Evaluating optimal bilateral biliary stenting in endoscopic reintervention after initial plastic stent dysfunction for unresectable malignant hilar biliary obstruction: Retrospective cross-sectional study.

OBJECTIVES: The placement of plastic stents (PS), including intraductal PS (IS), is useful in patients with unresectable malignant hilar biliary obstruction (UMHBO) because of patency and ease of endoscopic reintervention (ERI). However, the optimal stent replacement method for PS remains unclear. METHODS: This retrospective study included 322 patients with UMHBO. Among them, 146 received PS placement as initial drainage (across-the-papilla PS [aPS], 54; IS, 92), whereas 75 required ERI. Eight bilateral aPS, 21 bilateral IS, and 17 bilateral self-expandable metallic stent (SEMS) placements met the inclusion criteria. Rates of technical and clinical success, adverse events, recurrent biliary obstruction (RBO), time to RBO (TRBO), overall survival, and secondary ERI were compared. RESULTS: There were no significant intergroup differences in rates of technical or clinical success, adverse events, RBO occurrence, or overall survival. The median TRBO was significantly shorter in the aPS group (47 days) than IS (91 days; P = 0.0196) and SEMS (143 days; P < 0.01) groups. Median TRBO did not differ significantly between the IS and SEMS groups (P = 0.44). On Cox multivariate analysis, the aPS group had the shortest stent patency (hazard ratio 2.67 [95% confidence interval 1.05-6.76], P = 0.038). For secondary ERI, the median endoscopic procedure time was significantly shorter in the IS (22 min) vs. SEMS (40 min) group (P = 0.034). CONCLUSIONS: Bilateral IS and SEMS placement featured prolonged patency after first ERI. Because bilateral IS placement is faster than SEMS placement and IS can be removed during secondary ERI, it may be a good option for first ERI.

The evaluation of bilateral stenting using braided or laser-cut self-expandable metallic stent for malignant hilar biliary obstruction.

OBJECTIVES: Bilateral self-expandable metallic stent (SEMS) placement for unresectable malignant hilar biliary obstruction (UMHBO) is an effective option for biliary drainage with long-term stent patency. Laser-cut and braided SEMS can be used for bilateral SEMS placement. This study aimed to clarify any differences in the clinical features and proper use of the laser-cut and braided SEMS placement using the stent-in-stent method for UMHBO. METHODS: In this study, 78 patients who underwent bilateral stent-in-stent SEMS placement for UMHBO were included. The patients were divided into the laser-cut (n = 33) and braided groups (n = 45). Both groups were compared for technical and clinical success, adverse events (AEs), time to recurrent biliary obstruction (TRBO), overall survival, and endoscopic reintervention (ERI). RESULTS: There were no significant differences in technical and clinical success rates (laser-cut vs. braided group, 97% vs. 95.6%, P = 1.0), AEs (21.2% vs. 15.6%. P = 0.56), median TRBO (242 days vs. 140 days, P = 0.36), and median overall survival (654 days vs. 675 days, P = 0.58). ERI was required in 15 patients in the laser-cut group and in 20 patients in the braided group. The technical and clinical success rates of ERI (60% vs. 85%) were not significantly different (P = 0.13); however, the median ERI procedure time was significantly longer in the laser-cut group (38 min) than in the braided group (22 min; P = 0.02). CONCLUSION: No significant difference in initial SEMS placement was noted between the laser-cut and braided groups; however, the laser-cut group required a longer ERI procedure time than that required by the braided group. The use of braided SEMS may be a convenient option for ERI.

Utility of bilateral intraductal plastic stent for malignant hilar biliary obstruction compared with bilateral self-expandable metal stent: a propensity score-matched cohort analysis.

