Tumour-associated myeloid cells expressing IL-10R2/IL-22R1 as a potential biomarker for diagnosis and recurrence of pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a poor survival rate, largely due to the lack of early diagnosis. Although myeloid cells are crucial in the tumour microenvironment, whether their specific subset can be a biomarker of PDAC progression is unclear. METHODS: We analysed IL-22 receptor expression in PDAC and peripheral blood. Additionally, we analysed gene expression profiles of IL-10R2+/IL-22R1+ myeloid cells and the presence of these cells using single-cell RNA sequencing and murine orthotropic PDAC models, respectively, followed by examining the immunosuppressive function of IL-10R2+/IL-22R1+ myeloid cells. Finally, the correlation between IL-10R2 expression and PDAC progression was evaluated. RESULTS: IL-10R2+/IL-22R1+ myeloid cells were present in PDAC and peripheral blood. Blood IL-10R2+ myeloid cells displayed a gene expression signature associated with tumour-educated circulating monocytes. IL-10R2+/IL-22R1+ myeloid cells from human myeloid cell culture inhibited T cell proliferation. By mouse models for PDAC, we found a positive correlation between pancreatic tumour growth and increased blood IL-10R2+/IL-22R1+ myeloid cells. IL-10R2+/IL-22R1+ myeloid cells from an early phase of the PDAC model suppressed T cell proliferation and cytotoxicity. IL-10R2+ myeloid cells indicated tumour recurrence 130 days sooner than CA19-9 in post-pancreatectomy patients. CONCLUSIONS: IL-10R2+/IL-22R1+ myeloid cells in the peripheral blood might be an early marker of PDAC prognosis.

Magnetic Compression Anastomosis for the Treatment of Complete Biliary Obstruction After Cholecystectomy.

BACKGROUND & AIMS: Post-cholecystectomy biliary strictures can be treated surgically or non-surgically. Although endoscopic or percutaneous treatments are the preferred approaches, these methods are not feasible in cases where complete stricture occlusion prevents the successful passage of a guidewire. The utility of magnetic compression anastomosis (MCA) in patients with post-cholecystectomy complete biliary obstruction that cannot be treated conventionally was evaluated. METHODS: MCA was performed in 10 patients with post-cholecystectomy biliary strictures that did not resolve with conventional endoscopic or percutaneous treatment. One magnet was delivered through the percutaneous transhepatic biliary drainage tract, and another was advanced via endoscopic retrograde cholangiopancreatography(ERCP) of the common bile duct. After magnet approximation and recanalization, a fully covered self-expandable metal stent (FCSEMS) was placed for 3 months and then replaced for a further 3 months. Stricture resolution was evaluated after FCSEMS removal. RESULTS: Among the 10 patients who underwent MCA for post-cholecystectomy biliary stricture, the biliary injury was Strasberg type B in 2, type C in 3, and type E in 5. Recanalization was successful in all patients (technical success rate 100%). The mean follow-up period after recanalization was 50.2 months (range 13.2-116.8 months). Partial restenosis after MCA occurred in two patients at 24.1 and 1.6 months after stent removal. ERCP with FCSEMS placement resolved the recurrent stenosis in both patients. CONCLUSIONS: MCA is a useful alternative nonsurgical treatment for complete biliary obstruction after cholecystectomy that cannot be resolved by conventional methods.

EUS-guided FNA and biopsy for cytohistologic diagnosis of gallbladder cancer: a multicenter retrospective study.

