Pannala, Rahul

Background Dysphagia palliation in inoperable esophageal cancer continues to be a challenge. Self-expandable metal stents have been the mainstay of endoscopic palliation but have a significant risk of adverse events (AEs). Liquid nitrogen spray cryotherapy is an established modality that can be used with systemic therapy. This study reports the outcomes of cryotherapy, including dysphagia and quality of life (QoL), in patients receiving systemic therapy. Methods This was a prospective multicenter cohort study of adults with inoperable esophageal cancer who underwent cryotherapy. QoL and dysphagia scores before and after cryotherapy were compared. Results 55 patients received 175 cryotherapy procedures. After a mean of 3.2 cryotherapy sessions, mean QoL improved from 34.9 at baseline to 29.0 at last follow-up (P < 0.001) and mean dysphagia improved from 1.9 to 1.3 (P = 0.004). Patients receiving more intensive cryotherapy (≥ 2 treatments within 3 weeks) showed a significantly greater improvement in dysphagia compared with those not receiving intensive therapy (1.2 vs. 0.2 points; P = 0.003). Overall, 13 patients (23.6 %) received another intervention (1 botulinum toxin injection, 2 stent, 3 radiation, 7 dilation) for dysphagia palliation. Within the 30-day post-procedure period, there were three non-cryotherapy-related grade ≥ 3 AEs (all deaths). The median overall survival was 16.4 months. Conclusion In patients with inoperable esophageal cancer receiving concurrent systemic therapy, adding liquid nitrogen spray cryotherapy was safe and associated with improvement in dysphagia and QoL without causing reflux. More intensive treatment showed a greater improvement in dysphagia and should be considered as the preferred approach.

A combination of several factors, including the increasing use of cross-sectional imaging and an aging population, has led to pancreatic cystic lesions (PCLs) becoming the most detected incidental pancreatic lesions. Accurate diagnosis and risk stratification of PCLs is challenging. In the last decade, several evidence-based guidelines have been published addressing the diagnosis and management of PCLs. However, these guidelines cover different subsets of patients with PCLs and offer varying recommendations regarding diagnostic assessment, surveillance, and surgical resection. Further, recent studies comparing the accuracy of various guidelines have reported significant variations in the rate of missed cancer versus unnecessary surgical resections. In clinical practice, it is challenging to decide which guideline to follow specifically. This article reviews the varying recommendations of the major guidelines and results of comparative studies, provides an overview of newer modalities not included in the guidelines, and offers perspectives on translating the guidelines into clinical practice.

Abstract Background and study aims Optical coherence tomography (OCT) is a new technology available for evaluation of indeterminate biliary strictures. It allows under-the-surface visualization and preliminary studies have confirmed standardized characteristics associated with malignancy. The aim of this study is to evaluate the first interobserver agreement in identifying previously agreed upon OCT criteria and diagnosing of malignant versus benign disease. Patients and methods Fourteen endoscopists were asked to review an atlas of reference clips and images of eight criteria derived from expert consensus A total of 35 de-identified video clips were then evaluated for presence of the eight criteria and for final diagnosis of malignant versus benign using the atlas as reference Intraclass correlation (ICC) analysis was done to evaluate interrater agreement. Results Clips of 23 malignant lesions and 12 benign lesions were scored. Excellent interobserver agreement was seen with dilated hypo-reflective structures (0.85) and layering effacement (0.89); hyper-glandular mucosa (0.76), intact layering (0.81), and onion-skin layering (0.77); fair agreement was seen with scalloping (0.58), and thickened epithelium (0.4); poor agreement was seen with hyper-reflective surface (0.36). The diagnostic ICC for both neoplastic (0.8) and non-neoplastic (0.8) was excellent interobserver agreement. The overall diagnostic accuracy was 51 %, ranging from 43 % to 60 %. Conclusions Biliary OCT is a promising new modality for evaluation of indeterminate biliary strictures. Interobserver agreement ranged from fair to almost perfect on eight previously identified criteria. Interobserver agreement for malignancy diagnosis was substantial (0.8). Further studies are needed to validate this data.