BACKGROUND AND AIMS: Intraductal plastic stent (IS) placement for unresectable malignant hilar biliary obstruction (UMHBO) is an effective option for biliary drainage. However, the effectiveness of bilateral IS placement compared with bilateral self-expandable metal stent (SEMS) placement remains unclear. METHODS: Overall, 301 patients with UMHBO were enrolled; 38 patients underwent bilateral IS placement (IS group) and 38 patients underwent SEMS placement (SEMS group) in the propensity score-based cohort. Both groups were compared for technical and clinical success, adverse events (AEs), recurrent biliary obstruction (RBO), time to RBO (TRBO), overall survival (OS), and endoscopic reintervention (ERI). RESULTS: No significant differences were observed between the groups regarding technical and clinical success, AEs and RBO occurrence rates, TRBO, or OS. The median initial endoscopic procedure time was significantly shorter in the IS group (23 vs 49 minutes, P < .01). ERI was performed on 20 and 19 patients in the IS and SEMS groups, respectively. The median ERI procedure time was significantly shorter in the IS group (22 vs 35 minutes, P = .04). Median TRBO after ERI with plastic stent placement tended to be longer in the IS group (306 vs 56 days, P = .068). A Cox multivariate analysis showed that the IS group was the significant related factor for TRBO after ERI (hazard ratio, .31; 95% confidence interval, .25-.82; P = .035). CONCLUSIONS: Bilateral IS placement can reduce the duration of the endoscopic procedure and provide sufficient stent patency both initially and after ERI stent placement, and the stents are removable. Bilateral IS placement is considered a good option for initial UMHBO drainage. (Clinical trial registration number: UMIN000050546.).

Efficacy of Contrast-Enhanced Endoscopic Ultrasonography for the Differentiation of Non-Hodgkin's Lymphoma: A Single-Center Retrospective Cohort Study.

BACKGROUND: Contrast-enhanced endoscopic ultrasound (CE-EUS) is a promising diagnostic modality for differentiating malignant and benign lymph nodes. This study aimed to evaluate the diagnostic capability of CE-EUS in differentiating indolent non-Hodgkin's lymphoma (NHL) from aggressive NHL. METHODS: Patients who underwent CE-EUS and endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for lymphadenopathy and were diagnosed with NHL were included in this study. Echo features on B-mode endoscopic ultrasound (EUS) and vascular and enhancement patterns on CE-EUS were qualitatively evaluated. The enhancement intensity of the lymphadenopathy on CE-EUS over 60 s was also quantitatively evaluated using time-intensity curve (TIC) analysis. RESULTS: A total of 62 patients who were diagnosed with NHL were enrolled in this study. Regarding qualitative evaluation using B-mode EUS, there were no significant differences in the echo features between aggressive NHL and indolent NHL. With regard to qualitative evaluation using CE-EUS, aggressive NHL showed a heterogeneous enhancement pattern that is significantly more frequent than indolent NHL (95% confidence interval: 0.57 to 0.79, p = 0.0089). When heterogeneous enhancement was defined as aggressive NHL, the sensitivity, specificity, and accuracy of the qualitative evaluation when using CE-EUS were 61%, 72%, and 66%, respectively. In TIC analysis, the velocity of reduction for homogeneous lesions was significantly higher in aggressive NHL than in indolent NHL (p < 0.0001). The sensitivity, specificity, and accuracy of CE-EUS in differentiating indolent NHL from aggressive NHL improved to 94%, 69%, and 82%, respectively, when combined with qualitative and quantitative evaluations. CONCLUSIONS: CE-EUS before EUS-FNA for mediastinal or abdominal lymphadenopathy may be useful for improving the diagnostic capability of differentiating between indolent NHL and aggressive NHL (clinical trial registration number: UMIN000047907).

Effect of ursodeoxycholic acid after self-expandable metal stent placement in malignant distal biliary obstruction: a propensity score-matched cohort analysis.

BACKGROUND AND AIMS: Sludge occlusion is a primary reason for recurrent biliary obstruction (RBO) after self-expandable metallic stent (SEMS) placement. However, the efficacy of ursodeoxycholic acid (UDCA) for SEMS occlusion remains unexplored to date. This study aimed to evaluate the efficacy of UDCA after SEMS placement for malignant distal biliary obstruction (MDBO). METHODS: Three hundred fifty-four patients were included, of which 60 received UDCA. Additionally, we conducted a propensity score-matched cohort analysis on 110 patients with SEMS placement for MDBO to reduce selection bias. Patients were categorized into 2 groups of 55 each, based on whether they received UDCA. In the UDCA group, the treatment was administered for more than a month. The primary endpoint was the time to RBO (TRBO) after SEMS placement. The secondary endpoint was to evaluate SEMS occlusion rate and early adverse events (AEs). RESULTS: The cumulative SEMS occlusion rate was 41.8% and 18.2% in the groups with and without UDCA, respectively (P = .0119). Median TRBO was significantly longer in the control group than in the UDCA group (528 vs 154 days, P = .0381). In the multivariate analysis, UDCA administration was identified as the independent risk factor for reducing TRBO (hazard ratio, 2.28; 95% confidence interval, 1.06-4.88; P = .0348). The overall early AE rate showed insignificant differences between groups. CONCLUSIONS: Administering UDCA after SEMS placement was not efficacious for prolonging the TRBO in MDBO. Moreover, administering UDCA beyond a month might increase the risk of stent sludge occlusion. (Clinical trial registration number: UMIN000046862.).

