[An analysis on clinical characteristics and prognosis-related risk factors in patients with drug-induced liver injury].

Objective: To explore the drugs and clinical characteristics causing drug-induced liver injury (DILI) in recent years, as well as identify drug-induced liver failure, and chronic DILI risk factors, in order to better manage them timely. Methods: A retrospective investigation and analysis was conducted on 224 cases diagnosed with DILI and followed up for at least six months between January 2018 and December 2020. Univariate and multivariate logistic regression analyses were used to identify risk factors for drug-induced liver failure and chronic DILI. Results: Traditional Chinese medicine (accounting for 62.5%), herbal medicine (accounting for 84.3% of traditional Chinese medicine), and some Chinese patent medicines were the main causes of DILI found in this study. Severe and chronic DILI was associated with cholestatic type. Preexisting gallbladder disease, initial total bilirubin, initial prothrombin time, and initial antinuclear antibody titer were independent risk factors for DILI. Prolonged time interval between alkaline phosphatase (ALP) and alanine aminotransferase (ALT) falling from the peak to half of the peak (T(0.5ALP) and T(0.5ALT)) was an independent risk factor for chronic DILI [area under the receiver operating characteristic curve (AUC) = 0.787, 95%CI: 0.697~0.878, P < 0.001], with cutoff values of 12.5d and 9.5d, respectively. Conclusion: Traditional Chinese medicine is the main contributing cause of DILI. The occurrence risk of severe DILI is related to preexisting gallbladder disease, initial total bilirubin, prothrombin time, and antinuclear antibodies. T(0.5ALP) and T(0.5ALT) can be used as indicators to predict chronic DILI.

Robotic management of primary cholecystoduodenal fistula: A case report and brief literature review.

BACKGROUND: Cholecystoduodenal fistula (CDF) arises from persistent biliary tree disorders, causing fusion between the gallbladder and duodenum. Initially, open resection was common until laparoscopic fistula closure gained popularity. However, complexities within the gallbladder fossa yielded inconsistent outcomes. Advanced imaging and robotic surgery now enhance precision and detection. METHOD: A 62-year-old woman with chronic cholangitis attributed to cholecystoduodenal fistula underwent successful robotic cholecystectomy and fistula closure. RESULTS: Postoperatively, the symptoms subsided with no complications during the robotic procedure. Existing studies report favourable outcomes for robotic cholecystectomy and fistula closure. CONCLUSIONS: Our case report showcases a rare instance of successful robotic cholecystectomy with CDF closure. This case, along with a review of previous cases, suggests the potential of robotic surgery as the preferred approach, especially for patients anticipated to face significant laparoscopic morbidity.

Low-dose biliatresone treatment of pregnant mice causes subclinical biliary disease in their offspring: Evidence for a spectrum of neonatal injury.

Biliary atresia is a neonatal disease characterized by damage, inflammation, and fibrosis of the liver and bile ducts and by abnormal bile metabolism. It likely results from a prenatal environmental exposure that spares the mother and affects the fetus. Our aim was to develop a model of fetal injury by exposing pregnant mice to low-dose biliatresone, a plant toxin implicated in biliary atresia in livestock, and then to determine whether there was a hepatobiliary phenotype in their pups. Pregnant mice were treated orally with 15 mg/kg/d biliatresone for 2 days. Histology of the liver and bile ducts, serum bile acids, and liver immune cells of pups from treated mothers were analyzed at P5 and P21. Pups had no evidence of histological liver or bile duct injury or fibrosis at either timepoint. In addition, growth was normal. However, serum levels of glycocholic acid were elevated at P5, suggesting altered bile metabolism, and the serum bile acid profile became increasingly abnormal through P21, with enhanced glycine conjugation of bile acids. There was also immune cell activation observed in the liver at P21. These results suggest that prenatal exposure to low doses of an environmental toxin can cause subclinical disease including liver inflammation and aberrant bile metabolism even in the absence of histological changes. This finding suggests a wide potential spectrum of disease after fetal biliary injury.

Outcomes after laparoscopic cholecystectomy in patients older than 80 years: two-years follow-up.

