Hydatid hepatopleural fistula causing biliothorax: minimally invasive approach with ERCP stent placement and chest tube drainage: a case report.

Introduction and importance: Biliothorax and hydatid bilio-bronchial fistula (HBBF) are rare complications of hydatid cysts of the liver with high perioperative mortality. Case presentation and clinical discussion: The authors here report the case of a patient with a right massive pleural effusion with evidence of HBBF in imaging studies, who underwent surgical resection of a hydatid cyst of the liver 8 years ago. The patient was managed with intercostal chest tube drainage for biliothorax and endoscopic sphincterotomy with biliary stent placement for the re-establishment of internal biliary drainage, which ultimately allowed the fistulous tract to heal without any major surgical intervention. Conclusion: This article focuses on the successful management of the HBBF at our institution. Our findings emphasize the significance of early diagnosis and the criticality of implementing aggressive and early interventions to minimize complications and fatalities. By examining this specific case and reviewing existing literature, the authors have determined that endoscopic treatment appears to be a viable, secure, and efficacious option for addressing postoperative HBBF.

A survey on the incidence of common musculoskeletal side effects among the patients taking long-term anti-ulcerant therapies in Bangladesh.

Background: Proton pump inhibitors (PPIs) and H2 blockers are commonly prescribed medications to treat ulcers in the stomach and the upper part of the small intestine and prescribed for some other common gastrointestinal complications such as gastroesophageal reflux disease, esophagitis, irritable bowel syndrome, and dyspepsia. Previous studies claimed that, apart from other side effects, these anti-ulcerant therapies significantly altered bone mineral density by interfering with intestinal reabsorption of minerals and vitamin B12, and the most widely prescribed PPIs were significantly associated with increased risks of hip and spine fractures. However, the potential skeletal side effects of these antiulcerants are unknown in Bangladesh. Methods: To examine safety concerns of anti-ulcer therapies and their impact on musculoskeletal health among patients in Bangladesh, the present work surveyed 200 patients in five different hospitals from December 2019 to February 2020. Results: The current study revealed that most respondents (95 %) received PPIs for gastrointestinal indications while the rest were taking H2 receptor antagonists for their gastric ailments. Most patients taking PPIs alone (> 3 years; 95 % of respondents) claimed some unusual musculoskeletal side effects, such as weakness, flank pain, spasm of hands and feet, muscle aches, numbness, and tremor. About 61 % of patients taking PPIs experienced low back pain whereas the respondents with neck pain and knee joint pain were 10 % and 7 %, respectively. However, few osteopenia and osteoporotic incidences have been also recorded. Although further studies are required to confirm the impact of these antiulcerants on the bone, these patient responses suggest that these musculoskeletal side effects might have some links with altered bone metabolism. Conclusions: It is possible that anti-ulcerant therapies may worsen the bone metabolism of patients suffering from osteoporosis or other bone disorders, and awareness and precautions should be raised among the patients and clinicians for the careful administration of PPIs to patients suffering from bone disorders.

Development of a prognostic MRCP-score (DiStrict) for individuals with large-duct primary sclerosing cholangitis.