Involvement of Cdk5 activating subunit p35 in synaptic plasticity in excitatory and inhibitory neurons.

Cyclin-dependent kinase 5 (Cdk5) /p35 is involved in many developmental processes of the central nervous system. Cdk5/p35 is also implicated in synaptic plasticity, learning and memory. Several lines of conditional Cdk5 knockout mice (KO) have been generated and have shown different outcomes for learning and memory. Here, we present our analysis of p35 conditional KO mice (p35cKO) in hippocampal pyramidal neurons or forebrain GABAergic neurons using electrophysiological and behavioral methods. In the fear conditioning task, CamKII-p35cKO mice showed impaired memory retention. Furthermore, NMDAR-dependent long-term depression (LTD) induction by low-frequency stimuli in hippocampal slices from CamkII-p35cKO mice was impaired compared to that in control mice. In contrast, Dlx-p35cKO mice showed no abnormalities in behavioral tasks and electrophysiological analysis in their hippocampal slices. These results indicated that Cdk5/p35 in excitatory neurons is important for the hippocampal synaptic plasticity and associative memory retention.

Impact of Controlling nutritional status (CONUT) in patients with unresectable advanced pancreatic cancer receiving multi-agent chemotherapy: A single center, retrospective cohort study.

Controlling nutritional status (CONUT) calculated using the serum albumin concentration, total lymphocyte count, and total cholesterol, was developed as a screening tool for the early detection of undernutrition. In addition, CONUT has been reported to be a prognostic predictor of various malignancies. AIM: To investigate the impact of CONUT in patients with advanced pancreatic cancer (APC). METHODS: Between June 2014 and October 2020, 110 consecutive patients with APC who received multi-agent chemotherapy were retrospectively reviewed. Patients were classified into four categories (normal, 1; light, 2; moderate, 3; severe, 4) based on CONUT. Progression-free survival (PFS) and overall survival (OS) were evaluated. RESULTS: Thirty-nine (35.4%), 63 (57.2%), and 8 (7.2%) patients had CONUT 1, 2, and 3, respectively, but no patients for CONUT 4. The baseline characteristics did not differ significantly between CONUT classifications. In the multivariate analyses, the presence of metastasis (hazard ratio [HR], 2.06; 95% confidence interval [CI], 1.22-3.52), CONUT 2 (HR, 2.15; 95% CI, 1.32-3.54), and CONUT 3 (HR, 9.18; 95% CI, 2.67-23.50) were independent risk factors for PFS. The presence of metastasis (HR, 1.76; 95% CI, 1.04-3.07), CONUT 2 (HR, 1.92; 95% CI, 1.16-3.24), and CONUT 3 (HR, 10.71; 95% CI, 3.87-27.63) were also independent risk factors for OS. A median OS in CONUT 1, 2, and 3 were 20, 14.5, and 3.5 months (CONUT 1 vs. CONUT 2, p = 0.02; CONUT 1 vs. CONUT 3, p < 0.01; CONUT 2 vs. CONUT 3, p < 0.01), respectively. CONCLUSION: CONUT could be a predictor of prognosis for survival in patients with APC.

Efficacy of Contrast-Enhanced Harmonic Endoscopic Ultrasound for Pancreatic Solid Tumors with a Combination of Qualitative and Quantitative Analyses: A Prospective Pilot Study.

