Single-cell transcriptome analysis reveals subtype-specific clonal evolution and microenvironmental changes in liver metastasis of pancreatic adenocarcinoma and their clinical implications.

BACKGROUND: Intratumoral heterogeneity (ITH) and tumor microenvironment (TME) of pancreatic ductal adenocarcinoma (PDAC) play important roles in tumor evolution and patient outcomes. However, the precise characterization of diverse cell populations and their crosstalk associated with PDAC progression and metastasis is still challenging. METHODS: We performed single-cell RNA sequencing (scRNA-seq) of treatment-naïve primary PDAC samples with and without paired liver metastasis samples to understand the interplay between ITH and TME in the PDAC evolution and its clinical associations. RESULTS: scRNA-seq analysis revealed that even a small proportion (22%) of basal-like malignant ductal cells could lead to poor chemotherapy response and patient survival and that epithelial-mesenchymal transition programs were largely subtype-specific. The clonal homogeneity significantly increased with more prevalent and pronounced copy number gains of oncogenes, such as KRAS and ETV1, and losses of tumor suppressor genes, such as SMAD2 and MAP2K4, along PDAC progression and metastasis. Moreover, diverse immune cell populations, including naïve SELLhi regulatory T cells (Tregs) and activated TIGIThi Tregs, contributed to shaping immunosuppressive TMEs of PDAC through cellular interactions with malignant ductal cells in PDAC evolution. Importantly, the proportion of basal-like ductal cells negatively correlated with that of immunoreactive cell populations, such as cytotoxic T cells, but positively correlated with that of immunosuppressive cell populations, such as Tregs. CONCLUSION: We uncover that the proportion of basal-like subtype is a key determinant for chemotherapy response and patient outcome, and that PDAC clonally evolves with subtype-specific dosage changes of cancer-associated genes by forming immunosuppressive microenvironments in its progression and metastasis.

Establishment of a patient-specific avatar organoid model derived from EUS-guided fine-needle biopsy for timely clinical application in pancreatic ductal adenocarcinoma (with video).

BACKGROUND AND AIMS: Pancreatic ductal adenocarcinoma (PDAC) has the worst survival rate among tumors. At the time of diagnosis, more than 80% of PDACs are considered to be surgically unresectable, and there is an unmet need for treatment options in these inoperable PDACs. This study aimed to establish a patient-derived organoid (PDO) platform from EUS-guided fine-needle biopsy (EUS-FNB) collected at diagnosis and to determine its clinical applicability for the timely treatment of unresectable PDAC. METHODS: Patients with suspected PDAC were prospectively enrolled at the Samsung Medical Center from 2015 to 2019. PDAC tissues were acquired by means of EUS-FNB to establish PDAC PDOs, which were comprehensively analyzed for histology, genomic sequencing, and high-throughput screening (HTS) drug sensitivity test. RESULTS: PDAC PDOs were established with a success rate of 83.2% (94/113). It took approximately 3 weeks from acquiring minimal EUS-FNB specimens to generating sufficient PDAC PDOs for the simultaneous HTS drug sensitivity test and genomic sequencing. The high concordance between PDAC tissues and matched PDOs was confirmed, and whole-exome sequencing revealed the increased detection of genetic alterations in PDOs compared with EUS-FNB tissues. The HTS drug sensitivity test showed clinical correlation between the ex vivo PDO response and the actual chemotherapeutic response of the study patients in the real world (13 out of 15 cases). In addition, whole-transcriptome sequencing identified candidate genes associated with nab-paclitaxel resistance, such as ITGB7, ANPEP, and ST3GAL1. CONCLUSIONS: This PDAC PDO platform allows several therapeutic drugs to be tested within a short time window and opens the possibility for timely personalized medicine as a "patient avatar model" in clinical practice.

Bleeding after endoscopic papillectomy and its risk factors: A single center experience of 196 cases.

