Safety and efficacy of remimazolam versus propofol during endoscopic ultrasound: A multicenter randomized controlled study.

BACKGROUND AND AIMS: Propofol, a widely used sedative in gastrointestinal endoscopic procedures, is associated with cardiorespiratory suppression. Remimazolam is a novel ultra-short-acting benzodiazepine sedative with rapid onset and minimal cardiorespiratory depression. This study aimed to compare the safety and efficacy of remimazolam and propofol during endoscopic ultrasound (EUS) procedures. METHODS: A multicenter randomized controlled study was conducted between October 2022 and March 2023 in patients who underwent EUS procedures. Patients were randomly assigned to receive either remimazolam or propofol as a sedative agent. The primary endpoint was cardiorespiratory adverse events during the procedure, including desaturation, respiratory depression, hypotension, and tachycardia. Secondary endpoints included the time to achieve sedation, recovery time, quality of sedation, pain at the injection site, and satisfaction of both the endoscopists and patients. RESULTS: Four hundred patients enrolled in the study: 200 received remimazolam (10.8±7.7 mg) and 200 received propofol (88.0±49.1 mg). For cardiorespiratory adverse events, the remimazolam group experienced fewer occurrences than the propofol group (8.5% vs. 16%, p=0.022). There was a non-significant trend toward less oxygen desaturation (1.0% vs 3.5%, p= 0.09), respiratory depression (0.5% vs 1.5%, p= 0.62), hypotension (2.5% vs 5.5%, p=0.12) and tachycardia (4.5% vs 5.5%, p=0.68) with remimazolam than with propofol. Remimazolam showed a shorter induction time than propofol, while maintaining comparable awakening and recovery times. Injection site pain was significantly lower in the remimazolam group than in the propofol group. The remimazolam group demonstrated a significantly higher quality of sedation and satisfaction scores than the propofol group, as evaluated by both endoscopists and patients. CONCLUSION: Remimazolam was superior to propofol in terms of safety and efficacy during EUS examinations.

The Impact of Statins on the Survival of Patients with Advanced Hepatocellular Carcinoma Treated with Sorafenib or Lenvatinib.

We aimed to evaluate the survival benefits of coadministering statins and multityrosine kinase inhibitors (TKIs) in patients with advanced hepatocellular carcinoma (HCC). Data from the Health Insurance Review and Assessment Service in Korea (2010-2020) were utilized. Statin use (≥28 cumulative defined daily doses) was analyzed, with 1534 statin users matched to 6136 non-users (1:4 ratio) using propensity scores. Primary and secondary outcomes were overall survival (OS) and progression-free survival (PFS). Statin use significantly improved OS (hazard ratio [HR] 0.77, 95% confidence interval [CI] 0.72-0.82, p < 0.001) and PFS (HR 0.78, 95% CI 0.74-0.84, p < 0.001). Continuous or post-TKI statin users had better OS, while discontinuation after TKI use led to poorer OS. Both lipophilic and hydrophilic statins improved OS and PFS, particularly with ≥730 cumulative defined daily doses. In conclusion, combining statins and TKIs in patients with advanced HCC yielded significant survival benefits, influenced by statin dosage and duration. Continuous statin administration post-TKI treatment is crucial for improving outcomes in patients with HCC.

Side-by-side placement of fully covered metal stents versus conventional 7F plastic stents in malignant hilar biliary obstruction: Prospective randomized controlled trial.

OBJECTIVES: We aimed to evaluate the efficacy and safety of metal stents compared with plastic stents when bilateral side-by-side stents were deployed for malignant hilar biliary obstruction (MHBO). METHODS: Fifty patients with unresectable advanced MHBO were randomly assigned to the metal stent (MS, n = 25) or plastic stent group (PS, n = 25). Fully covered self-expandable metal stents with 6 mm diameter and plastic stents with either 7F straight or double pigtail were used for MS and PS groups, respectively. Time to recurrent biliary obstruction (TRBO) was evaluated as the primary outcome. RESULTS: Both groups had 100% technical success rates; 88% and 76% of clinical success rates were obtained in MS and PS, respectively. Although stent migrations were more frequent in MS than PS (48% vs. 16%, P = 0.02), the mean TRBO was significantly longer in MS (190 days; 95% confidence interval [CI] 121-260 days vs. 96 days; 95% CI 50-141 days, P = 0.02). The placement of plastic stents (hazard ratio 2.42; 95% CI 1.24-4.73; P = 0.01) was the only significant risk factor associated with TRBO in multivariable analysis. The rates of adverse events were similar between the two groups (difference 0%; 95% CI -25% to 25%; P > 0.99). CONCLUSIONS: During bilateral side-by-side deployment in MHBO, the use of metal stents appears to be preferable to plastic stents in terms of TRBO, despite a higher frequency of stent migration.

