A Short Fully Covered Self-Expandable Metal Stent for Management of Benign Biliary Stricture Not Caused by Living-Donor Liver Transplantation.

Background: This study evaluated the effectiveness of short fully covered self-expanding metal stents (FCSEMS) with an anti-migration design in treating benign biliary strictures (BBS) not related to living donor liver transplantation (LDLT). Methods: A retrospective analysis was conducted on 75 patients who underwent FCSEMS insertion for BBS management. Stents were initially kept for 3 months and exchanged every 3 months until stricture resolution. Adverse events and stricture recurrence after FCSEMS removal were assessed during follow-up. Results: The study outcomes were technical success, stenosis resolution, and treatment failure. Technical success was 100%, with stricture resolution in 99% of patients. The mean onset time of BBS post-surgery was 4.4 years, with an average stent indwelling period of 5.5 months. Stricture recurrence occurred in 20% of patients, mostly approximately 18.8 months after stent removal. Early cholangitis and stent migration were noted in 3% and 4% of patients, respectively. Conclusions: This study concludes that short FCSEMS demonstrate high efficacy in the treatment of non-LDLT-related BBS, with a low incidence of interventions and complications. Although this is a single-center, retrospective study with a limited sample size, the findings provide preliminary evidence supporting the use of short FCSEMS as a primary treatment modality for BBS. To substantiate these findings, further research involving multicenter studies is recommended to provide additional validation and a broader perspective.

Comparison of long-term outcomes of endoscopic ultrasound-guided hepaticogastrostomy and choledochoduodenostomy for distal malignant biliary obstruction: a multicenter retrospective study.

Background: Endoscopic ultrasound-guided biliary drainage (EUS-BD), classified as choledochoduodenostomy (CDS) and hepaticogastrostomy (HGS), is a feasible and effective alternative for distal malignant biliary obstruction (MBO) in failed endoscopic retrograde cholangiopancreatography. However, the preferred technique for better outcomes has not yet been evaluated. Objectives: We compared the long-term outcomes between the techniques. Design: Retrospective comparative study. Methods: We reviewed consecutive patients who underwent EUS-CDS or EUS-HGS with transmural stent placement for distal MBO between 2009 and 2022. The primary outcome was the stent patency. The secondary outcomes were technical and clinical success, adverse events (AEs) of each technique, and independent risk factors for stent dysfunction. Results: In all, 115 patients were divided into EUS-CDS (n = 56) and EUS-HGS (n = 59) groups. Among them, technical success was achieved in 98.2% of EUS-CDS and 96.6% of EUS-HGS groups. Furthermore, clinical success was 96.4% in EUS-CDS and 88.1% in EUS-HGS groups, without significant difference (p = 0.200). The mean duration of stent patency for EUS-CDS was 770.3 days while that for EUS-HGS was 164.9 days (p = 0.010). In addition, the only independent risk factor for stent dysfunction was systematic treatment after EUS-BD [hazard ratio and 95% confidence interval 0.238 (0.066-0.863), p = 0.029]. The incidence of stent dysfunction of EUS-HGS was higher than EUS-CDS (35.1% versus 18.2%, 0.071), despite no significant differences even in late AEs. Conclusion: In distal MBO, EUS-CDS may be better than EUS-HGS with longer stent patency and fewer AEs. Furthermore, systematic treatment after EUS-BD is recommended for the improvement of stent patency.

Endoscopic Ultrasound-guided Fine Needle Aspiration and Biopsy for Cytohistological Diagnosis of Gallbladder Cancer: a multicenter retrospective study.

BACKGROUND AND AIMS: Endoscopic ultrasonography-guided fine-needle aspiration and biopsy (EUS-FNAB) is a standard diagnostic procedure for pancreatic masses but not gallbladder (GB) cancer. We aimed to investigate the efficacy and safety of EUS-FNAB for patients with suspected GB cancer (GBC). METHODS: We analyzed data from patients who underwent EUS-FNAB for suspected GBC in three hospitals between 2010 and 2023. We calculated and compared the diagnostic performance and safety of EUS-FNAB according to characteristic factors. 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%, respectively, whereas those for patients without GB samples were 90.7% and 91.1%, respectively. The sensitivity and accuracy were higher with FNB 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 (LN) 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 LNs would be a good strategy with comparable outcomes.