Background & Aims: Magnetic resonance cholangiopancreatography (MRCP) is used for the diagnosis and follow-up of individuals with primary sclerosing cholangitis (PSC). The aim of our study is to develop an MRCP-score based on cholangiographic findings previously associated with outcomes and assess its reproducibility and prognostic value in PSC. Methods: The score (DiStrict score) was developed based on the extent and severity of cholangiographic changes of intrahepatic and extrahepatic bile ducts (range 0-8) on 3D-MRCP. In this retrospective, multicentre study, three pairs of radiologists with different levels of expertise from three tertiary centres applied the score independently. MRCP examinations of 220 consecutive individuals with PSC from a prospectively collected PSC-cohort, with median follow-up of 7.4 years, were reviewed. Inter-reader and intrareader agreements were assessed via intraclass correlation coefficient (ICC). After consensus, the prognostic value of the score was assessed using Cox-regression and outcome-free survival rates were assessed via Kaplan-Meier estimates. Harrell's C-statistic was calculated. Results: Forty patients developed outcomes (liver transplantation or liver-related death). Inter-reader agreement between experienced radiologists was good (ICC 0.82; 95% CI 0.74-0.87, and ICC 0.81; 95% CI 0.70-0.87, respectively) and better than the agreement for the pair of experienced/less-experienced radiologists (ICC 0.48; 95% CI 0.05-0.72). Agreement between radiologists from the three centres was good (ICC 0.76; 95% CI 0.57-0.89). Intrareader agreement was good to excellent (ICC 0.85-0.93). Harrell's C was 0.78. Patients with a DiStrict score of 5-8 had 8.2-fold higher risk (hazard ratio 8.2; 95% CI 2.97-22.65) of developing outcomes, and significantly worse survival (p <0.001), compared to those with a DiStrict score of 1-4. Conclusions: The novel DiStrict score is reproducible and strongly associated with outcomes, indicating its prognostic value for individuals with PSC in clinical practice. Impact and implications: The diagnosis of primary sclerosing cholangitis (PSC) is based on magnetic resonance cholangiopancreatography (MRCP). However, the role of MRCP in the prognostication of PSC is still unclear. We developed a novel, simple, and reproducible risk-score, based on MRCP findings, that showed a strong association with prognosis in individuals with PSC (DiStrict score). This score can be easily used in clinical practice and thus has the potential to be useful in clinical trials and in patient counselling and management.

Quantitative magnetic resonance cholangiopancreatography metrics are associated with disease severity and outcomes in people with primary sclerosing cholangitis.

Background & Aims: People with primary sclerosing cholangitis (PSC) have a variable and often progressive disease course that is associated with biliary and parenchymal changes. These changes are typically assessed by magnetic resonance imaging (MRI), including qualitative assessment of magnetic resonance cholangiopancreatography (MRCP). Our aim was to study the association of novel objective quantitative MRCP metrics with prognostic scores and patient outcomes. Methods: We performed a retrospective study including 77 individuals with large-duct PSC with baseline MRCP images, which were postprocessed to obtain quantitative measures of bile ducts using MRCP+™. The participants' ANALI scores, liver stiffness by vibration-controlled transient elastography, and biochemical indices were collected at baseline. Adverse outcome-free survival was measured as the absence of decompensated cirrhosis, liver transplantation (LT), or liver-related death over a 12-year period. The prognostic value of MRCP+-derived metrics was assessed by Cox regression modelling. Results: During a total of 386 patients-years, 16 cases of decompensation, 2 LTs, and 5 liver-related deaths were recorded. At baseline, around 50% of the patients were classified as being at risk of developing disease complications. MRCP+ metrics, particularly those describing the severity of bile duct dilatations, were correlated with all prognostic factors. Univariate analysis showed that MRCP+ metrics representing duct diameter, dilatations, and the percentage of ducts with strictures and/or dilatations were associated with survival. In a multivariable-adjusted analysis, the median duct diameter was significantly associated with survival (hazard ratio 10.9, 95% CI 1.3-90.3). Conclusions: MRCP+ metrics in people with PSC correlate with biochemical, elastographic, and radiological prognostic scores and are predictive of adverse outcome-free survival. Lay summary: In this study, we assessed in people with primary sclerosing cholangitis (PSC) the association of novel objective quantitative MRCP metrics automatically provided by a software tool (MRCP+) with prognostic scores and patient outcomes. We observed that MRCP+ metrics in people with PSC correlate with biochemical, elastographic, and radiological prognostic scores and are predictive of adverse outcome-free survival.

Duct-to-duct biliary reconstruction with or without an intraductal removable stent in liver transplantation: The BILIDRAIN-T multicentric randomised trial.

