Fish Oil Emulsion Reduces Liver Injury and Liver Transplantation in Children with Intestinal Failure-Associated Liver Disease: A Multicenter Integrated Study.

OBJECTIVE: To compare the aspartate aminotransferase to platelet ratio index, liver transplantation, and mortality rates between children with intestinal failure-associated liver disease who received fish oil lipid emulsion (FOLE) or soybean oil intravenous lipid emulsion (SOLE). STUDY DESIGN: In this multicenter integrated analysis, FOLE recipients (1 g/kg/d) (n = 189) were compared with historical controls administered SOLE (≤3 g/kg/d) (n = 73). RESULTS: Compared with SOLE, FOLE recipients had a higher direct bilirubin level at baseline (5.8 mg/dL vs 3.0 mg/dL; P < .0001). Among FOLE recipients, 65% experienced cholestasis resolution vs 16% of SOLE recipients (P < .0001). The aspartate aminotransferase to platelet ratio index scores improved in FOLE recipients (1.235 vs 0.810 and 0.758, P < .02) but worsened in SOLE recipients (0.540 vs 2.564 and 2.098; P ≤ .0003) when baseline scores were compared with cholestasis resolution and end of study, respectively. Liver transplantation was reduced in FOLE vs SOLE (4% vs 12%; P = .0245). The probability of liver transplantation in relation to baseline direct or conjugated bilirubin (DB) was lower in FOLE vs SOLE recipients (1% vs 9% at DB of 2 mg/dL; 8% vs 35% at DB of 12.87 mg/dL; P = .0022 for both). Death rates were similar (FOLE vs SOLE: 10% vs 14% at DB of 2 mg/dL; 17% vs 23% at a DB of 12.87 mg/dL; P = .36 for both). CONCLUSIONS: FOLE recipients experienced a higher rate of cholestasis resolution, lower aspartate aminotransferase to platelet ratio index, and fewer liver transplants compared with SOLE. This study demonstrates that FOLE may be the preferred parenteral lipid emulsion in children with intestinal failure-associated liver disease when DB reaches 2 mg/dL. TRIAL REGISTRATION: Clinicaltrials.gov: NCT00910104 and NCT00738101.

Percutaneous stent-in-stent placement with large cell-type stents for malignant hilar biliary obstruction.

BACKGROUND: To overcome the technical difficulty of bilateral stent-in-stent placement, large cell-type biliary stents have been developed. However, most of the studies using large cell-type stents were conducted with endoscopic method. PURPOSE: To evaluate the efficacy and safety of percutaneous stent placement with a stent-in-stent method using large cell-type stents in patients with malignant hilar biliary obstruction. MATERIAL AND METHODS: From December 2015 and October 2018, 51 patients with malignant hilar biliary obstruction were retrospectively studied. All of the patients underwent bilateral (n=46) or unilateral (n=5) stenting in a T, Y, or X configuration with a stent-in-stent method using large cell-type stents. Technical success, complications, successful internal drainage, stent patency, and patient survival were analyzed. RESULTS: A total of 118 stents were successfully placed in 51 patients (100.0%). Three patients had minor complications with self-limiting hemobilia. Major complications were not observed in any patient. Successful internal drainage was achieved in 45 patients (88.2%). Clinical follow-up information until death or the end of the study was available for 50 of 51 patients. The median patient survival was 285.5 days (95% confidence interval [CI] 197-374). Stent dysfunction occurred in 16 patients (35.6%) due to tumor ingrowth (n=9) or tumor ingrowth combined with biliary sludge (n=7) among the patients who achieved successful internal drainage. Median stent patency was 179 days (95% CI 104-271). CONCLUSION: Percutaneous stent-in-stent placement with large cell-type stents is technically feasible and safe, and can be an effective technique in patients with malignant hilar biliary obstruction.

Folfirinox chemotherapy prolongs stent patency in patients with malignant biliary obstruction due to unresectable pancreatic cancer.