INTRODUCTION: Image evaluation of contrast-enhanced harmonic endoscopic ultrasound (CEH-EUS) and additional time-intensity curve (TIC) analysis enable qualitative and quantitative analyses of pancreatic tumor based on real-time perfusion imaging. AIMS: To evaluate the efficacy of CEH-EUS with a combination of qualitative and quantitative analyses of pancreatic solid tumors. METHODS: Patients were scheduled to undergo EUS-guided fine needle aspiration (FNA) for pancreatic solid tumors were prospectively enrolled between 11/2016 and 12/2018 and underwent CEH-EUS. The vascular and enhancement patterns were qualitatively evaluated and heterogeneous enhancement was defined to be indicative of malignancy. The echo intensity change during 60 s in the tumor was quantitatively evaluated by time intensity curve analysis. RESULTS: In total, 100 patients were enrolled in this study. The final diagnoses were malignant lesions in 87 patients and benign legions in 13 patients. There were four categories of enhancement and patterns: hypovascular with heterogeneous, hypovascular with homogeneous, hypervascular heterogeneous, and hypervascular homogeneous enhancement. The diagnostic capability of qualitative analysis was the sensitivity, specificity, and accuracy of 89%, 62%, and 85%, respectively. With respect to time intensity curve analysis, the time to peak of malignant lesions was significantly shorter than those of benign lesions (P = 0.0009) with an optimal cutoff value of 12.81 s on the receiver operating characteristic curve analysis. With the combination of qualitative and quantitative analyses, the sensitivity, specificity, and accuracy were improved to 100%, 54%, and 94%, respectively. CONCLUSIONS: CEH-EUS with combined qualitative and quantitative analyses for pancreatic tumors might be useful as a complement for EUS-FNA. The UMIN Clinical Trials Registry (UMIN000025192).

Automatic Segmentation of Pancreatic Tumors Using Deep Learning on a Video Image of Contrast-Enhanced Endoscopic Ultrasound.

BACKGROUND: Contrast-enhanced endoscopic ultrasound (CE-EUS) is useful for the differentiation of pancreatic tumors. Using deep learning for the segmentation and classification of pancreatic tumors might further improve the diagnostic capability of CE-EUS. AIMS: The aim of this study was to evaluate the capability of deep learning for the automatic segmentation of pancreatic tumors on CE-EUS video images and possible factors affecting the automatic segmentation. METHODS: This retrospective study included 100 patients who underwent CE-EUS for pancreatic tumors. The CE-EUS video images were converted from the originals to 90-s segments with six frames per second. Manual segmentation of pancreatic tumors from B-mode images was performed as ground truth. Automatic segmentation was performed using U-Net with 100 epochs and was evaluated with 4-fold cross-validation. The degree of respiratory movement (RM) and tumor boundary (TB) were divided into 3-degree intervals in each patient and evaluated as possible factors affecting the segmentation. The concordance rate was calculated using the intersection over union (IoU). RESULTS: The median IoU of all cases was 0.77. The median IoUs in TB-1 (clear around), TB-2, and TB-3 (unclear more than half) were 0.80, 0.76, and 0.69, respectively. The IoU for TB-1 was significantly higher than that of TB-3 (p < 0.01). However, there was no significant difference between the degrees of RM. CONCLUSIONS: Automatic segmentation of pancreatic tumors using U-Net on CE-EUS video images showed a decent concordance rate. The concordance rate was lowered by an unclear TB but was not affected by RM.

Clinical Outcomes of Conversion Surgery after FOLFIRINOX in Patients with Unresectable Advanced Pancreatic Cancer: A Retrospective Cohort Study at a Single Center.

