Introduction: Carbimazole is a first-line therapy for thyrotoxicosis and is generally well tolerated. Drug-induced liver injury is rare (<1%) and typically presents as cholestatic hepatotoxicity, in contrast to propylthiouracil, which more commonly causes hepatocellular injury. Clinical presentation may mimic obstructive jaundice, and delayed recognition can lead to unnecessary investigations and interruption of definitive thyroid management. : A 70-year-old female with toxic multinodular goiter developed painless jaundice 4 weeks after starting carbimazole 20 mg daily for thyrotoxicosis precipitated by urinary tract infection. She had no prior liver disease or alcohol exposure. Examination revealed isolated icterus without features of chronic liver disease. Initial thyroid function tests showed suppressed thyroidstimulating hormone (<0.01 mIU/L) with markedly elevated free T4 (>100 pmol/L), improving after 4 weeks (free T4 29.1 pmol/L). She subsequently developed progressive jaundice without abdominal pain, fever, pruritus, or encephalopathy. Liver biochemistry demonstrated a cholestatic pattern (R factor 1.1) with conjugated hyperbilirubinemia (peak bilirubin 227 µmol/L), mild transaminitis, and elevated alkaline phosphatase. Imaging, including hepatobiliary ultrasonography, contrast computed tomography, and endoscopic ultrasound, excluded biliary obstruction. Viral, autoimmune, and structural causes were negative. Carbimazole-induced cholestatic jaundice was diagnosed based on temporal association and exclusion of alternatives. Carbimazole was discontinued, ursodeoxycholic acid was initiated, and radioactive iodine therapy was performed, followed by gradual recovery. Conclusion Carbimazole-induced hepatotoxicity (0.1–0.2%) is likely idiosyncratic and not dose dependent. Differentiating drug-induced liver injury from thyrotoxicosis-related liver dysfunction is critical, as restoration of euthyroidism alone may normalize liver enzymes. Diagnosis relies on the exclusion of obstruction and recognition of drug chronology. Early drug withdrawal and multidisciplinary management are essential to prevent progression while ensuring timely definitive therapy.
Thyrotoxicosis ; Cholestasis

BACKGROUND AND OBJECTIVES

Hepatobiliarypancreatic tuberculosis (HBPTB) is a less common form of tuberculosis that often presents as malignancy or lithiasis. Advances in diagnostics and minimally invasive procedures have led to the detection of more patients with milder forms of TB requiring surgical management. Due to the low incidence rates and lack of standardized approaches, additional studies are needed to improve patient outcomes. This study examined the risk factors, diagnostic methods, and treatments for HBPTB patients at the University of the Philippines – Philippine General Hospital (UP-PGH) from January 1, 2014 to December 31, 2021.

This retrospective descriptive study utilized our institutional database to identify patients who underwent a surgical procedure for HBPTB and their associated risk factors. Inclusion criteria required biopsy or microbiologic proof of tuberculous involvement of the biliary tract or nearby structures.

Among a total of 45 patients, the most common admitting diagnosis were HBP tuberculosis (37.8%) and malignancy (35.6%). 47.6% of patients had a previous or concurrent TB exposure. Sixty percent had subclinical malnutrition indicated by normal weight and low albumin. The liver (37.8%) and the bile ducts (33.3%) were the most common organs involved. The most common surgical procedures done were ultrasound-guided liver biopsy, biliary enteric anastomosis, percutaneous transhepatic biliary drainage (PTBD), and endoscopic retrograde cholangiopancreatography with or without stenting (ERCP).

This study provides additional data for clinicians to tailor diagnostic and treatment plans accordingly. Striking a balance between surgical procedures and appropriate anti-tuberculous therapy (ATT) is essential for successful treatment. Local data can be useful to help identify tuberculosis patterns unique to Filipinos and highlight socio-economic factors contributing to this rare presentation of TB.