BACKGROUND: Stent insertion for biliary decompression to relieve jaundice and subsequent biliary infection is necessary for patients with biliary obstruction caused by pancreatic cancer, and it is important to keep the stent patent as long as possible. However, few studies have compared stent patency in terms of chemotherapy in patients with pancreatic cancer. This study aimed to evaluate the differences in stent patency in terms of recently evolving chemotherapy. METHODS: Between January 2015 and May 2017, 161 patients with pancreatic cancer who had undergone biliary stent insertion with a metal stent were retrospectively analyzed. The relationship between chemotherapy and stent patency was assessed. Additionally, overall survival according to the treatment, risk factors for stent patency, and long-term adverse events were evaluated. RESULTS: Median stent patency was 42 days for patients with the best supportive care and 217 days for patients with chemotherapy (conventional gemcitabine-based chemotherapy and folfirinox) (P < 0.001). Furthermore, the folfirinox group showed the longest median stent patency and overall survival, with 283 days and 466 days, respectively (P < 0.001) despite higher adverse events rate. Patients who underwent folfirinox chemotherapy after stent insertion had better stent patency in multivariate analysis (HR = 0.26; 95% CI: 0.12-0.60; P = 0.001). CONCLUSIONS: Compared with patients who received best supportive care only, patients who underwent chemotherapy after stent insertion had better stent patency. More prolonged stent patency can be expected for patients with folfirinox than conventional gemcitabine-based chemotherapy.

Percutaneous Biliary Metallic Stent Insertion in Patients with Malignant Duodenobiliary Obstruction: Outcomes and Factors Influencing Biliary Stent Patency.

OBJECTIVE: To investigate the technical and clinical efficacy of the percutaneous insertion of a biliary metallic stent, and to identify the factors associated with biliary stent dysfunction in patients with malignant duodenobiliary obstruction. MATERIALS AND METHODS: The medical records of 70 patients (39 men and 31 women; mean age, 63 years; range, 38-90 years) who were treated for malignant duodenobiliary obstruction at our institution between April 2007 and December 2018, were retrospectively reviewed. Variables found significant by univariate log-rank analysis (p < 0.2) were considered as suitable candidates for a multiple Cox's proportional hazard model. RESULTS: The biliary stents were successfully placed in all 70 study patients. Biliary stent insertion with subsequent duodenal stent insertion was performed in 33 patients and duodenal stent insertion with subsequent biliary stent insertion was performed in the other 37 study subjects. The median patient survival and stent patency time were 107 days (95% confidence interval [CI], 78-135 days) and 270 days (95% CI, 95-444 days), respectively. Biliary stent dysfunction was observed in 24 (34.3%) cases. Multiple Cox's proportional hazard analysis revealed that the location of the distal biliary stent was the only independent factor affecting biliary stent patency (hazard ratio, 3.771; 95% CI, 1.157-12.283). The median biliary stent patency was significantly longer in patients in whom the distal end of the biliary stent was beyond the distal end of the duodenal stent (median, 327 days; 95% CI, 249-450 days), rather than within the duodenal stent (median, 170 days; 95% CI, 115-225 days). CONCLUSION: The percutaneous insertion of the biliary metallic stent appears to be a technically feasible, safe, and effective method of treating malignant duodenobiliary obstruction. In addition, a biliary stent system with a distal end located beyond the distal end of the duodenal stent will contribute towards longer stent patency in these patients.

Placement of a newly designed partially covered T- or Y-configured self-expanding metallic stent for hilar biliary obstruction: technical note.

PURPOSE: To investigate the technical success, efficacy, and safety of a newly designed partially covered bilateral self-expanding metallic stent (SEMS) in patients with malignant biliary obstruction. MATERIAL AND METHODS: From May 2016 to November 2017, ten patients with malignant hilar biliary stenosis (bismuth type II-IV) underwent stent placement with the newly designed partially covered T/Y-configured SEMS. Technical success, drainage catheter removal, jaundice remission, early and late complications, stent patency, and overall survival were analyzed. RESULTS: The stent was successfully deployed in all patients. The total bilirubin level significantly decreased one month after stent placement (P < 0.05). Drainage catheter removal rate was 90%. Two cases (20%) experienced early complications (bile duct hemorrhage and cholangitis) and two cases (20%) experienced late complications (hepatic abscess and cholangitis). During the follow-up (mean 276 days; range 57-503 days) stent occlusion occurred in three patients (30%), and two patents died of hepatic failure. The median stent patency and overall survival were 275 days (95% CI 223.8-326.3 days) and 428.9 days (95% CI 347.9-509.8 days), respectively. CONCLUSION: The newly designed partially covered T/Y-configured SEMS is technically feasible and clinically effective for biliary trifurcation obstruction.