Pancreatic cancer is one of the most lethal cancers. To improve its prognosis, conversion surgery for initially unresectable advanced pancreatic cancer (UAPC) after chemotherapy has been reported in recent years. METHODS: A retrospective analysis of the patients with initially UAPC underwent conversion surgery after the first-line modified FOLFIRINOX (mFX) was conducted at a single tertiary care center between January 2014 and March 2020. RESULTS: Among 79 patients with UAPC who had mFX, 8 patients with a median age of 63 years, including 5 males (3 with locally advanced and 5 metastatic lesions), underwent conversion surgery after a median of 20 cycles of mFX. Conversion surgery was performed in 10.1% of patients (8/79) and surgical resection was successful in all with R0 resection. Postoperative major adverse events were seen in 2 patients, but no perioperative deaths were recognized. Recurrence was confirmed in 3 patients, and these 3 patients died due to cancer recurrence in 17.7, 30.6 and 57.8 months after mFX initiation. 5 patients were still alive without recurrence. The median OS in the patients who underwent conversion surgery was estimated as 65.9 months and was significantly longer than that of the patients without conversion surgery or that in the patients who had a partial response for mFX but did not have conversion surgery. The median follow-up period for the patients who had conversion surgery was 35.2 months. CONCLUSION: Conversion surgery achieved long-term survival in patients with UAPC who were treated with the first-line mFX, although controversy still remained.

Endoscopic ultrasound-guided fine-needle aspiration of pelvic lesions via the upper and lower gastrointestinal tract approaches.

BACKGROUND: Combining upper and lower gastrointestinal tract (GI) approaches allows expansion of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) indications for pelvic lesions. The upper GI approach has been used for pelvic lesions around the level of the aortoiliac bifurcation in our institution. The aim of this study is to evaluate the feasibility and safety of EUS-FNA for pelvic lesions via the upper and lower GI approaches. METHODS: All consecutive patients who underwent EUS-FNA for the pelvic lesion between January 2008 and December 2018 were retrospectively analyzed. Pelvic lesions were defined as lesions located around and below the aortoiliac bifurcation level. The primary outcome was technical success rate, and the secondary outcomes were the diagnostic capability of EUS-FNA for malignancy and the safety. RESULTS: EUS-FNA for pelvic lesions was performed in 49 patients: upper and lower GI approaches were used in 28 and 21 patients, respectively. The technical success rates were 91.8% (45/49) in all patients: 89.3% (25/28) and 95.2% (20/21) with the upper and lower GI approaches, respectively. Among patients who achieved technical success, the diagnostic accuracy for malignancy was 97.8% (44/45) in all patients: 100% (25/25) and 95.0% (19/20) with the upper and lower GI approaches, respectively. One (2.0%) patient developed an adverse event of sigmoid colon perforation. CONCLUSIONS: EUS-FNA for pelvic lesions via the upper and lower GI approaches was a safe, feasible, and effective method, although careful endoscopic manipulation is required to avoid perforation, especially with the lower GI approach. Further large-scale, well-designed studies are needed to validate our findings.

The impact of sarcopenia and decrease in skeletal muscle mass in patients with advanced pancreatic cancer during FOLFIRINOX therapy.

Sarcopenia, defined as decrease in skeletal muscle mass (SMM) and strength, might be associated with reduced survival. We investigated the impact of sarcopenia and decrease in SMM in patients with advanced pancreatic cancer during FOLFIRINOX (FX) therapy. Consecutive sixty-nine patients who received FX were evaluated. Skeletal muscle index (SMI) (cm2/m2) was used to evaluate SMM. The cut-off value of sarcopenia was defined as SMI <42 for males and <38 for females, based on the Asian Working Group for sarcopenia criteria. Sarcopenia was diagnosed in thirty-three (48 %) subjects. Comparison of baseline characteristics of the two groups (sarcopenia group: non-sarcopenia group) showed a significant difference in sex, tumour size and BMI. There was no significant difference in the incidence of adverse events with grades 3-5 and progression-free survival (PFS) during FX between the two groups (PFS 8·1 and 8·8 months; P = 0·88). On the multivariate analysis, progressive disease at the first follow-up computed tomography (hazard ratio (HR) 3·87, 95 % CI 1·53, 9·67), decreased SMI ≥ 7·9 % in 2 months (HR 4·02, 95 % CI 1·87, 8·97) and carcinoembryonic antigen ≥ 4·6 (HR 2·52, 95 % CI 1·10, 6·11) were significant risk factors associated with poor overall survival (OS), but sarcopenia at diagnosis was not. OS in patients with decreased SMI of ≥7·9 % and <7·9 % were 10·9 and 21·0 months (P < 0·01), respectively. In conclusion, decrease in SMM within 2 months after the initiation of chemotherapy had significantly shorter OS, although sarcopenia at diagnosis did not affect OS. Therefore, it might be important to maintain SMM during chemotherapy for a better prognosis.