Factors Influencing the Diagnostic Performance of Repeat Endoscopic Ultrasound-Guided Fine-Needle Aspiration/Biopsy after the First Inconclusive Diagnosis of Pancreatic Solid Lesions.

Background/Aims: Endoscopic ultrasound-guided fine-needle aspiration/biopsy (EUS-FNA/B) is essential in diagnosing solid pancreatic lesions (SPLs), but without rapid on-site evaluation (ROSE), a repeat EUS-FNA/B is crucial for clarifying an inconclusive diagnosis. We aimed to evaluate factors associated with improved diagnostic performance of repeat EUS-FNA/B for initially inconclusive SPL diagnoses without ROSE. Methods: Of 5,894 patients subjected to EUS-FNA/B, 237 (4.0%) with an initially inconclusive diagnosis of SPLs were retrospectively enrolled from five tertiary medical centers between January 2016 and June 2021. Diagnostic performance and procedural factors of EUS-FNA/B were analyzed. Results: The diagnostic accuracies of first and repeat EUS-FNA/B were 96.2% and 67.6%, respectively. Of 237 patients with an inconclusive diagnosis from initial EUS-FNA/B, 150 were pathologically diagnosed after repeat EUS-FNA/B. In multivariate analysis of repeat EUS-FNA/B, tumor location (body/tail vs head: odds ratio [OR], 3.74; 95% confidence interval [CI], 1.48 to 9.46), number of needle passes (≥4 vs ≤3: OR, 4.80; 95% CI, 1.44 to 15.99), needle type (FNB vs FNA: OR, 3.26; 95% CI, 1.44 to 7.36), needle size (22 gauge vs 19/20 gauge: OR, 2.35; 95% CI, 1.19 to 4.62), and suction method (suction vs others: OR, 5.19; 95% CI, 1.30 to 20.75) were associated with a significantly improved diagnostic performance. Conclusions: Repeat EUS-FNA/B is essential for patients with an inconclusive EUS-FNA/B without ROSE. To improve the diagnostic performance of repeated EUS-FNA/B, it is recommended that 22-gauge FNB needles, ≥4 needle passes, and suction methods are used.

Prediction of Prognosis in Pancreatic Cancer According to Methionyl-tRNA Synthetase 1 Expression as Determined by Immunohistochemical Staining.

The serum level of CA 19-9 is a prognostic marker for pancreatic ductal adenocarcinoma (PDAC). We evaluated the ability of the expression level of methionyl-tRNA synthetase 1 (MARS1)-which facilitates cancer growth by modulating protein synthesis and the cell cycle-to predict the prognosis of PDAC. Immunohistochemical (IHC) staining was performed on pancreatic specimens obtained from patients with PDAC who were undergoing surgery. High MARS1 expression was defined as equal to, or greater than, that in normal acinar cells. Low MARS1 expression was defined as weaker than in normal acinar cells, and stronger than in the pancreatic duct epithelium. Univariate and multivariate analyses were performed on other factors related to prognosis. Among 137 PDAC patients, no significant differences in baseline characteristics were found between those with high (n = 82) and low (n = 55) MARS1 expression. The median overall survival time of patients with high MARS1 expression was shorter than that of those with low expression (15.2 versus 17.2 months, log-rank test p = 0.044). The median disease-free survival (DFS) was not significantly different between the two groups. However, the DFS was shorter in patients with high than in those with low MARS1 expression (8.9 versus 11.2 months, log-rank test p = 0.067). In a multivariate analysis, lymph node metastasis and high MARS1 expression were associated with a poor prognosis of PDAC. Elevated MARS1 expression detected by IHC staining is associated with a poor prognosis of PDAC, suggesting that MARS1 has potential as a prognostic marker.

