Randomized Trial of Prophylactic Antibiotics for Endoscopic Retrograde Cholangiopancreatography in Patients With Biliary Obstruction.

INTRODUCTION: The incidence of postendoscopic retrograde cholangiopancreatography (ERCP) infections is reported to be up to 18% in patients with biliary obstruction. Antibiotic prophylaxis may reduce the risk of infectious complications after ERCP; however, the clinical value of prophylactic antibiotics in ERCP remains controversial. METHODS: We conducted a double-blind, placebo-controlled, randomized trial to investigate whether the use of prophylactic antibiotics would reduce infectious complications after ERCP in patients with biliary obstruction. We randomly assigned patients in a 1:1 ratio to receive either a single dose of 1 g intravenous cefoxitin or normal saline as a placebo 30 minutes before undergoing ERCP. The primary outcome was the incidence of infectious complications after ERCP. RESULTS: We enrolled 378 patients, and 189 patients were assigned to each group. The risk of infectious complications after ERCP was 2.8% (5 of 176 patients) in the antibiotic prophylaxis group and 9.8% (17 of 173 patients) in the placebo group (risk ratio, 0.29; 95% confidence interval [CI], 0.11-0.74, P = 0.0073). The incidence rates of bacteremia were 2.3% (4 of 176 patients) and 6.4% (11 of 173 patients), respectively (risk ratio, 0.36; 95% CI, 0.12-1.04; P = 0.0599). The incidence rate of cholangitis was 1.7% (3 of 176 patients) in the antibiotic prophylaxis group and 6.4% (11 of 173 patients) in the placebo group (risk ratio, 0.27; 95% CI, 0.08-0.87; P = 0.0267). DISCUSSION: Antibiotic prophylaxis before ERCP in patients with biliary obstruction resulted in a significantly lower risk of infectious complications, especially cholangitis, than placebo ( ClinicalTrials.gov trial number NCT02958059).

Transgelin-2, a novel cancer stem cell-related biomarker, is a diagnostic and therapeutic target for biliary tract cancer.

BACKGROUND: Biliary tract cancer (BTC) is a relatively rare but aggressive gastrointestinal cancer with a high mortality rate. Cancer stem cell (CSC) populations play crucial roles in tumor biology and are responsible for the low response to anti-cancer treatment and the high recurrence rate. This study investigated the role of Transgelin-2 (TAGLN2), overexpressed in CSC in BTC cells, and analyzed its expression in patient tissues and serum to identify potential new targets for BTC. METHODS: TAGLN2 expression was suppressed by small-interfering or short hairpin RNAs, and its effects on tumor biology were assessed in several BTC cell lines. Furthermore, the effects of TAGLN2 silencing on gemcitabine-resistant BTC cells, differentially expressed genes, proteins, and sensitivity to therapeutics or radiation were assessed. TAGLN2 expression was also assessed using western blotting and immunohistochemistry in samples obtained from patients with BTC to validate its clinical application. RESULTS: Suppression of TAGLN2 in BTC cell lines decreased cell proliferation, migration, invasion, and tumor size, in addition to a reduction in CSC features, including clonogenicity, radioresistance, and chemoresistance. TAGLN2 was highly expressed in BTC tissues, especially in cancer-associated fibroblasts in the stroma. Patients with a low stromal immunohistochemical index had prolonged disease-free survival compared to those with a high stromal immunohistochemical index (11.5 vs. 7.4 months, P = 0.013). TAGLN2 expression was higher in the plasma of patients with BTC than that in those with benign diseases. TAGLN2 had a higher area under the curve (0.901) than CA19-9, a validated tumor biomarker (0.799; P < 0.001). CONCLUSION: TAGLN2 plays a critical role in promoting BTC cell growth and motility and is involved in regulating BTC stemness. Silencing TAGLN2 expression enhanced cell sensitivity to radiation and chemotherapeutic drugs. The expression of TAGLN2 in patient tissue and plasma suggests its potential to serve as a secretory biomarker for BTC. Overall, targeting TAGLN2 could be an appropriate therapeutic strategy against advanced cancer following chemotherapy failure.

Magnetic compression anastomosis for the treatment of complete biliary obstruction after cholecystectomy.

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

Clinical impact of pancreatic steatosis measured by CT on the risk of post-ERCP pancreatitis: a multicenter prospective trial.