BACKGROUND AND AIMS: EUS-guided FNA and biopsy (EUS-FNAB) is a standard diagnostic procedure for pancreatic masses but not gallbladder (GB) cancer (GBC). The aim of this study was to investigate the efficacy and safety of EUS-FNAB for patients with suspected GBC. METHODS: Data were analyzed from patients who underwent EUS-FNAB for suspected GBC in 3 hospitals between 2010 and 2023. The diagnostic performance and safety of EUS-FNAB according to characteristic factors were calculated and compared. RESULTS: Of 170 patients, 163 had GBC. EUS-FNAB samples were obtained from the GB in 125 patients and sites other than the GB in 45 patients. The overall sensitivity, specificity, and accuracy were 83.4%, 100%, and 84.1%, respectively. The sensitivity and accuracy for patients with GB samples were 80.8% and 81.6%; for patients without GB samples, these values were 90.7% and 91.1%. The sensitivity and accuracy were higher with fine-needle biopsy needles than with FNA needles and with ≤22-gauge needles than with 25-gauge needles. However, no significant differences were observed between the GB and lymph node samples. GB lesions <40 mm in size, wall-thickening type, fundal location, absence of extensive liver invasion, and distant metastasis were more frequent in patients without GB samples than in patients with GB samples. Four mild bleeding events were the only reported adverse events. CONCLUSIONS: EUS-FNAB was safe and showed high diagnostic performance for patients with suspected GBC, regardless of the target site. When appropriate GB targeting is difficult, targeting the lymph nodes would be a good strategy with comparable outcomes.

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.

Improved predictability of pancreatic ductal adenocarcinoma diagnosis using a blood immune cell biomarker panel developed from bulk mRNA sequencing and single-cell RNA-sequencing.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) remains a devastating cancer due to its poor survival rate, early detection, and resectability. This study aimed to determine the peripheral blood mononuclear cell (PBMC) immune biomarkers in patients with PDAC and investigate the PDAC-specific peripheral blood biomarker panel and validate its clinical performance. METHODS: In this prospective, blinded, case-control study, a biomarker panel formula was generated using a development cohort-including healthy controls, patients at high risk of PDAC, and patients with benign pancreatic disease, PDAC, or other gastrointestinal malignancies-and its diagnostic performance was verified using a validation cohort, including patients with ≥ 1 lesion suspected as PDAC on computed tomography (CT). RESULTS: RNA-sequencing of PBMCs from patients with PDAC identified three novel immune cell markers, IL-7R, PLD4, and ID3, as specific markers for PDAC. Regarding the diagnostic performance of the regression formula for the three biomarker panels, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 84.0%, 78.8%, 47.2%, 95.6%, and 79.8%, respectively. Based on the formula scores for the biomarker panel, the false-negative rate (FNR) of the biomarkers was 8% (95% confidence interval [CI] 3.0-13.0), which was significantly lower than that based on CT in the validation cohort (29.2%, 95% CI 20.8-37.6). CONCLUSIONS: The regression formula constructed using three PBMC biomarkers is an inexpensive, rapid, and convenient method that shows clinically useful performance for the diagnosis of PDAC. It aids diagnoses and differential diagnoses of PDAC from pancreatic disease by lowering the FNR compared to CT. Clinical trial registration Clinical Research Information Service, KCT0004614 (08 January 2020).

Efficacy analysis of hemostatic spray following endoscopic papillectomy: A multicenter comparative study.

BACKGROUND AND AIM: Endoscopic post-papillectomy bleeding is a serious adverse event with a prevalence ranging from 2% to 45.3%. Conventional hemostatic methods, including diluted epinephrine injection before papillectomy or argon plasma coagulation after papillectomy, did not show a preventive role in reducing immediate or delayed post-papillectomy bleeding. Therefore, we aimed to assess the efficacy and safety of a hemostatic powder spray for post-papillectomy bleeding and compare with those of conventional modalities. METHODS: Patients who underwent endoscopic papillectomy were enrolled in five tertiary hospitals. The group was divided into hemostatic spray and conventional control groups according to the bleeding control methods. The main outcome measurements were delayed bleeding rate and any adverse events related to the procedures. RESULTS: A total of 40 patients who received a hemostatic spray (n = 18) or conventional hemostatic methods (n = 22) after endoscopic papillectomy were included. The prevalence of delayed bleeding was not different in the two groups: 27.8% and 36.4% in hemostatic spray and conventional control groups (P = 0.564), respectively. The adverse events such as post-papillectomy pancreatitis and cholangitis were not different in the two groups. There were no procedure-related mortalities. CONCLUSION: Hemostatic spray is technically feasible and safe for the prevention or management of post-papillectomy bleeding. Hemostatic spray can be one of the options for post-papillectomy bleeding control methods owing to its convenient use.

