tbuckley/cabot-search huggingface dataset:
Renal Handling of Ketones in Response to Sodium–Glucose Cotransporter 2 Inhibition in Patients With Type 2 Diabetes
Authors: Ele Ferrannini, Simona Baldi, Silvia Frascerra, Brenno Astiarraga, Elisabetta Barsotti, Aldo Clerico, Elza Muscelli
Journal: Diabetes Care (2017)

OBJECTIVE Pharmacologically induced glycosuria elicits adaptive responses in glucose homeostasis and hormone release, including decrements in plasma glucose and insulin levels, increments in glucagon release, enhanced lipolysis, and stimulation of ketogenesis, resulting in an increase in ketonemia. We aimed at assessing the renal response to these changes. RESEARCH DESIGN AND METHODS We measured fasting and postmeal urinary excretion of glucose, β-hydroxybutyrate (β-HB), lactate, and sodium in 66 previously reported patients with type 2 diabetes and preserved renal function (estimated glomerular filtration rate ≥60 mL · min−1 · 1.73 m−2) and in control subjects without diabetes at baseline and following empagliflozin treatment. RESULTS With chronic (4 weeks) sodium–glucose cotransporter 2 inhibition, baseline fractional glucose excretion (&amp;lt;2%) rose to 38 ± 12% and 46 ± 11% (fasting vs. postmeal, respectively; P &amp;lt; 0.0001) over a range of BMIs (range 23–41 kg/m2) and creatinine clearance (65–168 mL · min−1 · m−2). Excretion of β-HB (median [interquartile range]: 0.08 [0.10] to 0.31 [0.43] µmol · min−1), lactate (0.06 [0.06] to 0.28 [0.25] µmol · min−1), and sodium (0.27 [0.22] to 0.36 [0.16] mEq · min−1) all increased (P ≤ 0.001 for all) and were each positively related to glycosuria (P ≤ 0.001). These parameters changed in the same direction in subjects without diabetes, but changes were smaller than in the patients with diabetes. Although plasma N-terminal pro–B-type natriuretic peptide levels were unaltered, plasma erythropoietin concentrations increased by 31 (64)% (P = 0.0078). CONCLUSIONS We conclude that the sodium–glucose cotransporter 2 inhibitor–induced increase in β-HB is not because of reduced renal clearance but because of overproduction. The increased lactate excretion contributes to lower plasma lactate levels, whereas the increased natriuresis may help in normalizing the exchangeable sodium pool. Taken together, glucose loss through joint inhibition of glucose and sodium reabsorption in the proximal tubule induces multiple changes in renal metabolism.
Initial therapy with transarterial chemoembolization (TACE) versus Yttrium90 radioembolization (Y90) for hepatocellular carcinoma (HCC).
Authors: Hanna Kelly Sanoff, YunKyung Chang, Jennifer Leigh Lund, Til Sturmer
Journal: Journal of Clinical Oncology (2014)

e15131 Background: TACE is standard initial therapy for patients (pts) with intermediate stage HCC. Nonrandomized comparisons from specialty centers suggest Y90 may be as effective as TACE but adequately powered studies in similar risk pts have not been conducted. We sought to examine the comparative effectiveness of TACE vs Y90 in routine care settings. Methods: Pts diagnosed with HCC from 2004-2009 treated initially with TACE or Y90 were identified from SEER-Medicare, including pts eligible on the basis of disability. Key covariates included age, diagnoses for complications and cause of cirrhosis, stage. Treatment was determined from procedure codes. Multilevel Poisson models clustered by hospital compared frequency of emergency room (ER) visits and hospital admissions ≤90 days from treatment. Survival (OS) in the entire cohort was compared using multivariable Cox proportional hazards. We used PS weighting to compare the relative risk (RR) of mortality of Y90 to TACE among pts with similar risk as those selected for initial TACE. Results: In total, 1,651 pts with HCC received initial TACE (1,528; 93%) or Y90 (123; 7%). Y90 use rose over the study period from 3% in 2004 to 9% in 2009. Y90 was more likely in older pts with more advanced cancer but fewer cirrhotic complications and less comorbidity. 63% of Y90 and 66% of TACE pts had 2nd line therapy, including curative surgery in 1-2% of Y90 vs 6% of TACE pts. Rates of ER visits and admissions did not differ by treatment. Crude median OS from treatment was longer in TACE than Y90 (14 vs 9 m), but no difference was seen in the adjusted hazard ratio 1.18, 95% CI .91-1.5. As TACE was used in younger, earlier stage pts we compared RR of mortality among a population of pts with the same risk characteristics of the TACE population. In this group of lower stage younger pts, 2 year mortality was higher in Y90 than TACE patients, RR 1.19, 95% CI 1.05-1.35, p=0.006. Conclusions: Y90 is used rarely as initial therapy for HCC, typically in older patients with more advanced cancer stage. Despite a trend towards increasing use over the study period, in this cohort there is no evidence that earlier, more widespread use of Y90 will improve outcomes for intermediate stage HCC.