BACKGROUND AND AIMS: Pancreatic steatosis (PS) may be a risk factor for acute pancreatitis. Whether it is also a risk factor for post-ERCP pancreatitis (PEP) has not been evaluated. This study aimed to determine the impact of PS on PEP development. METHODS: This multicenter prospective trial enrolled 786 consecutive patients who underwent contrast-enhanced abdominal CT and subsequent first-time ERCP. PS was evaluated based on pancreatic attenuation on unenhanced CT images. The risk of PS for the development of PEP was evaluated using a logistic regression model. RESULTS: Of 527 patients included in the study, 157 (29.8%) had PS and 370 (70.2%) did not. At 24 hours after ERCP, there was a significant difference in the PEP identified in 22 patients (14.0%) in the PS group and 23 patients (6.2%) in the "no PS" (NPS) group (P = .017). Diabetes and hypertension were more common in the PS group than in the NPS group; no differences in dyslipidemia were found. Patients with PS had a higher risk for the development of PEP than those with NPS (odds ratio, 2.09; 95% confidence interval, 1.08-4.03). No other variables were identified as risk factors for PEP. CONCLUSIONS: PS is a significant risk factor for PEP for which preventive measures should be considered. Standardized measurement protocols to assess PS by CT are needed. (Clinical trial registration number: KCT0006068.).

Safety and efficacy of remimazolam versus propofol during EUS: a multicenter randomized controlled study.

BACKGROUND AND AIMS: Propofol, a widely used sedative in GI endoscopic procedures, is associated with cardiorespiratory suppression. Remimazolam is a novel ultrashort-acting benzodiazepine sedative with rapid onset and minimal cardiorespiratory depression. This study compared the safety and efficacy of remimazolam and propofol during EUS procedures. METHODS: A multicenter randomized controlled study was conducted between October 2022 and March 2023 in patients who underwent EUS procedures. Patients were randomly assigned to receive either remimazolam or propofol as a sedative agent. The primary endpoint was cardiorespiratory adverse events (AEs) during the procedure, including desaturation, respiratory depression, hypotension, and tachycardia. Secondary endpoints were the time to achieve sedation, recovery time, quality of sedation, pain at the injection site, and satisfaction of both endoscopists and patients. RESULTS: Four hundred patients enrolled in the study: 200 received remimazolam (10.8 ± 7.7 mg) and 200 received propofol (88.0 ± 49.1 mg). For cardiorespiratory AEs, the remimazolam group experienced fewer occurrences than the propofol group (8.5% vs 16%, P = .022). A nonsignificant trend was found toward less oxygen desaturation (1.0% vs 3.5%, P = .09), respiratory depression (.5% vs 1.5%, P = .62), hypotension (2.5% vs 5.5%, P = .12), and tachycardia (4.5% vs 5.5%, P = .68) with remimazolam than with propofol. Remimazolam showed a shorter induction time than propofol while maintaining comparable awakening and recovery times. Injection site pain was significantly lower in the remimazolam group than in the propofol group. The remimazolam group demonstrated a significantly higher quality of sedation and satisfaction scores than the propofol group, as evaluated by both endoscopists and patients. CONCLUSIONS: Remimazolam was superior to propofol in terms of safety and efficacy during EUS examinations. (Clinical trial registration number: KCT 0007643.).

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.).

A phase I/II study of ivaltinostat combined with gemcitabine and erlotinib in patients with untreated locally advanced or metastatic pancreatic adenocarcinoma.

This phase I/II study evaluated the safety and efficacy of a new histone deacetylase (HDAC) inhibitor, ivaltinostat, in combination with gemcitabine and erlotinib for advanced pancreatic ductal adenocarcinoma (PDAC). Patients diagnosed with unresectable, histologically confirmed PDAC who had not undergone previous therapy were eligible. Phase I had a 3 + 3 dose escalation design to determine the maximum tolerable dose (MTD) of ivaltinostat (intravenously on days 1, 8 and 15) with gemcitabine (1000 mg/m2 intravenously on days 1, 8 and 15) and erlotinib (100 mg/day, orally) for a 28-day cycle. In phase II, patients received a six-cycle treatment with the MTD of ivaltinostat determined in phase I. The primary endpoint was the objective response rate (ORR). Secondary endpoints included overall survival (OS), disease control rate (DCR) and progression-free survival (PFS). The MTD of ivaltinostat for the phase II trial was determined to be 250 mg/m2 . In phase II, 24 patients were enrolled. The median OS and PFS were 8.6 (95% confidence interval [CI]: 5.3-11.2) and 5.3 months (95% CI: 3.7-5.8). Of the 16 patients evaluated for response, ORR and DCR were 25.0% and 93.8% with a median OS/PFS of 10.8 (95% CI: 8.3-16.7)/5.8 (95% CI: 4.6-6.7) months. Correlative studies showed that mutation burden detected by cfDNA and specific blood markers such as TIMP1, pro-MMP10, PECAM1, proMMP-2 and IGFBP1 were associated with clinical outcomes. Although the result of a small study, a combination of ivaltinostat, gemcitabine and erlotinib appeared to be a potential treatment option for advanced PDAC.

