Doppler-Guided Second-Look Endoscopy in Peptic Ulcer Bleeding: A Randomised Controlled Trial.

BACKGROUND: Endoscopic treatment guided by Doppler endoscopic probes (DEPs) during index endoscopy may be associated with improved outcome in patients with peptic ulcer bleeding (PUB). As competencies for DEP evaluation are not always available for index endoscopy, we examined the outcome associated with DEP evaluation at second-look endoscopy. METHODS: The study was designed as a non-blinded, parallel group, randomised controlled trial. Patients admitted with PUB from Forrest Ia-IIb ulcers, controlled by endoscopic therapy, were randomised (1:1 ratio) to second-look endoscopy <24 h with DEP evaluation of the bleeding ulcer or continued standard treatment. Patients were followed up for 30 days. The primary outcome was rebleeding. Secondary outcomes included the number of transfusions, length of hospital stay, and 30-day mortality. RESULTS: A total of 62 patients were included. At second-look endoscopy, 91% (29/32) of patients had a positive DEP signal at the ulcer base and were treated with contact thermal therapy (n = 29), injection of diluted adrenaline (n = 23), and haemoclips (n = 7). Among the 32 patients treated with DEP evaluation, only one rebled (3%) compared to four patients (13%) in the control group (p = 0.20). There were no differences in the secondary outcomes between groups, and there were no complications related to DEP evaluation. CONCLUSIONS: Second-look endoscopy with DEP-guided evaluation and treatment is safe and associated with a very low risk of rebleeding (3%) in patients with PUB. Second-look endoscopy with DEP evaluation may be considered in selected PUB patients at high risk of rebleeding, and may represent an alternative to the use of DEP for index endoscopy. Nevertheless, we did not find that second-look endoscopy with DEP evaluation significantly improved patient outcome compared to standard treatment.

Investigating hypozincemia and validity of plasma zinc measurements in infected patients.

Hypozincemia is a well-known phenomenon in patients with infection caused by the activation of the acute phase response (APR). Zn status is still based upon plasma Zn levels in venous blood samples. Recent trials have questioned the validity of this measurement in infected patients. The aim of this study was to assess plasma levels of Zn, albumin and Zinc-binding capacity in patients during and following infection. Furthermore, to assess if an assay for albumin-corrected Zn could potentially replace or add knowledge to existing tools for assessment of Zinc-status. A prospective clinical observational trial was conducted. Associations between P-Zn, -Albumin, -Albumin-corrected Zn and Zn binding capacity were analyzed. Analyzes were based upon two venous blood samples drawn during and following infection, respectively. Twenty-three patients admitted to a medical ward showing paraclinical signs of infection were included in the study. Significantly lower levels of Zn and albumin were found during infection compared with the levels post-infection. These findings corresponded to the changes found in Zn binding capacity. About 52% of patients were deemed Zn deficient by plasma Zn levels during infection but after applying the correction for P-Albumin, all patients were found to be within normal ranges of Zn levels. Furthermore, we found no statistically significant difference between albumin-corrected Zn during infection and P-Zn post-infection. The new assay was found to accurately estimate the 'true' Zn levels in infected patients. Based on our findings, we propose albumin-corrected P-Zn as a promising new tool, which may result in more precise diagnostics and treatment.

Rebleeding in peptic ulcer bleeding - a nationwide cohort study of 19,537 patients.

BACKGROUND: Rebleeding is a frequent complication of peptic ulcer bleeding (PUB). The associated prognosis remains rather unclear because previous studies generally also included non-ulcer lesions. OBJECTIVE: We aimed to identify predictors for rebleeding; clarify the prognostic consequence of rebleeding; and develop a score for predicting rebleeding. METHODS: Nationwide cohort study of consecutive patients presenting to hospital with PUB in Denmark from 2006-2014. Logistic regression analyses were used to identify predictors for rebleeding, evaluate the association between rebleeding and 30-day mortality, and develop a score to predict rebleeding. Patients with persistent bleeding were excluded. RESULTS: Among 19,258 patients (mean age 74 years, mean ASA-score 2.4), 10.8% rebled, and 10.2% died. Strongest predictors for rebleeding were endoscopic high-risk stigmata of bleeding (Odds Ratio (OR): 2.12 [95% Confidence Interval (CI): 1.91-2.36]), bleeding from duodenal ulcers (OR: 1.87 [95% CI: 1.69-2.08]), and presentation with hemodynamic instability (OR: 1.55 [95% CI: 1.38-1.73]). Among patients with all three factors (7.9% of total), 24% rebled, 50% with rebleeding failed endoscopic therapy, and 23% died. Rebleeding was associated with increased mortality (OR: 2.04 [95% CI: 1.78-2.32]). We were unable to develop an accurate score to predict rebleeding. CONCLUSION: Rebleeding occurs in ∼10% of patients with PUB and is overall associated with a two-fold increase in 30-day mortality. Patients with hemodynamic instability, duodenal ulcers, and high-risk endoscopic stigmata are at highest risk of rebleeding. When rebleeding occurs in such patients, consultation with surgery and/or interventional radiology should be obtained prior to repeat endoscopy.