Six-month Survival of Patients with Malignant Distal Biliary Stricture Following Endoscopic Biliary Stent Procedure and Its Associated Factors.

BACKGROUND: unresectable malignant distal biliary stricture patients require endoscopic biliary stent placement procedure. The survival rate and its associated factors in Indonesia are unknown. OBJECTIVES: To identify 6-month survival of patients with malignant distal biliary stricture following endoscopic biliary stent procedure and its associated factors. METHODS: a retrospective cohort study was conducted using medical records of patients with unresectable malignant distal biliary stricture, which involved caput of pancreas, ampulla of Vater or distal cholangiocarcinoma following endoscopic biliary stent procedure between June 2015 and August 2017 at Cipto Mangunkusumo National Central General Hospital. The cumulative survival was defined by using the Kaplan-Meier curve. Bivariate and multivariate analyses were performed using Cox regression of some factors including failure of biliary stent insertion, bleeding, sepsis, comorbidities, malnutrition, and serum albumin levels. RESULTS: out of total 120 subjects, 85 subjects died within 6 months following the stent procedure with a proportion of 180-day survival of 24% and a median survival of 81 days (CI 95%: 56-106 days). In bivariate analysis, factors of comorbidities, sepsis, malnutrition and albumin levels ≤ 3.0 g/dL had p values of < 0.25; while the subsequent multivariate analysis showed that albumin level of ≤ 3.0 g/dL had HR of 2.73 (CI 95%: 1.48 - 5.05; p = 0.001). CONCLUSION: the 6-month survival following endoscopic biliary stent procedure is 24% with a median survival of 81 days. Albumin level of ≤ 3.0 g/dL has a 2.73 times greater risk for 6-month mortality rate.

Ursodeoxycholic acid use is associated with significant risk of morbidity and mortality in infants with cholestasis: A strobe compliant study.

The off-label use of medications is a "right" for pediatricians, owing to lack of enough safety and effectiveness drug trials in pediatric age group. Pediatricians have to rely on their personal judicial use of medications in children.We studied off-label use of ursodeoxycholic acid (UDCA) retrospectively during 2005 to 2015 among those who attended the Pediatic Hepatology Unit, Cairo University.We analyzed data of 779 neonates and infants with cholestasis. 15% dropped out. Males comprised 374 (56.5%). Cholestasis was due to surgical causes in 129 (19.5%), neonatal hepatitis in 445 (67.2%), and paucity of intrahepatic bile ducts in 88 (13.3%). Three hundred sixty (54.4%) received UDCA (15-30 mg/kg/d), and 302 (45.6%) did not. Both groups were matched as regards causes and severity of cholestasis. Those who received UDCA had worse outcome (P < .001), and more complications (P < .001). A total of 73.1% (221) achieved cure without UDCA compared to only 45.8% (165) of those on UDCA (P < .001).UDCA is not effective and not safe in Egyptian neonates and infants with cholestasis. UDCA use compromises chance of cure, and is associated with serious morbidity, progression of disease, and death. UDCA off-label use mortality was absolutely preventable. Off- label use of UDCA in neonates and children should be utterly prohibited. Information of use of off-label medications, effectiveness, and safety, should be recorded, analyzed, and made available within context of Off-label Use Registry Studies with informed consent of parents.

Stent placement with iodine-125 seeds strand effectively extends the duration of stent patency and survival in patients with unresectable malignant obstructive jaundice.

