Morbidity and mortality in patients with stage IV pancreatic adenocarcinoma and acute cholangitis: Outcomes and risk prognostication.

BACKGROUND: Acute cholangitis (AC) is a common complication of pancreatic ductal adenocarcinoma (PDAC). Herein, we evaluated outcomes after the first AC episode and predictors of mortality and AC recurrence in patients with stage IV PDAC. METHODS: We conducted a single-center, retrospective observational study using institutional databases. Clinical data and outcomes for patients with stage IV PDAC and at least one documented episode of AC, were assessed. Overall survival (OS) was estimated using the Kaplan-Meier method, and Cox regression model was employed to identify predictors of AC recurrence and mortality. RESULTS: One hundred and twenty-four patients with stage IV PDAC and AC identified between January 01, 2014 and October 31, 2020 were included. Median OS after first episode of AC was 4.1 months (95 % CI, 4.0-5.5), and 30-day, 6, and 12-month survival was 86.2 % (95 % CI, 80.3-92.5), 37 % (95 % CI, 29.3-46.6 %) and 18.9 % (95 % CI, 13.1-27.3 %), respectively. Primary tumor in pancreatic body/tail (HR 2.29, 95 % CI: 1.26 to 4.18, p = 0.011), concomitant metastases to liver and other sites (HR 1.96, 95 % CI: 1.16 to 3.31, p = 0.003) and grade 3 AC (HR 2.26, 95 % CI: 1.45 to 3.52, p < 0.001), predicted worse outcomes. Intensive care unit admission, sepsis, systemic therapy, treatment regimen, and time to intervention did not predict survival or risk of recurrence of AC. CONCLUSIONS: AC confers significant morbidity and mortality in advanced PDAC. Worse outcomes are associated with higher grade AC, primary tumor location in pancreatic body/tail, and metastases to liver and other sites.

National trends and outcomes in timing of ERCP in patients with cholangitis.

INTRODUCTION: Guidelines recommend early endoscopic retrograde cholangiopancreatography for the management of acute cholangitis, but the definition of the term "early" remains debatable. This study analyzed national trends in the timing of endoscopic retrograde cholangiopancreatography and identified the ideal time to perform preoperative endoscopic retrograde cholangiopancreatography in patients with acute cholangitis. METHODS: The 2005 to 2016 National Inpatient Sample was used to identify patients undergoing cholecystectomy for acute cholangitis. Severity of cholangitis was defined using the 2013 Tokyo Grading Criteria, where Tokyo grade III patients were defined as having organ dysfunction and non-Tokyo grade III patients were defined as grades I and II. Multivariable regressions (accounting for patient and hospital characteristics) were used to identify the timing of preoperative endoscopic retrograde cholangiopancreatography associated with the least mortality risk. RESULTS: Of 91,051 patients undergoing cholecystectomy for cholangitis, 55% underwent preoperative endoscopic retrograde cholangiopancreatography: 24% of patients received endoscopic retrograde cholangiopancreatography on the day of admission, 41% on hospital day 2, and the use of endoscopic retrograde cholangiopancreatography decreased gradually thereafter. Mortality rates remained under 1% if endoscopic retrograde cholangiopancreatography was performed during the first 3 days and increased as endoscopic retrograde cholangiopancreatography was performed during days 4 to 7 (P < .001). On multivariable regression, endoscopic retrograde cholangiopancreatography performed >72 hours after admission was associated with increased mortality (adjusted odds ratio 1.80, P = .01). Receiving endoscopic retrograde cholangiopancreatography P > 72 hours increased risk of death among Tokyo grade III patients (adjusted odds ratio 1.88, P = .01). Overall, during the study period, the utilization of preoperative endoscopic retrograde cholangiopancreatography for all grades of acute cholangitis increased from 39% of patients in 2005 to 51% in 2016 (P < .001). CONCLUSION: There has been an increase in the use of endoscopic retrograde cholangiopancreatography for acute cholangitis. Although endoscopic retrograde cholangiopancreatography on the day of admission was not associated with a decrease in mortality in patients with Tokyo grade III disease, endoscopic retrograde cholangiopancreatography within 72 hours of hospitalization was associated with decreased in-hospital mortality.