Background & Aims: Biliary complications (BC) following liver transplantation (LT) are responsible for significant morbidity. No technical procedure during reconstruction has been associated with a risk reduction of BC. The placement of an intraductal removable stent (IRS) during reconstruction followed by its endoscopic removal showed feasibility and safety in a preliminary study. This multicentric randomised controlled trial aimed at evaluating the impact of an IRS on BC following LT. Methods: This multicentric randomised controlled trial was conducted in 7 centres from April 2015 to February 2019. Randomisation was done during LT when a duct-to-duct anastomosis was confirmed with at least 1 of the stump diameters ≤7 mm. In the IRS group, a custom-made segment of a T-tube was placed into the bile duct to act as a stake during healing and was removed endoscopically 4 to 6 months post LT. The primary endpoint was the incidence of BC (fistulae and strictures) within 6 months post LT. The secondary criteria were complications related to the IRS placement or extraction, including endoscopic retrograde cholangio-pancreatography (ERCP)-related complications. Results: In total, 235 patients were randomised: 117 in the IRS group and 118 in the control group. BC occurred in 31 patients (26.5%) in the IRS group vs. 24 (20.3%) in the control group (p = 0.27), including 16 (13.8%) and 15 (12.8%) strictures, respectively. IRS migration occurred in 24 patients (20.5%), cholangitis in 1 (0.9%), acute pancreatitis in 2 (1.8%), and difficulty during endoscopic extraction in 19 (19.4%). No predictive factor for BC was identified. Conclusions: IRS does not prevent BC after LT and may require specific endoscopic expertise for removal. Trial registration number ClinicalTrialsgov: NCT02356939 (https://clinicaltrials.gov/ct2/show/NCT02356939?term=NCT02356939&draw=2&rank=1). Lay summary: Liver transplantation is a life-saving treatment for many patients with end-stage liver disease. However, it can be associated with complications involving the bile duct reconstruction. Herein, the placement of a specific stent called an intraductal removable stent was trialled as a way of reducing bile duct complications in patients undergoing liver transplantation. Unfortunately, it did not help preventing such complications.

Delayed presentation of isolated ductal rupture of pancreatic head from blunt abdominal trauma managed conservatively: A case report.

Introduction: and Importance: Blunt abdominal injury causing significant and isolated major pancreatic injury is rare in adolescents and young adults, with a controversial approach to its management. Case presentation: We present our experience of diagnosis and management of the ductal injury of the pancreatic head (Grade III) in the setting of blunt abdominal trauma in a 20-year-old male diagnosed by a series of various tests including magnetic resonance cholangiopancreatography (MRCP) and managed by pigtail drainage and octreotide alone; contrary to the previous recommendations of management of high-grade pancreatic trauma through surgical approach or endoscopic retrograde cholangiopancreatography (ERCP) and stenting. Clinical discussion: Isolated ductal rupture of the pancreatic head can have delayed presentation within a window of time and can be diagnosed by a series of tests including hematological, biochemical, and radiological investigations. Conservative treatment is generally recommended for Grade I and II whereas a surgical approach is preferred for higher grade pancreatic injury. Conclusions: Pancreatic ductal injury must be kept in mind when present with vague symptoms in the setting of blunt abdominal trauma. Magnetic resonance cholangiopancreatography (MRCP) is the investigation of choice for the diagnosis of pancreatic ductal injury. Even higher-grade pancreatic injury (grade III) can be managed with a conservative approach with pigtail drainage and an appropriate dosage of octreotide.

Role of Percutaneous Transhepatic Biliary Drainage as an Adjunct to Endoscopic Retrograde Cholangiopancreatography.

Background: There is limited literature on the role of percutaneous transhepatic biliary drainage (PTBD) as an adjunct to endoscopic retrograde cholangiopancreatography (ERCP). This study evaluates the role of PTBD in patients with failed ERCP or post-ERCP cholangitis. Methods: Retrospective evaluation of clinical and intervention records of patients with biliary obstruction referred for PTBD following failed ERCP or post-ERCP cholangitis was performed. The cause of biliary obstruction, baseline serum bilirubin, white blood cell (WBC) count, serum creatinine, and procalcitonin were recorded. Technical success and clinical success (resolution of cholangitis, reduction in bilirubin levels, WBC count, creatinine, and procalcitonin) were assessed. Results: Sixty-three patients (35 females, mean age 51.4 years) were included. Indications for ERCP included malignant causes in 47 (74.6%) cases and benign causes in 16 (25.4%) cases. Indications for PTBD were failed ERCP in 21 (33.3%) and post-ERCP cholangitis in 42 (66.7%). PTBD was technically successful in all patients. Clinical success rate was 68.2% in the overall group. Mild hemobilia was noted in five (7.9%) patients. There were no major complications or PTBD related mortality. Cholangitis and acute kidney injury resolved following PTBD in 63.1% and 80% of the patients, respectively. Total serum bilirubin reduced by 47.8% and 69.4% after one week and one month of the PTBD, respectively. The average fall in procalcitonin was 5.17 ng/mL after one week of the PTBD. Conclusion: PTBD is an important adjunctive drainage procedure in patients with ERCP failure or post-ERCP cholangitis.