Background: This study aimed to compare the treatment outcomes and safety between stent placement with or without Iodine-125 (125I) seeds strand for patients with unresectable malignant obstructive jaundice (MOJ).Methods: A total of 84 patients with unresectable MOJ treated in our hospital were retrospectively included and divided into the stent group (n = 54) undergoing biliary stent placement and the stent + seeds group (n = 30) receiving stent placement with 125I seeds strand. The therapeutic outcome, postoperative complications, duration of patient survival and stent patency were compared between groups. Kaplan-Meier survival analysis was performed to compare the duration of patient survival and stent patency between groups. Cox-regression analysis was performed to investigate predictive factors for disease-free survival and overall survival.Results: The stent + seeds group had significantly longer duration of patency (231.57 ± 256.54 vs. 110.37 ± 120.52) and overall survival (310.57 ± 330.54 vs. 173.15 ± 219.40) than the stent group (both p < .05). In addition, Kaplan-Meier survival analysis confirmed that the stent + seeds group had longer duration of patency (log-rank test, p = .001) and higher overall survival rate (log-rank test, p = .020) than the stent group. Furthermore, Cox-regression analysis demonstrated that treatment methods was an independent factor associated with disease-free survival (HR: 0.36, 95% CI: 0.19-0.70; p = .003) and overall survival (HR: 1.01, 95% CI: 1.00-1.01; p < .001).Conclusion: The stent placement with 125I seeds strand can significantly improve the primary patency rate and overall survival time in MOJ patients.

Biliary palliation for unresectable pancreatic adenocarcinoma: surgical bypass or self-expanding metal stent?

BACKGROUND: Standard of care guidelines endorse self-expanding metal stents (SEMS) rather than open surgical biliary bypass (OSBB) for biliary palliation in the setting of unresectable pancreatic ductal adenocarcinoma (PDAC). This study used competing risk analysis to compare short- and long-term morbidity and overall survival among patients undergoing SEMS or OSBB after unresectable or metastatic disease is identified at the time of exploration. METHODS: Single institution retrospective cohort study (n = 127) evaluating outcomes after OSBB and SEMS for biliary palliation in patients found to have unresectable PDAC at exploration. Short-term, long-term, and lifetime risk of biliary occlusion and survival were compared after adjustment for stage and comprehensive complication index (CCI). RESULTS: Baseline demographics and tumor characteristics were equivalent between cohorts. Short-term complications were more frequent after OSBB, whereas late complications were greater after SEMS. The cumulative incidence of recurrent biliary obstruction was greater after SEMS, but lifetime complication burden and median survival were equivalent. CONCLUSION: OSBB was associated with longer hospital stays and more short-term complications, and SEMS was associated with a higher risk of recurrent biliary obstruction among surgical patients with unresectable PDAC. Patient preference should be defined pre-operatively in the case the unresectable disease is encountered during attempted resection.

No evidence of improved efficacy of covered stents over uncovered stents in percutaneous palliation of malignant hilar biliary obstruction: results of a prospective randomized trial.

OBJECTIVE: To investigate whether covered stents show a higher efficacy than uncovered stents in percutaneous treatment of malignant hilar biliary obstruction. METHODS: Patients with obstructive jaundice caused by an unresectable hilar malignancy were included after failed endoscopic intervention in a prospective randomized trial comparing expanded polytetrafluoroethylene and fluorinated ethylene propylene (ePTFE-FEP)-covered nitinol stents with uncovered nitinol stents. Exclusion criteria were as follows: primary tumors existing more than 3 months, a biliodigestive anastomosis, previous stenting, and a Karnofsky score of less than 50. Safety, clinical success, and adjuvant chemotherapy were compared as well as occlusion rate, patency, and survival. RESULTS: A total of 120 patients were included. One patient was post hoc excluded. Fourteen patients who died within 7 days and one patient without patency data were excluded from patency analysis. Serious adverse events (p = 0.4), 30-day mortality (p = 0.5), and clinical success (p = 0.8) were equivalent for both stent groups. Twenty-one out of 61 (34%) patients in the covered and 24/58 (41%) in the uncovered stent groups received adjuvant chemotherapy (p = 0.5). Occlusion rate was 54% (27/50) in the covered stent group and 57% (31/54) in the uncovered stent group (p = 0.8). Median patency was 229 days (95% CI 113-345) for covered stents and 130 days (95% CI 75-185) for uncovered stents (p = 0.1). Median survival in patients with covered stents was 79 days (95% CI 52-106) and with uncovered stents 92 days (95% CI 60-124) (p = 0.3). CONCLUSION: In malignant hilar biliary obstruction, there is no evidence that ePTFE-FEP-covered stents are superior to uncovered stents in terms of safety, clinical success, adjuvant chemotherapy, patency, or survival. KEY POINTS: • Percutaneous palliation of hilar biliary obstruction is feasible with both uncovered and covered stents. • Clinical success in terms of bilirubin decrease and adjuvant chemotherapy is achievable with both stents. • Thirty-day mortality is considerable when stenting is also offered to patients with a low performance status.