Prognostic Impact of Minimal Pelvic Fluid in Locally Advanced Pancreatic Cancer: A Multicenter Retrospective Study.

BACKGROUND/AIMS: Minimal pelvic fluid (MPF) is occasionally encountered on computed tomography (CT) scans during the initial staging of newly diagnosed pancreatic cancer. However, its clinical relevance has scarcely been studied. This study intends to explore the incidence of minimal pelvic fluid and its relevance in terms of survival in locally advanced pancreatic cancer (LAPC) patients. MATERIALS AND METHODS: The medical records of patients with LAPC at 4 tertiary referral institutions were retrospectively reviewed from January 2005 to December 2015. Minimal pelvic fluid was defined as a fluid collection volume in the pelvic cavity of <100 mL as determined by abdominal CT. The association between the presence of MPF and patient survival was evaluated. RESULTS: A total of 59 patients (male:female, 33:26; median age, 68 years; range 46-82 years) with LAPC were enrolled. Of the 59 patients, 22.0% (n = 13) had MPF, and 78.0% (n = 46) had no pelvic fluid (NPF). Baseline clinical characteristics in the 2 groups, including extent of the tumor stage, extent of spread to the lymph nodes stage, and pattern of treatments, were not significantly different. However, median overall survival was significantly less in the MPF group [9.7 months, (95% CI, 5.9-13.5)] than in the NPF group as determined by the log-rank test [16.9 months, (95% CI, 9.3-24.5)] (P = .002), and univariate and multivariate analyses showed that the presence of MPF independently predicted a poor prognosis. CONCLUSION: The presence of MPF was found to be significantly associated with reduced survival and an independent poor prognostic biomarker in LAPC patients.

Annotation-Efficient Deep Learning Model for Pancreatic Cancer Diagnosis and Classification Using CT Images: A Retrospective Diagnostic Study.

The aim of this study was to develop a novel deep learning (DL) model without requiring large-annotated training datasets for detecting pancreatic cancer (PC) using computed tomography (CT) images. This retrospective diagnostic study was conducted using CT images collected from 2004 and 2019 from 4287 patients diagnosed with PC. We proposed a self-supervised learning algorithm (pseudo-lesion segmentation (PS)) for PC classification, which was trained with and without PS and validated on randomly divided training and validation sets. We further performed cross-racial external validation using open-access CT images from 361 patients. For internal validation, the accuracy and sensitivity for PC classification were 94.3% (92.8-95.4%) and 92.5% (90.0-94.4%), and 95.7% (94.5-96.7%) and 99.3 (98.4-99.7%) for the convolutional neural network (CNN) and transformer-based DL models (both with PS), respectively. Implementing PS on a small-sized training dataset (randomly sampled 10%) increased accuracy by 20.5% and sensitivity by 37.0%. For external validation, the accuracy and sensitivity were 82.5% (78.3-86.1%) and 81.7% (77.3-85.4%) and 87.8% (84.0-90.8%) and 86.5% (82.3-89.8%) for the CNN and transformer-based DL models (both with PS), respectively. PS self-supervised learning can increase DL-based PC classification performance, reliability, and robustness of the model for unseen, and even small, datasets. The proposed DL model is potentially useful for PC diagnosis.

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 Suprapapillary versus Transpapillary Self-Expandable Metal Stents According to the Level of Obstruction in Malignant Extrahepatic Biliary Obstruction.