Impact of pancreatic fat on the risk of post-endoscopic retrograde cholangiopancreatography pancreatitis.

BACKGROUND AND STUDY AIMS: Fatty pancreas is a potential risk factor for acute pancreatitis; however, whether it is also a risk factor for post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) has not been evaluated. We aimed to determine the impact of fatty pancreas on the development of PEP. METHODS: We analyzed the data of patients who underwent abdominal computed tomography (CT) scan and sequential therapeutic endoscopic retrograde cholangiopancreatography (ERCP). Fatty change in the pancreas was evaluated based on pancreatic attenuation of unenhanced image on CT scan. The risk of fatty pancreas for the development of PEP was evaluated using a logistic regression model. RESULTS: Of a total of 858 patients included in the study, 354 (41.3%) had fatty pancreas, while 504 (58.7%) did not have fatty pancreas. PEP developed in 28 patients (7.9%) in the fatty pancreas group and in 13 patients (2.6%) in the no fatty pancreas group. Fatty pancreas was significantly associated with the development of PEP (odds ratio [OR] [95% confidence interval [CI]] 2.38 [1.16-4.87]). A history of acute pancreatitis, female sex, difficult cannulation, and endoscopic papillary balloon dilation were also risk factors for the development of PEP. The risk for moderate-to-severe PEP development tended to be higher in the fatty pancreas group than in the no fatty pancreas group (OR [95% CI] 5.61 [0.63-49.62]). CONCLUSIONS: Fatty pancreas is a significant risk factor for the development of PEP. Clinicians need to be aware of the risk of fatty pancreas for the development of PEP prior to performing ERCP.

GLRX3, a novel cancer stem cell-related secretory biomarker of pancreatic ductal adenocarcinoma.

BACKGROUND: Cancer stem cells (CSCs) are implicated in carcinogenesis, cancer progression, and recurrence. Several biomarkers have been described for pancreatic ductal adenocarcinoma (PDAC) CSCs; however, their function and mechanism remain unclear. METHOD: In this study, secretome analysis was performed in pancreatic CSC-enriched spheres and control adherent cells for biomarker discovery. Glutaredoxin3 (GLRX3), a novel candidate upregulated in spheres, was evaluated for its function and clinical implication. RESULTS: PDAC CSC populations, cell lines, patient tissues, and blood samples demonstrated GLRX3 overexpression. In contrast, GLRX3 silencing decreased the in vitro proliferation, migration, clonogenicity, and sphere formation of cells. GLRX3 knockdown also reduced tumor formation and growth in vivo. GLRX3 was found to regulate Met/PI3K/AKT signaling and stemness-related molecules. ELISA results indicated GLRX3 overexpression in the serum of patients with PDAC compared to that in healthy controls. The sensitivity and specificity of GLRX3 for PDAC diagnosis were 80.0 and 100%, respectively. When GLRX3 and CA19-9 were combined, sensitivity was significantly increased to 98.3% compared to that with GLRX3 or CA19-9 alone. High GLRX3 expression was also associated with poor disease-free survival in patients receiving curative surgery. CONCLUSION: Overall, these results indicate GLRX3 as a novel diagnostic marker and therapeutic target for PDAC targeting CSCs.

Peripheral natural killer cell activity is associated with poor clinical outcomes in pancreatic ductal adenocarcinoma.