Post-operative ascites of unknown origin after laparoscopic cholecystectomy: Case report.

Introduction and importance: Post Laparoscopic cholecystectomy ascites is a rare complication that might be due to biliary leak, lymph duct injuries, infections, peritoneal reaction bowel injuries, malignancies and etc. Case presentation: Here we have reported post-cholecystectomy ascites presented with hypovolemic shock in a women of unknown origin. Different possible etiologies have been ruled out for her but her intra-peritoneal secretions had been decreased about one week of hospitalization and was discharged without figuring out its etiology. Clinical discussion: Post-cholecystectomy ascites is a rare condition that could be caused by biliary leak, lymphatic leak, ovarian hyper stimulation syndrome, infections, peritoneal reactions and malignancies that all of them should be considered for these patients to manage their problem. Conclusion: The exact cause of ascites in the presented case was still unknown and the condition was controlled by administration of corticosteroids, octreotide, albumin, and insertion of the stents in biliary ducts. More investigation esp. on immunologic causes are needed.

Misdiagnosis of sphincter of Oddi disorder treated as familial Mediterranean fever for ten years: A case report.

INTRODUCTION: Sphincter of Oddi dysfunction is a rare disease caused by sphincter of Oddi functional or mechanical abnormality. Misdiagnosis of familial Mediterranean fever is very high due to overlapping symptoms with many diseases. Our case is the first case report in the medical literature which describes the misdiagnosis of Sphincter of Oddi dysfunction as familial Mediterranean fever. CASE PRESENTATION: A 46-year-old woman presented with recurrent episodes of abdominal pain and arthralgia. The patient had familial Mediterranean fever for ten years which was diagnosed clinically without performing genetic tests. Analysis of the mutation in the MEFV gene was performed and was negative. Thereby, the diagnosis of familial Mediterranean fever was eliminated and colchisine was discontinued. Afterward, laboratory and radiological tests were performed, and the diagnosis of sphincter of Oddi disfunction was confirmed. The patient underwent biliary sphincterotomy and take sulpiride daily. DISCUSSION: The most common diseases were misdiagnosed with familial Mediterranean fever are appendicitis, acute rheumatic fever, gastrointestinal diseases and inflammatory arthritis. Endoscopic retrograde cholangiopancreatography with Manometry of the Sphincter of Oddi is the gold-standard test. CONCLUSION: Sphincter of Oddi dysfunction may interfere with many other disorders and should be considered as a differential diagnosis for any recurrent abdominal pain. Misdiagnosis of familial Mediterranean fever is common in endemic countries due to the reliance on clinical symptoms without analysis of the mutations in the MEFV genes particularly, before 1997.

Diagnostic Reference Levels for Fluoroscopy-guided Gastrointestinal Procedures in Japan from the REX-GI Study: A Nationwide Multicentre Prospective Observational Study.