Microbiology and clinical characteristics of acute cholangitis with their impact on mortality; a retrospective cross sectional study.

OBJECTIVE: To evaluate microbiological and clinical characteristics of acute cholangitis along with their impact on mortality, and to compare the role of early versus late biliary drainage in the management of cholangitis. METHODS: The retrospective study was conducted at the Shaukat Khanum Memorial Cancer Hospital Research Centre, Lahore, Pakistan, and comprised records of all patients presenting with acute cholangitis from June, 2012, to June, 2017. The risk factors, presence of bacteremia, resistance pattern of microbial pathogens and severity were assessed according to Tokyo guidelines in addition to associated mortality and recurrence at 3 months. Data was analysed using SPSS 20. RESULTS: Of the 230 patients, 137(59.6%) were male. The overall mean age was 56±13 years. The most common isolated organism was Escherichia coli 54(70.1%). Clinical severity (p=0.001), late biliary drainage (p=0.001) and use of multiple stents (p=0.03) were associated with increased mortality. However, in multivariable analysis, only high body mass index (p=0.01) and Tokyo severity grades II (p=0.04) and III (p=0.001) were significant factors associated with mortality. CONCLUSIONS: Early identification of risk factors, administration of appropriate antibiotics and establishing early biliary drainage were found to be the key management steps to reduce cholangitis-related mortality.

The Complementary Value of Magnetic Resonance Imaging and Vibration-Controlled Transient Elastography for Risk Stratification in Primary Sclerosing Cholangitis.

OBJECTIVES: Magnetic resonance (MR) risk scores and liver stiffness (LS) have individually been shown to predict clinical outcomes in primary sclerosing cholangitis (PSC). The aim of this study was to assess their complementary prognostic value. METHODS: Patients with PSC from 3 European centers with a 3-dimensional MR cholangiography available for central reviewing and a valid LS measurement assessed by vibration-controlled transient elastography by FibroScan performed within a 6-month interval were included in a longitudinal retrospective study. The MR score (Anali) without gadolinium (Gd) was calculated according to the formula: (1 × dilatation of intrahepatic bile ducts) + (2 × dysmorphy) + (1 × portal hypertension). The primary end point was survival without liver transplantation or cirrhosis decompensation. The prognostic values of LS and Anali score without Gd were assessed using Cox proportional hazard models. RESULTS: One hundred sixty-two patients were included. Over a total follow-up of 753 patient-years, 40 patients experienced an adverse outcome (4 liver transplantations, 6 liver-related deaths, and 30 cirrhosis decompensations). LS and Anali score without Gd were significantly correlated (ρ = 0.51, P < 0.001) and were independently associated with the occurrence of an adverse outcome. Optimal prognostic thresholds were 10.5 kPa for LS and 2 for the Anali score without Gd. Hazard ratios (95% confidence interval) were 2.07 (1.06-4.06) and 3.78 (1.67-8.59), respectively. The use in combination of these 2 thresholds allowed us to separate patients into low-, medium-, and high-risk groups for developing adverse outcomes. The 5-year cumulative rates of adverse outcome in these 3 groups were 8%, 16%, and 38% (P < 0.001), respectively. DISCUSSION: The combined use of MRI and vibration-controlled transient elastography permits easy risk stratification of patients with PSC.

Prognostic Value of Noninvasive Fibrosis Scores in Primary Biliary Cholangitis.