BACKGROUND AND AIM: We aimed to measure the natural killer (NK) cell activity and pro-inflammatory cytokine levels in the peripheral blood of pancreatic cancer patients and investigate the correlation of NK cell activity and cytokines with cancer status and clinical outcomes. METHODS: We prospectively enrolled patients who were pathologically diagnosed with pancreatic ductal adenocarcinoma (PDAC) between 2016 and 2017 at a tertiary hospital in Seoul, South Korea. As a control group, healthy participants were enrolled by mobile application recruitment. RESULTS: A total of 203 patients were enrolled for this study (PDAC, n = 102; healthy participants, n = 101). The peripheral blood NK cell activity of PDAC patients was significantly lower than that of healthy participants (median level, 95 pg/mL vs 2000 pg/mL, P < 0.001), and decreased NK cell activity was correlated to poor clinical outcome in terms of response to chemotherapy, tumor progression, and survival. The pro-inflammatory cytokine interleukin-6 had a strong negative correlation with NK cell activity. CONCLUSIONS: In pancreatic cancer patients, NK cell activity decreased as cancer progressed, and decreased NK cell activity was associated with poor clinical outcomes.

Optimal drainage of anastomosis stricture after living donor liver transplantation.

BACKGROUND: Endoscopic biliary stenting (EBS) with a fully covered, self-expandable metallic stent (FC-SEMS) and plastic stent (PS) is safe and efficient for biliary anastomotic strictures (ASs) after a deceased donor liver transplantation. Limited studies have investigated the use of FC-SEMSs for biliary strictures post-living donor liver transplantation (LDLT). We compared the resolution rate of biliary ASs post-LDLT and the 12-month recurrence rates post-stent removal between EBS with an FC-SEMS, PS, and percutaneous transhepatic biliary drainage (PTBD). METHODS: Patients with biliary ASs after an LDLT (mean age: 57.3 years, 76.1% men) hospitalized between 2014 and 2017 were enrolled. Endoscopic retrograde cholangiopancreatography (ERCP) was repeated every 3-4 months. Patients were followed-up for at least 1-year post-stent removal. RESULTS: Of the 75 patients enrolled, 16, 20, and 39 underwent EBS with an FC-SEMS, PS, and PTBD, respectively. Median follow-up period was 39.2 months. Fewer ERCP procedures were needed in the FC-SEMS group than in the PS group (median, 2 vs. 3; P = 0.20). Median stent indwelling periods were 4.7, 9.3, and 5.4 months in the FC-SEMS, PS, and PTBD groups, respectively (P = 0.006). The functional resolution rate was lower in the PS group (16/20) than in the FC-SEMS (16/16) or PTBD (39/39) group (P = 0.005). The radiologic resolution rate was higher in the FC-SEMS group (16/16) than in the PS group (14/20) (P = 0.07). The 12-month recurrence rates showed no significant differences (FC-SEMS, 4/16; PS, 3/16; PTBD, 6/39; P = 0.66). The rates of complications during treatment differed significantly between the groups (P = 0.04). Stent migration occurred in 1 (6.3%) and 5 (25.0%) patients in the FC-SEMS and PS groups, respectively (P = 0.59). CONCLUSIONS: EBS with an FC-SEMS is comparable with EBS with a PS or PTBD in terms of biliary stricture resolution and 12-month recurrence rates. The use of FC-SEMSs is potentially effective and safe for biliary AS resolution after LDLT.

Efficacy and safety of palliative endobiliary radiofrequency ablation using a novel temperature-controlled catheter for malignant biliary stricture: a single-center prospective randomized phase II TRIAL.

BACKGROUND: Endobiliary radiofrequency ablation (EB-RFA) has emerged as a palliative treatment for malignant biliary strictures (MBSs); however, concerns about complications related to thermal injury remain. In this study, we evaluated the efficacy and safety of EB-RFA with a novel catheter for MBS. METHODS: Patients with inoperable cancer causing MBS were randomly assigned to either the radiofrequency ablation (RFA) group or the non-RFA group. The RFA group underwent EB-RFA at the stricture site with a temperature-controlled catheter (ELRA™; STARmed Co., Goyang, Korea) followed by deployment of a self-expanding metal stent (SEMS). For the non-RFA group, only SEMS placement was performed. The duration of stent patency, overall survival (OS), and 30-day complication rate were evaluated. This trial was registered at ClinicalTrials.gov (number NCT02646514). RESULTS: A total of 48 patients were enrolled (24 in each group). During a median follow-up period of 135.0 days (RFA group) and 119.5 days (non-RFA group), the 90-day stent patency rate, median duration of stent patency, and median OS were not different between the groups (58.3% vs. 45.8% [P = 0.386], 132.0 days vs. 116.0 days [P = 0.440], and 244.0 days vs. 180.0 days [P = 0.281], respectively). In the RFA group, procedure-related complications including thermal injury-related complications, such as bile duct perforation or hemobilia, were not reported. The early complication (< 7 days) rates were not different between the groups (4.2% vs. 12.5%, P = 0.609), and there were no late complications (7-30 days) in both groups. CONCLUSION: EB-RFA with a temperature-controlled catheter followed by SEMS placement for patients with inoperable MBS can be safe and feasible with acceptable biliary patency.