Background/Aims: The use of a self-expandable metal stent (SEMS) is recommended for unresectable malignant biliary obstruction (MBO). Stent-related adverse events might differ according to the position of the stent through the ampulla of Vater (AOV). We retrospectively evaluated SEMS patency and adverse events according to the position of the SEMS. Methods: In total, 280 patients who underwent endoscopic SEMS placement due to malignant distal biliary obstruction were analyzed retrospectively. Suprapapillary and transpapillary SEMS insertions were performed on 51 patients and 229 patients, respectively. Results: Between the suprapapillary group (SPG) and transpapillary group (TPG), the stent patency period was not significantly different (median [95% confidence interval]: 107 days [82.3 to 131.7] vs 120 days [99.3 to 140.7], p=0.559). There was also no significant difference in the rate of adverse events. In subgroup analysis, the stent patency for an MBO located within 2 cm from the AOV was found to be significantly shorter than that for an MBO located more than 2 cm from the AOV in the SPG (64 days [0 to 160.4] vs 127 days [82.0 to 171.9], p<0.001) and TPG (87 days [52.5 to 121.5] vs 130 [97.0 to 162.9], p<0.001). Patients with an MBO located within 2 cm from the AOV in both groups had a higher percentage of duodenal invasion (SPG: 40.0% vs 4.9%, p=0.002; TPG: 28.6% vs 2.9%, p<0.001) than patients with an MBO located more than 2 cm from the AOV. Conclusions: The SPG and TPG showed similar results in terms of stent patency and rate of adverse events. However, patients with an MBO located within 2 cm from the AOV had a higher percentage of duodenal invasion with shorter stent patency than those with an MBO located more than 2 cm from the AOV, regardless of stent position.

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 Interleukin-6, C-Reactive Protein, Procalcitonin, and the Computed Tomography Severity Index for Early Prediction of Severity of Acute Pancreatitis.

Background/Aims: Acute pancreatitis (AP) is a common gastrointestinal disease associated with hospitalization. With the increase in its incidence, AP has become a greater burden on healthcare resources. Early identification of patients with mild AP can facilitate the appropriate use of resources. We aimed to investigate the ability of inflammatory markers, including interleukin-6 (IL-6), procalcitonin, and C-reactive protein (CRP), as well as various scoring systems to differentiate mild AP from more severe diseases. Methods: We retrospectively investigated patients hospitalized with AP, for whom severity assessment and clinical course confirmation were possible. Inflammatory markers were measured at admission, and CRP levels were measured 24 hours after admission (CRP2). Predictive values were calculated using the area under the receiver operating characteristic curve (AUROC) and logistic regression model analysis. Results: Of 103 patients with AP, 42 (40.8%) were diagnosed with mild AP according to the revised Atlanta classification. Based on the AUROC, IL-6 (0.755, p<0.001), CRP2 (0.787, p<0.001), and computed tomography severity index (CTSI) (0.851, p<0.001) were useful predictors of mild AP. With standard cutoff values, the diagnostic sensitivity, specificity, and accuracy were 83.3%, 62.3%, and 70.9% for IL-6 (<50 pg/mL), and 78.6%, 63.9%, and 69.9% for CRP2 (<50 mg/L), respectively. The AUROC of IL-6 and CRP2 were significantly higher than those of other inflammatory markers and were not significantly different from that of CTSI. Conclusions: IL-6, CRP2, and CTSI are helpful for early differentiation of AP severity. Among inflammatory markers, IL-6 has the advantage of early prediction of mild pancreatitis at the time of admission.

Diagnostic performance of endoscopic ultrasound elastography for differential diagnosis of solid pancreatic lesions: A propensity score-matched analysis.

BACKGROUND: Endoscopic ultrasound-elastography (EUS-EG) is a non-invasive complementary diagnostic method for differential diagnosis of solid pancreatic lesions (SPL). However, the optimal strain ratio (SR) value and diagnostic performance of EUS-EG have not yet been determined in pancreatic neuroendocrine neoplasm (PNEN), mass-forming pancreatitis (MFP), and pancreatic ductal adenocarcinoma (PDAC). We aimed to determine the optimal SR value in EUS-EG for differential diagnosis of SPLs. METHODS: Patients who underwent EUS-EG for SPL evaluation between July 2016 and June 2019 were retrospectively investigated. Patients were divided into three groups based on the final diagnosis (PNEN, MFP, or PDAC). Patient demographics, characteristics of SPL, and EUS-EG were compared. RESULTS: The mean (± standard deviation) SR value for each group were 11.85 ± 7.56 (PNEN, n = 10), 11.45 ± 5.97 (MFP, n = 37), and 22.50 ± 13.19 (PDAC, n = 87). Multinomial logistic regression analysis revealed that an increase of SR value was significantly associated with PDAC (PNEN versus PDAC, p = 0.0216; MFP versus PDAC, p = 0.0006). The optimal cut-off value for differential diagnosis was confirmed as 17.14 after propensity score matching. CONCLUSIONS: We provided the optimal cut-off SR values for differential diagnosis between MFP and PDAC. EUS-EG can be used as a supplementary diagnostic method in the diagnosis of SPLs. (Clinical trial registration number: https://cris.nih.go.kr/cris: KCT0002082).