Albumin-corrected Zn and available free Zn-binding capacity as indicators of Zn status - potential for clinical implementation.

We have established and describe two measurement procedures to diagnose possible zinc (Zn) deficiency; albumin-corrected Zn concentration and available free Zn-binding capacity. Reference intervals for both biomarkers were established in healthy adults from the Danish population. The clinical usefulness of the measurement procedures was investigated in patients with cirrhosis and in patients given parenteral nutrition due to short bowel syndrome. The results of both methods indicate that there is a risk of overdiagnosing Zn deficiency based on low plasma Zn concentrations. Needless Zn supplementation may thus be avoided by using the albumin-corrected Zn concentration or available free Zn-binding capacity.

Hypotension develops one to two hours before other symptoms in peptic ulcer rebleeding; a matched cohort study.

BACKGROUND: Rebleeding is a frequent complication of peptic ulcer bleeding (PUB) and is associated with increased mortality. Blood pressure and heart rate are two easy non-invasive measurements to evaluate the hemodynamics and therefore a standard observation during hospitalization. OBJECTIVE: We aimed to investigate the dynamics of systolic blood pressure and heart rate up to time of peptic ulcer rebleeding. DESIGN: Retrospective matched cohort study. Hemodynamics in patients with peptic ulcer rebleeding was compared to hemodynamics in a matched control group consisting of patients with PUB without rebleeding. Blood pressure and heart rate in the six hours up to diagnosis of rebleeding was compared with baseline in the case cohort as well as with the matched control group. RESULTS: Thirty-eight patients with peptic ulcer rebleeding and 66 controls were included. Mean age was 75 years, 62% were males and 30-day mortality was 23%. Baseline systolic blood pressure in cases was 114 mmHg. Compared to baseline, we found significant decrease in systolic blood pressure two hours before rebleeding (4 mmHg; p = 0.041) and one hour before rebleeding (14 mmHg; p = 0.0002). Mean systolic blood pressure 30 min before rebleeding was 89 mmHg. No significant change was found in heart rate (p = 0.99). In the control group no change was found in systolic blood pressure or heart rate. CONCLUSION: In patients with peptic ulcer rebleeding, hypotension develops 1-2 h before other symptoms of rebleeding. Thus, close monitoring of blood pressure is needed in order to ensure early identification of rebleeding in high-risk patients.

Whole genome sequencing identifies rare germline variants enriched in cancer related genes in first degree relatives of familial pancreatic cancer patients.

First-degree relatives (FDRs) of familial pancreatic cancer (FPC) patients have increased risk of developing pancreatic ductal adenocarcinoma (PDAC). Investigating and understanding the genetic basis for PDAC susceptibility in FPC predisposed families may contribute toward future risk-assessment and management of high-risk individuals. Using a Danish cohort of 27 FPC families, we performed whole-genome sequencing of 61 FDRs of FPC patients focusing on rare genetic variants that may contribute to familial aggregation of PDAC. Statistical analysis was performed using the gnomAD database as external controls. Through analysis of heterozygous premature truncating variants (PTV), we identified cancer-related genes and cancer-driver genes harboring multiple germline mutations. Association analysis detected 20 significant genes with false discovery rate, q < 0.05 including: PALD1, LRP1B, COL4A2, CYLC2, ZFYVE9, BRD3, AHDC1, etc. Functional annotation showed that the significant genes were enriched by gene clusters encoding for extracellular matrix and associated proteins. PTV genes were over-represented by functions related to transport of small molecules, innate immune system, ion channel transport, and stimuli-sensing channels. In conclusion, FDRs of FPC patients carry rare germline variants related to cancer pathogenesis that may contribute to increased susceptibility to PDAC. The identified variants may potentially be useful for risk prediction of high-risk individuals in predisposed families.