BACKGROUND: Diagnostic reference levels (DRLs) are required to optimize medical exposure. However, data on DRLs for interventional fluoroscopic procedures are lacking, especially in gastroenterology. This study aimed to prospectively collect currently used radiation doses and help establish national DRLs for fluoroscopy-guided gastrointestinal procedures in Japan. METHODS: This multicentre, prospective, observational study collected actual radiation dose data from endoscopic retrograde cholangiopancreatography (ERCP), interventional endoscopic ultrasound (EUS), balloon-assisted enteroscopy (BAE), enteral metallic stent placement, and enteral tube placement from May 2019 to December 2020. The study outcomes were fluoroscopy time (FT: min), air kerma at the patient entrance reference point (Ka,r: mGy), air kerma area product (PKA: Gycm2), and radiation dose rate (RDR: mGy/min). Additionally, the basic settings of fluoroscopy equipment and the factors related to each procedure were investigated. This study was registered in the UMIN Clinical Trial Registry (UMIN 000036525). FINDINGS: Overall, 12959 fluoroscopy-guided gastrointestinal procedures were included from 23 hospitals in Japan. For 11162 ERCPs, the median/third quartile values of Ka,r (mGy), PKA (Gycm2), and FT (min) were 69/145 mGy, 16/32 Gycm2, and 11/20 min, respectively. Similarly, these values were 106/219 mGy, 23/41 Gycm2 and 17/27 min for 374 interventional EUSs; 53/104 mGy, 16/32 Gycm2 and 10/15 min for 523 metallic stents; 56/104 mGy, 28/47 Gycm2, and 12/18 min for 599 tube placements; and 35/81 mGy, 16/43 Gycm2 and 7/15 min for 301 BAEs, respectively. For the overall radiation dose rate, the median/third quartile values of RDR were 5.9/9.4 (mGy/min). The RDR values at each institution varied widely. INTERPRETATION: This study reports the current radiation doses of fluoroscopy-guided gastrointestinal procedures expressed as DRL quantities. This will serve as a valuable reference for national DRL values. FUNDING: This work was supported by a clinical research grant from the Japanese Society of Gastroenterology.

Type Va Duplication of the Common Bile Duct With Type IIIa Intrahepatic Bile Duct Anatomy: A Rare Combination of Dual Biliary Ductal Anomaly With Difficulty to Extract Common Bile Duct Stone.

Extrahepatic duplication of the common bile duct (CBD) is an extremely rare anatomic variation seen in the biliary tract. It represents failure of regression of the primitive duplicated biliary ductal system, resulting in five different subtypes of the duplicated CBD as described by Choi et al. To date, only few such cases have been reported in the literature. Associated variation in branching of intrahepatic bile ducts presenting as combined dual ductal anomaly is even rarer phenomena to be seen. We report a case of a 67-year-old man with chronic kidney disease and obstructive jaundice resulting from choledocholithiasis. Evaluation revealed type IIIa branching of intrahepatic bile ducts with type Va duplication of the CBD.

Human Fascioliasis: Report of Two Cases from Kashmir Valley.

Although few case reports of human fascioliasis have been reported from different parts of India, there is no case reported from the Kashmir valley to date. Herein we report two cases of human fascioliasis. Both patients presented with fever, marked eosinophilia, and liver lesions on imaging. Hepatobiliary imaging showed vague features like mild biliary dilatation and liver lesions representing burrows. A liver biopsy in one of the patients revealed eosinophilic granuloma. Both patients were diagnosed definitively with endoscopic retrograde cholangiopancreatography (ERCP) by demonstrating live adult fasciola worms. Any patient presenting with fever, marked eosinophilia, and liver lesions on imaging should be evaluated for fascioliasis.

Gangliocytic paraganglioma leading to duodeno-jejunal intussusception: A case report.

The intussusception of the small bowel is rarely encountered in adult patients and is frequently associated with a lead point that is often malignant. In a 69-year-old female patient with an episode of gastrointestinal (GI) bleeding, computed tomography (CT) showed a duodenal-jejunal intussusception caused by an intraluminal mass. Open polypectomy and reduction of intussusception were performed and the diagnosis of gangliocytic paraganglioma was made at pathological evaluation. It would be important to consider neoplasms like gangliocytic paraganglioma in the setting of adult small bowel intussusception.

Biliary Strictures and Cholangiocarcinoma - Untangling a Diagnostic Conundrum.

Cholangiocarcinoma is an uncommon and highly aggressive biliary tract malignancy with few manifestations until late disease stages. Diagnosis is currently achieved through a combination of clinical, biochemical, radiological and histological techniques. A number of reported cancer biomarkers have the potential to be incorporated into diagnostic pathways, but all lack sufficient sensitivity and specificity limiting their possible use in screening and early diagnosis. The limitations of standard serum markers such as CA19-9, CA125 and CEA have driven researchers to identify multiple novel biomarkers, yet their clinical translation has been slow with a general requirement for further validation in larger patient cohorts. We review recent advances in the diagnostic pathway for suspected CCA as well as emerging diagnostic biomarkers for early detection, with a particular focus on non-invasive approaches.