No Advantage of Expanded Polytetrafluoroethylene and Fluorinated Ethylene Propylene-Covered Stents over Uncovered Nitinol Stents for Percutaneous Palliation of Malignant Infrahilar Biliary Obstruction: Results of a Single-Center Prospective Randomized Trial.

PURPOSE: To prove that covered stents are more efficacious than uncovered stents regarding patency, safety, enabling of chemotherapy, and survival in percutaneous palliation of malignant infrahilar biliary obstruction. MATERIALS AND METHODS: After failed endoscopic treatment, 154 patients with obstructive jaundice caused by unresectable infrahilar malignancy were randomly allocated to receive an expanded polytetrafluoroethylene and fluorinated ethylene propylene-covered or an uncovered nitinol stent. Occlusion rate, patency, and survival were assessed. Safety and clinical success in terms of chemotherapy were compared. RESULTS: Three patients were excluded post hoc. Fifteen patients died within 7 d and were excluded from patency analysis. Occlusion rates were 32% (21 of 66) for covered and 29% (20 of 70) for uncovered stents (P = .7). Estimated median patency durations were 308 d (95% confidence interval [CI], 178-438 d) for covered and 442 d (95% CI, 172-712 d) for uncovered stents (P = .1). Serious adverse events (P = 1.0) and 30-day mortality (P = .5) were equivalent between groups. At hospital discharge, median bilirubin reduction of 8 mg/dL was found in both groups (P < .001). In the covered stent group, 35 patients (48%) received palliative chemotherapy, vs 29 (37%) in the uncovered stent group (P = .2). Estimated median survival times were 96 days (95% CI, 68-124 d) with covered stents and 75 days (95% CI, 42-108 d) with uncovered stents (P = .6). CONCLUSIONS: In malignant infrahilar biliary obstruction not amenable to endoscopy, no improvement in patency or survival with percutaneously placed covered stents could be confirmed. Covered and uncovered stent types exhibit similar safety profiles and clinical success rates.

Early Warning Models to Estimate the 30-Day Mortality Risk After Stent Placement for Patients with Malignant Biliary Obstruction.

PURPOSE: To develop, validate, and compare early warning models of the 30-day mortality risk for patients with malignant biliary obstruction (MBO) undergoing percutaneous transhepatic biliary stent placement (PTBS). MATERIALS AND METHODS: Between January 2013 and October 2018, this multicenter retrospective study included 299 patients with MBOs who underwent PTBS. The training set consisted of 166 patients from four cohorts, and another two independent cohorts were allocated as external validation sets A and B with 75 patients and 58 patients, respectively. A logistic model and an artificial neural network (ANN) model were developed to predict the risk of 30-day mortality after PTBS. The predictive performance of these two models was validated internally and externally. RESULTS: The ANN model had higher values of area under the curve than the logistic model in the training set (0.819 vs 0.797), especially in the validation sets A (0.802 vs 0.714) and B (0.732 vs 0.568). Both models had high accuracy in the three sets (75.9-83.1%). Along with a high specificity, the ANN model improved the sensitivity. The net reclassification improvement and integrated discrimination improvement also demonstrated that the ANN model led to improvements in predictive ability compared with the logistic model. CONCLUSIONS: Early warning models were proposed to predict the risk of 30-day mortality after PTBS in patients with MBO. The ANN model has higher accuracy and better generalizability than the logistic model.

Percutaneous transpapillary biliary stent placement for distal malignant biliary obstruction: Outcomes and survival analysis.