BACKGROUND: Endoscopic papillectomy (EP) is an effective method to remove an ampulla of Vater (AoV) adenoma with minimal invasiveness. We reviewed the clinical outcomes and prognosis of patients undergoing EP, including tumor recurrence and adverse events. METHODS: A total of 196 patients who underwent EP from January 2004 to December 2017 were included. Clinical information was collected through electronic medical records, and risk factors to predict post-procedural bleeding were analyzed using a multivariate logistic regression model. RESULTS: A total of 93.9% patients (184/196) underwent complete resection. During the follow-up period, 14.7% patients (27/184) experienced tumor recurrence, and two of seven surgically resected tumors were malignant. A total of 45.4% patients (89/196) experienced adverse events related to EP. Delayed bleeding occurred in 16.3% of the patients (32/196), and they were all successfully treated with endoscopic hemostasis and conservative management. The most frequent site of delayed bleeding was the distal end of the papillary orifice, and 56.2% (18/32) patients of delayed bleeding were classified as having mild severity, the others had moderate severity. Familial adenomatous polyposis (FAP) [odds ratio (OR) = 3.80, 95% confidence interval (CI): 1.01-14.29; P < 0.05] and male sex (OR = 2.82, 95% CI: 1.04-7.63; P = 0.04) showed statistical significance in predicting delayed post-EP bleeding. CONCLUSIONS: EP for AoV adenoma was a highly effective and safe procedure. The risk of post-EP delayed bleeding was increased in patients with FAP syndrome and male patients, and post-EP bleeding occurred most commonly in the distal part of the AoV.

Genetic assessment of pathogenic germline alterations in lysosomal genes among Asian patients with pancreatic ductal adenocarcinoma.

BACKGROUND: Lysosomes are closely linked to autophagic activity, which plays a vital role in pancreatic ductal adenocarcinoma (PDAC) biology. The survival of PDAC patients is still poor, and the identification of novel genetic factors for prognosis and treatment is highly required to prevent PDAC-related deaths. This study investigated the germline variants related to lysosomal dysfunction in patients with PDAC and to analyze whether they contribute to the development of PDAC. METHODS: The germline putative pathogenic variants (PPV) in genes involved in lysosomal storage disease (LSD) was compared between patients with PDAC (n = 418) and healthy controls (n = 845) using targeted panel and whole-exome sequencing. Furthermore, pancreatic organoids from wild-type and KrasG12D mice were used to evaluate the effect of lysosomal dysfunction on PDAC development. RNA sequencing (RNA-seq) analysis was performed with established PDAC patient-derived organoids (PDOs) according to the PPV status. RESULTS: The PPV in LSD-related genes was higher in patients with PDAC than in healthy controls (8.13 vs. 4.26%, Log2 OR = 1.65, P = 3.08 × 10-3). The PPV carriers of LSD-related genes with PDAC were significantly younger than the non-carriers (mean age 61.5 vs. 65.3 years, P = 0.031). We further studied a variant of the lysosomal enzyme, galactosylceramidase (GALC), which was the most frequently detected LSD variant in our cohort. Autophagolysosomal activity was hampered when GALC was downregulated, which was accompanied by paradoxically elevated autophagic flux. Furthermore, the number of proliferating Ki-67+ cells increased significantly in pancreatic organoids derived from Galc knockout KrasG12D mice. Moreover, GALC PPV carriers tended to show drug resistance in both PDAC cell line and PDAC PDO, and RNA-seq analysis revealed that various metabolism and gene repair pathways were upregulated in PDAC PDOs harboring a GALC variant. CONCLUSIONS: Genetically defined lysosomal dysfunction is frequently observed in patients with young-onset PDAC. This might contribute to PDAC development by altering metabolism and impairing autophagolysosomal activity, which could be potentially implicated in therapeutic applications for PDAC.

Analysis of risk factors for delayed bleeding after semi-closed hemorrhoidectomy.

PURPOSE: The aim of this study was to determine the incidence of delayed post-hemorrhoidectomy bleeding (DPHB) after hemorrhoidectomy using a semi-closed procedure. We also investigated risk factors associated with DPHB. METHODS: This retrospective study enrolled a total of 1645 consecutive patients with symptomatic grade II to IV hemorrhoids who underwent a semi-closed procedure at the Seoul Songdo Hospital between September 2018 and May 2019. All patients underwent a semi-closed procedure with submucosal feeding vessel ligation, a method commonly performed at our institution. RESULTS: A total of 1645 patients (mean age: 48.67 (±14.38) years, 823 (50.0%) male/822 (50.0%) female) underwent semi-closed hemorrhoidectomy. Critically, 24 (1.5%) patients experienced DPHB. Of these patients, 13 (0.8%) experienced stump bleeding, whereas 11 (0.7%) experienced marginal bleeding. The mean bleeding period was 8.21±4.45 days. Multivariate analysis showed that male sex, drinking history, more than four hemorrhoid piles, and laxative agents were independent risk factors for DPHB. The risk of stump bleeding was significantly associated with male sex (OR=5.55, 95% CI 1.23-25.14, p=0.026), more than four hemorrhoid piles (OR=5.90, 95% CI 1.62-21.53, p=0.007), and laxative usage (OR=3.92, 95% CI 1.31-11.74, p=0.015). Conversely, the risk of marginal bleeding were significantly associated with drinking history (OR=10.48, 95% CI 1.34-82.03, p=0.025) and more than four hemorrhoid piles (OR=4.71, 95% CI 1.24-17.81, p=0.023). CONCLUSION: Male sex, drinking history, more than four hemorrhoid piles, and laxative usage were independent risk factors for DPHB in patients undergoing semi-closed hemorrhoidectomy. The risk factors for stump bleeding included male sex, more than four hemorrhoid piles, and laxative usage. In contrast, the risk factors for marginal bleeding were drinking history and more than four hemorrhoid piles.