In-stent radiofrequency ablation with uncovered metal stent placement for tumor ingrowth/overgrowth causing self-expandable metal stent occlusion in distal malignant biliary obstruction: multicenter propensity score-matched study.

BACKGROUND AND AIMS: In patients with unresectable malignant biliary obstruction (MBO), endoscopic drainage with a self-expandable metal stent (SEMS) is a well-established treatment, but stent patency is limited. This study aimed to evaluate the efficacy of in-stent radiofrequency ablation (IS-RFA) followed by uncovered SEMS placement for the management of occluded SEMSs. METHODS: From 2016 to 2020, 48 patients with recurrent biliary obstruction due to tumor ingrowth or overgrowth after SEMS placement for pancreatobiliary cancer in 3 tertiary hospitals were analyzed. For distal MBO, patients in the RFA group were treated with IS-RFA and uncovered SEMS placement, and those in the control group were treated with uncovered SEMS placement alone. Patients in both groups were matched on the basis of propensity scores in a 1:1 ratio. RESULTS: The median time to recurrent biliary obstruction (TRBO) was 117 days in the RFA group and 82.5 days in the control group (P = .029). No significant differences in median overall survival were detected between the 2 groups (170 days vs 72 days; P = .902). No significant adverse events were reported after the second SEMS placement in either group, but 2 cases of mild cholangitis were reported in the control group. Ablation was interrupted in 5 patients (35.7%) of the RFA group owing to in-stent contact, but sufficient ablative energy was delivered in the majority of the patients (92.9%) after IS-RFA was repeated in the same session. CONCLUSIONS: IS-RFA followed by an uncovered SEMS is safe and feasible and may improve TRBO as a stent revision for occluded SEMSs in pancreatobiliary cancer.

Features on Computed Tomography That Correlate With Acute Appendicitis.

Background: The purpose of this study is to investigate the relevant findings in adult patients admitted to Cabell Huntington Hospital who were diagnosed with acute appendicitis. Methods: Patients who had the postoperative diagnosis of acute appendicitis and a preoperative computed tomography (CT) scan from January 2011 through December 2016 were included in this retrospective chart review. Results: There were 592 patients. A thick, edematous appendix was the most common CT finding in acute appendicitis. The average diameter was 12.6 mm. The wall thickness correlated to the diameter of the appendix (P < 0.001). For comparison, we reviewed the CT scans of 50 trauma patients who had normal abdominal CT scans. The average diameter of a normal appendix was 4.9 mm (SD 1.139) with a range of 4-7 mm. Interestingly, the admission white blood cell count (P = 0.0372) as well as the thickness of the appendix (P < 0.0001) were strongly associated with increased length of stay. Conclusions: An appendiceal diameter greater than 9 mm should be considered abnormal and associated with acute appendicitis. Appendiceal size, white blood cell count, and age correlate with length of stay. Early antibiotics and early surgical intervention may decrease length of stay.

Covered versus uncovered double bare self-expandable metal stent for palliation of unresectable extrahepatic malignant biliary obstruction: a randomized controlled multicenter trial.