BACKGROUND/AIMS: For distal malignant biliary obstruction (MBO), a percutaneous metal stent is usually inserted by the transpapillary method. However, stent-related complications and recurrent biliary obstruction following transpapillary stent placement are concerns, and survival analysis of patients with distal MBO has rarely been done. MATERIALS AND METHODS: From January 2012 to March 2016, 104 patients underwent transpapillary uncovered metal stent placement for distal MBO at our institution. Clinical success, complications, recurrent biliary obstruction rates, and predictors of survival were analyzed. RESULTS: Of the total 104 patients, clinical success after stent insertion was achieved in 93 patients (90.3%). Major complications were observed in 24 patients (23.1%), which were as follows: cholangitis in 19 patients; pancreatitis in four patients; and biloma in one patient. Recurrent biliary occlusion was observed in 28 patients (26.9%). The median overall survival period was 162 days. The 3-, 6-, and 12-month overall survival rates after stent insertion were 64.4%, 41.3%, and 10.6%, respectively. Results of multivariate analysis indicated that metastatic carcinoma compared with ampullary carcinoma (HR=3.82; 95% CI, 1.30-11.24; p=0.015) and longer biliary stricture (HR=1.04; 95% CI, 1.02-1.06; p<0.001) were independent risk factors for worse survival after metal stent insertion. CONCLUSION: Transpapillary stent placement was found to be effective with acceptable complication rates for treating distal MBO. Primary tumor and length of biliary stricture were found to be statistically significant independent prognostic factors for survival.

Endoscopic biliary drainage in unresectable biliary obstruction: the role of endoscopic ultrasound-guidance in a cohort study.

BACKGROUND AND STUDY AIMS: the use of endoscopic ultrasound-guided biliary drainage (EUS-BD) has increased in cases of failed endoscopic retrograde cholangiopancreatography (ERCP) and there are some concerns. The main aim of the study was to determine the role of EUS-BD in a palliative case cohort. The secondary aim was to compare the efficacy, safety and survival of EUS-BD and ERCP procedures. PATIENTS AND METHODS: this was an observational study at a single tertiary institution, with a consecutive inclusion from January 2015 to December 2016. The inclusion criteria were unresectable tumors of the biliopancreatic region with an indication of BD. Statistical comparison analysis was performed between the ERCP and EUS-BD groups. The incidence between groups was compared using the Chi-square and Fisher exact tests. The log rank test was used to compare the risk of death. RESULTS: fifty-two cases with an indication of palliative BD were included in the study. Transpapillary drainage via ERCP was possible in 44 procedures and EUS-BD was required in eight cases; 15.4% of the cohort and seven using lumen apposing metal stent (LAMS). The technical and clinical success of global endoscopic BD was 100% and 88.5% (ERCP: 84.6% and 78.9%; EUS-BD: 100% and 62.5%, respectively). Pancreatitis was the most frequent adverse event (AE) in the ERCP group (9.62%) and bleeding in the EUS-BD (25%). There were fatal AEs in ERCP (1.9%) and EUS-BD (25%) cases. Patient survival was higher with ERCP transpapillary stents compared to EUS-guided stents, which was statistically significant (p = 0.007). CONCLUSIONS: the requirement of EUS-BD in palliative biliopancreatic pathology is not marginal. EUS-BD is associated with a lower survival rate and a higher rate of fatal AE, which argues against its use as a first choice procedure.

Contributing factors and outcomes of burn-associated cholestasis.

BACKGROUND & AIMS: Cholestasis often occurs after burn injuries. However, the prevalence of cholestasis and its effect on outcomes in patients with severe burn injuries are unknown. The aim of this study was to describe the course and the burden of cholestasis in a cohort of severely burned adult patients. METHODS: We investigated the relationship between burn-associated cholestasis (BAC) and clinical outcomes in a retrospective cohort of patients admitted to our unit for severe burn injuries between 2012 and 2015. BAC was defined as an increased level of serum alkaline phosphatase (ALP) ≥1.5x the upper limit of normal (ULN) with an increased level of gamma-glutamyltransferase (GGT) ≥3x ULN, or as an increased level of total bilirubin ≥2x ULN. RESULTS: A total of 214 patients were included: 111 (52%) patients developed BAC after a median (IQR) stay of 9 (5-16) days. At 90 days, the mortality rate was 20%, including 34 and 9 patients with and without BAC (p <0.001), respectively, which corresponded to a 2.5-fold higher (95% CI 1.2-5.2, p = 0.012) risk of 90-day mortality for patients with BAC. After being adjusted for severity of illness, patients with BAC, hyperbilirubinemia and without elevated ALP and GGT levels had a hazard ratio of 4.51 (95% CI 1.87-10.87) for 90-day mortality. BAC was associated with the severity of the burn injury, shock and bacteraemia. BAC was present in 38 (51%) patients at discharge, and 7 (18%) patients had secondary sclerosing cholangitis. These patients maintained elevated levels of ALP and GGT that were 5.8x (1.7-15) the ULN and 11x the ULN (4.5-22), respectively, 20 months (3.5-35) after discharge. CONCLUSION: BAC is prevalent among patients with severe burn injuries and is associated with worse short-term outcomes, especially when total bilirubin levels were increased without elevated ALP and GGT levels. BAC survivors are at risk of developing sclerosing cholangitis. LAY SUMMARY: Cholestasis is common after burn injuries and is associated with burn severity, sepsis, organ failure and mortality. Patients with hyperbilirubinemia without elevated alkaline phosphatase and gamma-glutamyltransferase levels after the burn injury have a poor prognosis. Patients with burn-associated cholestasis may develop sclerosing cholangitis and secondary biliary cirrhosis.