Levator plate descent angle in pelvic floor disorders.

BACKGROUND: The levator plate descent angle (LPDA) quantifies the levator plate position with reference to the pubic bone and perineal body at rest. Unfortunately, research on this notable new parameter is lacking, but it is clear that levator ani deficiency (LAD) will undermine the fundamental role of the levator ani muscle (LAM) in organ support. The aim of this study was to establish the relationship between the LPDA and LAD in patients with pelvic floor disorders. METHODS: This retrospective study was conducted at Seoul Songdo Hospital, Korea between August 2019 and August 2020 on women with symptoms of pelvic floor disorder such as urinary incontinence, constipation, and fecal incontinence. In all cases, three-dimensional pelvic floor ultrasound was performed for LAD scoring, minimal levator hiatus, and LPDA evaluation. We evaluated LAD using a scoring system that graded levator injury according to the insertion point of each subdivision scored unilaterally. For the entire LAM group, a cumulative LAD score that ranged between 0 and 18 was possible. Scores were categorized as mild (0-6 points), moderate (7-12 points), and severe (13-18 points) deficiency RESULTS: A total of 93 patients were included in the study (mean age 65.89 ± 11.12 [range, 34-86] years). Thirteen participants had mild LAD scores (14.0%), 42 had moderate LAD scores (45.2%), and 38 had severe LAD scores (40.9%). There was a significant difference in mean age (59.23 ± 12.55 years vs. 64.43 ± 10.03 vs. 69.79 ± 10.55 years, p = 0.005) and mean parity (1.85 ± 0.90 vs 2.48 ± 1.15 vs 2.76 ± 1.10, p = 0.038) of patients between groups. There was also a significant difference in the mean Wexner incontinence score (7.14 ± 3.63 vs 7.24 ± 5.76 vs 11.41 ± 5.54, p = 0.028) and in the mean fecal incontinence quality of life (FIQOL) score (12.91 ± 3.11 vs 14.10 ± 3.87 vs 10.41 ± 3.65, p = 0.014). The mean value of the LPDA in the group with mild LAD scores was 14.65° (SD ± 3.54) and in the group with moderate LAD scores was 9.66° (SD ± 3.36). In the group with severe LAD scores, the mean LPDA was 1.83° (SD ± 4.71). The mean value for minimal levator hiatus (MLH) area in the mild LAD score group was 14.16cm2 (SD ± 2.72), that in the moderate LAD score group was 15.82cm2 (SD ± 2.30), and that in the severe LAD score group was 17.99cm2 (SD ± 2.81). There were significant differences between the three groups both in decreasing LPDA (p < 0.001) and increasing MLH (p < 0.001). There was a negative correlation between the LAD score and LPDA and the Pearson correlation coefficient was -0.528 (moderate correlation). There was a positive correlation between the LAD score and MLH, and the Pearson correlation coefficient was 0.303 (weak correlation). CONCLUSIONS: The LAD score and LPDA have a moderate negative correlation. In patients with severe pelvic floor symptoms and extensive LAM injury, high LAD scores and low LPDA results were confirmed. In the treatment of patients with pelvic floor disorders, the LPDA seems to be a very useful parameter in determining the severity of structural defects.

Multiple-Cycle Polymeric Extracellular Vesicle Precipitation and Its Evaluation by Targeted Mass Spectrometry.

The multiple roles of extracellular vesicles (EVs) in pathogenesis have received much attention, as they are valuable as diagnostic and prognostic biomarkers. We employed polymeric EV precipitation to isolate EVs from clinical specimens to overcome the limitations of ultracentrifugation (UC), such as low protein yields, a large volume of specimens used, and time requirements. Multiple-cycle polymeric EV precipitation was applied to enhance the purity of the EV fractions with a small sample volume. Then, the purity was assessed using a multiple reaction monitoring (MRM) panel consisting of alpha-2-macroglobulin (A2M), thrombospondin 1 (THBS 1), galectin 3 binding protein (LGALS3BP), and serum albumin (ALB). For purity evaluation, the EV fractions isolated from blood specimens were subjected to shotgun proteomics and MRM-based targeted proteomics analyses. We demonstrate that the modified method is an easy and convenient method compared with UC. In the shotgun proteomics analysis, the proteome profile of EV fraction contains 89% EV-related proteins by matching with the EVpedia database. In conclusion, we suggest that multiple-cycle polymeric EV precipitation is not only a more effective method for EV isolation for further proteomics-based experiments, but may also be useful for further clinical applications due to the higher EV yield and low sample requirements.