BACKGROUND AND AIMS: In a recent randomized controlled trial, a double bare metal stent (DBS) showed better stent patency than single-layer metal stents. However, clear evidence comparing the efficacy of uncovered (UCDBS) and partially covered (PCDBS) DBSs for distal malignant biliary obstruction (MBO) is lacking. Therefore, we compared the clinical outcomes including stent patency of UCDBSs versus PCDBSs. METHODS: A multicenter, randomized study was performed in patients with distal MBO. The primary endpoint was stent patency. Secondary endpoints were the proportion of patients with patent stents at 6 months, risk factors for stent dysfunction, overall survival, technical and clinical success rates of stent placement, and other adverse events (AEs). RESULTS: Among 258 included patients, 130 were randomly assigned to the PCDBS group and 128 to the UCDBS group. The mean duration of stent patency of the PCDBS (421.2 days; 95% confidence interval [CI], 346.7-495.7) was longer than that of the UCDBS (377.4 days; 95% CI, 299.7-455.0), although total stent dysfunction and stent dysfunction within 6 months were not different between groups. Multivariate analysis indicated that chemotherapy after stent placement was a significant factor for overall survival (hazard ratio, .570; 95% CI, .408-.796) and had a marginal impact on stent patency (hazard ratio, 1.569; 95% CI, .923-2.667). There were no remarkable differences in AEs, including pancreatitis, cholecystitis, and stent migration, between the 2 groups. CONCLUSIONS: The use of PCDBSs compared with UCDBSs in patients with distal MBO has unclear benefits regarding stent patency and overall survival, although PCDBSs have a lower rate of tumor ingrowth. (Clinical trial registration number: NCT02937246.).

Safety and Efficacy of Allogeneic Natural Killer Cells in Combination with Pembrolizumab in Patients with Chemotherapy-Refractory Biliary Tract Cancer: A Multicenter Open-Label Phase 1/2a Trial.

BACKGROUND AND AIM: This study investigated the administration of combination therapy, allogeneic natural killer (NK) cells and pembrolizumab in the treatment of advanced biliary tract cancer to determine the safety and tolerability (phase 1) and the efficacy and safety (phase 2a). METHODS: Forty patients (phase 1, n = 6; phase 2a, n = 34) were enrolled between December 2019 and June 2021. The patients received highly activated allogeneic NK cells ("SMT-NK") on weeks 1 and 2 and pembrolizumab on week 1. This 3-week schedule (one cycle) was repeated until confirmed disease progression, intolerable adverse events (AEs), patient withdrawal, or finishing the maximum treatment schedule. The tumor response was evaluated after every three cycles. RESULTS: In phase 1, four patients (66.7%) experienced seven AEs, but no severe AE was observed. In phase 2a, 126 AEs occurred in 29 patients (85.3%). Severe AEs (≥grade 3) were reported in 16 patients (47.1%). The overall response rate (ORR) was 17.4% in the full analysis set and 50.0% in the per-protocol set. CONCLUSIONS: SMT-NKs plus pembrolizumab resulted in no severe AEs directly related to the drug combination. The combination therapy also exerted antitumor activity with improved efficacy compared to the recent monotherapy with pembrolizumab in patients with advanced biliary tract cancer.

Safety and Efficacy of a Large-Bore Biliary Metallic Stent for Malignant Biliary Obstruction.

Self-expandable metallic stents (SEMSs) are typically inserted in patients with unresectable malignant biliary obstruction. However, SEMSs are susceptible to occlusion. To overcome this issue, we developed a large-bore, dumbbell-shaped, fully covered SEMS (FCSEMS-L) and compared its efficacy and safety with those of a conventional FCSEMS (FCSEMS-C) in patients with malignant biliary obstruction. METHODS: Patients with unresectable distal malignant biliary obstruction were retrospectively enrolled between January 2011 and February 2021. All patients underwent endoscopic insertion of FCSEMSs. Recurrent biliary obstruction (RBO), patient survival time, complications, and prognosis were analyzed. RESULTS: RBO occurred in 31 patients (35.6%) who received an FCSEMS-L, and in 34 (45.9%) who received an FCSEMS-C. Stent occlusion occurred in 19 patients (21.8%) who received an FCSEMS-L, and in 22 (29.7%) who received an FCSEMS-C. Stent migration occurred in 12 patients (13.8%) with an FCSEMS-L and 12 (16.2%) with an FCSEMS-C. The median time to RBO (TRBO) was 301 days with an FCSEMS-L and 203 days with an FCSEMS-C. The median survival time was 479 days with an FCSEMS-L and 523 days with an FCSEMS-C. The TRBO and patient survival time did not significantly differ between the two groups. CONCLUSIONS: There were no significant differences in efficacy and complication rates between the fully covered large bore SEMSs and conventional fully covered SEMSs.