Crosstalk between PARP-1 and NF-κB signaling pathways as a potential determinant of PARPi sensitivity in trastuzumab resistant HER2+ breast cancer cell lines.
Authors: Monicka Wielgos, Tiffiny Cooper, Andres Forero-Torres, Francisco J. Esteva, Rachel Schiff, C. Kent Osborne, Albert F. LoBuglio, Eddy Shih-Hsin Yang
Journal: Journal of Clinical Oncology (2015)

606 Background: We have previously found that HER2+ breast cancer cells, despite being DNA repair proficient, are sensitive to poly (ADP-Ribose) polymerase inhibitors (PARPi). In this study, we investigated whether PARPi susceptibility would be retained in HER2+ breast cancer cells that are resistant to the HER2 targeted agent trastuzumab. Methods: Human HER2+ breast cancer cell lines BT-474, UACC812, SKBR3 and their trastuzumab resistant counterparts were used in this study. Cells were treated with vehicle or 10µM ABT-888 or transfected with scrambled or PARP-1 siRNA. We assessed cell survival by colony formation assays. Western blot analysis was used to measure protein expression. Cell cycle distribution was evaluated by propidium iodide and measured by flow cytometry. NF-κB transcriptional activity was determined via a NF-κB-driven luciferase reporter assay. The nCounter Gene Expression Assay along with qRT-PCR were used to measure the expression levels of NF-κB target genes. Tumor growth delay was assessed in mice bearing tumor xenografts. Results: Similar to parental cells, trastuzumab resistant HER2+ breast cancer cells retained PARPi sensitivity both in-vitro and in-vivo. The cytotoxicity in these cells was associated with greater than 40% attenuation of NF-κB transcriptional activity. Results were validated with PARP-1 siRNA. Further, re-expression of PARP-1 rescued NF-κB activity in PARP-1 knockdown cells. The expression of several NF-κB target genes, including IL-8, BRCA2, and VEGFC, was reduced with PARP inhibition or knockdown. The effects of PARP inhibition via ABT-888 or PARP-1 siRNA were independent of cell cycle redistribution. Conclusions: Inhibition of NF-κB signaling via pharmacological or genetic modulation of PARP-1 induces a cytotoxic response in trastuzumab resistant HER2+ tumors. This warrants the testing of PARP inhibitors as a novel therapeutic strategy for patients with HER2+ breast cancer.
START: A phase III study of L-BLP25 cancer immunotherapy for unresectable stage III non-small cell lung cancer.