BACKGROUND: The laparoscopic cholecystectomy is the treatment of choice for patients with benign biliary disease. It is necessary to evaluate survival after laparoscopic cholecystectomy in patients over 80 years old to determine whether the long-term mortality rate is higher than the reported recurrence rate. If so, this age group could benefit from a more conservative approach, such as antibiotic treatment or cholecystostomy. Therefore, the aim of this study was to evaluate the factors associated with 2 years survival after laparoscopic cholecystectomy in patients over 80 years old. METHODS: We conducted a retrospective observational cohort study. We included all patients over 80 years old who underwent laparoscopic cholecystectomy. Survival analysis was conducted using the Kaplan‒Meier method. Cox regression analysis was implemented to determine potential factors associated with mortality at 24 months. RESULTS: A total of 144 patients were included in the study, of whom 37 (25.69%) died at the two-year follow-up. Survival curves were compared for different ASA groups, showing a higher proportion of survivors at two years among patients classified as ASA 1-2 at 87.50% compared to ASA 3-4 at 63.75% (p = 0.001). An ASA score of 3-4 was identified as a statistically significant factor associated with mortality, indicating a higher risk (HR: 2.71, CI95%:1.20-6.14). CONCLUSIONS: ASA 3-4 patients may benefit from conservative management due to their higher risk of mortality at 2 years and a lower probability of disease recurrence.

Use of a Fatty Meal Cholecystagogue Protocol in Hepatobiliary Scintigraphy for Chronic Functional Gallbladder Disease.

Chronic functional gallbladder disorder, characterized by biliary pain in the absence of structural pathology, poses a diagnostic challenge necessitating reliable cholecystagogues for accurate evaluation. However, recurrent shortages of synthetic cholecystokinin analogs have prompted the exploration of alternative agents. This paper describes the efficacy of Ensure Plus as a viable fatty meal substitute for hepatobiliary scintigraphy in assessing chronic functional gallbladder disorder. Through comparative studies, Ensure Plus demonstrates comparable diagnostic accuracy to cholecystokinin in similar patient populations. Furthermore, Ensure Plus demonstrates significant symptom improvement after cholecystectomy in patients with anomalous gallbladder ejection fractions. This paper offers a detailed protocol for the seamless integration of Ensure Plus into hepatobiliary scintigraphy, providing clinicians with a valuable tool to navigate cholecystokinin shortages while maintaining diagnostic precision in cases of chronic functional gallbladder disorder. The use of Ensure Plus not only addresses practical supply challenges but also underscores its potential as a cost-effective and clinically sound alternative in biliary diagnostics.

Biliary Disorders, Anomalies, and Malignancies in Children.

Biliary abnormalities in children are uncommon, and the spectrum of biliary disorders is broader than in adult patients. Unlike in adults, biliary disorders in children are rarely neoplastic and are more commonly rhabdomyosarcoma rather than cholangiocarcinoma. Pediatric biliary disorders may be embryologic or congenital, such as anatomic gallbladder anomalies, anomalous pancreaticobiliary tracts, various cholestatic processes, congenital cystic lesions, or genetic conditions. They may also be benign, such as biliary filling anomalies, biliary motility disorders, and biliary inflammatory and infectious disorders. Distinguishing these entities with a single imaging modality is challenging. US is the primary imaging modality for initial evaluation of biliary abnormalities in children, due to its wide availability, lack of ionizing radiation, and low cost and because it requires no sedation. Other examinations such as MRI, CT, and nuclear medicine examinations may provide anatomic and functional information to narrow the diagnosis further. Hepatobiliary-specific contrast material with MRI can provide better assessment of biliary anatomy on delayed images than can traditional MRI contrast material. MR cholangiopancreatography (MRCP) allows visualization of the intra- and extrahepatic biliary ducts, which may not be possible with endoscopic retrograde cholangiopancreatography (ERCP). Suspected biliary atresia requires multiple modalities for diagnosis and timely treatment. Determining the type of choledochal cyst calls for a combination of initial US and MRCP. Many benign and malignant biliary masses require biopsy for definitive diagnosis. Knowledge of the imaging appearances of different pediatric biliary abnormalities is necessary for appropriate imaging workup, providing a diagnosis or differential diagnosis, and guiding appropriate management. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material.

Causes of death and nomogram for patients with oncologic hepato-biliary-pancreatic disorders: A large-cohort study.