Long-term outcomes and predictors of adverse events of EUS-guided hepatico-gastrostomy for malignant biliary obstruction: Multicenter, retrospective study.

BACKGROUND AND AIMS: Endoscopic ultrasound (EUS)-guided hepaticogastrostomy (HGS) may be a feasible and useful alternative in patients with malignant biliary obstruction (MBO) after failed endoscopic retrograde cholangiopancreatography (ERCP). To date, the risk factors for adverse events (AEs) and long-term outcomes of EUS-HGS have not been fully explored according to stent type. Therefore, we evaluated potential risk factors for AEs and long-term outcomes of EUS-HGS. METHODS: In total, 120 patients who underwent EUS-HGS were retrospectively reviewed. A multivariate analysis through Cox proportional hazard and logistic regression model was used to identify the risk factors for stent dysfunction and AEs, respectively. Stent patency and patient survival were evaluated using Kaplan-Meier plots with a log-rank test for each stent. RESULTS: The technical and clinical success rates were 96.2% (102/106) and 83.0% (88/106). The median duration of stent patency was longer in self-expandable metal stents (SEMS) compared to plastic stents (PS) (158 vs. 108 days). Kaplan-Meier analysis indicated that the type of stent was not associated with stent patency (Hazard ratios [HR] 0.997, 95% confidence interval [CI] [0.525-1.896]) or overall survival. In addition, multivariate analysis indicated that hilar MBO significantly associated with stent dysfunction (HR, 2.340; 95% CI, 1.028-5.326, p = 0.043) and late AEs. CONCLUSIONS: Given the lower incidence of AEs and better long-term outcomes of EUS-HGS, it can be considered a safe alternative to ERCP or percutaneous approaches regardless of which stent is used. Furthermore, hilar MBO was established as a potential risk factor for stent dysfunction and late AEs.

Efficacy of Chenodeoxycholic Acid and Ursodeoxycholic Acid Treatments for Refractory Functional Dyspepsia.

Refractory functional dyspepsia (RFD) is diagnosed when symptoms persist for at least 6 months despite at least two medical treatments. No consensus treatment guidelines exist. The implicated causes of functional biliary dyspepsia are a narrowed cystic duct, Sphincter of Oddi dysfunction, microlithiasis, and gallbladder dyskinesia. We investigated the treatment effects of litholytic agents. RFD patients were prospectively enrolled in six tertiary medical centers. All subjects took chenodeoxycholic and ursodeoxycholic acids (CNU) twice daily for 12 weeks. We monitored their medication adherence, laboratory results, and complications. The 7-point global symptom scale test scores were determined before and after treatment. Of the 52 patients who were prospectively screened, 37 were included in the final analysis. The mean age was 51.3 years: 14 were males, and 23 were females. Before treatment, the mean number and duration of symptoms were 2.4 and 48.2 months, and a mean of 3.3 FD-related drugs were taken. The mean CNU adherence was 95.3%. The mean global symptom scale score decreased from 5.6 pretreatment to 2.6 posttreatment. The symptom improvement rate was 94.6% (35 out of 37 patients). The only adverse event was mild diarrhea (10.8%) that was resolved after conservative management. Conclusions: CNU improved the symptoms of RFD patients who did not respond to conventional medications. Litholytic agents are good treatment options for patients with RFD and biliary dyspepsia secondary to biliary microlithiasis. Further prospective, large-scale mechanistic studies are warranted.