Cohort profile and heritability assessment of familial pancreatic cancer: a nation-wide study.

BACKGROUND: Familial Pancreatic Cancer (FPC) is responsible for up to 10% of all cases of pancreatic ductal adenocarcinoma (PDAC). Individuals predisposed for FPC have an estimated lifetime risk of 16-39% of developing PDAC. While heritability of PDAC has been estimated to be 36% in a Nordic twin study, no heritability estimate specific on FPC has been reported. METHODS: A national cohort of Danish families with predisposition for FPC is currently included in a screening program for PDAC at Odense University Hospital. Family members included in the screening program were interviewed for pedigree data including: cases of PDAC among first-degree relatives (FDRs) and number of affected/unaffected siblings. Heritability for FPC in the predisposed families was assessed by doubling the estimated intra-class correlation coefficient (ICC) from a random intercept logistic model fitted to data on FDRs. RESULTS: Among families with predisposition for FPC, 83 cases of PDAC were identified. The median age at diagnosis of PDAC was 66 years, and median time from diagnosis to death was 7.6 months. A total of 359 individuals were found as unaffected FDRs of the 83 PDAC cases. The retrieved FDRs included a total of 247 individuals in sibship and 317 individuals in parent-offspring relatedness. We estimated an ICC of 0.25, corresponding to a narrow sense additive heritability estimate of 0.51 in the FPC family cohort. CONCLUSION: We have established a nation-wide cohort of FPC families to facilitate clinical and genetic studies on FPC. The estimated heritability of 51% prominently underlines a strong genetic background of FPC.

How dyspepsia, gastroesophageal reflux symptoms, and overlapping symptoms affect quality of life, use of health care, and medication - a long-term population based cohort study.

BACKGROUND AND AIM: The prevalence of gastroesophageal reflux symptoms (GERS) and dyspepsia is high. Overlapping of GERS and dyspepsia has been described to affect quality of life. However, studies are few. This long-term population-based study evaluates how GERS, dyspepsia, and overlapping symptoms, affect quality of life, and the use of health care and medication. METHODS: This study presents data for the control group of the randomised population study, HEP-FYN. At baseline 10,000 individuals, aged 40-65 years, received questionnaires at baseline and after 1, 5 and 13 years. The questionnaire included questions regarding demographics, use of health care resources, gastrointestinal symptoms (the Gastrointestinal Symptom Rating Scale (GSRS)), and the Short-Form 36-Item Health Survey (SF-36) to assess quality of life. RESULTS: Complete data was available for 4.403 individuals at 13-year follow-up. Of these 13.6% reported GERS only, 11.6% dyspepsia only, and 27.1% overlapping symptoms during follow-up. Individuals reporting overlapping symptoms had compared to individuals reporting GERS only or dyspepsia only more visits at general practitioner (last year:16.7% vs. 8.5% vs. 12.3%), more sick leave days (last month: 4.3% vs. 2.9% vs 0.7%), used more ulcer drugs (last month: 30.5% vs 16.4% vs 9.4%). In addition, individuals with overlapping symptoms reported a lower quality of life in all eight dimensions of SF-36 compared to individuals with GERS alone or dyspepsia alone. CONCLUSIONS: Overlapping symptoms was associated with lower quality of life scores and substantial use of health-care resources. Having solely GERS affected quality of life and health care use least.

Analysis of patterns of bacteremia and 30-day mortality in patients with acute cholangitis over a 25-year period.

