre-Emptive Endoluminal Negative Pressure Therapy at the Anastomotic Site in Minimally Invasive Transthoracic Esophagectomy (the preSPONGE Trial): Study Protocol for a Multicenter Randomized Controlled Trial.

INTRODUCTION: Anastomotic leakage (AL) accounts for a significant proportion of morbidity following oesophagectomy. Endoluminal negative pressure (ENP) therapy via a specifically designed polyurethane foam (EsoSponge®, B.Braun Medical, Melsungen, Germany) has become the standard of care for AL in many specialized centres. The prophylactic (pENP) application of this technique aims to reduce postoperative morbidity and is a novel approach which has not yet been investigated in a prospective study. The aim of this study is therefore to assess the effect of pENP at the anastomotic site in high-risk patients undergoing minimally invasive transthoracic Ivor Lewis oesophagectomy. METHODS AND ANALYSIS: The study design is a prospective, multi-centre, two-arm, parallel-group, randomised controlled trial and will be conducted in two phases. Phase one is a randomised feasibility and safety pilot trial involving 40 consecutive patients. After definitive sample size calculation, additional patients will be included accordingly during phase two. The primary outcome of the study will be the postoperative length of hospitalization until reaching previously defined "fit for discharge criteria". Secondary outcomes will include postoperative morbidity, mortality and postoperative AL-rates based on 90-day follow-up. A confirmatory analysis based on intention-to-treat will be performed. ETHICS AND DISSEMINATION: The ethics committee of the University of Zurich approved this study (2019-00562), which has been registered with ClinicalTrials.gov on 14.11.2019 (NCT04162860) and the Swiss National Clinical Trials Portal (SNCTP000003524). The results of the study will be published and presented at appropriate conferences.

Variation in pre-PCR processing of FFPE samples leads to discrepancies in BRAF and EGFR mutation detection: a diagnostic RING trial.

AIMS: Mutation detection accuracy has been described extensively; however, it is surprising that pre-PCR processing of formalin-fixed paraffin-embedded (FFPE) samples has not been systematically assessed in clinical context. We designed a RING trial to (i) investigate pre-PCR variability, (ii) correlate pre-PCR variation with EGFR/BRAF mutation testing accuracy and (iii) investigate causes for observed variation. METHODS: 13 molecular pathology laboratories were recruited. 104 blinded FFPE curls including engineered FFPE curls, cell-negative FFPE curls and control FFPE tissue samples were distributed to participants for pre-PCR processing and mutation detection. Follow-up analysis was performed to assess sample purity, DNA integrity and DNA quantitation. RESULTS: Rate of mutation detection failure was 11.9%. Of these failures, 80% were attributed to pre-PCR error. Significant differences in DNA yields across all samples were seen using analysis of variance (p<0.0001), and yield variation from engineered samples was not significant (p=0.3782). Two laboratories failed DNA extraction from samples that may be attributed to operator error. DNA extraction protocols themselves were not found to contribute significant variation. 10/13 labs reported yields averaging 235.8 ng (95% CI 90.7 to 380.9) from cell-negative samples, which was attributed to issues with spectrophotometry. DNA measurements using Qubit Fluorometry demonstrated a median fivefold overestimation of DNA quantity by Nanodrop Spectrophotometry. DNA integrity and PCR inhibition were factors not found to contribute significant variation. CONCLUSIONS: In this study, we provide evidence demonstrating that variation in pre-PCR steps is prevalent and may detrimentally affect the patient's ability to receive critical therapy. We provide recommendations for preanalytical workflow optimisation that may reduce errors in down-stream sequencing and for next-generation sequencing library generation.