The improvement of digestive cancer survival results in increased morbidity of noncancerous comorbidities. This study aimed at clarifying causes of death (COD) and predicting overall survival (OS) in patients diagnosed with liver cancer, gallbladder cancer, cholangiocarcinoma, and pancreatic cancer. We used the Surveillance, Epidemic, and End Results database to extract information. Nomograms of multivariate Cox regression was used to predict OS of cancer patients. The models were evaluated using the concordance indexes (C-indexes), the receiver operating characteristic curves and calibration curves. Respectively 58,895, 15,324, 30,708, and 109,995 cases with cancer of liver, gallbladder, bile duct or pancreas were retrieved between 2000 and 2020. Approximately 80% deaths occurred within 1 years after cancer diagnosis. Sequence in noncancerous COD proportion was diverse, while diseases of heart always accounted for a great part. Risks of death from most noncancerous COD were significantly higher than that of the cancer-free population. Nomograms were developed by predictors of interest such as age, therapy and TNM stage. The concordance indexes of nomograms were 0.756, 0.729, 0.763, and 0.760 respectively, well-calibrating to the reality. The 0.5-, 1-, and 2-year areas under the receiver operating characteristic curve were about 0.800, indicating good reliability and accuracy. Noncancerous COD accounted for larger part in gallbladder cancer and cholangiocarcinoma. Noncancerous COD showed an upward trend as follow-up time extended and the majorities were diseases of heart, cerebrovascular disease, chronic liver disease and cirrhosis. The novel OS-nomograms can provide personalized prognosis information with satisfactory accuracy.

Advances in the management of gallbladder polyps: establishment of predictive models and the rise of gallbladder-preserving polypectomy procedures.

Gallbladder polyps are a common biliary tract disease whose treatment options have yet to be fully established. The indication of "polyps ≥ 10 mm in diameter" for cholecystectomy increases the possibility of gallbladder excision due to benign polyps. Compared to enumeration of risk factors in clinical guidelines, predictive models based on statistical methods and artificial intelligence provide a more intuitive representation of the malignancy degree of gallbladder polyps. Minimally invasive gallbladder-preserving polypectomy procedures, as a combination of checking and therapeutic approaches that allow for eradication of lesions and preservation of a functional gallbladder at the same time, have been shown to maximize the benefits to patients with benign polyps. Despite the reported good outcomes of predictive models and gallbladder-preserving polypectomy procedures, the studies were associated with various limitations, including small sample sizes, insufficient data types, and unknown long-term efficacy, thereby enhancing the need for multicenter and large-scale clinical studies. In conclusion, the emergence of predictive models and minimally invasive gallbladder-preserving polypectomy procedures has signaled an ever increasing attention to the role of the gallbladder and clinical management of gallbladder polyps.

[Microbiome and Biliary Tract Cancer].

Biliary tract cancers encompass a group of malignancies that affect the bile ducts and gallbladder and are associated with a poor prognosis, often due to late diagnosis and limited treatment options. The incidence of biliary tract cancer has been increasing gradually, underscoring the need for a better understanding of its pathogenesis and potential risk factors. Research suggests that biliary tract cancer may develop through a combination of genetic and epigenetic alterations, as well as environmental factors. The role of microbial exposure and the human microbiome in the pathogenesis of biliary tract cancer is an emerging area of interest. Traditionally, the biliary tree was considered sterile under normal conditions, but recent studies have identified associations between specific microbiological patterns and inflammatory biliary diseases and cancer. The human microbiome plays a crucial role in maintaining host homeostasis and interacting with the host's immune system. Dysbiosis, or an imbalance in the microbiome composition, has been implicated in the development of various diseases, including cancer. Hence, dysbiosis in the biliary tract might trigger the pathogenesis of biliary tract cancer. Advances in next-generation sequencing technology have provided researchers with a more comprehensive view of the microbiota and their potential roles in health and disease, providing more evidence of the relationship between the microbiota and biliary tract cancer. This review summarizes the latest evidence of the microbiome that would be associated with biliary tract cancer.

Risk stratification model for incidentally detected gallbladder polyps: A multicentre study.