Low circulating concentrations of citrulline and FGF19 predict chronic cholestasis and poor survival in adult patients with chronic intestinal failure: development of a Model for End-Stage Intestinal Failure (MESIF risk score).

BACKGROUND: Patients with chronic intestinal failure (CIF) often develop cholestatic liver injury, which may lead to liver failure and need for organ transplantation. OBJECTIVES: The aim of this study was to investigate whether citrulline (CIT) and the enterokine fibroblast growth factor 19 (FGF19) are associated with chronic cholestasis and survival in adult CIF patients, and to develop a risk score to predict their survival. METHODS: We studied 135 adult CIF patients on intravenous supplementation (>3 mo). Associations of plasma CIT and FGF19 with chronic cholestasis and survival were estimated by logistic and Cox regression models. A predictive risk score was developed and validated internally. RESULTS: Patients with chronic cholestasis (17%) had a reduced 5-y survival rate compared with patients without chronic cholestasis (38% and 62%, respectively). In multivariable analysis, low FGF19, low CIT, and female sex were associated with chronic cholestasis. Patients with low rather than high CIT or FGF19 also had reduced 5-y survival rates (29% compared with 69%; 54% compared with 66%, respectively). Risk factors identified in multivariable analysis of survival were low FGF19 (HR: 3.4), low CIT (HR: 3.3), and number of intravenous infusions per week (HR: 1.4). These 3 predictors were incorporated in a risk model of survival termed Model for End-Stage Intestinal Failure (MESIF) (C-statistic 0.78). The 5-y survival rates for patients with MESIF scores of 0 to <20 (n = 47), 20-40 (n = 75), and >40 (n = 13) were 80%, 58%, and 14%, respectively. CONCLUSIONS: CIT and FGF19 predict chronic cholestasis and survival in this cohort of adult CIF patients, and the derived MESIF score is associated with their survival. Pending external validation, the MESIF score may help to identify patients for closer clinical monitoring or earlier referral to intestinal transplantation centers.

Risk Factors for the Development of Stent-Associated Cholangitis Following Endoscopic Biliary Stent Placement.

BACKGROUND AND AIM: To elucidate the overall risk and risk factors for developing cholangitis following biliary stent placement by endoscopic retrograde cholangiopancreatography (ERCP) and to determine the clinical outcomes of these individuals. METHODS: We performed a retrospective review of 796 patients who had undergone 1127 ERCPs with biliary stent placement between 2007 and 2015 at a single tertiary care center. There were 91 episodes of stent-associated cholangitis (SAC) during the study period. Data obtained through the medical records included ERCP indication, patient factors (biliary anatomy, demographics, and comorbidities), stent characteristics (material, length, and design), change in serum bilirubin, stent indwelling time, rates and etiologies of bacteremia, and the mortality rate. RESULTS: Those with SAC were more likely to have an anatomic biliary stricture (13.1% vs. 2.3%, p < .0001), with hilar and multiple strictures having the highest risk (19.1% vs. 11.6%, p = .04). The ERCP indication of malignant biliary obstruction was associated with higher rates of SAC (15.6% vs. 3.4%, p = < .0001). Rates of SAC were higher in those who failed to normalize total bilirubin (16.9% vs. 7.8%, p = .0005), and these episodes occurred earlier compared to those who normalized total bilirubin (median 30.5 days vs. 140.5 days, p < .0001). CONCLUSIONS: Patients at increased risk of SAC include those with an anatomic stricture, malignant biliary obstruction, and those who fail to normalize total bilirubin after biliary stent placement. Future protocols should be designed to reduce the risk of cholangitis in these populations.