Malignant potential of small pancreatic neuroendocrine neoplasm and its risk factors: A multicenter nationwide study.

BACKGROUND: Pancreatic neuroendocrine neoplasms (PNENs) show heterogeneous biological behavior, and most small PNENs show indolent features. Consequently, selected cases can be considered for observation only, according to the National Comprehensive Cancer Network guideline, however, supporting clinical evidence is lacking. We investigated the clinical course of small PNENs and their risk factors for malignant potential. METHODS: A total of 158 patients with small pathologically confirmed PNENs ≤2 cm in initial imaging were retrospectively enrolled from 14 institutions. The primary outcome was any metastasis or recurrence event during follow-up. RESULTS: The median age was 57 years (range, 22-82 years), and 86 patients (54%) were female. The median tumor size at initial diagnosis was 13 mm (range, 7-20 mm). PNENs were pathologically confirmed by surgery in 137 patients and by EUS-guided fine needle aspiration biopsy (EUS-FNAB) in 21 patients. Eight patients underwent EUS-FNAB followed by surgical resection. The results of WHO grade were available in 150 patients, and revealed 123 grade 1, 25 grade 2, and 2 neuroendocrine carcinomas. A total of 145 patients (92%) underwent surgical resection, and three patients had regional lymph node metastasis. During the entire follow-up of median 45.6 months, 11 metastases or recurrences (7%) occurred. WHO grade 2 (HR 13.97, 95% CI 2.60-75.03, p = 0.002) was the only predictive factor for malignant potential in multivariable analysis. CONCLUSIONS: WHO grade is responsible for the malignant potential of small PNENs ≤2 cm. Thus, EUS-FNAB could be recommended in order to provide early treatment strategies of small PNENs.

Clinical utility of methionyl-tRNA synthetase 1 immunostaining in cytologic brushings of indeterminate biliary strictures: a multicenter prospective study.

BACKGROUND AND AIMS: Endobiliary brushings are routinely used in the diagnosis, treatment, and prognostication of biliary strictures. However, standard Papanicolaou (Pap) staining has a low sensitivity in this setting, and the accuracy of brush cytology has not been established for indeterminate strictures. We therefore evaluated the diagnostic merit of methionyl-transfer RNA synthetase 1 (MARS1) immunofluorescence (IF) staining in such cytologic specimens. METHODS: During ERCP, endobiliary brushings were obtained from patients with extrahepatic biliary strictures prospectively enrolled at 6 tertiary hospitals. Using liquid-based cytologic preparations of these samples, we performed Pap and MARS1 IF staining. RESULTS: In total, 240 patients were eligible; of these, we compared the Pap and MARS1 IF staining results of 218 (malignant, 157; benign, 61). By conventional Pap staining, the diagnoses were distributed as follows: malignant, 55; suspicious of malignancy, 60; atypical, 45; negative for malignancy, 58. MARS1 IF staining was strongly positive in malignant biliary stricture but not so in specimens negative for malignancy. The diagnostic parameters (sensitivity, specificity, positive predictive value, negative predictive value, and accuracy) of the MARS1 IF (93.6%, 96.7%, 98.7%, 85.5%, and 94.5%, respectively) and conventional Pap (73.2%, 100%, 100%, 59.2%, and 80.7%, respectively) staining methods differed significantly (P < .0001). CONCLUSIONS: The high sensitivity and accuracy of MARS1 IF staining enabled the detection of malignancy in patients with biliary strictures. Further prospective studies are needed to validate our findings. (Clinical trial registration number: NCT03708445.).