OBJECTIVE: To explore the prognostic value of several widely used noninvasive fibrosis scores (NIFS) for the mortality due to liver-related events in Chinese primary biliary cholangitis (PBC) population. STUDY DESIGN: An observational study. PLACE AND DURATION OF STUDY: Department of Infectious Diseases and Hepatology, the Second Hospital of Shandong University, Jinan, China, from August 2008 to July 2018. METHODOLOGY: Patients were diagnosed as PBC when they fulfilled at least two of the following criteria: presence of antimitochondrial antibodies (AMA), or other PBC-specific autoantibodies; and/or biochemical evidence of cholestasis; and/or histological evidence of liver biopsy. Patients were excluded if they were just started UDCA administration within last year, followed up for less than a year, diagnosed as overlap syndrome, or suffered from other coexisting hepatic diseases. Clinical data were recorded and scores of 11 generally accepted NIFS were calculated. Cox proportional hazards model was performed to explore independent predictors of liver-related mortality. RESULTS: Sixty-five PBC patients were included in the current cohort. Five patients died due to liver-related events during a median of 35-month follow-up. The 5-year cumulative survival rate was 88.4%. Non-survival patients were characterised with lower platelet count (p=0.049), lower level of albumin (p=0.018), higher fibrosis index (p<0.001) and higher Doha score (p=0.006). Multivariate Cox regression analysis identified fibrosis index (HR 17.449, 95% CI 1.410-215.989, p=0.026) and Doha score (HR 1.782, 95% CI 1.146-2.771, p=0.010) as independent predictors for liver-related mortality of PBC patients. CONCLUSION: Fibrosis index and Doha score could serve as valuable prognostic factors for liver-related mortality in Chinese PBC population.

Timing of Cholecystectomy after Emergent Endoscopic Retrograde Cholangiopancreatography for Cholangitis.

Debate remains regarding the timing of laparoscopic cholecystectomy after emergent endoscopic retrograde cholangiopancreatography (ERCP) for acute cholangitis. We hypothesized that patients undergoing early laparoscopic cholecystectomy would have fewer operative complications and a lower conversion rate. This study is a retrospective review of an ERCP database from 2012 to 2016 of adults with a diagnosis of cholangitis secondary to choledocholithiasis who underwent ERCP followed by a laparoscopic cholecystectomy. Patient demographics, ERCP details, timing of operation (<72 hours vs >72 hours after ERCP), complications, and mortality were recorded. Analysis included chi-square, Fisher's exact, and Wilcoxon rank-sum tests, where appropriate. In the 127 patients (65 per cent male; median age, 67 years; 48 (38%) early surgery), there were no differences in demographics, BMI, vital signs, or laboratory values. Patients in the late surgery group were more likely to have a Charlson Comorbidity Index > 3 (P = 0.002), require pre-operative endoscopic sphincterotomy (P < 0.002), need pre-operative insertion of a ductal stent (P < 0.03), and had more postoperative complications (P = 0.04). Patients in the late laparoscopic cholecystectomy group had more comorbidities and suffered more complications.

[A retrospective analysis of clinical characteristics and mortality risks in elderly patients with acute cholecystitis and cholangitis].

Objective: To analyze the clinical characteristics and explore the risk predictors on mortality in elderly patients with acute cholecystitis and cholangitis. Methods: We conducted a retrospective analysis of elderly patients hospitalized in the Second Medical Center of General Liberation Army Hospital for acute cholecystitis and cholangitis during 2000 to 2018. Clinical data and risk predictors on mortality were assessed. The patients were stratified into three groups based on age:Ⅰ (65-74 years old),Ⅱ (75-84 years old), and Ⅲ (≥85 years old). Logistic regression analysis was used to identify the predictors of mortality. Results: A total of 574 patients were finally enrolled with the mean age 87.6 years including 191 in group Ⅰ, 167 in group Ⅱ, and 216 in group Ⅲ. The main cause of acute cholecystitis and cholangitis was gallstone (76.3%),and the main symptom was abdominal pain (62.9%),followed by chills(62.5%),fever(59.8%),jaundice (47.2%) and septic shock(26.3%). Cholecystitis was the most common diagnosis in groups Ⅰ and Ⅱ,whereas it was cholangitis in group Ⅲ. Percutaneous transhepatic biliary/gallbladder drainage (PTBD/PTGD) and endoscopic retrograde cholangiopancreatography (ERCP) were administrated more frequently in groups Ⅲ. A total of 35 patients (6.1%) died during follow-up. Senior in age (OR=11.1),the Charlson comorbidity index (OR=19.5),cancers (OR=9.6),blood stream infections (OR=7.4),severity of cholecystitis and cholangitis (OR=4.2) were risk factors associated with mortality. Conclusions: Even in the elderly patients with acute cholecystitis and cholangitis,comorbidity is one of the main factors affecting clinical outcomes. Due to the poor performance, this group of population presents more severe disease and undergoes conservative treatment strategies.