Endoscopic ultrasound-rendezvous versus percutaneous-endoscopic rendezvous endoscopic retrograde cholangiopancreatography for bile duct access: Systematic review and meta-analysis.

OBJECTIVES: Endoscopic ultrasound (EUS) or percutaneous-assisted antegrade guidewire insertion can be used to achieve biliary access when standard endoscopic retrograde cholangiopancreatography (ERCP) fails. We conducted a systematic review and meta-analysis to evaluate and compare the effectiveness and safety of EUS-assisted rendezvous (EUS-RV) and percutaneous rendezvous (PERC-RV) ERCP. METHODS: We searched multiple databases from inception to September 2022 to identify studies reporting on EUS-RV and PERC-RV in failed ERCP. A random-effects model was used to summarize the pooled rates of technical success and adverse events with 95% confidence interval (CI). RESULTS: In total, 524 patients (19 studies) and 591 patients (12 studies) were managed by EUS-RV and PERC-RV, respectively. The pooled technical successes were 88.7% (95% CI 84.6-92.8%, I2 = 70.5%) for EUS-RV and 94.1% (95% CI 91.1-97.1%, I2 = 59.2%) for PERC-RV (P = 0.088). The technical success rates of EUS-RV and PERC-RV were comparable in subgroups of benign diseases (89.2% vs. 95.8%, P = 0.068), malignant diseases (90.3% vs. 95.5%, P = 0.193), and normal anatomy (90.7% vs. 95.9%, P = 0.240). However, patients with surgically altered anatomy had poorer technical success after EUS-RV than after PERC-RV (58.7% vs. 93.1%, P = 0.036). The pooled rates of overall adverse events were 9.8% for EUS-RV and 13.4% for PERC-RV (P = 0.686). CONCLUSIONS: Both EUS-RV and PERC-RV have exhibited high technical success rates. When standard ERCP fails, EUS-RV and PERC-RV are comparably effective rescue techniques if adequate expertise and facilities are feasible. However, in patients with surgically altered anatomy, PERC-RV might be the preferred choice over EUS-RV because of its higher technical success rate.

Simultaneous establishment of pancreatic cancer organoid and cancer-associated fibroblast using a single-pass endoscopic ultrasound-guided fine-needle biopsy specimen.

Considering the critical roles of cancer-associated fibroblasts (CAFs) in pancreatic cancer, recent studies have attempted to incorporate stromal elements into organoid models to recapitulate the tumor microenvironment. This study aimed to evaluate the feasibility of patient-derived organoid (PDO) and CAF cultures by using single-pass endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) samples from prospectively enrolled pancreatic cancer patients. The obtained samples were split into two portions for PDO and CAF cultures. PDOs and CAFs were cultured successfully in 54.4% (31/57) and 47.4% (27/57) of the cases, respectively. Both components were established in 21 cases (36.8%). Various clinicopathologic factors, including the tumor size, tumor location, clinical stage, histologic subtype, and tumor differentiation, did not influence the PDO establishment. Instead, the presence of necrosis in tumor samples was associated with initial PDO generation but no further propagation beyond passage 5 (P = 0.024). The "poorly cohesive cell carcinoma pattern" also negatively influenced the PDO establishment (P = 0.018). Higher stromal proportion in tumor samples was a decisive factor for successful CAF culture (P = 0.005). Our study demonstrated that the coestablishment of PDOs and CAFs is feasible even with a single-pass EUS-FNB sample, implying an expanding role of endoscopists in future precision medicine.