Imaging phenotype using 18F-fluorodeoxyglucose positron emission tomography-based radiomics and genetic alterations of pancreatic ductal adenocarcinoma.

PURPOSE: This study aimed to determine if major gene mutations including in KRAS, SMAD4, TP53, and CDKN2A were related to imaging phenotype using 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)-based radiomics in patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: Data on 48 PDAC patients with pretreatment FDG PET/CT who underwent genomic analysis of their tumor tissue were retrospectively analyzed. A total of 35 unique quantitative radiomic features were extracted from PET images, including imaging phenotypes such as pixel intensity, shape, and textural features. Targeted exome sequencing using a customized cancer panel was used for genomic analysis. To assess the predictive performance of genetic alteration using PET-based radiomics, areas under the receiver operating characteristic curve (AUC) were used. RESULTS: Mutation frequencies were KRAS 87.5%, TP53 70.8%, SMAD4 25.0%, and CDKN2A 18.8%. KRAS gene mutations were significantly associated with low-intensity textural features, including long-run emphasis (AUC = 0.806), zone emphasis (AUC = 0.794), and large-zone emphasis (AUC = 0.829). SMAD4 gene mutations showed significant relationships with standardized uptake value skewness (AUC = 0.727), long-run emphasis (AUC = 0.692), and high-intensity textural features such as run emphasis (AUC = 0.775), short-run emphasis (AUC = 0.736), zone emphasis (AUC = 0.750), and short-zone emphasis (AUC = 0.725). No significant associations were seen between the imaging phenotypes and genetic alterations in TP53 and CDKN2A. CONCLUSION: Genetic alterations of KRAS and SMAD4 had significant associations with FDG PET-based radiomic features in PDAC. PET-based radiomics may help clinicians predict genetic alteration status in a noninvasive way.

Using single-operator cholangioscopy for endoscopic evaluation of indeterminate biliary strictures: results from a large multinational registry.

BACKGROUND: Peroral cholangioscopy (POCS) of indeterminate biliary strictures aims to achieve a diagnosis through visual examination and/or by obtaining targeted biopsies under direct visualization. In this large, prospective, multinational, real-life experience of POCS-guided evaluation of indeterminate biliary strictures, we evaluated the performance of POCS in this difficult-to-manage patient population. METHODS: This prospective registry enrolled patients, with indeterminate biliary strictures across 20 centers in Asia, the Middle East, and Africa. The primary end points were the ability to visualize the lesion, obtain histological sampling when intended, and an assessment of the diagnostic accuracy of POCS for malignant strictures. Patients were followed for 6 months after POCS or until a definitive malignant diagnosis was made, whichever occurred first. RESULTS: 289 patients underwent 290 POCS procedures with intent to biopsy in 182 cases. The stricture/filling defect was successfully visualized in 286/290 (98.6 %), providing a visual diagnostic impression in 253/290 (87.2 %) and obtaining adequate biopsies in 169/182 (92.9 %). Procedure-related adverse events occurred in 5/289 patients (1.7 %). POCS influenced patient management principally by elucidating filling defects or the causes of bile duct stricture or dilation. The visual impression of malignancy showed 86.7 % sensitivity, 71.2 % specificity, 65.8 % positive and 89.4 % negative predictive value, and 77.2 % overall accuracy compared with final diagnosis. Histological POCS-guided samples showed 75.3 % sensitivity, 100 % specificity, 100 % positive and 77.1 % negative predictive value, and 86.5 % overall accuracy. CONCLUSION: In this large, real-life, prospective series, POCS was demonstrated to be an effective and safe intervention guiding the management of patients with indeterminate biliary strictures.

Intraductal placement of non-flared fully covered metallic stent for refractory anastomotic biliary strictures after living donor liver transplantation: Long-term results of prospective multicenter trial.