Unchanged mortality in patients with acute cholangitis despite an increase in malignant etiologies - a 25-year epidemiological study.

Background and aims: Acute cholangitis (AC) is a rare but serious condition, with an incidence of 7.0 per 10,000 people and mortality rates up to 10%. The aim of this study was to describe changes in obstruction etiology, comorbidities, clinical factors, and mortality among AC patients during a 25-year period. Methods: Using a database of 11,563 consecutive ERCP-procedures performed from 1990-2015 at Odense University Hospital, we identified all AC cases during that period. Clinical and epidemiological data were collected from the database and the Danish Patient Registry. Association with 30-day mortality was investigated using multiple logistic regression analysis with adjustment for confounding factors. Results: In total, 775 consecutive and individual cases of AC were included. Among cases, 42% (n = 326) were of malignant etiology, with an increasing incidence over time (regression coefficient [95% CI]: 0.03 [0.01-0.04] per year; p = .01). Mean Charlson Comorbidity Index was 1.4, with an increase over time (regression coefficient [95% CI]: 0.04 [0.03-0.05] per year; p < .01). Malignant obstruction etiology was associated with 30-day mortality (OR [95% CI]: 1.11 [1.04-1.18]; p < .01). Overall 30-day mortality was 12% (n = 91). After adjustment for confounding factors, no significant changes in 30-day mortality were observed over time (OR [95% CI]: 1 [1-1.00]; p = .91 per year). Conclusion: Significant increases in the incidence of malignant obstruction etiology and severity of comorbidities among AC patients were observed during the study period. Despite those findings, 30-day mortality remained unchanged, potentially reflecting a general improvement in the management of AC.

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.

Biliary Atresia-associated Cholangitis: The Central Role and Effective Management of Bile Lakes.

OBJECTIVES: Cholangitis and bile lakes are incompletely understood complications after portoenterostomy (PE). We investigated relationships between recurrent cholangitis, bile lakes, and clinical outcomes as well as surgical management of bile lakes. METHODS: In this retrospective observational single institution study medical records and imaging studies of all patients who had undergone PE for biliary atresia during 1987 to 2016 (N = 61) were reviewed. We related occurrence of cholangitis episodes with the presence of intrahepatic bile lakes, patient characteristics, and PE outcomes. Risk factors for recurrent cholangitis and bile lakes, and management of bile lakes were analyzed. RESULTS: Despite routine antibiotic prophylaxis median of 3.0 cholangitis episodes (0.75 episodes/year) occurred in 48 (79%) patients. Intrahepatic bile lakes were discovered in 8 (13%) patients by 16 months after PE. Overall, 54% had survived with their native liver at median age of 7.3 years and 28 (46%) patients had ≥1 cholangitis episodes/year. Number and frequency of cholangitis episodes were >5 times higher among patients with bile lakes (P < 0.001). Six patients underwent Roux-en-Y bile lake-jejunostomy, resulting in regression/disappearance of bile lakes and normalization of serum bilirubin in 5 with reduction of median yearly cholangitis rate from 8.8 to 1.1 (P = 0.028) and native liver survival of 6.3 (range, 1.3-17) years after the operation. CONCLUSIONS: Bile lakes are a significant risk factor for recurrent cholangitis after PE and efficiently treated by operative intestinal drainage providing prolonged jaundice-free native liver survival. Bile lakes should be actively screened among patients presenting with recurrent cholangitis after PE.

Inflammation, Active Fibroplasia, and End-stage Fibrosis in 172 Biliary Atresia Remnants Correlate Poorly With Age at Kasai Portoenterostomy, Visceral Heterotaxy, and Outcome.