PURPOSE: We aimed to develop a 4-level risk stratification model using a scoring system based on conventional ultrasound to improve the diagnosis of gallbladder polyp. METHOD: Patients with histopathologically confirmed gallbladder polyps were consecutively recruited from three medical centres. Conventional ultrasound findings and clinical characteristics were acquired prior to cholecystectomy. Risk factors for neoplastic and malignant polyps were used to build a risk stratification system via interobserver agreement and multivariate logistic regression analysis. The model was retrospectively trained using 264 pre-surgical samples and prospectively validated using 106 pre-surgical samples. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC) and malignant polyp rate. RESULTS: In total, 370 patients (mean age, 51.68 ± 14.41 years, 156 men) were enrolled in this study. Size (≥12 mm), shape (oblate or round), single, vascularity, gallbladder stone or sludge were considered risk factors for neoplastic polyps. Size (≥14 mm), shape (oblate), single, disrupted gallbladder wall, and gallbladder stone or sludge were risk factors for malignant polyps (all p < 0.05). In the scoring system, the sensitivity, specificity, and AUC of score ≥ 9 in diagnosing neoplastic polyps were 0.766, 0.788, and 0.876 respectively; and the sensitivity, specificity, and AUC of score ≥ 15 in diagnosing malignant polyps were 0.844, 0.926, and 0.949 respectively. In our model, the malignancy rates at the four levels were 0 % (0/24), 1.28 % (2/156), 9.26 % (5/54), and 70.37 % (38/54), respectively. CONCLUSIONS: The 4-level risk stratification model based on conventional ultrasound imaging showed excellent performance in classifying gallbladder polyps.

Gallbladder strangulation caused by a fibrotic band due to chlamydia infection: A case report.

Acute cholecystitis, a very common disease, is usually caused by gallstone obstruction of the cystic duct. Meanwhile, strangulated cholecystitis is extremely rare, and it develops when the gallbladder is strangled by a band. It is very similar to gallbladder torsion in terms of imaging findings and obstruction of blood and biliary flow, and it requires emergency surgery. We herein report a case of a 90-year-old woman with gallbladder strangulation caused by a fibrotic band due to a chlamydia infection, and we also reviewed some literature on strangulated cholecystitis.

Increases in pediatric cholecystectomy during the COVID-19 pandemic: An interrupted time series analysis.

BACKGROUND: Historically, cholecystectomy is infrequently performed in children. Lifestyle changes, delays in healthcare access, and increases in childhood obesity occurred during the COVID-2019 pandemic. It is unclear whether these changes impacted pediatric gallbladder disease and the need for cholecystectomy. METHODS: A retrospective study of children ≤18 years old undergoing cholecystectomy from January 1, 2016, to July 31, 2022, at a tertiary children's hospital was conducted. On March 19, 2020, a statewide mandatory coronavirus disease 2019 stay-at-home policy began. Differences in children undergoing cholecystectomy before and during the pandemic were identified using bivariate comparisons. An interrupted time series analysis identified differences in case volume trends. RESULTS: Overall, 633 children were identified-293 pre-pandemic and 340 pandemic. A majority were female sex (76.3%) and Hispanic (67.5%), with a median age of 15 years (interquartile range: 13.0-16.0). Children who underwent cholecystectomy during the pandemic had significantly higher body mass index (28.4 versus 25.8, P = .002), and obesity (body mass index >30) was more common (45.3% versus 31.7%, P = .001). During the pandemic, significant increases in complicated biliary disease occurred-symptomatic cholelithiasis decreased (41.5% versus 61.8%, P < .001) and choledocholithiasis (17.9% versus 11.6%, P = .026), gallstone pancreatitis (17.4% versus 10.6%, P = .015), and chronic cholecystitis (4.7% versus 1.0%, P = .007) increased. The number of cholecystectomies performed per month increased during the pandemic, and on interrupted time series analysis, there was a significant increase in month-to-month case count during the pandemic (P = .003). CONCLUSION: Cholecystectomy case volume significantly increased during the coronavirus disease 2019 pandemic, possibly secondary to increases in childhood obesity. Future studies are needed to determine whether this increased frequency of pediatric cholecystectomy is representative of broader shifts in pediatric health and healthcare use after coronavirus disease 2019.

