Establishment of a patient-specific avatar organoid model derived from endoscopic ultrasonography-guided fine needle biopsy for timely clinical application in pancreatic ductal adenocarcinoma.

BACKGROUND AND AIMS: Pancreatic ductal adenocarcinoma (PDAC) has the worst survival rate among tumors. At the time of diagnosis, more than 80% of PDACs are considered to be surgically unresectable, and there is an unmet need for treatment options in these inoperable PDACs. This study aimed to establish a patient-derived organoid (PDO) platform from endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) collected at diagnosis and to determine its clinical applicability for the timely treatment of unresectable PDAC. METHODS: Patients with suspected PDAC were prospectively enrolled at the Samsung Medical Center from 2015 to 2019. PDAC tissues were acquired by means of EUS-FNB to establish PDAC PDOs, which were comprehensively analyzed for histology, genomic sequencing, and high-throughput screening (HTS) drug sensitivity test. RESULTS: PDAC PDOs were established with a success rate of 83.2% (94/113). It took approximately 3 weeks from acquiring minimal EUS-FNB specimens to generating sufficient PDAC PDOs for the simultaneous HTS drug sensitivity test and genomic sequencing. The high concordance between PDAC tissues and matched PDOs was confirmed, and whole-exome sequencing revealed the increased detection of genetic alterations in PDOs compared with EUS-FNB tissues. The HTS drug sensitivity test showed clinical correlation between the ex vivo PDO response and the actual chemotherapeutic response of the study patients in the real world (13 out of 15 cases). In addition, whole-transcriptome sequencing identified candidate genes associated with nab-paclitaxel resistance, such as ITGB7, ANPEP, and ST3GAL1. CONCLUSIONS: This PDAC PDO platform allows several therapeutic drugs to be tested within a short time window and opens the possibility for timely personalized medicine as a "patient avatar model" in clinical practice.

Helicobacter pylori Infection and the Development of Advanced Colorectal Neoplasia.

BACKGROUND: An association between Helicobacter pylori infection and colorectal neoplasia has been reported in cross-sectional studies. GOALS: We examined the association between H. pylori infection and the development of advanced colorectal neoplasia (AN) in a screening cohort. STUDY: We identified 3753 adults, who underwent screening and subsequent surveillance colonoscopies. The primary outcome was the development of metachronous AN, as confirmed by surveillance colonoscopy. H. pylori infection status was assessed by an H. pylori-specific immunoglobulin G antibody test. Sensitivity analysis was also performed by H. pylori infection status on the basis of histology. RESULTS: During a median follow-up of 41 months, the incidence of AN was 3.2% and 1.7% in participants with and without H. pylori infection, respectively. In multivariable analysis adjusted for age, body mass index, smoking status, alcohol intake, family history of colorectal cancer, and baseline adenoma characteristics, the hazard ratio [95% confidence interval (CI)] for metachronous AN was 1.74 (1.11-2.73) in participants with H. pylori seropositivity, compared with those without H. pylori seropositivity. The association was consistent with H. pylori infection status on the basis of histology (adjusted hazard ratio, 3.51; 95% CI, 1.64-7.51). In the subgroup analysis, the positive association was observed in both no-adenoma and adenoma removal subgroups. CONCLUSIONS: In a cohort study, H. pylori infection was associated with an increased risk of AN development. This association was consistent in both the serological and histologic assessment of H. pylori infection. Prospective studies are necessary to determine whether H. pylori eradication can reduce the risk of colorectal neoplasia.

Risk Factors for Pancreatitis and Cholecystitis after Endoscopic Biliary Stenting in Patients with Malignant Extrahepatic Bile Duct Obstruction.

BACKGROUND/AIMS: For the treatment of malignant biliary obstruction, endoscopic retrograde biliary drainage (ERBD) has been widely accepted as a standard procedure. However, post-ERBD complications can affect the lives of patients. The purpose of this study was to identify the predictive factors for these complications, including the patient's status, cancer status, and stent type. METHODS: This was a retrospective analysis conducted in a single tertiary hospital from January 2007 to July 2017. The following variables were evaluated: sex, age, body mass index, cancer type, history of pancreatitis, gallbladder stone, previous biliary stenting, precut papillotomy, stent type, contrast injection into the pancreatic duct or gallbladder, cystic duct invasion by the tumor, and occlusion of the cystic duct orifice by a metal stent. RESULTS: Multivariate analysis showed that contrast injection into the pancreatic duct was a risk factor for pancreatitis. Patients with a history of bile drainage showed a lower risk of pancreatitis. For cholecystitis, the analysis revealed contrast injection into the gallbladder and cystic duct invasion by the tumor as important predictive factors. Metal stents showed a greater risk of post-procedure pancreatitis than plastic stents, but did not affect the incidence of cholecystitis. CONCLUSION: Considering that contrast injection is the most important factor for both complications, a careful approach by the physician is essential in preventing the occurrence of any complications. Further, choosing the type of stent is an important factor for patients at a risk of post-procedure pancreatitis.