BACKGROUND AND AIM: Fully covered self-expandable metallic stent (FCSEMS) may be an effective modality for managing anastomotic biliary stricture (ABS) after liver transplantation. However, stent migration and stent-induced ductal injury are the main limitations. The objective of this study was to evaluate the usefulness of an unflared, intraductal FCSEMS that was designed to minimize migration and ductal injury for refractory ABS after living donor liver transplantation (LDLT). METHODS: A total of 32 consecutive patients with symptomatic ABS after LDLT unresolved by plastic stents with or without balloon dilation at four tertiary medical centers were prospectively enrolled. A short (3 or 5 cm) FCSEMS having long lasso (10 cm) used in this study had unflared convex ends to minimize tissue hyperplasia and smaller center portion to prevent migration. The FCSEMS was placed above the papilla and removed at 3-4 months after stenting. RESULTS: Technical and clinical success rates of intraductal placement with FCSEMS were 100% (32/32) and 81.2% (26/32), respectively. Early stent migration was observed in five (15.6%) patients. However, three patients with early stent migration had stricture resolution without needing additional intervention. Intended stent removal was successful in 27 (100%) patients (median, 101 days; range, 23-118 days). No stent-induced ductal change was observed in all patients. Stricture recurrence was observed in 11.5% (3/26) of patients during 639 days of median duration of follow-up (range, 366-2079 days). CONCLUSIONS: Intraductal placement of an unflared short FCSEMS may be a promising option for refractory ABS after LDLT with minimal stent-induced ductal injury and stent migration.

Efficacy of a novel lumen-apposing metal stent for the treatment of symptomatic pancreatic pseudocysts (with video).

BACKGROUND AND AIMS: Recently, a newly designed lumen-apposing metal stent (LAMS) with a conventional delivery system was developed. The purpose of this study was to evaluate the effectiveness and safety of a newly designed LAMS for EUS-guided drainage to treat symptomatic pancreatic pseudocysts. METHODS: This prospective multicenter cohort study included 34 patients with symptomatic pancreatic pseudocysts from 2016 to 2017. The patients underwent EUS-guided drainage with the newly designed LAMS (Niti-S SPAXUS; Taewoong Medical Co, Ltd, Ilsan, South Korea). Effectiveness outcome measurements included technical success rate, clinical success rate, successful stent removal rate, and procedural time. Safety outcome measurements included procedure and/or stent-related adverse events (AEs) and overall AEs. Patients were prospectively followed, and consecutive data were collected at discharge, at stent removal, and 20 days after stent removal. RESULTS: Thirty-four patients (mean age 51.7 ± 13.3 years, 26 men) were enrolled. The mean pseudocyst size was 9.23 ± 3.54 cm. The technical success rate was 97.1% (33/34). The clinical success rate was 94.1% (32/34). All stents were successfully removed. The mean procedural time from needle puncture to stent deployment was 10.3 ± 5.7 minutes. Four patients (11.8%) experienced procedure and/or stent-related AEs, including stent maldeployment (n = 1) and pseudocyst infection (n = 3). All patients completely recovered from the AEs. Bleeding caused by the stent or buried LAMS syndrome was not observed. No unplanned endoscopic procedures were required. CONCLUSIONS: This study showed that EUS-guided drainage using the newly designed LAMS is technically feasible and effective for the treatment of symptomatic pancreatic pseudocysts. (Clinical trial registration number: NCT02730663.).

Cholangioscopy-guided lithotripsy for difficult bile duct stone clearance in a single session of ERCP: results from a large multinational registry demonstrate high success rates.

BACKGROUND: Peroral cholangioscopy (POCS) can be useful for difficult bile duct stone clearance. Large prospective multinational data on POCS-guided lithotripsy for clearing difficult bile duct stones in a single session of endoscopic retrograde cholangiopancreatography (ERCP) are missing. METHODS: Patients with difficult bile duct stones (defined as one or more of: largest stone diameter ≥ 15 mm, failed prior attempt at stone clearance, impacted, multiple, hepatic duct location, or located above a stricture) were enrolled at 17 centers in 10 countries. The principal endpoint was stone clearance in a single ERCP procedure using POCS. RESULTS : 156 patients underwent 174 sessions of POCS-guided electrohydraulic or laser lithotripsy. Stone clearance had failed in a previous ERCP using traditional techniques in 124/156 patients (80 %), while 32 /156 patients (21 %) were referred directly to POCS-guided therapy based on preprocedural assessment of the difficulty of stone clearance. In 101/156 patients (65 %), there were impacted stones. POCS-guided stone clearance was achieved in a single POCS procedure in 125 /156 patients (80 %, 95 % confidence interval [CI] 73 % - 86 %), and was significantly more likely for stones ≤ 30 mm compared with > 30 mm (odds ratio 7.9, 95 %CI 2.4 - 26.2; P = 0.002). Serious adverse events occurred in 3/156 patients (1.9 %, 95 %CI 0.4 % - 5.5 %), and included pancreatitis, perforation due to laser lithotripsy, and cholangitis (n = 1 each), all resolved within 1 week. CONCLUSION: POCS-guided lithotripsy is highly effective for clearance of difficult bile duct stones in a single procedure and successfully salvages most prior treatment failures. It may also be considered first-line therapy for patients with difficult choledocholithiasis to avoid serial procedures.