Endoscopic ultrasound guided-antegrade biliary stenting vs percutaneous transhepatic biliary stenting for unresectable distal malignant biliary obstruction in patients with surgically altered anatomy.

BACKGROUND/PURPOSE: Unresectable distal malignant biliary obstruction (DMBO) in patients with surgically altered anatomy is traditionally managed with percutaneous transhepatic biliary drainage (PTBD) and stenting because the anatomical features complicate the endoscopic approach to the biliary orifice. EUS-guided approaches recently emerged as alternative treatments; however, limited data comparing the procedures are available. The aim of this study was to compare EUS-antegrade biliary stenting (ABS) with PTBD for DMBO in patients with surgically altered anatomy. METHODS: The medical records of patients who underwent EUS-ABS or PTBD for the management of DMBO and had a history of upper intestinal surgery at two tertiary centers between 2007 and 2019 were retrospectively evaluated. The study outcomes were technical, clinical, and internalization success rates and adverse event rates. RESULTS: Of the 64 enrolled patients, 35 underwent EUS-ABS and 29 had PTBD. Basic characteristics including age, sex, performance status, primary malignancy, and reconstruction method did not differ significantly between groups. The technical, clinical, and internalization success rates in the EUS-ABS and PTBD groups were 97.1% vs 96.6% (P = 1.00), 97.1% vs 93.1% (P = .586), and 97.1% vs 75.9% (P = .01), respectively. The adverse event rate was 11.4% vs 27.6% (P = .119). No significant long-term difference was seen in time to recurrent biliary obstruction and survival. Multivariate analysis confirmed EUS-ABS was not an independent risk factor for survival. CONCLUSIONS: Similar to PTBD, EUS-ABS can effectively and safely manage DMBO in patients with surgically altered anatomy. Further well-designed trials are warranted to confirm these findings.

The Efficacy of Over-the-Scope Clip Closure for Gastrointestinal Iatrogenic Perforation During Endoscopic Ultrasound and Endoscopic Retrograde Cholangiopancreatography for Pancreaticobiliary Diseases.

BACKGROUND: Intestinal perforation is a severe adverse event during pancreaticobiliary endoscopy. The use of over-the-scope clip (OTSC) has recently increased; however, the efficacy of OTSC during pancreaticobiliary endoscopy has not been well studied. AIMS: To evaluate the efficacy of OTSC for the closure of gastrointestinal iatrogenic perforation during pancreaticobiliary endoscopy. PATIENTS AND METHODS: This was a retrospective multicenter cohort study conducted at 3 tertiary care centers. The inclusion criteria were patients who had gastrointestinal perforation during endoscopic procedures for pancreaticobiliary diseases and underwent perforation closure using OTSC. The primary outcome was the clinical success rate. Secondary outcomes were technical success rates, adverse event rates, and the duration until the start of oral intake after OTSC. RESULTS: Ten patients were treated by OTSC from January 2013 to December 2017. In 2 out of 10, the perforations could not be closed completely. In the remaining 8, perforations were closed completely, but intestinal obstruction caused by OTSC occurred in 1 patient. The clinical success rate was 80% (8/10). The technical and adverse event rates were 80% (8/10) and 10% (1/10), respectively. A median resumption timing of oral intake was 5 days (range, 3 to 10 d). CONCLUSION: OTSC is considered as effective management for perforations during pancreaticobiliary endoscopy, although careful consideration is required for the indication of OTSC.

Endoscopic Ultrasound-Guided Fine Needle Biopsy Using 22-Gauge Franseen Needle for the Histological Diagnosis of Solid Lesions: A Multicenter Prospective Pilot Study.