Authors: Charles Andrew Butts, Mark A. Socinski, Paul Mitchell, Nick Thatcher, Libor Havel, Maciej Jerzy Krzakowski, Sergiusz Nawrocki, Tudor-Eliade Ciuleanu, Lionel Bosquée, Jose Manuel Trigo Perez, Alexander I. Spira, Lise Tremblay, Jan Nyman, Rodryg Ramlau, Christoph Helwig, Martin H. Falk, Frances A. Shepherd
Journal: Journal of Clinical Oncology (2013)

7500 Background: L-BLP25 is a MUC1 antigen specific cancer immunotherapy. We report results from the phase III START study of L-BLP25 in patients (pts) not progressing after primary chemoradiotherapy (CRT) for stage III NSCLC. Methods: From Jan 2007 to Nov 2011, 1513 pts with unresectable stage III NSCLC that did not progress after CRT (platinum based chemo and ≥50 Gy) were randomized (2:1; double-blind) to L-BLP25 (806 µg lipopeptide) or placebo (PBO) SC weekly x 8 then Q6 weeks until disease progression or withdrawal. Cyclophosphamide 300 mg/m 2 x 1 or saline was given 3 days prior to first L-BLP25/PBO dose. Primary endpoint was overall survival (OS). Results: The primary analysis population (n=1239) was defined prospectively to try to account for a clinical hold by excluding pts randomized 6 months (m) before the hold. Arms were balanced for baseline characteristics. Median age was 61 y; 38.2% had stage IIIA and 61.3% IIIB; 65% had concurrent and 35% sequential CRT. Median OS was 25.6 m with L-BLP25 vs. 22.3 m with PBO (adjusted HR 0.88, 95% CI 0.75-1.03, p=0.123). Secondary endpoints time-to-progression and time-to-symptom-progression support consistency of results: HR 0.87 (95% CI 0.75-1.00, p=0.053) and 0.85 (95% CI 0.73-0.98, p=0.023). In predefined subgroup analyses, pts with concurrent CRT (n=806) had median OS of 30.8 m (L-BLP25) vs. 20.6 m (PBO; HR 0.78, 95% CI 0.64-0.95, p=0.016), while median OS with sequential CRT was 19.4 m (L-BLP25) vs. 24.6 m (PBO; HR 1.12, 95% CI 0.87-1.44, p=0.38; interaction p=0.032, Cox PH model). Sensitivity analyses revealed that there was no OS benefit in pts randomized 6 m before the hold (HR 1.09, CI 0.75-1.56, p=0.663). LEBLP25 was well tolerated with no safety concerns identified and no emergent evidence of immune related adverse events. Conclusions: L-BLP25 maintenance therapy in stage III NSCLC was well tolerated, but did not significantly prolong OS. Sensitivity analyses showed a smaller treatment effect due to the clinical hold, suggesting that longer uninterrupted treatment with L-BLP25 is required. Clinically meaningful prolongation of OS was observed in the predefined subgroup of pts with primary concurrent CRT. Clinical trial information: NCT00409188.
The impact of sarcopenia on toxicity and pharmacokinetics of 5-fluorouracil (5FU) in colorectal cancer.
Authors: Grant Richard Williams, Allison Mary Deal, Shlomit S. Shachar, Christine Marie Walko, Jai Narendra Patel, Bert H. O'Neil, Howard L. McLeod, Marc Weinberg, Seul Ki Choi, Hyman B. Muss, Hanna Kelly Sanoff
Journal: Journal of Clinical Oncology (2017)

633 Background: Great heterogeneity exists in the ability of adults with cancer to tolerate treatment. Variability in body composition may affect rates of metabolism of cytotoxic agents and contribute to the variable chemotherapy toxicity observed. The goal of this study was to explore the impact of body composition, in particular sarcopenia, on the pharmacokinetics of 5-fluorouracil (5FU) in a cohort of patients receiving FOLFOX +/- bevacizumab for colorectal cancer. Methods: We performed a secondary analysis of a completed multicenter trial that investigated pharmacokinetic-guided 5FU in patients receiving mFOLFOX6 +/- bevacizumab [Patel et al. The Oncologist 2014]. Computed Tomography (CT) images that were performed as part of routine care were used to for body composition analysis. Skeletal muscle area (SMA) and density (SMD) were analyzed from CT scan L3 lumbar segments using radiological software. SMA and height (m 2 ) were used to calculate skeletal muscle index (SMI = SMA/m 2 ). Skeletal Muscle Gauge (SMG) was created by multiplying SMI x SMD. Differences were compared using two group t-tests and fisher’s exact tests. Results: Of the 70 patients from the original study, 25 had available CT imaging. The mean age was 59, 52% female, 80% Caucasian, and 92% with either stage III or IV disease. Eleven patients (44%) had grade 3/4 toxicity, and 12 patients were identified as sarcopenic (48%) [per Martin et al. JCO 2013]. Sarcopenic patients had numerically higher first cycle 5FU AUCs compared to non-sarcopenic patients (19.3 vs. 17.3 AUC, p= 0.43) and higher grade 3/4 toxicities (50 vs 38.5%, p= 0.70). Patients with low SMG ( &lt; 1475 AU) had higher grade 3/4 toxicities (62 vs 25%, p= 0.11) and higher hematologic toxicities (46 v 8%, p= 0.07). Conclusions: CRC patients with sarcopenia had numerically higher first cycle AUCs of 5FU and a higher incidence of severe toxicities; however, this was not statistically significant, possibly due to limited sample size. SMG, an integrated muscle measure, was more highly correlated with toxicity outcomes than either SMI or SMD alone. Further research exploring the role of body composition in pharmacokinetics is needed with a focus on alternative dosing strategies in sarcopenic patients.
