Efficient Establishment of Bile-Derived Organoids From Biliary Cancer Patients.

Patient-derived tumor organoids have considerable potential as an in vitro diagnostic tool for drug susceptibility testing. In the present study, we investigated whether bile collected for diagnostic purposes could be a potential source for the establishment of biliary cancer organoids. Among 68 cases of biliary cancer, we successfully generated 60 bile-derived organoids (BDOs) from individual patients. Consistent with previous reports that described biliary cancer organoids from surgical tissues, the BDOs showed diverse morphologies such as simple cysts, multiloculated cysts, thick capsulated cysts, and solid masses. They also harbored mutations in KRAS and TP53 at frequencies of 15% and 55%, respectively. To enrich the cancer organoids by removing contaminated noncancerous components of BDOs, we attempted to verify the effectiveness of 3 different procedures, including repeat passage, xenografting, and selection with an MDM2 inhibitor for TP53 mutation-harboring BDOs. By monitoring the sequence and expression of mutated TP53, we found that all these procedures successfully enriched the cancer organoids. Our data suggest that BDOs can be established with minimal invasiveness from almost all patients with biliary cancers, including inoperable cases. Thus, despite some limitations with respect to the characterization of BDOs and methods for the enrichment of cancer cell-derived organoids, our data suggest that BDOs could have potential applications in personalized medicine.

Rectal varix treated with endoscopic cyanoacrylate injection therapy.

There is no established treatment for rectal varices. Although endoscopic cyanoacrylate (N-butyl 2-cyanoacrylate) injection therapy is the standard treatment for gastric varices, there are few reports of its use for rectal varices. We present a case of rectal varix that was successfully treated with endoscopic cyanoacrylate injection therapy. An 80-year-old man with cirrhosis was treated for rectal varices with interventional radiology 2 years earlier. At his current presentation, he underwent colonoscopy for hematochezia and anemia, which showed recurrence of rectal varix. We performed endoscopic cyanoacrylate injection therapy for the lesion. However, since we observed bleeding from the treated varix the next day, additional cyanoacrylate was injected. Thereafter, there was no re-bleeding and no recurrence was observed at the 3-year follow-up. According to the previous reports, interventional radiology (IVR), endoscopic sclerotherapy (EIS), and endoscopic variceal ligation (EVL) have been mainly used to treat rectal varices; however, there are few reports of endoscopic cyanoacrylate injection therapy. Our case suggests that endoscopic cyanoacrylate injection therapy might be a useful and safe treatment option for rectal varices.

Efficacy of vonoprazan for initial and maintenance therapy in reflux esophagitis, nonerosive esophagitis, and proton pump inhibitor-resistant gastroesophageal reflux disease.

Proton pump inhibitors (PPIs) have been the first line treatment for gastroesophageal reflux disease (GERD). The aim of this study was to evaluate the efficacy of vonoprazan (VPZ), a potassium-competitive acid blocker for reflux esophagitis (RE), nonerosive reflux disease (NERD), and PPI-resistant GERD patients.An open-label, single-center, observational study in our hospital was performed from August 2016 to August 2017. All patients diagnosed with GERD were asked to self-report a questionnaire of frequency scale for the symptoms of GERD (FSSG) and rate their degree of satisfaction with the treatment of GERD during outpatient visit. A total of 200 (RE 47, NERD 49, PPI-resistant GERD 104) patients were included in the present study. The primary endpoint was the change of FSSG and the proportion of degree of satisfaction with the treatment at the end of the initial therapy. A percentage of improvement (improvement rate) and resolution (resolution rate) at the end of the initial therapy were evaluated. Secondary endpoint included the proportion of patients with symptomatic relapse in the 24-week maintenance phase.FSSG and the degree of satisfaction were significantly improved after the initial therapy in every group. Improvement and resolution rate after the initial therapy were 83.0% and 67.0% in RE, 66.7% and 60.4% in NERD, and 76.0% and 60.4% in PPI-resistant group. There was no significance between after the initial therapy and 24 weeks in improvement and resolution rate. Thirty-two of the total 48 patients did not take VPZ at 24 weeks. Total FSSG score in each group was 1.67 ±â€Š1.97, 2.71 ±â€Š4.91, and 4.0 ±â€Š4.93. The nonrelapse rate at 24 weeks in each group was 66.7%, 60.0%, and 50.0%. The resolution rate at 24 weeks in each group was 38.9%, 45.0%, and 30.0%.The VPZ therapy is effective for initial and maintenance therapy and improves heartburn and patient's satisfaction significantly in all 3 groups. Among patients who stopped taking VPZ during the maintenance period, 42.0% of RE and NERD group and 30% of PPI-resistant group experience complete remission from GERD at 24 weeks by introduction of VPZ.

Multicenter prospective evaluation study of endoscopic ultrasound-guided hepaticogastrostomy combined with antegrade stenting (with video).

BACKGROUND AND AIM: Endoscopic ultrasonography-guided hepaticogastrostomy (EUS-HGS) is often indicated for advanced stage patients. Therefore it is important to prevent adverse events associated with EUS-HGS procedures and obtain long stent patency. EUS-guided antegrade stenting (AS) has been developed as an advanced technique. Thus, to prevent adverse events and achieve long stent patency, EUS-AS combined with EUS-HGS (EUS-HGAS) has been reported. The aim of the present study was to evaluate the technical feasibility and efficacy of EUS-HGAS in a multicenter, prospective study. METHODS: This prospective study was carried out at each hospital of the Therapeutic Endoscopic Ultrasound Group. Primary endpoint of this multicenter prospective study was stent patency of EUS-HGAS. RESULTS: A total of 49 patients were enrolled. Technical success rate of EUS-HGS was 95.9% (47/49). EUS-AS failed in five patients because the guidewire could not be advanced into the intestine across the bile duct obstruction site. Therefore, EUS-HGAS was successfully carried out in 40 patients (technical success rate: 85.7%). Median overall survival was 114 days. Median stent patency including stent dysfunction and patient death was 114 days. In contrast, mean stent patency was 320 days. Adverse events were seen in 10.2% (5/49) of cases. Hyperamylasemia was seen in four patients, and bleeding was seen in one patient. CONCLUSIONS: The present study is the first to evaluate EUS-HGAS. EUS-HGAS has clinical benefit for obtaining long stent patency and avoiding adverse events, although the possibility of acute pancreatitis as a result of obstruction of the orifice of the pancreatic duct must be considered.