Alteration of the fecal microbiome in patients with cholecystectomy: potential relationship with postcholecystectomy diarrhea - before and after study.

BACKGROUND: Bile acid (BA) is a crucial determinant of the gut microbiome, and cholecystectomy can alter the physiology of BA. Physiological changes in BA resulting from cholecystectomy can also influence the gut microbiome. We aimed to identify the specific taxa associated with perioperative symptoms, including postcholecystectomy diarrhea (PCD), and to evaluate the effect of cholecystectomy on the microbiome by investigating the fecal microbiome of patients with gallstones. METHODS: We analyzed the fecal samples of 39 patients with gallstones (GS group) and 26 healthy controls (HC group) to evaluate their gut microbiome. We also collected fecal samples from GS group 3 months postcholecystectomy. Symptoms of patients were evaluated before and after cholecystectomy. Further, 16S ribosomal RNA amplification and sequencing were performed to determine the metagenomic profile of fecal samples. RESULTS: The microbiome composition of GS differed from that of HC; however, the alpha diversity was not different. No significant microbiome alterations were observed before and after cholecystectomy. Moreover, GS group showed a significantly lower Firmicutes to Bacteroidetes ratio before and after cholecystectomy than the HC group (6.2, P< 0.05). The inter-microbiome relationship was lower in GS than in HC and tended to recover 3 months after surgery. Furthermore, ~28.1% ( n =9) of patients developed PCD after surgery. The most prominent species among PCD (+) patients was Phocaeicola vulgatus. Compared with the preoperative state, Sutterellaceae , Phocaeicola , and Bacteroidals were the most dominant taxa among PCD (+) patients. CONCLUSION: GS group showed a different microbiome from that of HC; however, their microbiomes were not different 3 months after cholecystectomy. Our data revealed taxa-associated PCD, highlighting the possibility of symptom relief by restoring the gut microbiome.

Comparison between three types of needles for endoscopic ultrasound-guided tissue acquisition of pancreatic solid masses: a multicenter observational study.

It is debatable which needle has clear superiority of diagnostic performance in endoscopic ultrasound (EUS)-guided fine needle biopsy (FNB) of solid pancreatic masses. This study aimed to compare the performance of three needles and determine the variables that affect diagnostic accuracy. From March 2014 to May 2020, 746 patients with solid pancreatic masses who underwent EUS-FNB using three types of needles (Franseen needle, Menghini-tip needle, and Reverse-bevel needle) were retrospectively reviewed. Multivariate analysis using a logistic regression model was used to identify factors related to diagnostic accuracy. There were significant differences between the groups regarding the procurement rate of the histologic and optimal quality cores (Franseen vs. Menghini-tip vs. Reverse-bevel: 98.0% [192/196] vs. 85.8% [97/113] vs. 91.9% [331/360], P < 0.001 and 95.4% [187/196] vs. 65.5% [74/113] vs. 88.3% [318/360], P < 0.001, respectively). The sensitivity and accuracy using histologic samples were 95.03% and 95.92% for Franseen, 82.67% and 88.50% for Menghini-tip, and 82.61% and 85.56% for Reverse-bevel needles, respectively. In direct comparison between the needles using histologic samples, the Franseen needle showed significantly superior accuracy than the Menghini-tip (P = 0.018) and Reverse-bevel needles (P < 0.001). Multivariate analysis indicated that tumor size ≥ 2 cm (odds ratio [OR] 5.36, 95% confidence interval [CI] 3.40-8.47, P < 0.001) and fanning technique (OR 1.70, 95% CI 1.00-2.86, P = 0.047) were significantly associated with an accurate diagnosis. EUS-FNB using the Franseen needle enables the acquisition of a larger and more adequate histologic core tissue and achieves an accurate histological diagnosis when using the fanning technique.

Comparison of the long-term outcomes between proximal and distal IgG4-related sclerosing cholangitis: A multicenter cohort study.