A phase (Ph) 1/2 trial of rituximab (RX), imprime PGG (IP), and alemtuzumab (AL) in the early treatment of patients (Pts) with high risk chronic lymphocytic leukemia (CLL).
Authors: Nandita Bose, Clive Zent, George J. Weiner, Betsy LaPlant, Nadine Ottoson, Steven Leonardo, Adria Jonas, Richard Dale Huhn, Ada H. Braun, Stephen Maxted Ansell
Journal: Journal of Clinical Oncology (2015)

7078 Background: IP, a beta 1,3/1,6 glucan, can prime innate immune cells via complement receptors to kill antibody (Ab)-targeted, complement-opsonized tumor cells. Endogenous anti-beta glucan Abs (ABA) are required for IP binding and activation of innate immune cells. In stage IV NSCLC, serum ABA levels correlate with response to IP-containing therapy. Results from the Ph 1 portion of this study showed that IP in combination with RX and AL was well tolerated and associated with 73% complete response (CR) rate (Blood 120: abstr 1792, 2013). Here, we report clinical and translational results at the end of Ph 2. Methods: Primary endpoint of Ph 2 was % pts with CR 3 mos after completing 5 wks of IP + RX + AL. Eligible pts (n = 14) had CLL (per standard IWCLL criteria), high risk molecular features, no prior treatment, no standard indication for treatment initiation, adequate performance status and organ function. Planned enrollment was up to 39 pts. The study was terminated early due to slow accrual. Translational studies evaluated baseline serum ABA levels and in vitro IP binding to healthy donor whole blood immune cell subsets. Results: Among 14 pts enrolled, 6 (43%), 5 (36%) and 3 (21%) had Rai Stage 0, 1 and 2, respectively. CLL risk factors were 17p13- (21%), 11q22- (36%), and unmutated IGHV or VH3-21 use with ZAP70 and/or CD38 (43%). Grade 3/4 AEs were diarrhea, transaminase increase, dehydration, gastritis, hypertension, hyponatremia, neutropenia and febrile neutropenia. 13 (93%) pts responded to therapy (7 CR, 2 CR w/incomplete marrow recovery, 1 nodular PR and 3 PR by IWCLL-NCI 2008 criteria). As of 9/23/14 cutoff, median (med) f/u was 18.0 mo (range 9.5 - 28.0). Overall med duration of response was not reached: only 5/13 responders had progressed (med 5.6 mo; range 2.9 - 8.5); 8 are progression-free after med 10.2 mo (range 5.8 - 21.0). There were no deaths. ABA correlated with IP binding to neutrophils, monocytes and B-cells but not clinical response. Macrophage Ab-dependent cellular phagocytosis was enhanced in vitroand may contribute to anti-tumor mechanisms. Conclusions: IP in combination with RX and AL was safe and well tolerated, with high response rates. Clinical trial information: NCT01269385.
Online survey of young adult cancer survivors and illness-related stressors.
Authors: Ava Golchin, George Anthony Dawson
Journal: Journal of Clinical Oncology (2017)

33 Background: Post-traumatic stress disorder (PTSD) in cancer patients and those with life threatening illnesses has been officially recognized in the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition: DSM-4, since 1994. However, the updated 2013 DSM-V has redefined the idea of trauma and stress-related disorders resulting from life threatening illness as an amalgam of anxiety and adjustment disorders which must meet heightened criteria to be diagnosed as cancer-related PTSD (ca-PTSD) (1). Methods: In this pilot survey of Millennials and Generation X cancer survivors, ages 18-35 and 35-50 respectively, we queried based on DSM-V guidelines for basic demographics, illness-related stressors, as well as knowledge of ca-PTSD. We sent an electronic survey to 20 members of a social support group in May 2016. Results: Of the 13 survey respondents, 9 were female and 4 were male. Half of the respondents were from the Generation X and Millennial groups. None were military veterans. 6 were single, 4 were married, and 3 were in stable long term relations. 11 of 13 had a college degree or greater, and all but one had their cancer diagnosed after 2010. Respondents rated illness stressors as: 92% Possible illness progression; 77% Romance and/or reproductive; 77% Job-related; 77% Family dynamics and insecurities; 69% Social interaction insecurities; 69% Physician or Care-provider interactions and insecurities. All were aware of PTSD in general but only 4 reported discussion with a care provider. None recalled being screened for PTSD. Eight were unsure if more emphasis should be placed on ca-PTSD. Conclusions: This cohort further validates the new DSM-V inclusion of illness-adjustment and resultant anxiety to diagnose cancer related stress disorders, narrowing the scope of ca-PTSD diagnosis.With this survey we underline the importance of identifying illness-related stressors utilizing psychological distress monitoring, educating patients on symptoms and prevalence of cancer related stress disorders, and communication with the patient concerning cancer-related stress disorders and ca-PTSD diagnosis.