INTRODUCTION: Acute cholangitis (AC) is a condition of bacterial infection in the biliary tract with a high mortality rate of around 10%. Direct association between presence of bacteremia and 30-day mortality among AC patients is sparsely investigated and remains unclear. AIMS AND METHODS: Our aim was to investigate association between bacteremia and 30-day mortality among patients with AC included over a period of 25 years. All AC patients that underwent endoscopic retrograde cholangiopancreatography (ERCP) at Odense University Hospital, between 1 January 1990 and 31 October 2015, were identified using a prospective ERCP database. Blood culture results from the patients along with antimicrobial resistance patterns were collected from a bacteremia research database. RESULTS: During the study period, 775 consecutive AC patients underwent ERCP and blood cultures were collected from 528 patients. Among these patients 48% (n = 260) had bacteremia. Overall, 30-day mortality in patients with blood cultures performed was 13% (n = 69). In patients with bacteremia, 30-day mortality was 19% (n = 49), compared to 7% (n = 20) in patients without bacteremia (p < .01). Presence of bacteremia was associated with increased 30-day mortality (OR [95% CI]: 3.43 [1.92-6.13]; p < .01) following adjustment for confounding factors. Among the species, bacteremia with Enterobacter cloacae was significantly associated with increased 30-day mortality (OR [95% CI]: 2.97 [1.16-7.62]; p = .02). CONCLUSION: Our results indicate that presence of bacteremia was associated with a nearly fourfold increase in 30-day mortality among AC patients.

Validation of a Simple Quality-of-Life Score for Identification of Minimal and Prediction of Overt Hepatic Encephalopathy.

Minimal hepatic encephalopathy (MHE) is underdiagnosed because most clinics refrain from psychometric testing. Diagnostic activities need to go up so patients with MHE can get the treatment their condition requires. The sickness impact profile questionnaire for covert hepatic encephalopathy (SIPCHE) score is based on quality-of-life outcomes and has been proposed as a simple, patient-administered diagnostic score for grade 1 and MHE. Validate the SIPCHE for MHE identification and overt hepatic encephalopathy (OHE) prediction. 110 patients with liver cirrhosis (age 60 years, Model for End-Stage Liver Disease score of 11.4, 80% blue-collar) provided information for SIPCHE scoring: gender, age, and four SIP statements: "I do not maintain balance (physically)," "I act irritable or impatient with myself," "I am not doing any of the usual physical recreation or activities," and "I am eating much less than usual." MHE was diagnosed using an abnormal continuous reaction time test and/or portosystemic encephalopathy syndrome test score. Patients were followed for 2.7 years on average. SIPCHE score positivity had high sensitivity (82%) but low specificity (38%) for MHE detection. Patients with an abnormal SIPCHE had a higher incidence of OHE during follow-up (35% vs. 14%, P = 0.05). OHE prediction sensitivity was 87% and exclusion sensitivity was 85%. The patients with an abnormal SIPCHE had twice as many subsequent episodes of OHE, and despite their high mortality, also a higher risk. An abnormal SIPCHE had a high sensitivity and low specificity for MHE identification. An abnormal SIPCHE was associated with a more than doubled risk of OHE, even with death as a competing event. SIPCHE could be used as a high-sensitivity, low-cost, surrogate marker of MHE in clinics without availability of psychometric tests and allow more patients to benefit from anti-MHE treatment.

Gene Expression Network Analysis of Precursor Lesions in Familial Pancreatic Cancer.

Purpose: High-grade pancreatic intraepithelial neoplasia (PanIN) are aggressive premalignant lesions, associated with risk of progression to pancreatic ductal adenocarcinoma (PDAC). A depiction of co-dysregulated gene activity in high-grade familial pancreatic cancer (FPC)-related PanIN lesions may characterize the molecular events during the progression from familial PanIN to PDAC. Materials and Methods: We performed weighted gene coexpression network analysis (WGCNA) to identify clusters of coexpressed genes associated with FPC-related PanIN lesions in 13 samples with PanIN-2/3 from FPC predisposed individuals, 6 samples with PDAC from sporadic pancreatic cancer (SPC) patients, and 4 samples of normal donor pancreatic tissue. Results: WGCNA identified seven differentially expressed gene (DEG) modules and two commonly expressed gene (CEG) modules with significant enrichment for Gene Ontology (GO) terms in FPC and SPC, including three upregulated (p < 5e-05) and four downregulated (p < 6e-04) gene modules in FPC compared to SPC. Among the DEG modules, the upregulated modules include 14 significant genes (p < 1e-06): ALOX12-AS1, BCL2L11, EHD4, C4B, BTN3A3, NDUFA11, RBM4B, MYOC, ZBTB47, TTTY15, NAPRT, LOC102606465, LOC100505711, and PTK2. The downregulated modules include 170 genes (p < 1e-06), among them 13 highly significant genes (p < 1e-10): COL10A1, SAMD9, PLPP4, COMP, POSTN, IGHV4-31, THBS2, MMP9, FNDC1, HOPX, TMEM200A, INHBA, and SULF1. The DEG modules are enriched for GO terms related to mitochondrial structure and adenosine triphosphate metabolic processes, extracellular structure and binding properties, humoral and complement mediated immune response, ligand-gated ion channel activity, and transmembrane receptor activity. Among the CEG modules, IL22RA1, DPEP1, and BCAT1 were found as highly connective hub genes associated with both FPC and SPC. Conclusion: FPC-related PanIN lesions exhibit a common molecular basis with SPC as shown by gene network activities and commonly expressed high-connectivity hub genes. The differential molecular pathology of FPC and SPC involves multiple coexpressed gene clusters enriched for GO terms including extracellular activities and mitochondrion function.