BACKGROUND AND AIMS: Immunoglobulin G4-related sclerosing cholangitis (IgG4-SC) is considered a biliary manifestation of IgG4-related diseases. However, there has been a controversy on the clinical outcomes according to the location of the involved bile duct. We therefore compared the clinical outcomes and long-term prognosis of IgG4-SC with proximal bile duct involvement (proximal IgG4-SC) and IgG4-SC with distal bile duct involvement (distal IgG4-SC). METHODS: We reviewed the data of patients with IgG4-SC that were prospectively collected at 10 tertiary centers between March 2002 and October 2020. Clinical manifestations, outcomes, association with autoimmune pancreatitis (AIP), steroid-responsiveness, and relapse of IgG4-SC were evaluated. RESULTS: A total of 148 patients (proximal IgG4-SC, n = 59; distal IgG4-SC, n = 89) were analyzed. The median age was 65 years (IQR, 56.25-71), and 86% were male. The two groups were similar in terms of jaundice at initial presentation (51% vs 65%; P = 0.082) and presence of elevated serum IgG4 (66% vs 70%; P = 0.649). The two groups showed significant differences in terms of steroid-responsiveness (91% vs 100%; P = 0.008), association with AIP (75% vs 99%; P = 0.001), and occurrence of liver cirrhosis (9% vs 1%; P = 0.034). During a median follow-up of 64 months (IQR, 21.9-84.7), the cumulative relapse-free survival was significantly different between the two groups (67% vs 79% at 5 years; P = 0.035). CONCLUSIONS: Relapse of IgG4-SC frequently occurred during follow-up. Proximal IgG4-SC and distal IgG4-SC had different long-term outcomes in terms of steroid-responsiveness, occurrence of liver cirrhosis, and recurrence. It may be advantageous to determine the therapeutic and follow-up strategies according to the location of bile duct involvement.

EUS-guided tissue acquisition using a novel torque technique is comparable with that of the fanning technique for solid pancreatic lesions: A multicenter randomized trial.

BACKGROUND: The torque and fanning techniques allow for multiple areas within pancreatic lesions to be targeted using different maneuvers and can, hence, enhance diagnostic outcomes. We compared the diagnostic performance of endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) for pancreatic masses using the torque and fanning techniques. METHODS: This multicenter randomized trial enrolled a total of 160 consecutive patients who underwent EUS-FNB for solid pancreatic tumors using either the torque or fanning technique. Three passes were permitted for each lesion, and the technique sequence was randomly assigned as either torque first or fanning first with the standard technique as a reference. RESULTS: The median quality score of the histological samples was significantly higher in the torque and fanning group than in the standard group (p < .001). Furthermore, the torque technique provided improved sensitivity of 93.38% and accuracy of 94.30%. The standard technique provided diagnostic sensitivity of 68.84% and accuracy of 72.96%, while the fanning technique showed sensitivity of 91.85% and accuracy of 93.04%. CONCLUSIONS: The new torque technique enables the acquisition of better-quality samples and can potentially increase the diagnostic outcomes in the EUS-FNB of pancreatic solid masses, with the same recommendations as those for the fanning technique.

Impact of guideline adherence on the prognosis of Barcelona clinic liver cancer stage B hepatocellular carcinoma.