Association of increase in <i>BRCA2</i> gene mutations in microsatellite instable (MSI-H) colorectal ancer (CRC) with increased c-MET expression.
Authors: Elena Shagisultanova, Namrata Vijayvergia, Raji Shameem, Aarti Khushal Bhatia, Joanne Xiu, Zoran Gatalica, Wafik S. El-Deiry
Journal: Journal of Clinical Oncology (2015)

e14684 Background: BRCA1 or BRCA2 mutations can promote CRC. Repetitive DNA sequences in BRCA1/2 may be impacted by DNA repair defects characteristic of MSI-H tumors that comprise ~15% of CRC. We investigated therapeutically relevant biomarkers in MSI-H vs non-MSI-H CRC including BRCA1/2 as mutation may alter treatment options. Methods: 26 MSI-H & 558 non-MSI-H CRCs were profiled at Caris Life Sciences (Phoenix, AZ). Immunohistochemistry (IHC) & genomic analyses were performed in BRCA-mutant (MT) & BRCA-wild type (WT) MSI-H tumors. Fisher’s exact test was used to compare categorical variables. Results: MSI-H CRCs had significantly higher mutations in BRCA1 (19% vs. 5%, p = 0.02) & BRCA2 (50% vs. 14%, p < 0.0001) compared to non-MSI-H CRCs. PolyPhen-2 software (http://tinyurl.com/lvnrq46) predicted BRCA1 mutations likely neutral while 8 of 14 BRCA2 alterations (57%) were frame-shifts in simple repeats truncating the protein. TP53 mutations were significantly lower (23% vs. 63%, p < 0.0001) while CTNNB1 (b-catenin) mutations were higher in MSI-H vs. non-MSI-H CRCs (12% vs. 1%, p = 0.03). APC trended towards higher mutation rate in non-MSI-H vs. MSI-H CRCs (61% vs. 40%, p = 0.058). MSI-H CRCs had mutations in KRAS, BRAF, PIK3CA, PTEN & NRAS at 38%, 27%, 20%, 12% & 0%, respectively, and these were not different between BRCA-MT & -WT MSI-H CRCs. c-MET expression was significantly higher in the MT vs WT BRCA group [9/14 (64%) in MT vs 2/12 (16%) in WT, p = 0.02], while other proteins including TOP2a (92%), EGFR (79%), RRM-1 (81%), TS (81%), PTEN (73%), PD-1 (69%), PD-L1 (3.8%), TOPO1 (42%), MGMT (65%), & TLE-3 (35%) were similar. 7/8 (87.5%) MSI-H tumors with BRCA2 frame-shift mutation had high c-MET expression. Conclusions: BRCA2 mutations are highly enriched (50%) in MSI-H CRC & most with predicted loss of BRCA2 function have high expression of c-MET. PARP inhibitors, cisplatin & c-MET inhibitors should be investigated as potential therapy options for BRCA-mutant MSI-H CRC subsets.
Untreated metastatic diffuse gastric adenocarcinoma (DGAC): Randomized phase III study of S-1 and cisplatin vs. 5-FU and cisplatin (the DIGEST trial).