BACKGROUND: Recently, a novel 22-gauge needle with three symmetric needle points and crown-shaped cutting heels, known as a Franseen needle, has been developed for endoscopic ultrasound-guided fine needle biopsy (EUS-FNB). AIM: To assess the histological material acquisition rate and histological diagnostic capability of the 22-gauge Franseen needle (AC22) during EUS-FNB for solid lesions. METHODS: This study was designed as an open-label, multicenter, prospective, single-arm pilot study of EUS-FNB using AC22 for the diagnosis of solid lesions. Three passes of FNB using AC22 were performed for all lesions. The primary endpoints were the histological material acquisition rate and histological diagnostic capability. The secondary endpoints were the technical success rate, quality of histological samples, number of passes for diagnosis, and safety. RESULTS: Between September 2017 and May 2018, 75 patients were enrolled. The final diagnoses were malignancy in 65 and benign in 10. Three passes of FNB were technically successful in all patients. The sensitivity, specificity, and accuracy for the malignancy of histological analyses were 92.3% (60/65), 100% (10/10), and 93.3% (70/75), respectively, for the first pass and 95.4% (62/65), 100% (10/10), and 96% (72/75), respectively, for combined three passes. The diagnostic yield plateaued after the second pass. Sufficient tissue samples for histological interpretation were obtained in 96% (72/75) and 100% (75/75) patients for the single pass and combined three passes, respectively. Two patients (2.7%) developed mild pancreatitis as an adverse event. CONCLUSION: EUS-FNB using AC22 showed high histological diagnostic capability with the high first pass yield. CLINICAL TRIALS REGISTRY: UMIN Clinical Trials Registry (UMIN ID: UMIN000036641).

Utility of endoscopic ultrasound and endoscopic ultrasound-guided fine-needle aspiration for the diagnosis and management of pancreatic cystic lesions: Differences between the guidelines.

Recent advances and frequent use of cross-sectional imaging studies have increased opportunities for incidental diagnoses of pancreatic cystic lesions (PCL). In the management of PCL, distinguishing between mucinous versus non-mucinous and malignant versus benign cysts is important to diagnose pancreatic cancer in its early stage. For this reason, there have been several guidelines to manage PCL. Endoscopic ultrasound (EUS) and EUS-guided fine-needle aspiration (FNA) play important roles in the guidelines, although there are some differences in their roles. In this review, we aimed to evaluate the current status of EUS and EUS-FNA in the management of PCL and the status of these procedures in the guidelines.

Second-Line Gemcitabine Plus Nab-Paclitaxel for Patients with Unresectable Advanced Pancreatic Cancer after First-Line FOLFIRINOX Failure.

FOLFIRINOX (FX) and gemcitabine (GEM) plus nab-paclitaxel (GnP) have been reported as effective regimens for unresectable advanced pancreatic cancer (APC). FX may be more effective but is also associated with more adverse events (AEs). Therefore, first-line treatment with FX followed by second-line GnP may be appropriate. AIMS: To assess the safety and efficacy of second-line GnP for patients with APC after first-line FX failure. METHODS: This study was a multicenter prospective phase II study evaluating second-line GnP in patients with APC after failed first-line FX. The primary endpoint was response rate (RR), and the secondary endpoints were overall survival (OS), progression free survival (PFS), and the frequency and degree of adverse events (AEs). RESULTS: Thirty patients (14 male; median age, 64 years) were enrolled. The RR was 13.3%, with a median follow-up time of 9.3 months. The median OS and PFS were 7.6 and 3.8 months, respectively. From the beginning of first-line treatment, the median OS and PFS were 14.2 and 9.3 months, respectively. Grade 3 or 4 AEs were seen in 70% of patients. CONCLUSION: Second-line GnP after FX failure for patients with APC could be more effective than GEM alone. Further comparison studies are warranted.

Evaluation of endoscopic reintervention for self-expandable metallic stent obstruction after stent-in-stent placement for malignant hilar biliary obstruction.

BACKGROUND: Bilateral self-expandable metallic stent (SEMS) placement is effective for long-term management of unresectable malignant hilar biliary obstruction (UMHBO). However, endoscopic reintervention (ERI) for bilateral SEMSs is not well-studied. This study aimed to evaluate ERI efficacy after stent-in-stent placement. METHODS: Data of 31 patients who underwent ERI from May 2000 to July 2018 were analyzed. RESULTS: The technical success rate was 80.7% (25/31) and no adverse events occurred. The functional success rate was 100% (25/25). In a multivariate logistic regression analysis, the angle between the bilateral SEMSs (ABBS) >104° (odds ratio 50.49, 95% CI 3.370-2131, P = 0.0039) and overgrowth (odds ratio 25.70, 95% CI 1.121-1234, P = 0.0423) were risk factors for ERI failure. Multiple liver metastases, which sometimes cause overgrowth, were also risk factors. After ERI, some patients underwent additional SEMS (n = 4), plastic stent (n = 14) placement, or internal cleaning of the initial SEMS alone (n = 7). There were no significant intergroup differences in the 50% time to recurrent biliary obstruction. CONCLUSIONS: ABBS >104° and overgrowth were risk factors for ERI failure after stent-in-stent placement. In the decision-making process for initial SEMS placement for UMHBO, patient condition should be considered, including the angle between bilateral bile ducts and multiple liver metastases.