[Hereditary pancreatitis].

Hereditary pancreatitis (HP) is an autosomal dominant disease with 80% penetrance. HP is characterised by the debut of recurrent acute pancreatitis episodes during childhood with gradual progression to chronic pancreatitis. Patients with phenotypic HP have a significantly increased lifetime risk of developing pancreatic ductal adenocarcinoma (PDAC). Patients with HP represent a rare but important group of high-risk individuals in need of early diagnosis and screening for potential PDAC. The aim of this review is to provide an overview of the epidemiology, genetics and clinical aspects of HP.

Prediction of overt hepatic encephalopathy by the continuous reaction time method and the portosystemic encephalopathy syndrome test in clinically mentally unimpaired patients with cirrhosis.

BACKGROUND AND AIM: Predicting overt hepatic encephalopathy (OHE) is important because the condition is frequent, often requires hospitalization and is potentially preventable. The risk of OHE is related to pre-existing discrete cognitive defects, and for clinical practice it is recommended to apply two different psychometric tests to detect such deficits. We used the continuous reaction time test (CRT) and the portosystemic encephalopathy (PSE) syndrome test and examined their single and combined value for OHE prediction in cirrhosis patients. PATIENTS AND METHODS: We studied 130 clinically mentally unimpaired cirrhosis patients by the two tests and followed them for an average of 38.5 months. The CRT measures velocity and stability of motor reaction times to 150 repeated auditory signals. The PSE is a five sub-set paper-and-pencil test battery evaluating cognitive and psychomotor processing, speed and vision-motor coordination. We collected data on episodes of OHE during follow-up. The clinical course was analysed in patient groups according to the outcome of each test and of both tests together. No anti-HE treatment was initiated except for cases with OHE. RESULTS: At baseline, the CRT test was abnormal in 74 patients and the PSE in 47. During follow-up 35 patients (27%) experienced 74 OHE events. 23 patients with abnormal CRT experienced OHE (prediction sensitivity 65%). The PSE predicted OHE in 14 patients (prediction sensitivity 40%). One or both tests were abnormal in 87/130 (67%) and this predicted OHE in 27 patients (21%) (prediction sensitivity 77%). CONCLUSION: The CRT test was clinically useful in identifying two-thirds of clinically mentally unimpaired cirrhosis patients who later experienced OHE, and the use of both the CRT and PSE showed satisfactory prediction by identifying three-fourths of later OHE cases.

[17q12 deletion as a possible cause of agenesis of the dorsal pancreas and polycystic kidney disease].

This case report describes the diagnostic approach to an 18-year-old woman, known with Asperger's syndrome (AS). She presented with abdominal pain, weight loss, nausea and a loss of appetite. Ultrasound and magnetic resonance imaging showed polycystic kidney disease (PKD) and agenesis of the dorsal pancreas (DPA). Genetic testing revealed a 1.5 mega-base deletion at chromosome 17q12, which included the HNF1ß. She was diagnosed with 17q12 microdeletion syndrome, which could explain the presence of both DPA, PKD and AS.

[Autoimmune pancreatitis].

The aim of this review is to summarise the status of autoimmune pancreatitis (AIP), which is a rare disease, occasionally misdiagnosed as pancreatic cancer. AIP consists of two distinct types, which differ in histopathology, association with other diseases and age of onset. Clinically, it is characterised by obstructive jaundice and abdominal pain. The disease shows rapid response to steroids. Rituximab can also be used as induction therapy. Often long-term treatment is necessary to maintain remission.