Published histologic studies of the hilar plate or entire biliary remnant at the time of Kasai portoenterostomy (KHPE) have not provided deep insight into the pathogenesis of biliary atresia, relation to age at surgery, prognosis or the basis for successful drainage. We report detailed histologic findings in 172 centrally reviewed biliary remnants with an average of 6 sections per subject. Active lesions were classified as either necroinflammatory (rare/clustered in a few subjects) or active concentric fibroplasia with or without inflammation (common). Inactive lesions showed bland replacement by collagen and fibrous cords with little or no inflammation. Heterogeneity was common within a given remnant; however, relatively homogenous histologic patterns, defined as 3 or more inactive or active levels in the hepatic ducts levels, characterized most remnants. Homogeneity did not correlate with age at KHPE, presence/absence of congenital anomalies at laparotomy indicative of heterotaxy and outcome. Remnants from youngest subjects were more likely than older subjects to be homogenously inactive suggesting significantly earlier onset in the youngest subset. Conversely remnants from the oldest subjects were often homogenously active suggesting later onset or slower progression. More data are needed in remnants from subjects <30 days old at KHPE and in those with visceral anomalies. Prevalence of partially preserved epithelium in active fibroplastic biliary atresia lesions at all ages suggests that epithelial regression or injury may not be a primary event or that reepithelialization is already underway at the time of KHPE. We hypothesize that outcome after KHPE results from competition between active fibroplasia and reepithelialization of retained, collapsed but not obliterated lumens. The driver of active fibroplasia is unknown.

Effect of preoperative cholangitis on prognosis of patients with hilar cholangiocarcinoma: A systematic review and meta-analysis.

BACKGROUND: The aim of this study was to compare the clinical outcomes between patients with preoperative cholangitis and noncholangitis patients to determine whether the preoperative cholangitis would be able to serve as an independent predictive factor on hilar cholangiocarcinoma (HCC) outcomes. METHODS: A systematic literature search for reported preoperative cholangitis in patients with hilar cholangiocarcinoma was performed in 4 databases: PubMed, Web of Science, Embase, and the Cochrane Library, published from 1979 to 2017. RESULTS: In total, the initial search identified 1228 articles. Of these studies only 9 studies met the inclusion criteria and were included in this analysis. Differences between preoperative cholangitis existing and noncholangitis patients were observed in terms of mortality (RR = 2.29; 95% CI = 1.48-3.52; P = .0002), overall morbidity (RR = 1.15;95% CI = 1.00-1.32; P = .04), Liver failure (RR = 1.15;95% CI = 1.00-1.32; P = .04), Infection (RR = 1.52;95% CI = 1.16-2.00; P = .003), sepsis (RR = 2.40;95% CI = 1.25-4.5; P = .008). CONCLUSIONS: The results lend support to the notion that in hilar cholangiocarcinoma patients, the existence of preoperative cholangitis is statistically associated with the higher postoperative mortality and morbidity. Also that it increases the risk of liver failure and infection. therefore, it is very important to properly control the preoperative cholangitis before surgery.

Clinical applicability of Tokyo guidelines 2018/2013 in diagnosis and severity evaluation of acute cholangitis and determination of a new severity model.

OBJECTIVE: To determine the diagnostic accuracy of Tokyo guidelines (TG) 2018/2013 (TG18/TG13) and predictors of poor prognosis in acute cholangitis. METHODS: Retrospective 1-year study of consecutive hospital admissions for acute cholangitis. Prognosis was defined in terms of 30 d in-hospital mortality. RESULTS: Of the 183 patients with acute cholangitis, diagnostic accuracy based on Charcot's triad, TG07 and TG18/TG13 was 67.8, 86.9 and 92.3% (p < .001), respectively. Regarding severity based on TG18/TG13, 30.6% of cases were severe. A poor prognosis was found in 10.9% of patients. After multivariate analysis, systolic blood pressure <90 mmHg (OR 11.010; p < .001), serum albumin <3 g/dL (OR 1.355; p = .006), active oncology disease (OR 3.818; p = .006) and malignant aetiology of obstructive jaundice (OR 2.224; p = .021) were independent predictors of poor prognosis. The discriminative ability of the model with these four variables was high (AUROC 0.842; p < .001), being superior to TG18/TG13 (AUROC 0.693; p = .005). CONCLUSIONS: TG18/TG13 showed high diagnostic accuracy in acute cholangitis. Compared with TG18/TG13, the simplified severity model ≥2 allows easy selection of patients who will benefit from admission to the intensive care unit and early biliary decompression.

Tokyo Guidelines 2018: diagnostic criteria and severity grading of acute cholangitis (with videos).