Prognosis and prognostic factors in patients with advanced biliary tract cancer depending on its anatomical location.

Objective: Previous studies have revealed that biliary tract cancer (BTC) has different clinical characteristics depending on its anatomical location. However, clinical studies about the prognosis of BTC according to its anatomical location are lacking. We aimed to compare the prognosis of BTC according to its anatomical location. Methods: We retrospectively reviewed records of 311 patients with advanced BTC who received gemcitabine based palliative chemotherapy from January 2006 to December 2015 at Samsung medical Center. Results: During median follow-up of 7.67 months, the median overall survival (OS) times for patients with gallbladder (GB) cancer, intrahepatic cholangiocellular carcinoma (ICCC) and extrahepatic cholangiocellular carcinoma (ECCC) were 8.1 months, 7.7 months and 13.4 months, respectively. Median progression free survival (PFS) times for those with GB cancer, ICCC and ECCC were 4.1 months, 5.4 months and 7.2 months respectively. In multivariate analysis, anatomical location of cancer was a statistically significant factor for OS and PFS (p < .001). Prognostic factors associated with OS were also different according to the anatomical location of cancer: CA 19-9 and chemotherapy response for GB cancer; disease status, albumin and chemotherapy response for ICCC; performance status and chemotherapy response for ECCC. Conclusions: Prognosis and prognostic factors of BTC were significantly different depending on its anatomical location.

Long-term outcome and recurrence factors after percutaneous cholecystostomy as a definitive treatment for acute cholecystitis.

BACKGROUND AND AIM: Percutaneous cholecystostomy (PC) has been frequently used as an alternative treatment for acute cholecystitis in seriously ill patients unfit for surgery. The aim of this study was to investigate the recurrence rate and risk factors of recurrence. METHODS: Medical records of 102 patients who were followed up for more than 1 year after PC tube removal among 716 patients who underwent PC for acute cholecystitis treatment were retrospectively analyzed. RESULTS: The recurrence rate of acute cholecystitis after PC tube removal was 20.6% (21/102), and the mean time to recur was 660 days. Underlying cancer (odds ratio [OR]: 3.369; 95% confidence interval [CI]: 1.006-11.282; P = 0.0489), PC duration shorter than 44 days (OR: 5.596; 95% CI: 1.35-23.201; P = 0.0176), and the presence of common bile duct stone in initial imaging studies (OR: 24.393; 95% CI: 2.696-220.746; P = 0.0045) were positively correlated with recurrence. Tubogram before PC tube removal did not significantly lower the recurrence. However, PC tube clamping for several days significantly lowered the recurrence (OR: 0.108; 95% CI: 0.015-0.794; P = 0.0288). Fifty-nine (57.8%) had acalculous cholecystitis. Calculous cholecystitis was negatively correlated with recurrence (OR: 0.267; 95% CI: 0.074-0.967; P = 0.0444). Receiver operating characteristic curve of the prediction model for recurrence verified its accuracy (area under the curve: 0.8475). CONCLUSION: We should try to keep PC more than 6 weeks and clamp for 1-2 weeks before removal. For those with the presence of common bile duct stones, calculous cholecystitis, and underlying malignancy, we should keep PC for longer duration and carefully observe symptoms and signs of recurrence.

Efficacy of EUS-guided and ERCP-guided biliary drainage for malignant biliary obstruction: prospective randomized controlled study.