Comparison of 8- and 10-mm diameter fully covered self-expandable metal stents: A multicenter prospective study in patients with distal malignant biliary obstruction.

OBJECTIVES: The time to recurrent biliary obstruction (TRBO) of unresectable distal malignant biliary obstruction is generally thought to be longer when a self-expandable metal stent (SEMS) with a thicker inner diameter is used for drainage, but the dependence on the inner diameter using a fully covered SEMS (FCSEMS) is uncertain. The objective of this multicenter prospective study was to compare TRBO and adverse events, such as cholecystitis and pancreatitis, in treatment of patients with unresectable malignant biliary obstruction using 8- and 10-mm diameter FCSEMS. METHODS: Eighteen tertiary-care centers participated in the study. Patients were allocated to the 8- and 10-mm diameter groups. TRBO, non-inferiority of the 8-mm FCSEMS, overall survival time, frequency and type of adverse events, and non-recurrent biliary obstruction (RBO) rate at the time of death were compared between the two groups. RESULTS: Median TRBO did not differ significantly between the 8-mm (n = 102) and 10-mm (n = 100) groups (275 vs 293 days, P = 0.971). The hazard ratio of the 8- to 10-mm groups was 0.90 (80% confidence interval, 0.77-1.04; upper limit lower than the acceptable hazard ratio [1.33] of the null hypothesis). Based on these findings, the 8-mm diameter stent was determined to be non-inferior to the 10-mm diameter stent. Survival time, incidence of adverse events and non-RBO rate at the time of death did not differ significantly between the two groups. CONCLUSIONS: Time to RBO with an 8-mm diameter FCSEMS was non-inferior to that with a 10-mm diameter FCSEMS. This finding is important for development of future SEMS.

Intestinal failure associated cholestasis in surgical necrotizing enterocolitis and spontaneous intestinal perforation.

BACKGROUND: Surgery for necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP) is often complicated by intestinal failure (IF) and intestinal failure associated cholestasis (IFAC). OBJECTIVE: Assessment of incidence, predictors, and mortality associated with IFAC in surgically treated NEC and SIP. METHODS: A retrospective observational study based on hospital records during 1986-2014 in the two largest Finnish neonatal intensive care units was performed. IFAC was defined as conjugated bilirubin >34 µmol/l (2.0 mg/dl) for ≥ two postoperative weeks while receiving parenteral nutrition (PN). RESULTS: In total 225 patients underwent surgery for NEC (n = 142; 63%) or SIP (n = 83; 37%). Included were 57 survivors with ≥two weeks PN. Sixty-five (42%) patients developed IFAC. Two-year survival with IFAC was 80% and without IFAC 89% (p = 0.13). Of the 65 patients with IFAC, all eight with unresolved IFAC died in comparison to six of 57 (11%) whose IFAC resolved (p < 0.0001), while IFAC resolved in all survivors. Survival among patients with resolved IFAC was 89% and with unresolved IFAC (n = 8) 0%, (p < 0.0001). IFAC lasted for median 83 (IQR 45-120) days and correlated with the duration of PN (R2 = 0.16, p = 0.03), delay of starting enteral feeds (R2 = 0.12, p = 0.05) and PN lipid emulsion (RR = 1.0 (95% CI = 1.0-1.1) (p = 0.02). In multivariate logistic regression analysis, IFAC development associated with septicemias and reoperations. CONCLUSIONS: 42% of prematures who underwent surgery for NEC or SIP developed IFAC. Reoperations and septicemias increased the risk of IFAC. None of the patients with unresolved IFAC survived, but IFAC did not increase overall mortality. TYPE OF STUDY: Retrospective prognosis study. LEVEL OF EVIDENCE: Level II.