Diagnostic performance of endoscopic ultrasound-artificial intelligence using deep learning analysis of gallbladder polypoid lesions.

BACKGROUND AND AIM: Endoscopic ultrasound (EUS) is the most accurate diagnostic modality for polypoid lesions of the gallbladder (GB), but is limited by subjective interpretation. Deep learning-based artificial intelligence (AI) algorithms are under development. We evaluated the diagnostic performance of AI in differentiating polypoid lesions using EUS images. METHODS: The diagnostic performance of the EUS-AI system with ResNet50 architecture was evaluated via three processes: training, internal validation, and testing using an AI development cohort of 1039 EUS images (836 GB polyps and 203 gallstones). The diagnostic performance was verified using an external validation cohort of 83 patients and compared with the performance of EUS endoscopists. RESULTS: In the AI development cohort, we developed an EUS-AI algorithm and evaluated the diagnostic performance of the EUS-AI including sensitivity, specificity, positive predictive value, negative predictive value, and accuracy. For the differential diagnosis of neoplastic and non-neoplastic GB polyps, these values for EUS-AI were 57.9%, 96.5%, 77.8%, 91.6%, and 89.8%, respectively. In the external validation cohort, we compared diagnostic performances between EUS-AI and endoscopists. For the differential diagnosis of neoplastic and non-neoplastic GB polyps, the sensitivity and specificity were 33.3% and 96.1% for EUS-AI; they were 74.2% and 44.9%, respectively, for the endoscopists. Besides, the accuracy of the EUS-AI was between the accuracies of mid-level (66.7%) and expert EUS endoscopists (77.5%). CONCLUSIONS: This newly developed EUS-AI system showed favorable performance for the diagnosis of neoplastic GB polyps, with a performance comparable to that of EUS endoscopists.

Short fully covered self-expandable metal stent for treatment of proximal anastomotic benign biliary stricture after living-donor liver transplantation.

OBJECTIVES: Non-surgical methods have high success rates for treating benign biliary strictures (BBSs), but treatment of proximal strictures is difficult. Recent studies have reported that fully covered self-expandable metal stents (FCSEMSs) are useful for treating refractory BBSs. We investigated the efficacy of a short and removable FCSEMS with an anti-migration design for treatment of proximal BBSs. METHODS: Fully covered self-expandable metal stents were inserted endoscopically in patients with BBSs after living donor liver transplantation (LDLT). Each FCSEMS was initially maintained for 3 months and subsequently exchanged every 3 months until the stricture resolved. Adverse events and stricture recurrence after FCSEMS removal were assessed during follow-up. RESULTS: A total of 63 patients with a median age of 57 years were enrolled in this study; 50 were male. The most common underlying disease was hepatocellular carcinoma and the previous operation was LDLT. The mean duration from surgery to diagnosis of stricture was 8.5 months, and the mean stent indwelling time was 4.2 months. The technical success and stricture resolution rate were 100%. The recurrence rate was 23.8% and the adverse event rate was 12.7%. All stents were removable, and asymptomatic stent migration was observed in four patients (6.4%). CONCLUSIONS: The newly designed FCSEMS is effective in the treatment of proximal BBSs after LDLT.

Primary Needle-Knife Fistulotomy Versus Conventional Cannulation Method in a High-Risk Cohort of Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis.