If Hoofbeats are not From Horses, It Could be Zebras!! Isolated Hyper-alkaline Phosphatasemia.

Alkaline phosphatase (AP) is a membrane bound enzyme and when it is elevated in blood, it is mostly due to either hepatobiliary or bone diseases. We report isolated intestinal hyperphosphatasemia (IAP) in two sisters. Both sisters presented with identical trends of isolated AP elevation. Both underwent extensive workup for liver diseases including cholangiograms, and none was identified. Subsequent isoenzyme electrophoresis showed that 45%-56% of the elevated AP was due to IAP. This elevation of the intestinal AP is consistent with a rare hereditary biochemical abnormality, benign familial intestinal hyperphosphatemia. This condition should be considered in the differential diagnosis of otherwise isolated serum AP levels to avoid unnecessary investigations.

Impact of the COVID-19 Pandemic on Utilization of EGD and Colonoscopy in the United States: An Analysis of the GIQuIC Registry.

BACKGROUND AND AIMS: The coronavirus disease 2019 (COVID-19) pandemic has limited the ability to perform endoscopy. The aim of this study was to quantify the impact of the pandemic on endoscopy volumes and indications in the United States. METHODS: We performed a retrospective analysis of data from the GI Quality Improvement Consortium (GIQuIC) registry. We compared volumes of colonoscopy and esophagogastroduodenoscopy (EGD) during the pandemic (March-September 2020) to before the pandemic (January 2019-February 2020). The primary outcome was change in monthly volumes. Secondary outcomes included changes in the distribution of procedure indications and in procedure volume by region of United States, patient characteristics, trainee involvement, and practice setting, as well as colorectal cancer diagnoses. RESULTS: Among 451 sites with 3514 endoscopists, the average monthly volume of colonoscopies and EGDs dropped by 38.5% and 33.4%, respectively. There was regional variation, with the greatest and least decline in procedures in the Northeast and South, respectively. There was a modest shift in procedure indications from prevention to diagnostic, an initial increase in performance in the hospital setting, and a decrease in procedures with trainees. The decline in volume of colonoscopy and EGD during the first 7 months of the pandemic was equivalent to approximately 2.7 and 2.4 months of prepandemic productivity, respectively. Thirty percent fewer colorectal cancers were diagnosed compared to expected. CONCLUSION: These data on actual endoscopy utilization nationally during the pandemic can help in anticipating impact of delays in care on outcomes and planning for the recovery phase.

Diagnosing Biliary Strictures: Distinguishing IgG4-Related Sclerosing Cholangitis From Cholangiocarcinoma and Primary Sclerosing Cholangitis.

Biliary strictures caused by inflammation or fibrosis lead to jaundice and cholangitis which often make it difficult to distinguish malignant strictures. In cases when malignancy cannot be excluded, surgery is often performed. The concept of immunoglobulin G4 (IgG4)-related sclerosing cholangitis (SC) as a benign biliary stricture was recently proposed. The high prevalence of the disease in Asian countries has resulted in multiple diagnostic and treatment guidelines; however, there is need to formulate a standardized diagnostic strategy among various countries considering the utility, invasiveness, and cost-effectiveness. We evaluated accuracies of various diagnostic modalities for biliary strictures comparing pathology in the Delphi meetings which were held in Rochester, MN. The diagnostic utility for each modality was graded according to the experts, including gastroenterologists, endoscopists, radiologists, and pathologists from the United States and Japan. Diagnostic utility of 10 modalities, including serum IgG4 level, noninvasive imaging, endoscopic ultrasound, endoscopic retrograde cholangiopancreatography-related diagnostic procedures were advocated and the reasons were specified. Serum IgG4 level, noninvasive imaging, diagnostic endoscopic ultrasound and intraductal ultrasonography under endoscopic retrograde cholangiopancreatography were recognized as useful modalities for the diagnosis. The information in this article will aid in the diagnosis of biliary strictures particularly for distinguishing IgG4-SC from cholangiocarcinoma and/or primary SC.

Evaluation of Charcot Triad, Reynolds Pentad, and Tokyo Guidelines for Diagnosis of Cholangitis Secondary to Choledocholithiasis Across Patient Age Groups.