Initial experience of irreversible electroporation for locally advanced pancreatic cancer in a Korean population.

BACKGROUND: Locally advanced pancreatic cancer (LAPC) is one of the most aggressive malignancies. Irreversible electroporation (IRE) is a novel technique that uses a non-thermal ablation to avoid vessel or duct injury. PURPOSE: To investigate the safety and efficacy of IRE for the management of LAPC in a Korean population. MATERIAL AND METHODS: Twelve patients (median age 64 years; age range 46-73 years) treated between December 2015 and March 2017 underwent intraoperative IRE for LAPC. Technical success and clinical outcomes, including complications, serum pancreatic enzyme levels, overall survival (OS), and progression-free survival (PFS), were evaluated. RESULTS: Tumors were located in the pancreas head in 7 (58.3%) patients and in the body/tail in 5 (41.7%) patients. The median tumor diameter in the longest axis was 3.1 cm. Vascular invasion was observed in all patients and bowel abutment in 3 (25%) patients. Technical success was achieved in all patients. The median serum levels of amylase and lipase were 55 U/L and 31 U/L, respectively, at baseline, increased to 141.5 U/L (P = 0.008) and 53 U/L (P = 0.505), respectively, one day after IRE, and normalized after one week. The rate of 30-day mortality of unknown relation was 8.3% (one individual experienced massive hematemesis 12 days after IRE). The median OS from diagnosis and IRE was 24.5 months and 13.5 months, respectively. The median PFS from diagnosis and IRE was 19.2 months and 8.6 months, respectively. CONCLUSION: For patients with LAPC, IRE appears to be a promising treatment modality with an acceptable safety profile.

Radiographic portal or superior mesenteric vein invasion is an independent prognostic factor in non-metastatic pancreatic ductal adenocarcinoma: A missing block of clinical T staging?

BACKGROUND: Venous invasion is not included in the pancreatic ductal adenocarcinoma (PDAC) staging, and its correlation with prognosis remains unclear. We evaluated the prognostic impact of radiographic portal/superior mesenteric vein (PV/SMV) invasion, and its possibility of complementing T staging. METHODS: We identified patients with non-metastatic PDAC using our institutional cohort, and divided them according to PV/SMV invasion at imaging, defined as >180-degree tumor-vessel interface or contour deformity. We conducted Cox proportional hazard regression, and compared survival in the original and 1:1 propensity score matched datasets. RESULTS: We identified 454 patients [PV/SMV(+): 172; PV/SMV(-): 282]. In the multivariate analysis, PV/SMV invasion, age (≥70 years), performance status, tumor size (2-4, >4 cm), lymph nodes >4, and arterial invasion was correlated with prognosis. The PV/SMV(+) group had a shorter overall survival (OS) than the PV/SMV(-) group in the original (14.4 vs. 20.9 months; P < 0.001) and matched datasets (14.3 vs. 17.2 months; P = 0.009). Among patients without arterial invasion (cT1-cT3), the PV/SMV(+) group had a shorter OS (15.9 vs. 21.2 months; P = 0.002). Moreover, their OS did not differ from that of patients with arterial invasion (cT4) (15.9 vs. 14.4 months; P = 0.907). Patients with vessel (artery/vein) invasion had a shorter OS than those without vessel invasion (14.5 vs. 21.2 months; P < 0.001). CONCLUSIONS: Radiographic PV/SMV invasion in non-metastatic PDAC was correlated with a poor prognosis. It could identify a group with shorter OS among patients without arterial invasion (cT1-cT3). It is suggested that inclusion of PV/SMV invasion in clinical T4 criteria should be considered.

Preoperative prediction of futile surgery in patients with radiologically resectable or borderline resectable pancreatic adenocarcinoma.