OBJECTIVES: Successful biliary cannulation is a prerequisite and important component of endoscopic retrograde cholangiopancreatography, but conventional cannulation methods (CCMs) have a postendoscopic retrograde cholangiopancreatography pancreatitis (PEP) rate of 14.1% in patients at high risk for PEP. The aim of this study was to evaluate the effectiveness and safety of needle-knife fistulotomy (NKF), compared with a CCM, when used for primary biliary access in patients at high risk for developing PEP. METHODS: A total of 207 patients with one or more risk factors for PEP were prospectively enrolled. The patients were randomly allocated to one of 2 groups according to the primary biliary cannulation technique (NKF or CCM). We compared biliary cannulation success rates, cannulation and procedure times, and the incidence of adverse events, including PEP, between the groups. RESULTS: The mean number of PEP risk factors was similar between the groups (NKF, 2.2 ± 1.0; CCM, 2.2 ± 0.9). PEP occurred in 8 patients in the CCM group and in no patients in the NKF group (9.2% vs 0%, P < 0.001). The rates of other adverse events did not differ between the groups. The biliary cannulation success rate was high in the NKF group, but relatively low in the CCM group, possibly because of the stringent failure criteria aimed at reducing PEP. However, the mean cannulation and total procedural times were longer in the NKF group than in the CCM group. DISCUSSION: NKF is an effective and safe procedure to gain primary biliary access in patients at high risk for developing PEP. ClinicalTrials.gov, NCT02916199.

New staining method using methionyl-tRNA synthetase 1 antibody for brushing cytology of bile duct cancer.

BACKGROUND AND AIMS: Identifying malignant biliary strictures using endobiliary brushing cytology specimens is important for treatment decision-making and prognosis prediction. The sensitivity of brushing cytology specimens based on Papanicolaou (Pap) staining is low, which hampers accurate diagnosis of indeterminate strictures. Here, we assessed the diagnostic value of immunohistochemical (IHC) and immunofluorescence (IF) staining for methionyl-tRNA synthetase 1 (MARS1). METHODS: Endobiliary brushing cytology specimens were obtained during ERCP from 80 patients with an extrahepatic biliary stricture. Pap and MARS1 IF staining were performed on liquid-based cytology slides derived from these specimens. Sections of bile duct adenocarcinoma and normal bile duct tissue were obtained from 45 patients who underwent surgery for malignant biliary stricture, and MARS1 levels were evaluated by IHC staining. RESULTS: MARS1 IF staining was applied to brushing cytology specimens, and the results showed strong signals in malignant biliary structures but not in the negative for malignancy specimens. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 70.4%, 96.2%, 97.4%, 56.8%, and 78.8%, respectively, for conventional Pap staining and 98.1%, 96.1%, 98.1%, 96.2%, and 97.5%, respectively, for MARS1 IF (P < .0001). When IHC staining was used, MARS1 was detected in 45 bile duct adenocarcinoma sections but not in 15 normal bile duct sections. Moreover, MARS1 mRNA and protein levels were significantly higher in bile duct adenocarcinoma sections according to polymerase chain reaction and Western blot, respectively. CONCLUSIONS: The high sensitivity and accuracy of MARS1 IF staining enabled detection of malignancy in patients with indeterminate biliary stricture. Further prospective studies are needed to validate our findings. (Clinical trial registration number: KCT 0003285.).

Endoscopic revision efficacy after clinically successful bilateral metal stenting for advanced malignant hilar obstruction.

BACKGROUNDS AND AIM: Multiple insertions of self-expandable metal stents (SEMS) for advanced malignant hilar obstruction (MHO) are now considered to be an effective palliative method for adequate drainage of liver volume. However, the efficacy of endoscopic reintervention in technically and clinically successful bilateral SEMS is limited. This study investigated the endoscopic revision efficacy in patients who underwent bilateral SEMS in MHO. METHODS: Primary endoscopic revision using plastic or metal stents or an alternative percutaneous approach followed by secondary endoscopic revision was performed in patients who underwent clinically successful deployment of bilateral SEMS. The primary outcome was a technical success. Secondary outcomes were clinical success, adverse events, and patency duration after reintervention. RESULTS: A total of 55 patients (83.3%) out of 66 enrolled patients underwent reintervention: primary endoscopic reintervention (n = 47) and secondary endoscopic revision following percutaneous drainage (n = 8). Intended technical success rates of primary and secondary endoscopic reintervention were 93.6% (44/47) and 87.5% (7/8), respectively (P = 0.47). Clinical success rates were 72.3% and 50%, respectively (P = 0.23). Stent malfunction rate after reintervention was 48.9% (23/47) and 37.5% (3/8) (P = 0.70) during follow up, and median cumulative stent patency duration was 119 and 55 days, respectively (log-rank P = 0.68). Stent patent rate after reintervention was not different according to the time interval. In univariate and multivariate analysis for stent patency duration-related factors after reintervention, there were no meaningful factors. CONCLUSION: Primary endoscopic reintervention for bilateral SEMS in MHO was feasible technically and clinically. However, there were no statistically meaningful factors for stent patency duration after reintervention.