Although the diagnostic and severity grading criteria on the 2013 Tokyo Guidelines (TG13) are used worldwide as the primary standard for management of acute cholangitis (AC), they need to be validated through implementation and assessment in actual clinical practice. Here, we conduct a systematic review of the literature to validate the TG13 diagnostic and severity grading criteria for AC and propose TG18 criteria. While there is little evidence evaluating the TG13 criteria, they were validated through a large-scale case series study in Japan and Taiwan. Analyzing big data from this study confirmed that the diagnostic rate of AC based on the TG13 diagnostic criteria was higher than that based on the TG07 criteria, and that 30-day mortality in patients with a higher severity based on the TG13 severity grading criteria was significantly higher. Furthermore, a comparison of patients treated with early or urgent biliary drainage versus patients not treated this way showed no difference in 30-day mortality among patients with Grade I or Grade III AC, but significantly lower 30-day mortality in patients with Grade II AC who were treated with early or urgent biliary drainage. This suggests that the TG13 severity grading criteria can be used to identify Grade II patients whose prognoses may be improved through biliary drainage. The TG13 severity grading criteria may therefore be useful as an indicator for biliary drainage as well as a predictive factor when assessing the patient's prognosis. The TG13 diagnostic and severity grading criteria for AC can provide results quickly, are minimally invasive for the patients, and are inexpensive. We recommend that the TG13 criteria be adopted in the TG18 guidelines and used as standard practice in the clinical setting. Free full articles and mobile app of TG18 are available at: http://www.jshbps.jp/modules/en/index.php?content_id=47. Related clinical questions and references are also included.

Biliary Complications in Recipients of Living-Donor Liver Transplant: A Single-Center Review of 120 Patients.

OBJECTIVES: Biliary complications are common after living-donor liver transplant. This retrospective study reviewed our experience with biliary complications in recipients of living-donor liver transplant. MATERIALS AND METHODS: Over our 9-year study period, 120 patients underwent living-donor liver transplant. Patients were divided into 2 groups, with group A having biliary complications and group B without biliary complications. Both groups were compared, and different treatment modalities for biliary complications were evaluated. RESULTS: Group A included 45 patients (37.5%), whereas group B included 75 patients (62.5%). Biliary complications included bile leak in 17 patients (14.2%), biliary stricture in 11 patients (9.2%), combined biliary stricture with bile leak in 15 patients (12.5%), and sphincter of Oddi dysfunction and cholangitis in 1 patient each (0.8%). Cold ischemia time was significantly longer in group A (P = .002). External biliary drainage was less frequently used in group A (P = .031). Technical success rates of endoscopic biliary drainage and percutaneous transhepatic biliary drainage were 68.3% and 41.7%. Survival rate following relaparotomy for biliary complications was 62.5%. CONCLUSIONS: Graft ischemia is an important risk factor for biliary complications. Bile leaks can predispose to anastomotic strictures. The use of external biliary drainage seems to reduce the incidence of biliary complications. Endoscopic and percutaneous trans-hepatic approaches can successfully treat more than two-thirds of biliary complications. Relaparotomy can improve survival outcomes and is usually reserved for patients with intractable biliary complications.

Cholangitis Lenta: A Clinicopathologic Study of 28 Cases.

Cholangitis lenta, also known as ductular cholestasis, cholangiolar cholestasis, or subacute nonsuppurative cholangitis, is an uncommon type of cholangitis characterized by ductular reaction with inspissated bile in dilated ductules. The literature on this unique entity has been limited to only a few studies based on a very limited number of cases, which importantly suggest an association with sepsis and/or intra-abdominal infection. The clinical, laboratory, and histologic features of 28 cases of cholangitis lenta are herein investigated. Twenty-five (89.3%) patients were liver transplant recipients. Most notably, the majority of patients showed clinical signs and symptoms of sepsis, and positive microbiology cultures were demonstrated in 24 (85.7%) patients. Significantly, 15 (53.6%) patients died during their hospitalization, ranging from 2 days to 5 months after the initial liver biopsy that showed histologic features of cholangitis lenta. Among the 13 discharged patients, including 2 who received retransplantation, 4 (14.3%) subsequently died of pneumonia, graft dysfunction, or fungal infection within 7 months to 9.3 years. Only 9 (32.1%) patients were alive at the last follow-up, with the follow-up time ranging from 3.8 to 10.4 years. Our data show that the finding of cholangitis lenta on liver biopsy is thus frequently associated with sepsis and with a high mortality rate. Therefore, accurate diagnosis of this condition on liver biopsy is imperative as it is an indication that the patient may have a potentially life threatening condition that requires immediate medical attention and management.