BACKGROUND AND AIM: The aim of this study is to identify the predictive factors for futile surgery in patients with radiologically resectable or borderline resectable pancreatic cancer and to develop a prediction model. METHODS: This retrospective study included patients who underwent pancreatic surgery for pancreatic cancer between 2006 and 2017. To identify independent risk factors for futile surgery, logistic regression and random forest analyses were performed in the training cohort, based on which a nomogram was established. The predictive accuracy and discriminative ability of the nomogram were validated in the validation cohort. RESULTS: Of 389 patients who underwent pancreatic surgery, the laparotomy was futile in 40 patients (10.3%). In the training cohort, the univariate and multivariate logistic regression analyses revealed that serum carbohydrate antigen 19-9 level of ≥ 150 U/mL (P = 0.003), the presence of suspicious lymph node (P = 0.013), and more extensive peripancreatic tumor infiltration (P < 0.001) were independent predictive factors for futile surgery. The bootstrap-corrected concordance index of the nomogram was high in the training cohort, 0.826 with a 95% confidence interval of 0.745-0.907. This model also showed a good discriminative performance in the validation cohort, with a concordance index of 0.831. CONCLUSIONS: We established and validated a novel nomogram that predicts the risk of futile surgery due to occult distant metastasis in patients with radiologically resectable or borderline resectable pancreatic cancer.

Skeletal Muscle Mass Predicts Poor Prognosis in Patients with Advanced Pancreatic Cancer Undergoing Second-Line FOLFIRINOX Chemotherapy.

Objectives: Although the significance of skeletal muscle mass has been investigated in pancreatic cancer, there are no reports regarding the impact of skeletal muscle mass on prognosis in patients who have undergone second-line chemotherapy. We aimed to identify prognostic factors in patients with advanced pancreatic cancer treated with second-line FOLFIRINOX (folinic acid, fluorouracil, irinotecan, and oxaliplatin). Methods: We retrospectively reviewed the data of 57 pancreatic cancer patients treated with second-line FOLFIRINOX. Age, sex, body mass index, Eastern Cooperative Oncology Group (ECOG) performance status, carbohydrate antigen 19-9 levels, skeletal muscle area, skeletal muscle index (SMI), progression free survival (PFS), and overall survival (OS) were analyzed. Results: The median age of the 57 patients (male, 56.1%) was 60.4 years (38-78). Median PFS and OS were 2.6 and 6.6 months. On Kaplan-Meier curves, high SMI was associated with prolonged OS and PFS (P value = 0.003 and 0.015). In multivariate analysis, baseline SMI was significant independent prognostic factor in patients treated with second-line FOLFIRINOX. Conclusion: Baseline SMI has an impact on prognosis in patients who undergoing second-line chemotherapy for pancreatic cancer. Skeletal muscle mass may warrant consideration as a predictive factor with which to identify candidates for second-line chemotherapy for advanced pancreatic cancer.

Same-session endoscopic ultrasound-guided fine needle aspiration and endoscopic retrograde cholangiopancreatography-based tissue sampling in suspected malignant biliary obstruction: A multicenter experience.

BACKGROUND AND AIM: Few studies compared endoscopic ultrasound (EUS)-guided fine needle aspiration (EUS-FNA) with endoscopic retrograde cholangiopancreatography (ERCP)-based tissue sampling in terms of diagnostic accuracy in suspected malignant biliary obstruction. We evaluated and compared the diagnostic performance of EUS-FNA and ERCP-based tissue sampling. METHODS: This multicenter study included 263 patients with suspected malignant biliary obstruction who underwent same-session EUS and ERCP between 2012 and 2016. RESULTS: Malignancies were confirmed in 239 patients (90.9%) and benign in 24 patients (9.1%). Overall diagnostic sensitivity and accuracy were 73.6% and 76.1% for EUS-FNA, 56.5% and 60.5% for ERCP, and 85.8% and 87.1% for EUS/ERCP combination. EUS-FNA showed higher overall performances compared with ERCP (P < 0.001), whereas EUS/ERCP combination was superior to EUS-FNA alone (P-value < 0.001). EUS-FNA showed higher sensitivity and accuracy compared with ERCP for pancreatic masses (n = 187, both P-values < 0.001) but not for biliary lesions (n = 76, both P-values = 0.847). Sensitivity and accuracy of EUS/ERCP combination were superior to those of EUS-FNA for both pancreatic and biliary lesions (both P-values < 0.001). For patients with large mass (≥ 4 cm), there was no significant differences between ERCP/EUS combination and EUS-FNA (P-value = 0.31). CONCLUSIONS: Same-session EUS-FNA and ERCP combination was superior to EUS-FNA for both pancreatic masses and biliary lesions. Same-session EUS/ERCP combination can be considered a proper diagnostic method for suspected malignant biliary obstruction regardless of the origin of lesions. On the other hand, EUS-FNA alone was sufficient for diagnosis compared with EUS/ERCP combination in cases with large mass. Strategic diagnostic approach, according to clinical features of individual patient, is required.