Local Delivery of Gemcitabine Inhibits Pancreatic and Cholangiocarcinoma Tumor Growth by Promoting Epidermal Growth Factor Receptor Degradation.

Gemcitabine is clinically used to treat certain types of cancers, including pancreatic and biliary cancer. We investigated the signal transduction pathways underlying the local antitumor effects of gemcitabine-eluting membranes (GEMs) implanted in pancreatic/biliary tumor-bearing nude mice. Here, we report that GEMs increased the E3 ubiquitin ligase c-CBL protein level, leading to degradation of epidermal growth factor receptor (EGFR) in SCK and PANC-1 cells. GEMs decreased the RAS and PI3K protein levels, leading to a reduction in the protein levels of active forms of downstream signaling molecules, including PDK, AKT, and GSK3ß. GEM reduced proliferation of cancer cells by upregulating cell cycle arrest proteins, particularly p53 and p21, and downregulating cyclin D1 and cyclin B. Moreover, GEMs reduced the levels of proangiogenic factors, including VEGF, VEGFR2, CD31, and HIF-1α, and inhibited tumor cell migration and invasion by inducing the expression of E-cadherin and reducing that of N-cadherin, snail, and vimentin. We demonstrated that local delivery of gemcitabine using GEM implants inhibited tumor cell growth by promoting c-CBL-mediated degradation of EGFR and inhibiting the proliferation, angiogenesis, and epithelial-mesenchymal transition of pancreatic/biliary tumors. Use of gemcitabine-eluting stents can improve stent patency by inhibiting the ingrowth of malignant biliary obstructions.

Efficacy of a paclitaxel-eluting biliary metal stent with sodium caprate in malignant biliary obstruction: a prospective randomized comparative study.

BACKGROUNDS: The placement of a self-expandable metal stent (SEMS) is widely used in patients with unresectable malignant biliary obstructions, but SEMSs are susceptible to occlusion by tumor ingrowth or overgrowth. The efficacy and safety of a novel paclitaxel-eluting biliary metal stent incorporating sodium caprate (MSCPM-III) were compared prospectively with those of a covered metal stent (CMS) in patients with malignant biliary obstructions. METHODS: Patients with unresectable distal malignant biliary obstructions (n = 106) were prospectively enrolled in this study at multiple treatment centers. Stents were placed endoscopically: MSCPM-III in 54 patients and CMS in 51 patients. The patients received systemic chemotherapy regimens according to their disease characteristics. RESULTS: The two groups did not differ significantly in basic characteristics or mean follow-up period. Stent occlusion occurred in 14 patients who received MSCPM-III and in 11 patients who received CMS. Time to recurrent biliary obstruction (RBO) and survival time did not differ significantly between the two groups (P  = 0.84 and P = 0.29, respectively). However, tumor size at 2 months after stent insertion was significantly decreased in patients in the MSCPM-III group with bile duct cancers or those who experienced stent migration compared with the CMS group. Complications, including cholangitis and pancreatitis, were found to be acceptable in both groups. CONCLUSIONS: Although compared with a CMS the MSCPM-III did not significantly influence time to RBO or survival duration in patients with malignant biliary obstructions, MSCPM-III reduced tumor volume and was used safely in humans.

Comparison of endoscopic papillary large balloon dilation with or without endoscopic sphincterotomy for the treatment of large bile duct stones.