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.

The cost effectiveness of Helicobacter pylori population screening-economic evaluation alongside a randomised controlled trial with 13-year follow-up.

BACKGROUND: Helicobacter pylori eradication improves dyspeptic symptoms in 8%-10%, prevents peptic ulcer and may reduce the risk of gastric cancer. Availability of a high quality diagnostic test and an effective treatment makes population screening and eradication of Helicobacter pylori an attractive option. AIM: To evaluate the cost effectiveness of Helicobacter pylori population screening and eradication. METHODS: Cost effectiveness analysis and cost utility analysis alongside randomised controlled trial with 13 years follow-up. The evaluation has a societal perspective. A random general population sample of 20 011 individuals aged 40-65 were randomised and invited in 1998-1999; 12 530 were enrolled and, of these, 8658 have been successfully followed up at 1, 5, and 13 years after intervention. Questionnaires included the quality of life instrument SF-36. From SF-36 responses an SF-6D score was derived and used for calculation of quality-adjusted life years. Register data on costs, use of health care resources and medication were obtained for all randomised individuals. The intervention was an invitation to Helicobacter pylori screening by in-office blood test; positive tests were validated by 13 C-urea breath test. Those who tested positive were offered eradication therapy. Main outcome measures were Incremental cost per quality-adjusted life year and life-years gained. RESULTS: Helicobacter pylori population screening and eradication with 13 years follow-up was not effective in regards to quality of life and the cost per screened person was higher than not screening (mean difference 11 269 DKK [95% CI: 3175-19 362]). The probability of being cost-effective was 80% at a threshold of 400 000 DKK (approximately 53,800 Euros) of willingness-to-pay per life-year gained. CONCLUSIONS: Helicobacter pylori population screening and eradication with 13 years follow-up was not effective in regards to quality of life and the cost of screening was higher than not screening.

IgG4-Related Sclerosing Cholangitis Involving the Intrahepatic Bile Ducts Diagnosed with Liver Biopsy.

IgG4-related disease is characterized by lymphoplasmacytic inflammation and fibrosis, often leading to mass-forming lesions in different organs. When IgG4-related disease affects the bile ducts, it is called IgG4-related sclerosing cholangitis. A 74-year-old male complained of dysphagia and abdominal pain. Endoscopic retrograde cholangiography and magnetic resonance cholangiography revealed bile duct changes suspicious of a bile duct carcinoma or cholangitis. Liver biopsy showed storiform fibrosis, lymphoplasmacytic infiltration, obliterative phlebitis, and a portal-based inflammatory nodule with expansion of a portal tract. Hot spots revealed 339 IgG4-positive cells per high power field (HPF) and an IgG4/IgG ratio of 72%. Eight months earlier, an inguinal lymph node had been removed, showing expanded interfollicular zones and increased plasma cells. Hot spots revealed 593 IgG4-positive cells and an IgG4/IgG ratio of 92%. The serum IgG4 of the patient was elevated nearly 10 times upper limit of normal. The diagnosis of IgG4-related sclerosing cholangitis associated with IgG4-related lymphadenopathy was made. There was good response to treatment with prednisolone and azathioprine. The differentiation of IgG4-related sclerosing cholangitis from primary sclerosing cholangitis and bile duct carcinoma is often difficult. Liver biopsy only rarely contributes to this setting, but we describe and report in detail a case where liver biopsy showed a portal-based inflammatory nodule with the characteristic features of this disease.

[Timing of endoscopic retrograde cholangiopancreatography in patients with acute cholangitis].

The optimal timing for endoscopic retrograde cholangiopancreatography (ERCP) in patients with acute cholangitis (AC) remains unclear. The aim of this review is to clarify associations between timing of ERCP and clinical outcomes in patients with AC by discussing the current literature. Briefly, it is shown that ERCP before 72 and 48 hours of hospital admission is associated with reduced incidences of composite adverse outcomes and organ failure, respectively. ERCP before 24 hours seems to be associated with reduced 30-day mortality. Thus, performance of ERCP with biliary decompression within 24 hours from time of hospital admission is recommended in patients with AC.