KML001, an arsenic compound, as salvage chemotherapy in refractory biliary tract cancers: A prospective study.

BACKGROUND: Sodium meta-arsenite (NaAsO2, KML001) is a potential oral anticancer agent acting on telomerase and telomere length. This prospective study evaluated its safety, tolerability, and effectiveness as salvage chemotherapy in patients with advanced biliary tract cancer (BTC) resistant to gemcitabine-based chemotherapy. METHODS: Forty-four patients (21 women and 23 men) with advanced BTC and failure history of gemcitabine-based chemotherapy, performance status (PS) 0-2, normal cardiac, hepatic, and renal function were enrolled. Daily dose of KML001 (7.5 mg. p.o.) was administered to eligible subjects for 24 weeks divided into six treatment cycles. Response was evaluated bimonthly using CT. RESULTS: After an average of 1.5 months of treatment (range: 0.5-10.0), 3 patients (6.8%) obtained progression-free status, 23 patients (52.3%) had disease progression, and 18 patients (40.9%) dropped out before evaluation. One patient (2.3%) completed six treatment cycles without progression. During the treatment, morphine dosage kept the same or decreased in 20 patients (47.6%). Nine patients (20.5%) experienced grade-3 adverse events (AEs), while no patient experienced grade-4 AEs. The most common AEs were liver enzyme elevation (11/44, 25%) and anemia (10/44, 22.7%). KML001 was discontinued in six patients (13.6%) due to AEs, including liver toxicity (n = 3), QTc prolongation (n = 2), and abdominal pain (n = 1). CONCLUSIONS: KML001 did not have enough anticancer effect on patients with advanced BTC resistant to gemcitabine. However, KML001 was safe and well-tolerable in terms of AEs and pain control when used as salvage therapy. Further studies are needed to establish arsenic agents as a reliable treatment option in patients with BTC.

Long-term patterns of fasting blood glucose levels and pancreatic cancer incidence.

BACKGROUND: Whether type 2 diabetes is cause or consequence, or both, of pancreatic cancer (PaC) remains unresolved. Leveraging repeated measurements of fasting blood glucose (FBG), we examined the temporal relationship between hyperglycemia and PaC incidence. METHODS: We conducted a nested case-control study of 278 cases and 826 matched-controls from the Korean National Health Insurance Service-Health Screening Cohort. Over 11 years before index date (date of PaC diagnosis for cases), all participants had at least one FBG measurement in each of the three time windows: - 11 to - 8, - 7 to - 4, and - 3 to 0 years. Using conditional logistic regression, we estimated odds ratios(ORs) of PaC and 95% confidence intervals (CIs) for hyperglycemia in the overall period and at each interval; for major long-term patterns of FBG across the three intervals (recent-onset, medium-term, and long-standing hyperglycemia). RESULTS: Higher FBG over the past 11 years was associated with an increased odds of PaC (p trend < .0001), with recent FBG more predictive of PaC than distant FBG. By FBG assessed in the - 3 to 0 interval, OR was 1.97 (95% CI 1.32-2.93) for 110-125 mg/dL and 3.17 (95% CI 2.09-4.80) for ≥ 126 mg/dL. By long-term patterns of FBG, compared to consistent normoglycemia, OR was 2.02 (95% CI 1.24-3.31) for long-standing hyperglycemia and 3.38 (95% CI 1.87-6.13) for recent-onset hyperglycemia. These associations were more pronounced among never-smokers than ever-smokers (p interaction = .06). CONCLUSION: Recent-onset hyperglycemia may be an early manifestation of undetected PaC, while long-lasting hyperglycemia may serve as a moderate etiologic factor for PaC.