Concurrent hepatopathy in dogs with gallbladder mucocele: Prevalence, predictors, and impact on long-term outcome.

BACKGROUND: Information is limited regarding the prevalence and importance of hepatic histologic abnormalities in dogs with gallbladder mucocele (GBM). OBJECTIVES: To (a) report prevalence of hepatic histologic abnormalities in dogs with GBM (b) evaluate for association between hepatic abnormalities and outcome in dogs with GBM (c) evaluate whether neutrophil-to-lymphocyte ratio (NLR) differs in dogs with GBM with and without specific hepatic lesions. ANIMALS: Fifty-two dogs with grossly and histologically confirmed GBM. METHODS: Multicenter, retrospective study of dogs with GBM undergoing cholecystectomy with concurrent liver biopsy. Archived histological sections of gallbladder and liver evaluated by investigators blinded to data. Proportions of dogs with each histologic abnormality alive vs deceased at 1, 3, and 12 months post-cholecystectomy compared. Mann-Whitney U performed to determine if NLR differed in dogs with or without selected lesions. RESULTS: 51/52 (98%, 95% CI [89%, 99%]) dogs with GBM had at least 1 hepatic histologic abnormality. Hepatic fibrosis (37/51; 73%, 95% CI [59%, 83%]), biliary hyperplasia (29/52; 56%, 95% CI [42%, 68%]), and portal inflammation (25/52; 48%, 95% CI [35%, 61%]) were most common. The proportion of dogs alive vs dead differed based on the fibrosis score at 1, 3, and 12 (P ≤ .04) months post-cholecystectomy. Dogs with hepatic necrosis (P = .006) and cholangitis/cholangiohepatitis (P = .02) had higher NLRs compared to dogs without these lesions. CONCLUSIONS AND CLINICAL IMPORTANCE: Histologic abnormalities of the liver are common in dogs with GBM. A higher portal fibrosis score might be associated with shortened long-term survival after cholecystectomy for dogs with GBM. An increase in NLR might predict hepatic necrosis and cholangitis/cholangiohepatitis in dogs with GBM.

Gallbladder torsion: a rare cause of acute abdomen in a 12-month old child.

Background: Gallbladder torsion is a rare cause of an acute abdomen, predominantly occurring in elderly women and less frequently diagnosed in the pediatric population. The diagnosis is difficult and rarely made preoperatively. However, suspicion needs to be raised in children with acute onset of abdominal pain. Ultrasound can demonstrate different signs putting forward the diagnosis but findings are often non-specific, therefore clinical suspicion should prompt a laparoscopic exploration.Case presentation: We report a case of a 12-month old girl consulting with progressive abdominal discomfort and vomiting. Ultrasound revealed an enlarged gallbladder with thickening of the wall but without demonstrable color Doppler flow and a more horizontal orientation outside its normal anatomic fossa. Gallbladder torsion was suspected. Emergency laparoscopic exploration confirmed the diagnosis and a laparoscopic cholecystectomy was performed. The postoperative course was uneventful.Conclusions: Gallbladder torsion, although rare, should be included in the differential diagnosis of an acute abdomen in children. Early recognition is necessary for a favorable outcome. The diagnosis might be supported by ultrasound but remains difficult, which is why laparoscopic exploration should be considered when the diagnosis remains unclear.

Imaging update on gallbladder adenomyomatosis and its mimics.

Radiologists across many imaging modalities commonly encounter gallbladder adenomyomatosis. The classic imaging appearances of gallbladder adenomyomatosis are well described and confirm benignity. However, in clinical practice, adenomyomatosis can be challenging to differentiate from other gallbladder pathologies that require cholecystectomy. In this article, we describe the common and uncommon appearances of gallbladder adenomyomatosis on multimodality imaging, helping differentiate adenomyomatosis from non-benign gallbladder abnormalities. Accurately differentiating adenomyomatosis from its mimics provides the surgical team with important clinical and surgical management information, improving patient outcomes.

Is systematic histological examination of the cholecystectomy specimen always necessary?