BACKGROUND: Endoscopic papillary large balloon dilation (EPLBD) without prior endoscopic sphincterotomy (EST) produces excellent outcomes for the treatment of large common bile duct (CBD) stones. However, it remains unclear how the outcomes of EPLBD alone compare with those of EPLBD with EST. In this study, we assessed the safety and therapeutic outcomes of EPLBD with vs. without EST for the removal of large bile duct stones. METHODS: This prospective, multicenter study was conducted on 200 patients with bile duct stones of ≥ 10 mm in diameter. Patients were randomly assigned to an EPLBD alone group (n = 100) or an EPLBD with EST group (n = 100). These two groups were compared with respect to overall procedure-related adverse events, overall stone removal success rate, number of endoscopic sessions required for complete stone removal, need for mechanical lithotripsy, and total procedure time. RESULTS: The incidence of adverse events was not significantly different between the groups (EPLBD alone vs. EPLBD with EST: overall adverse events 6 % vs. 4 %, P = 0.75; pancreatitis 1 % vs. 3 %, P = 0.62). Overall success (P = 0.35), initial success (P = 0.28), and the need for mechanical lithotripsy (P = 0.39) were also similar between groups. Median total procedure time tended to be greater in the EPLBD alone group (20.5 minutes) than in the EPLBD with EST group (18 minutes; P = 0.08). CONCLUSION: The therapeutic outcomes and adverse events of EPLBD alone for the removal of large bile duct stones were comparable to those of EPLBD with EST.

Balloons larger than 15 mm can increase the risk of adverse events following endoscopic papillary large balloon dilation.

BACKGROUND AND AIM: Although endoscopic papillary large balloon dilation (EPLBD) has been widely used to facilitate the removal of difficult common bile duct stones, however, the outcomes have not yet been investigated in terms of the diameter of the balloon used. We aimed to compare the clinical outcomes between EPLBD using smaller (12-15 mm, S-EPLBD) and larger balloons (> 15 mm, L-EPLBD). METHODS: Six hundred seventy-two patients who underwent EPLBD with or without endoscopic sphincterotomy for common bile duct stone removal were enrolled from May 2004 to August 2014 at four tertiary referral centers in Korea. The outcomes, including the initial success rate, the success rate without endoscopic mechanical lithotripsy, the overall success rate, and adverse events between S-EPLBD and L-EPLBD groups, were retrospectively compared. RESULTS: The initial success rate, the success rate without mechanical lithotripsy, the overall success rate, and the overall adverse events were not significantly different between the two groups. The rate of severe-to-fatal adverse events was higher in the L-EPBLD group than in the S-EPLBD group (1.6% vs 0.0%, 0.020). One case of severe bleeding and two cases of fatal perforation occurred only in the L-EPLBD group. In the multivariate analysis, the use of a > 15-mm balloon was the only significant risk factor for severe-to-fatal adverse events (>0.005, 23.8 [adjusted odds ratio], 2.6-214.4 [95% confidence interval]). CONCLUSIONS: L-EPLBD is significantly related to severe-to-fatal adverse events compared with S-EPLBD for common bile duct stone removal.

Maintenance of the fistulous tract after recanalization via magnetic compression anastomosis in completely obstructed benign biliary stricture.

OBJECTIVE: This study compared the efficacy of a percutaneous transhepatic cholangioscopy (PTCS) catheter and a fully covered self-expandable metal stent (FCSEMS) for maintaining biliary tract patency after magnetic compression anastomosis (MCA). METHODS: This study included patients with completely obstructed benign biliary stricture (BBS), which was resolved by MCA and subsequent insertion of a PTCS catheter or FCSEMS. We compared the restenosis-free time after removal of the PTCS catheter or FCSEMS, and the rate of complications. RESULTS: A total of 49 patients were analyzed. The mean ages of the patients in these groups were 50.1 and 49.6 years, respectively. The predisposing conditions causing complete BBS were liver transplantation (n = 38), abdominal surgery (n = 10) and trauma (n = 1). The mean indwelling durations were 176 and 128 days in the PTCS catheter and FCSEMS groups, respectively. The mean follow-up duration after removal of the PTCS catheter and FCSEMS were 2259 and 680.5 days, respectively. Three patients in the PTCS group and three patients in the FCSEMS group experienced stricture relapse. The mean duration between recurrence and stent removal were 924 and 265 days, respectively, and the numbers of stricture-free days did not differ significantly between the two groups. The adverse event rate did not differ significantly between the PTCS and FCSEMS groups (50% vs. 24.2%, respectively). CONCLUSIONS: FCSEMSs have an efficacy and safety similar to those of PTCS catheters for maintaining biliary tract patency after MCA, but are more convenient for patients.