Cholangiohydatidosis: an Infrequent Cause of Obstructive Jaundice and Acute Cholangitis.

BACKGROUND: One of the evolutionary complications of hepatic echinococcosis (HE) is cholangiohydatidosis, a rare cause of obstructive jaundice and cholangitis. The aim of this study was to describe the results of surgical treatment on a group of patients with cholangiohydatidosis and secondary cholangitis in terms of post-operative morbidity (POM). MATERIAL AND METHOD: Case series of patients operated on for cholangiohydatidosis and cholangitis in the Department at Surgery of the Universidad de La Frontera and the Clínica Mayor in Temuco, Chile between 2004 and 2014. The minimum follow-up time was six months. The principal outcome variable was the development of POM. Other variables of interest were age, sex, cyst diameter, hematocrit, leukocytes, total bilirubin, alkaline phosphatase and transaminases, type of surgery, existence of concomitant evolutionary complications in the cyst, length of hospital stay, need for surgical re-intervention and mortality. Descriptive statistics were calculated. RESULTS: A total of 20 patients were studied characterized by a median age of 53 years, 50.0% female and 20.0% having two or more cysts with a mean diameter of 13.3 ± 6.3 cm. A median hospital stay of six days and follow-up of 34 months was recorded. POM was 30.0%, re-intervention rate was 10.0% and mortality rate was 5.0%. CONCLUSION: Cholangiohydatidosis is a rare cause of obstructive jaundice and cholangitis associated with significant rates of POM and mortality.

Characteristics, aetiology, antimicrobial resistance and outcomes of bacteraemic cholangitis in patients with solid tumours: A prospective cohort study.

OBJECTIVES: To asses the clinical features, aetiology, antimicrobial resistance and outcomes of bacteraemic cholangitis in patients with solid tumours (ST). METHODS: All consecutive episodes of bacteraemia in hospitalized patients were prospectively analysed (2006-2015). RESULTS: Of 1852 episodes of bacteraemia, 750 involved patients with ST. Among them, 173 episodes (23%) were due to cholangitis. The most frequent neoplasms were hepato-biliary-pancreatic tumours (68.2%) and gastrointestinal cancer (18.5%); 57.2% of patients had a biliary stent in place. The most frequent causative agents were Escherichia coli (39.3%) followed by Klebsiella pneumoniae (15.1%) and Enterococcus faecium (7.8%). Forty-one episodes (18.7%) were caused by multidrug-resistant (MDR) microorganisms. Patients with a second episode of cholangitis were more likely to have an MDR isolate and to had received inadequate empirical antibiotic therapy. 7-day and 30-day case-fatality rates were 7.6% and 26%, respectively. The only risk factors independently associated with 30-day case-fatality rate were corticosteroids and malignancy-related complications. CONCLUSIONS: Bacteraemic cholangitis is frequent in patients with ST, and is mainly caused by Enterobacteriaceae and E. faecium. The emergence of MDR is of special concern, particularly in patients with a second episode of bacteraemia. Case-fatality rates are high, especially among patients receiving corticosteroids and presenting malignancy-related complications.

Association of Admission Laboratory Values and the Timing of Endoscopic Retrograde Cholangiopancreatography With Clinical Outcomes in Acute Cholangitis.