BACKGROUND AND AIMS: ERCP-guided biliary drainage (ERCP-BD) is a criterion standard treatment for malignant biliary obstruction when curative surgery is not an option. Alternative methods such as percutaneous transhepatic biliary drainage would significantly lower the quality of life. EUS-guided biliary drainage (EUS-BD) has been developed and performed by experienced endoscopists. Therefore, the aims of this study were to evaluate the efficacy and safety of EUS-BD compared with ERCP in malignant biliary obstruction. METHODS: The prospective randomized controlled study was conducted, and 30 patients were enrolled: 15 for each EUS-BD and ERCP-BD arms. The technical success, procedural time, clinical success, and adverse events were evaluated. RESULTS: Thirty patients had extrahepatic malignant biliary tract obstruction (19 men, 11 women). Twenty-seven patients had unresectable pancreatic ductal adenocarcinomas, 1 patient had distal common bile duct cancer, and 2 patients had metastatic malignant lymphadenopathy. There were no significant differences both in terms of technical success rate and clinical success rate (100% vs 93% and 93% vs 100% in ERCP-BD vs EUS-BD, respectively; P = 1.00, P = 1.00). Four patients (31%) had tumor ingrowth-caused stent dysfunction in the ERCP-BD group, whereas 2 patients had food impaction and 2 patients had stent migration in the EUS-BD group. No significant procedure-related adverse events occurred in either group. CONCLUSIONS: This prospective randomized controlled study suggests that EUS-BD has similar safety to ERCP-BD. EUS-BD was not superior to ERCP-BD in terms of relief of malignant biliary obstruction. EUS-BD may have fewer cases of tumor ingrowth but may also have more cases of food impaction or stent migration. (Clinical trial registration number: NCT01421836.).

Preoperative EUS-guided FNA: effects on peritoneal recurrence and survival in patients with pancreatic cancer.

BACKGROUND AND AIMS: EUS-guided FNA (EUS-FNA) is an accurate and relatively safe tissue confirmation method for pancreatic cancer. However, there is concern that this procedure may spread tumor cells along the needle track or within the peritoneum. We aimed to estimate the effect of preoperative EUS-FNA on the risk of peritoneal recurrence and long-term outcomes in resected pancreatic cancer. METHODS: We retrospectively reviewed records of patients diagnosed with pancreatic cancer who had undergone curative resection between 2009 and 2013 to investigate the overall survival, cancer-free survival, and peritoneal recurrence. Peritoneal recurrence was diagnosed based on image findings or cytology-confirmed ascites. RESULTS: Of 411 patients, 90 underwent preoperative EUS-FNA (EUS-FNA group), whereas 321 did not (non-EUS-FNA group). The median length of follow-up was 16.2 months (range, 2-46). Peritoneal recurrence occurred in 131 patients: 30% (27/90) in the EUS-FNA group versus 32% (104/321) in the non-EUS-FNA group (P = .66). Cancer-free survival or overall survival was not significantly different between the 2 groups: median overall survival of 25.3 months in the EUS-FNA group versus 23.7 months in the non-EUS-FNA group (P = .36) and median cancer-free survival of 12.7 months in the EUS-FNA group versus 11.6 months in the non-EUS-FNA group (P = .38). CONCLUSIONS: Preoperative EUS-FNA for pancreatic cancer was not associated with an increased rate of peritoneal recurrence or mortality. Therefore, EUS-FNA is an accurate and safe method to obtain suspicious pancreatic mass tissue.

Aggressive intravenous hydration with lactated Ringer's solution for prevention of post-ERCP pancreatitis: a prospective randomized multicenter clinical trial.

BACKGROUND AND STUDY AIMS : The present study aimed to determine the type of intravenous hydration that is best suited to reducing the incidence of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. PATIENTS AND METHODS: In a prospective randomized multicenter trial, average-to-high risk patients who underwent first-time ERCP were randomly assigned to three groups (1:1:1) who received: aggressive intravenous hydration (3 mL/kg/h during ERCP, a 20-mL/kg bolus and 3 mL/kg/h for 8 hours after ERCP) with either lactated Ringer's solution (LRS) or normal saline solution (NSS), or standard intravenous hydration with LRS (1.5 mL/kg/h during and for 8 hours after ERCP). The primary end point was post-ERCP pancreatitis (PEP). RESULTS: 395 patients were enrolled, and 385 completed the protocols. The three groups showed no significant differences in demographic characteristics. There was a significant difference in the intention-to-treat (ITT) PEP rate between the aggressive LRS group (3.0 %, 95 % confidence interval [CI] 0.1 % - 5.9 %; 4 /132), the aggressive NSS group (6.7 %, 95 %CI 2.5 % - 10.9 %; 9 /134) and the standard LRS group (11.6 %, 95 %CI 6.1 % - 17.2 %; 15 /129; P = 0.03). In the two-group comparisons, the ITT PEP rate was significantly lower for the aggressive LRS group than for the standard LRS group (relative risk [RR] 0.26, 95 %CI 0.08 - 0.76; P = 0.008). There was no significant difference in the ITT PEP rate between the aggressive NSS group and the standard LRS group (RR 0.57, 95 %CI 0.26 - 1.27; P = 0.17). CONCLUSION: Aggressive hydration with LRS is the best approach to intravenous hydration for the prevention of PEP in average-to-high risk patients.