Efficacy of contrast-enhanced EUS for lymphadenopathy: a prospective multicenter pilot study (with videos).

BACKGROUND AND AIMS: Contrast-enhanced EUS (CE-EUS) allows qualitative and quantitative evaluation based on real-time perfusion imaging and may improve the diagnostic capability. The aim of this study was to evaluate the efficacy of CE-EUS in differentiating malignant from benign lymphadenopathy. METHODS: Patients undergoing EUS-FNA for abdominal or mediastinal lymphadenopathy were prospectively enrolled. The echofeatures on B-mode EUS and the vascular and enhancement patterns in CE-EUS were qualitatively evaluated. The echo intensity change during 60 seconds in the lymphadenopathy was quantitatively evaluated by time intensity curve (TIC) analysis. RESULTS: One hundred consecutive patients with 70 malignant and 30 benign lesions were enrolled. The sensitivity, specificity, and accuracy of the qualitative assessment in B-mode EUS were 77%, 17%, and 59%, respectively. When the heterogeneous enhancement was defined as malignancy, the sensitivity, specificity, and accuracy of the qualitative assessment in CE-EUS were 67%, 87%, and 73%, respectively. In TIC analysis, the velocity of reduction for homogeneous lesions showed a significant difference between malignant and benign lesions (P = .0011), and the receiver operating characteristic analysis showed an optimal cut-off value of .149 dB/s. The sensitivity, specificity, and diagnostic capabilities of CE-EUS for malignancy were improved to 89%, 77%, and 85%, respectively, on combining the qualitative and quantitative analyses. With regard to diagnostic accuracy, CE-EUS with combined qualitative and quantitative analyses was significantly higher than those of B-mode EUS or qualitative assessment of CE-EUS. CONCLUSIONS: CE-EUS with the combined qualitative and quantitative analyses for lymphadenopathy might be useful to complement regular EUS and EUS-FNA. (Clinical trial registration number: UMIN000024298.).

EUS-guided hybrid rendezvous technique as salvage for standard rendezvous with intra-hepatic bile duct approach.

EUS-guided rendezvous technique (EUS-RV) is an effective salvage technique for failed biliary cannulation during ERCP. However, it is still difficult to achieve cannulation in some cases, especially using the intrahepatic bile duct (IHBD) approach, which requires complicated guidewire manipulation. EUS-hybrid rendezvous technique (HRV) has been applied as a salvage technique for difficult guidewire placement during EUS-RV with IHBD approach. The aims of this study were to evaluate the efficacy and safety of EUS-HRV using a retrospective study. Database analysis revealed 29 patients who underwent EUS-RV for difficult biliary cannulation. Among them, 8 patients underwent EUS-HRV as a salvage technique for difficult guidewire placement during EUS-RV with the IHBD approach. In EUS-HRV, a 6-French dilator was advanced into the biliary system for better guidewire manipulation. After successful guidewire placement, the EUS scope was exchanged for a duodenoscope, keeping the guidewire and dilator in place. The EUS-placed guidewire was retrieved through the duodenoscope, followed by cannulation over the guidewire. The dilator remained at the fistula until completion of the procedure. The analysis showed that the guidewire placement and the subsequent scope exchange and deep biliary cannulation after the retrieval of the EUS-placed guidewire were successfully conducted for all 8 patients. Mild pancreatitis was recognized as an adverse event in 1 patient. The overall success rate of EUS-RV combined with EUS-HRV was improved up to 90% (26/29). Our results suggested that EUS-HRV can be an effective and safe salvage technique in cases wherein guidewire placement is difficult during EUS-RV with IHBD approach.