Importance: Acute cholangitis (AC), particularly severe AC, has historically required urgent endoscopic decompression, although the timing of decompression is controversial. We previously identified 2 admission risk factors for adverse outcomes in AC: total bilirubin level greater than 10 mg/dL and white blood cell count greater than 20 000 cells/µL. Objectives: To validate previously identified prognostic factors in AC, evaluate the effect of timing of endoscopic retrograde cholangiopancreatography on clinical outcomes, and compare recent experience with AC vs an historical cohort. Design, Setting, and Participants: A retrospective analysis (2008-2015) of patients with AC (validation cohort, n = 196) was conducted at 2 academic medical centers to validate predictors of adverse outcome. Timing of endoscopic retrograde cholangiopancreatography and outcome were stratified by severity using the Tokyo Guidelines for acute cholangitis diagnosis. Outcomes for the validation cohort were compared with the derivation cohort (1995-2005; n = 114). Data analysis was conducted from July 1, 2015, to September 9, 2015. Main Outcomes and Measures: Death and a composite outcome of death or organ failure. Results: The median age of patients in the derivation cohort was 54 years (interquartile range, 40-65 years) and in the validation cohort was 59 years (45-67 years). Multivariate logistic regression analysis of the validation cohort confirmed white blood cell count of more than 20 000 cells/µL (odds ratio, 3.4; 95% CI, 1.2-9.5; P = .02) and total bilirubin level of more than 10 mg/dL (odds ratio, 5.4; 95% CI, 1.8-16.4; P = .003) as independent risk factors for poor outcomes. In the validation cohort, timing of endoscopic retrograde cholangiopancreatography was not significantly different between those with and without an adverse outcome, even when stratified by AC severity (moderate: median, 0.6 hours [interquartile range (IQR), 0.5-0.9] vs 1.7 hours [IQR, 0.7-18.0] and severe: median, 10.6 hours [IQR, 1.2-35.1] vs 25.5 hours [IQR, 15.5-58.5] for those with and without adverse events, respectively). Patients in the validation cohort had a shorter hospital length of stay (median, 7 days [IQR, 4-10 days] vs 9 days [IQR, 5-16 days]) and lower rate of intensive care unit admission (26% vs 82%), despite a higher rate of severe cholangitis (n = 131 [67%] vs n = 29 [25%]). There were no significant differences in the composite outcome between the validation and derivation cohorts (22 [18.6%] vs 44 [22.4%]; P = .47). Adjusted analysis demonstrated decreased mortality in the validation cohort (odds ratio, 0.3; 95% CI, 0.1-0.7; P = .01). Conclusions and Relevance: White blood cell count greater than 20 000 cells/µL and total bilirubin level greater than 10 mg/dL are independent prognostic factors for adverse outcomes in AC. Consideration should be given to include these criteria in the Tokyo Guidelines severity assessment. Timing of endoscopic retrograde cholangiopancreatography does not appear to affect clinical outcomes in these patients. Management of AC has improved with time, with an overall shorter hospital length of stay, lower rate of intensive care unit admission, and a decreased adjusted mortality, demonstrating improvements in care efficiency and delivery.

A US Multicenter Study of Safety and Efficacy of Fully Covered Self-Expandable Metallic Stents in Benign Extrahepatic Biliary Strictures.

BACKGROUND: Endoscopic therapy is considered first line for management of benign biliary strictures (BBSs). Placement of plastic stents has been effective but limited by their short-term patency and need for repeated procedures. Fully covered self-expandable metallic stents (FCSEMSs) offer longer-lasting biliary drainage without the need for frequent exchanges. AIMS: The aim of this study was to assess the efficacy and safety of FCSEMS in patients with BBS. METHODS: A retrospective review of all patients who underwent ERCP and FCSEMS placement at five tertiary referral US hospitals was performed. Stricture resolution and adverse events related to ERCP and/or stenting were recorded. RESULTS: A total of 123 patients underwent FCSEMS placement for BBS and 112 underwent a subsequent follow-up ERCP. The mean age was 62 years (±15.6), and 57% were males. Stricture resolution occurred in 81% of patients after a mean of 1.2 stenting procedures (mean stent dwell time 24.4 ± 2.3 weeks), with a mean follow-up of 18.5 months. Stricture recurrence occurred in 5 patients, and 3 patients required surgery for treatment of refractory strictures. Stent migration (9.7%) was the most common complication, followed by stent occlusion (4.9%), cholangitis (4.1%), and pancreatitis (3.3%). There was one case of stent fracture during removal, and one stent could not be removed. There was one death due to cholangitis. CONCLUSIONS: Majority of BBS can be successfully managed with 1-2 consecutive FCSEMS with stent dwell time of 6 months.