Predictive Model for Neoplastic Potential of Gallbladder Polyp.

GOAL: To provide the statistical predictive model for neoplastic potential of gallbladder polyp (GBP). BACKGROUND: Many studies have attempted to define the risk factors for neoplastic potential of GBP. It remains difficult to precisely adapt the reported risk factors for the decision of surgery. Estimating the probability for neoplastic potential of GBP using a combination of several risk factors before surgical resection would be useful in patient consultation. STUDY: We collected data of patients confirmed as GBP through cholecystectomy at Samsung Medical Center between January 1997 and March 2015. Those with a definite evidence for malignancy, such as adjacent organ invasion, metastasis on preoperative imaging studies, polyp >15 mm, and absence of proper preoperative ultrasonographic imaging were excluded. A total of 1976 patients were enrolled. To make and validate the predictive model, we divided the cohort into the modeling group (n=979) and validation group (n=997). Clinical information, ultrasonographic findings, and blood tests were retrospectively analyzed. RESULTS: Clinical factors of older age, single lesion, sessile shape, and polyp size showed statistical significance for neoplastic potential of GBP in the modeling group. A predictive model for neoplastic potential of GBP was constructed utilizing the statistical outcome of the modeling group. Statistical validation was performed with the validation group to determine the optimal clinical sensitivity and specificity of the predictive model. Optimal cut-off value for neoplastic probability was 7.4%. CONCLUSIONS: The predictive model for neoplastic potential of GBP may support clinical decisions before cholecystectomy.

Long term outcome of EUS-based strategy for suspected choledocholithiasis but negative CT finding.

OBJECTIVES: The American Society for Gastrointestinal Endoscopy (ASGE) guidelines offered the risk-stratified approach in suspected choledocholithiasis. Previous studies have raised concern about the insufficient accuracy of the guideline, especially in high probability group. The purposes of this study were to authenticate the stratification and clinical predictors of the guidelines for suspected choledocholithiasis with no visible choledocholithiasis on computed tomography (CT) and to make clear the clinical strategy of endoscopic ultrasonography (EUS). MATERIALS AND METHODS: We carried out the retrospective single-center study of 156 patients with suspected choledocholithiasis but negative findings on CT who underwent EUS for about 8 years at Samsung Medical Center. We assessed the clinical predictors of the ASGE guidelines in predicting the presence of choledocholithiasis and the outcome of the EUS. RESULTS: Fifty-three of the 156 patients had positive findings on EUS that included choledocholithiasis (n = 43, 27.6%) or obstructive papillitis (n = 10, 6.4%). Among the 53 patients, 51 (96.2%) had choledocholithiasis or obstructive papillitis on ERCP. The 101 patients of 103 patients with negative finding on EUS did not show biliary events during follow-up period. EUS accuracy was 98.7% (sensitivity 100%; specificity 98.1%). Among the 49 patients with high probability, 21 (42.9%) had choledocholithiasis on ERCP. In 107 patients who were classified as intermediate probability, 30 (27.3%) had choledocholithiasis. There were no complications related to EUS. CONCLUSIONS: Not only intermediate probability group but also high probability group without definite acute cholangitis may require EUS. Application of EUS for suspected choledocholithiasis is highly accurate, safe and reduces unnecessary invasive ERCP in 57.1% of patients with high probability group.

Comparison of 22-gauge standard fine needle versus core biopsy needle for endoscopic ultrasound-guided sampling of suspected pancreatic cancer: a randomized crossover trial.

BACKGROUND: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is effective for tissue diagnosis of pancreatic mass. To improve diagnostic yield and drawbacks, 22-gauge (G) core biopsy (FNB) needle has been developed. This study aims to compare 22G FNA and FNB needles for EUS-guided sampling of suspected pancreatic cancer. METHODS: This is a randomized controlled crossover trial. A total of 60 patients with suspected unresectable pancreatic cancer referred for EUS-guided sampling were randomly assigned to two groups. Both groups had 22G FNA and FNB needles performed in a randomized order. The primary endpoint was the cytological, histological and overall diagnostic accuracy of pancreatic cancer. RESULTS: FNA and FNB needles reported similar level of diagnostic accuracy (FNA needle 95% vs. FNB needle 93.3%; p = .564), and it was not statistically different. However, cytological cellularity was significantly higher in the FNB needles compared to FNA needles (odds ratio 2.75, 95% confidence interval (CI)). There were no procedure-related complications in both needles. CONCLUSIONS: The diagnostic accuracy of EUS-guided sampling for pancreatic cancer using 22G FNA is comparable to FNB needles. The cytological quality of specimen is better in the FNB needle.