Authors: Jaffer A. Ajani, Mikhail Abramov, Volodymyr Bondar, Igor Bondarenko, Yaroslav V. Shparyk, Vera Gorbunova, Hontsa Anatoliy, Yuriy Vinnyk, Maria Alsina, Sergey Lazarev, Jaime Feliu, Anneli Elme, Vivian Esko, Gerardo Rosati, Kathia Cristina Abdalla, Udit N. Verma, Fabio M. Benedetti, Takekazu Aoyama, Hirokazu Mizuguchi, Lukas Makris
Journal: Journal of Clinical Oncology (2015)

4015 Background: The prognosis for metastatic DGAC is poor but the first line therapy for patients (pts) with DGAC is the same as that of without DGAC. Analyses of the FLAGS study suggested that S-1/Cisplatin might be better than 5-FU/cisplatin in DGAC. Therefore, a prospective international study was executed. Methods: Pts with metastatic DGAC (histology confirmed by central pathology review) with PS 0-1, adequate organ function, measurable/evaluable disease were consented and randomized to S-1 (25 mg/m2 po BID on days 1-21 q 4 weeks)/cisplatin (75 mg/m2 q 4 wks; CS) or 5-FU (800 mg/m2 continuous infusion for 5 days q 3 wks)/cisplatin (80 mg/m2 q 3 wks; CF). Randomization was 2:1 in favor of CS, stratified by histologic subtype, extent of metastasis, ECOG PS and geographical region. The primary endpoint was overall survival (OS). The study was stopped early after 361 pts were randomized versus a target 500 pts, and 264 events (deaths) were observed versus an analysis target of 427 events. Results: 690 pts were screened and 361 were randomized (239 to CS and 122 to CF). Both arms were well balanced with respective pts characteristics. For ITT pts, the median OS was 7.5 months (95%CI; 6.7-9.3) for CS and 6.6 months (5.7-8.1) for CF (HR 0.99, 95%CI; 0.76-1.28, p= 0.9312). There was no statistical difference in progression-free survival. Overall response rate was 34.7% for CS compared to 19.8% for CF (p= 0.012). The median number of cycles was 4 in both arms. The dose intensity was > 90% in both arms. The rate at least one Gr. ≥ 3 AE related to study medication was 45.2% in CS and 55.9% in CF. The most frequent ( ≥ 5%) Gr. ≥ 3 AEs for CS were neutropenia (27.3%), anemia (16.1%), fatigue (10.4%), hyponatremia (7.7%), abdominal pain (5.7%), and asthenia (5.7%) and for CF were neutropenia (28.3%), anemia (8%), asthenia (10.2%), hyponatremia (10%), hypophosphatemia (7.9%), hypokalemia (7%), anorexia (5.9%), and hyperkalemia (5%). One drug related death occurred in both CS (0.4%) and CF (0.8%). Conclusions: In the DIGEST trial, CS did not prolong OS of pts with metastatic DGAC compared to CF. However, efficacy and safety were similar for CS and CF. (Supported by Taiho Oncology Inc, NJ, USA). Clinical trial information: NCT01285557.
Risk factors associated with recurrent cholangitis in pancreatic and hepatobiliary cancers.
Authors: Apurva Jain, Juhee Song, Milind M. Javle, Marina C. George
Journal: Journal of Clinical Oncology (2017)

428 Background: Acute cholangitis due to malignant biliary obstruction is frequent in patients with pancreatic and hepatobiliary cancers. Recurrent cholangitis (RC) results in repeated hospitalization and delayed cancer care. The risk factors associated with RC are not yet defined. Methods: A pilot review was done on 146 patients admitted with a diagnosis of cholangitis from 2005 to 2014. We included demographics, cancer stage, details of first admission (FA) and interventions. Univariate and multivariate Fine-Gray models were used for statistical analysis. Results: The mean age at FA was 62 yrs, 84 (58%) were males and 99 (68%) were white. Most common cancer was pancreatic 100(69%) and 27(19%) pts had primary cholangitis at FA. During FA, interventions were performed in 114(78%), of whom 51 (45%) had percutaneous drainage (PTBD) and 63 (55%) had endoscopic drainage (ED). Readmission with cholangitis was noted in 35 (24%) cases. Univariate analysis did not show a difference between PTBD and ED. However, subgroup analysis showed external only PTBD and covered metallic stent ED had lower risk of RC. These variables remained significant on multivariate analysis (Subdistribution HR= 0.00, p&lt;.0001 for both). Multiple previous PTBD (≥2) before FA was significantly associated with increased risk of RC (Subdistribution HR= 2.64, p= 0.01) on univariate analysis. Conclusions: Having multiple previous PTBD is associated with recurrent cholangitis. Though no significant difference was noted between PTBD and ED, the subgroups indicated a trend towards less recurrent cholangitis with covered metallic stent. [Table: see text]