OBJECTIVE: To determine the prevalence of Charcot triad, Reynolds pentad, and Tokyo Guidelines criteria and clinical outcomes among patients with cholangitis across different age groups. PATIENTS AND METHODS: We conducted a retrospective analysis of 257 consecutive hospitalized adult patients with acute cholangitis due to endoscopic retrograde cholangiopancreatography-confirmed choledocholithiasis between January 1, 2015, and December 31, 2019. Patients were divided into 3 age groups: less than 65 years, 65 to 79 years, and 80 years or older. Symptoms, vital signs, and laboratory data on admission were collected. Outcomes included length of hospitalization, intensive care unit stay, and 3-month mortality. Nominal variables were tested with the Pearson χ2 test, and continuous variables were tested with the Wilcoxon rank sum test. RESULTS: Charcot triad decreased with older ages. In the group that was age 80 years or older, malaise was the most common symptom; 33.6% (37 of 110) presented with altered sensorium, 9.1% (10 of 110) had no pain, fever, or jaundice, and positive blood culture results were more frequent. Tokyo cholestasis criterion was present in 96.0% (247 of 257), while inflammation (considered essential for diagnosis) was present in 75.9% (195 of 257). Patients 80 years or older had significantly higher mean length of hospital stay (P<.001) and mean length of intensive care unit stay (P=.021). CONCLUSION: Compared with patients in younger age groups, patients with cholangitis who are 80 years or older are less likely to have Charcot triad, are more likely to have features of Reynolds pentad, or present with unexplained malaise. Within the Tokyo Guidelines, cholestasis should replace inflammation as an essential diagnostic criterion.

Low-phospholipid-associated cholelithiasis syndrome: Prevalence, clinical features, and comorbidities.

BACKGROUND & AIMS: Low-phospholipid-associated cholelithiasis (LPAC) syndrome, a rare genetic form of intrahepatic cholelithiasis in adults, is still poorly understood. We report the results of the largest-ever case-control study of patients with LPAC syndrome aiming to assess the prevalence, clinical features, and comorbidities of the disease. METHODS: We included all LPAC cases diagnosed between 2001 and 2016 in 11 French centres. Controls consisted of all patients who underwent a cholecystectomy for common gallstone disease in a single non-academic centre over 1 year. A logistic regression analysis was used to identify the clinical features associated with LPAC syndrome across several patient strata with increasing levels of diagnostic confidence. The ratio between the incident cases of LPAC syndrome and the total number of cholecystectomies for gallstones was used to assess the relative prevalence of the disease. RESULTS: In this study, 308 cases and 206 controls were included. LPAC syndrome accounted for 0.5-1.9% of all patients admitted with symptomatic gallstone disease. Age at first symptoms <40 years, absence of overweight, persistence of symptoms after cholecystectomy, intrahepatic micro- or macrolithiasis, common bile duct (CBD) lithiasis, and no history of cholecystitis were independently associated with LPAC diagnosis. ATP-binding cassette subfamily B member 4 (ABCB4) variants, present in 46% of cases, were associated with CBD lithiasis, chronic elevation of gamma-glutamyltransferase (GGT), and personal or family history of hepato-biliary cancer. CONCLUSIONS: In this case-control study, LPAC syndrome accounted for approximately 1% of symptomatic cholelithiasis in adults. In addition to pre-established diagnostic criteria, normal weight, CBD lithiasis, and no history of cholecystitis were significantly associated with the syndrome. ABCB4 gene variations in patients with LPAC were associated with CBD lithiasis, chronic cholestasis, and a personal or family history of hepato-biliary cancer. LAY SUMMARY: In the largest case-control study ever conducted in patients with LPAC syndrome, a rare genetic form of intrahepatic cholelithiasis in young adults, LPAC syndrome was found in approximately 1% of all patients admitted to the hospital for symptomatic gallstones and, in addition to the pre-established characteristics of the syndrome (age at first symptoms <40 years, recurrence of symptoms after cholecystectomy, and/or imaging evidence of intrahepatic microlithiasis), was associated with lower BMI, higher prevalence of common bile duct stones, and lower incidence of acute cholecystitis. ABCB4 gene variants, which were detected in about half of cases, were associated with common bile duct stones and a personal or family history of hepato-biliary cancer.