BACKGROUND: Patients with Barcelona clinic liver cancer (BCLC) stage B hepatocellular carcinoma (HCC) are considerably heterogeneous in terms of tumor burden, liver function, and performance status. To improve the poor survival outcomes of these patients, treatment approaches other than transarterial chemoembolization (TACE), which is recommended by HCC guidelines, have been adopted in real-world clinical practice. We hypothesize that this non-adherence to treatment guidelines, particularly with respect to the use of liver resection, improves survival in patients with stage B HCC. AIM: To assess guideline adherence in South Korean patients with stage B HCC and study its impact on survival. METHODS: A retrospective analysis was conducted using data from 2008 to 2016 obtained from the Korea Central Cancer Registry. Patients with stage B HCC were categorized into three treatment groups, guideline-adherent, upward, and downward, based on HCC guidelines recommended by the Asian Pacific Association for the Study of the Liver (APASL), the European Association for the Study of the Liver (EASL), and the American Association for the Study of Liver Diseases (AASLD). The primary outcome was HCC-related deaths; tumor recurrence served as the secondary outcome. Survival among the groups was compared using the Kaplan-Meier method and the log-rank test. Predictors of survival outcomes were identified using multivariable Cox regression analysis. RESULTS: In South Korea, over the study period from 2008 to 2016, a notable trend was observed in adherence to HCC guidelines. Adherence to the EASL guidelines started relatively high, ranging from 77% to 80% between 2008 and 2012, but it gradually declined to 58.8% to 71.6% from 2013 to 2016. Adherence to the AASLD guidelines began at 71.7% to 75.9% from 2008 to 2010, and then it fluctuated between 49.2% and 73.8% from 2011 to 2016. In contrast, adherence to the APASL guidelines remained consistently high, staying within the range of 90.14% to 94.5% throughout the entire study period. Upward treatment, for example with liver resection, liver transplantation, or radiofrequency ablation, significantly improved the survival of patients with BCLC stage B HCC compared to that of patients treated in adherence to the guidelines (for patients analyzed according to the 2000 EASL guidelines, the 5-year survival rates were 63.4% vs 27.2%, P < 0.001), although results varied depending on the guidelines. Progression-free survival rates were also significantly improved upon the use of upward treatments in certain groups. Patients receiving upward treatments were typically < 70 years old, had platelet counts > 105/µL, and serum albumin levels ≥ 3.5 g/dL. CONCLUSION: Adherence to guidelines significantly influences survival in South Korean stage B HCC patients. Curative treatments outperform TACE, but liver resection should be selected with caution due to disease heterogeneity.

Mechanistic loop resolution strategy for short-type single-balloon enteroscopy-assisted endoscopic retrograde cholangiopancreatography in patients with Roux-en-Y reconstruction after gastrectomy (with video).

BACKGROUND: Endoscopic access to the targeted site is a major challenge for the endoscopic retrograde cholangiopancreatography (ERCP) in patients undergoing Roux-en-Y (R-Y) reconstruction after total or subtotal gastrectomy. We aimed to evaluate the feasibility, reproducibility, and safety of mechanistic loop resolution strategies using a short-type single-balloon enteroscopy (short SBE) system. METHODS: Between February 2020 and March 2022, consecutive patients with a previous R-Y gastrectomy requiring ERCP were prospectively enrolled. Different mechanistic loop resolution strategies for two-dimensional loops, three-dimensionally rotated loops, and loops making a cane or S-shape were applied during the SBE approach. RESULTS: Forty-three short SBE-ERCP procedures were performed on 37 patients, with an approach success rate of 100.0% (43/43). The mean time to reach the jejunojejunal anastomosis and target site were 8.0 (6.0-11.0) minutes and 26.0 (16.0-36.0) minutes, respectively. The major challenges for the approach were the cane or S-shaped loop in the jejunojejunal anastomosis or Treitz ligament. The retroflex positioning of a SBE in front of the papilla was achieved in 86.0% (37/43), and the cannulation success rate in patients with an intact papilla was 90.9% (30/33). The initial, overall therapeutic successes, median total procedure time, and adverse event rate were 87.8%, 92.7%, 77.0 (IQR 56-100.5) minutes, and 11.6%, respectively. CONCLUSIONS: Short SBE-ERCP using standardized mechanistic loop resolution strategies is effective and reproducible in patients with R-Y reconstruction after gastrectomy. TRIAL REGISTRATION: ClinicalTrial.gov (NCT04847167).

Comparison of the Malignant Predictors in Intrahepatic and Extrahepatic Intraductal Papillary Neoplasm of the Bile Duct.