260 Background: dysphagia (dys) palliation in non-operable esophageal cancer (EC) continues to be a challenge. While chemotherapy and radiation help with dys, many patients require endoscopic interventions during their illness. Self-expanding metal stents have been the mainstay of endoscopic interventions but have a significant risk of severe adverse events and prevent the patient from being able to lie flat without severe reflux. Cryotherapy (cryo) is an emerging technique that can be used while the patient is receiving systemic therapy (ST). Previous retrospective studies showed improvement in dys with a favorable adverse event profile but did not report on quality of life (QOL) or reflux symptoms in patients receiving ST. Prospective studies have shown modest improvement in dys and QOL in patients not receiving ST. This prospective study reports the outcomes of cryo including dys, QOL, reflux symptoms and adverse events (AE) in patients receiving ST. Methods: A prospective multicenter cohort study of 35 adult inoperable EC patients undergoing cryo from Sep 2017 to Aug 2021. QoL was assessed using a modified EORTC QLQ-OES18 questionnaire (score 18 to 72, higher scores indicating worse QoL) while dys was measured using a 4-point Likert scale (0, no Dys; 1, Dys to solids; 2, Dys to semi-solids; 3, Dys to liquids; 4, Dys to saliva) at the start of cyro and 1-2 weeks post cryo. Paired t-test was used to evaluate changes in QoL and Dys between pre- and post-cryo. Results: There were 29 males and 6 females (30 stage IV and 5 stage III at diagnosis). Among 35 patients, a total of 104 cryo procedures were performed, with a mean of 3 per patient. The median number of tumor sites treated per cryo was 2 while the median number of cryo cycles delivered per tumor site was 3. The median total freeze time per tumor site was 60 seconds. The mean QoL score improved significantly from 31.8 pre-cryo to 28.2 with one cryo session (improvement of 3.6 points; p < 0.001). The mean dysphagia score improved significantly from 1.42 to 1.05 per cryo session (improvement of 0.37 points; p = 0.002). The mean After a mean of 3 cryo sessions, QoL score improved significantly from 35.9 pre-cryo to 29.8 post-cryo (improvement of 6 points; p = 0.001) and the mean dysphagia score improved significantly from 1.97 pre-cryo to 1.25 post-cryo (improvement of 0.72 points; p = 0.004). 86.5% of patient were able to sleep lying flat without heartburn or regurgitation. 6 patients received another intervention (1 stenting, 3 radiation and 2 dilation) for Dys palliation. 8 patients underwent feeding tube placement. Cryotherapy related grade 3 or higher adverse events occurred after 3 cryo sessions. Conclusions: Cryotherapy for palliation in non operable esophageal cancer improved dysphagia and quality of life without causing reflux and had a favorable adverse event profile with most patients not needing another intervention for dysphagia palliation.

INTRODUCTION: To report the prevalence and outcomes of unselected pancreatic cancer (PC) patients with pathogenic/likely pathogenic germline variants (PGVs) detected using a universal testing approach. METHODS: We undertook a prospective, multisite study of germline sequencing using a >80 gene next-generation sequencing platform among 250 patients with PC (not selected for age or family history of cancer) between April 1, 2018, and March 31, 2020. Demographic, tumor characteristics, and clinical outcomes were compared between PGV carriers and noncarriers. RESULTS: Of 250 patients, the mean age was 65 years (SD 8.7), 56% was male, 83.6% was White, and 65.6% had advanced disease (stages III and IV). PGVs were found in 15.2% (N = 38) of patients, and 2 patients had more than 1 PGV. Variants of uncertain significance were found in 44.4% (N = 111). Family history of cancer (odds ratio: 2.36, 95% confidence interval: 1.14–5.19, P = 0.025) was associated with a higher risk of PGV. In a median follow-up of 16.5 months, the median overall survival was 16.8 months in PGV carriers compared with 16.5 months in noncarriers (hazard ratio: 0.51, 95% confidence interval: 0.25–1.01, P = 0.05). Higher levels of carbohydrate antigen 19-9 and advanced disease stages (III and IV) were associated with worse outcomes in both groups. Overall, 68% of PGV carriers had mutations in homologous recombination repair genes, including BRCA1 , BRCA2 , PALB2 , ATM , CHEK2 , NBN , and RAD51C . DISCUSSION: Universal multigene panel testing in PC reveals that 1 in 6 patients are carriers of PGV. Multigene germline testing should be used to aid in treatment selection, prognostication, and familial cancer counseling.