INTRODUCTION: The histological examination (HE) of all cholecystectomy specimens removed for cholelithiasis is a widespread practice to rule out unrecognized gallbladder cancer. (GBC). But this dogmatic practice has been called into question by recent published data. The aim of this literature review was to answer two questions: (1) can HE be omitted in specific cases; (2) under what conditions is a selective strategy indicated? METHODS: A review of the literature was carried out that included selected multicenter studies, registry studies, or meta-analyses. A reliable technique for the surgeon's macroscopic examination of the specimen would allow the selection of dubious cases for HE. The cost-effectiveness of selective HE was discussed. The PICO methodology (population, intervention, comparator, outcome) was used in the selection of articles that compared routine and selective histological examination. RESULTS: If cases from countries with a high prevalence of gallbladder cancer are excluded and in the absence of high-risk situations (advanced age, female gender, calcified or porcelain gallbladder, acute cholecystitis, polyps, abnormalities noted intra-operatively), the macroscopic examination of the gallbladder in the operating room has a reliability approaching 100% in the majority of published studies. This would make it possible to omit systematic HE without compromising the diagnosis and prognosis of patients with unsuspected GBC and with a very favorable cost-effectiveness ratio. CONCLUSION: Through a selection of patients at very low risk of incidentally-discovered cancer and a routine macroscopic examination of the opened gallbladder, the strategy of selective HE could prove useful in both clinical and economic terms.

Functional gallbladder disorder: Interim analysis of a prospective cohort study.

BACKGROUND: Functional gallbladder disorder (FGBD) remains a controversial indication for cholecystectomy. METHODS: A prospective cohort study enrolled patients strictly meeting Rome criteria for FGBD, and cholecystectomy was performed. They were assessed pre- and 3 and 6 months postoperatively with surveys of abdominal pain and quality of life (RAPID and SF-12 surveys, respectively). Interim analysis was performed. RESULTS: Although neither ejection fraction nor pain reproduction predicted success after cholecystectomy, the vast majority of enrolled patients had a successful outcome after undergoing cholecystectomy for FGBD: of a planned 100 patients, 46 were enrolled. Of 31 evaluable patients, 26 (83.9 â€‹%) reported RAPID improvement and 28 (93.3 â€‹%) SF12 improvement at 3- or 6-month follow-up. CONCLUSION: FGBD, strictly diagnosed, should perhaps no longer be a controversial indication for cholecystectomy, since its success rate for biliary pain in this study was similar to that for symptomatic cholelithiasis. Larger-scale studies or randomized trials may confirm these findings.

Preoperative prediction model for non-neoplastic and benign neoplastic polyps of the gallbladder.

BACKGROUND: Gallbladder adenoma represents a precancerous lesion of gallbladder cancer. However, distinguishing it from cholesteryl polyps of the gallbladder before surgery is challenging. Thus, we aimed to comprehensively explore various risk factors contributing to the formation of gallbladder adenoma to facilitate an informed diagnosis and treatment by clinicians. METHODS: We conducted a retrospective analysis of patients who had undergone cholecystectomy at the Affiliated Hospital of Qingdao University between January 2015 and December 2022. Following postoperative pathological examination, patients were categorized into cholesterol polyp and adenoma groups. We analyzed their baseline characteristics, ultrasound imaging variables, and biochemical data using logistic, lasso, and stepwise regression. Subsequently, we constructed a preoperative prediction model based on the independent risk factors. RESULTS: Regression analysis of 520 gallbladder polyps and 288 gallbladder adenomas in the model group revealed that age, gallbladder wall thickness, polyp size, echogenicity, pedunculation, and adenosine deaminase (ADA) levels were independent predictors of gallbladder adenoma, all with P < 0.05. Using these indicators, we established a regression equation: Logistic (P) = -5.615 + 0.018 ∗ age - 4.64 ∗ gallbladder wall thickness + 1.811 ∗ polyp size + 2.855 ∗ polyp echo + 0.97∗ pedunculation + 0.092 ∗ ADA. The resulting area under the curve (AUC) value was 0.894 (95 % CI: 0.872-0.917, P < 0.01), with a sensitivity of 89.20 %, specificity of 79.40 %, and overall accuracy of 84.41 % for adenoma detection. CONCLUSION: Age, polyp size, gallbladder wall thickness, polyp echogenicity, pedunculation, and ADA levels emerge as independent risk factors for gallbladder adenoma.