Treatment of completely obstructed benign biliary strictures with magnetic compression anastomosis: follow-up results after recanalization.

BACKGROUND AND AIMS: Although nonsurgical methods produce high clinical success rates in the treatment of benign biliary stricture (BBS), conventional methods are not always successful in cases of severe biliary stricture or complete obstruction. Therefore, the efficacy of magnetic compression anastomosis (MCA) for treatment of refractory BBS was evaluated in a single-center, nonrandomized study. METHODS: MCA was performed in patients with BBS that was not resolved by conventional endoscopic or percutaneous treatments. One magnet was delivered through the percutaneous transhepatic biliary drainage tract, and the other advanced through 1 of 3 different routes. After magnet approximation and recanalization, an internal drainage catheter was placed for 6 months. RESULTS: This study followed 39 patients who underwent MCA after the development of postoperative or traumatic strictures. Recanalization was achieved successfully in 35 patients. There was an acceptable procedure-related adverse event of mild cholangitis in 1 patient and no procedure-related mortalities. The average elapsed time from magnet approximation to removal was 57.4 days (range, 13-182 days), and the mean follow-up period after recanalization was 41.9 months (range, 7.1-73.4 months). Restenosis after MCA recurred in 1 patient, and partial restenosis occurred in another patient, but recanalization in these patients was successful using a guidewire via the percutaneous and endoscopic tracts. CONCLUSIONS: MCA represents an alternative nonsurgical recanalization method for BBSs that cannot be treated by conventional methods. The rate of stricture recurrence after MCA was lower than that after conventional methods, likely because of the creation of a new fistula tract instead of dilation of a previous stricture.

Percutaneous biliary approach as a successful rescue procedure after failed endoscopic therapy for drainage in advanced hilar tumors.

BACKGROUND AND AIM: Palliative endoscopic or percutaneous biliary drainage is used for unresectable advanced hilar cancer (HC). The best option for drainage in Bismuth type III or IV HC has not been established. The aims of this study are to identify factors predictive of endoscopic stenting failure and evaluate the effectiveness of rescue percutaneous stenting in patients with advanced HC. METHODS: Data from 110 patients with inoperable advanced HC were retrospectively reviewed. All received bilateral self-expandable metallic stents. Patients were divided into three groups: I, successful initial endoscopic stenting; II, unsuccessful initial endoscopic stenting, followed by percutaneous stenting; and III, initial percutaneous stenting. We analyzed clinical results and radiologic tumor characteristics. RESULTS: Baseline characteristics and clinical outcomes of all groups were similar, except the hospital stay was longer in group III than group I. Technical success rate was higher in groups II and III (100%) than in group I (72.4%). The functional success rate, stent patency time, patient survival time, and complication rate were similar between groups. Endoscopic stenting failed because of guide-wire passage failure (n = 12) or stent passage failure (n = 7). The only factor significantly associated with endoscopic failure was a smaller left intrahepatic duct-common bile duct angle. CONCLUSIONS: As clinical outcomes were generally similar between approaches, percutaneous stenting is recommended for patients with Bismuth type III or IV advanced HC. Acute left intrahepatic duct-common bile duct angulation predicts endoscopic stenting failure. If endoscopic stenting fails, immediate conversion to the percutaneous approach is a necessary and effective rescue method.