Background: Intraductal papillary neoplasm of the bile duct (IPNB) is a precancerous lesion of cholangiocarcinoma, for which surgical resection is the most effective treatment. We evaluated the predictors of malignancy in IPNB according to anatomical location and the prognosis without surgery. Methods: A total of 196 IPNB patients who underwent pathologic confirmation by surgical resection or endoscopic retrograde cholangiography or percutaneous transhepatic cholangioscopic biopsy were included. Clinicopathological findings of IPNB with invasive carcinoma or mucosal dysplasia were analyzed according to anatomical location. Results: Of the 116 patients with intrahepatic IPNB (I-IPNB) and 80 patients with extrahepatic IPNB (E-IPNB), 62 (53.4%) and 61 (76.3%) were diagnosed with invasive carcinoma, respectively. Multivariate analysis revealed that mural nodule > 12 mm (p = 0.043) in I-IPNB and enhancement of mural nodule (p = 0.044) in E-IPNB were predictive factors for malignancy. For pathologic discrepancy before and after surgery, IPNB has a 71.2% sensitivity and 82.3% specificity. In the non-surgical IPNB group, composed of nine I-IPNB and seven E-IPNB patients, 43.7% progressed to IPNB with invasive carcinoma within 876 days. Conclusions: E-IPNB has a higher rate of malignancy than I-IPNB. The predictive factor for malignancy is mural nodule > 12 mm in I-IPNB and mural nodule enhancement in E-IPNB.

Pre- and post-procedure risk prediction models for post-endoscopic retrograde cholangiopancreatography pancreatitis.

BACKGROUND: Post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) is the most common serious adverse event. Given recent endoscopic advances, we aimed to develop and validate a risk prediction model for PEP using the latest clinical database. METHODS: We analyzed the data of patients with naïve papilla who underwent endoscopic retrograde cholangiopancreatography (ERCP). Pre-ERCP and post-ERCP risk prediction models for PEP were developed using logistic regression analysis. Patients were classified into low- (0 points), intermediate- (1-2 points), and high-risk (≥ 3 points) groups according to point scores. RESULTS: We included 760 and 735 patients in the derivation and validation cohorts, respectively. The incidence of PEP was 5.5% in the derivation cohort and 3.9% in the validation cohort. Age ≤ 65 (1 point), female sex (1 point), acute pancreatitis history (2 points), malignant biliary obstruction (2 points [pre-ERCP model] or 1 point [post-ERCP model]), and pancreatic sphincterotomy (2 points, post-ERCP model only) were independent risk factors. In the validation cohort, the high-risk group (≥ 3 points) had a significantly higher risk of PEP compared to the low- or intermediate-risk groups under the post-ERCP risk prediction model (low: 2.0%; intermediate: 3.4%; high: 18.4%), while there was no significant between-group difference under the pre-ERCP risk prediction model (low: 2.2%; intermediate: 3.8%; high: 6.9%). CONCLUSIONS: We developed and validated pre-ERCP and post-ERCP risk prediction models. In the latter, the high-risk group had a higher risk of PEP development than the low- or intermediate-risk groups. Our study findings will help clinicians stratify patient risk for the development of PEP.

The value of drain fluid amylase as a predictor of postoperative pancreatic fistula after pancreaticogastrostomy.

BACKGROUND: Drain fluid amylase is commonly used as a predictor of pancreatic fistula after pancreaticoduodenectomy (PD). This study aimed to determine the ideal cut-off value of drain fluid amylase on postoperative day 1 (DFA1) for predicting pancreatic fistula after pancreaticogastrostomy (PG). METHODS: Prospective data of 272 consecutive patients undergoing PG between 2010 and 2020 was collected and analysed to determine the postoperative pancreatic fistula (POPF) risk factors. RESULTS: The incidence of POPF was 143 cases (52.6%). The median DFA1 in patients with POPF was significantly higher than that of patients with NO-POPF (5483 versus 311, P < 0.001). DFA1 correlated with POPF in the area under the curve (AUC) of 0.84 (P < 0.001). When DFA1 was 2300 U/L, Youden index was the highest, with a sensitivity of 72.7% and a specificity of 82.9%. Logistic regression analysis showed that DFA1 ≥ 2300 U/L was an independent predictor of POPF (P < 0.001; OR: 12.855; 95% CI: 7.019-23.544). The AUC of DFA1 and clinically relevant postoperative pancreatic fistula (CR-POPF) was 0.674 (P < 0.001). CONCLUSION: DFA1 ≥ 2300 U/L can be used as an independent predictor of POPF after PG. DFA1 ≥ 3000 U/L can predict the occurrence of CR-POPF, when DFA1 ≥ 3000 U/L, the patients should be observed closely active for complications.