BACKGROUND AND OBJECTIVE

Choledochal cysts (CC) are rare congenital, cystic dilations of the biliary tree occurring predominantly in Asian populations and in females. Patients are usually children presenting with any of the following: abdominal pain, palpable abdominal mass, and jaundice. Its congenital nature hints at a potential genetic cause. A possible causal gene is TP53, a tumor suppressor with a germline variant called rs201753350 (c.91G>A) that changed from a G allele to an A allele, decreasing the cell proliferation suppressing activity of its functional protein. Currently, there is no information on the TP53 rs201753350 germline variant available for the Filipino population. This study determined the prevalence of rs201753350 and the association between the functional G allele, the rs201753350 germline variant A allele, and the occurrence of CCs in Filipino pediatric patients in a tertiary government hospital.

Genomic DNA was extracted from blood samples of pediatric patients clinically diagnosed with CC. Controls were DNA samples collected from a previous study. The samples underwent PCR, electrophoresis, and sequencing.

A total of 109 participants (22 cases and 87 controls) were included in the study. The A allele (22.94%) occurs at a lower frequency than the G allele (77.06%) among both cases and controls. More individuals have a homozygous G/G genotype (54.13%) than a heterozygous A/G genotype (45.87%) while the homozygous A/A genotype was not observed. The estimated risk of choledochal cyst occurrence is significantly lower in individuals with the A allele (PR: 0.08, 95% CI: 0.01 – 0.55) and the A/G genotype (PR: 0.06, 95% CI: 0.01 – 0.40).

There is no significant evidence to suggest an association between the TP53 rs201753350 germline variant and the occurrence of choledochal cysts in Filipinos. It is recommended that other mutations within and beyond the TP53 gene be investigated for possible associations with choledochal cyst occurrence.

BACKGROUND AND OBJECTIVE

Understanding the normal anatomy and size of the extrahepatic biliary tree is vital for surgeons to make informed decisions regarding the necessity of additional procedures beyond cholecystectomy. The extrahepatic bile duct (EHBD) comprises the common hepatic duct (CHD) and the common bile duct (CBD), with the former formed by the convergence of the right and left hepatic ducts and the latter extending from the CHD to the duodenum. A normal diameter is indicative of the absence of any signs of obstruction in the EHBD, and the determination of the average range for these ducts are essential for identifying pathologies that may require further surgical intervention. Cholecystolithiasis is a common condition managed at the Philippine General Hospital (PGH). Trans-abdominal ultrasonography is frequently utilized to diagnose cholecystolithiasis, and it can also be used to determine the size of the common bile duct. Knowledge of the normal CBD diameter aids clinicians in distinguishing obstructed bile ducts from normal ones, prompting further diagnostic tests for improved patient management. However, there is limited data on the average diameter of the CBD among Filipino patients with this condition. The study aimed to determine the mean diameter of the common bile duct and common hepatic duct among patients diagnosed with cholecystolithiasis with no signs of obstruction in the EHBD managed at the Philippine General Hospital.

This prospective cross-sectional study included 80 patients who underwent cholecystectomy with intraoperative cholangiography. The CBD and CHD diameters were measured using intraoperative ultrasonography, and the data were analyzed using descriptive statistics and independent t-test.

The mean diameter of the CBD was 5.17 mm, with a range of 2.7-10 mm (1.41) mm. The mean diameter of the CHD was 4.71 mm, with a range of 2.3- 10 mm (1.59) mm. There was no significant difference in the CBD and CHD diameters between male and female patients, and across different age groups.

In patients with cholecystolithiasis managed at the PGH, the mean diameter of the CBD and the CHD was 5.17 mm and 4.71 mm, respectively, with no significant difference between genders and age groups. The mean diameter of the CBD among Filipino patients with cholecystolithiasis is similar to those reported in other countries. These findings may have clinical implications for the management of patients with cholecystolithiasis, particularly in the planning of endoscopic retrograde cholangiopancreatography (ERCP) and laparoscopic cholecystectomy. Further studies with larger sample sizes and different populations are recommended to validate these results. These findings can aid clinicians in determining the need for pre-operative Magnetic Resonance Cholangiopancreatography (MRCP) or selective intraoperative cholangiography to detect extrahepatic bile duct obstruction.

OBJECTIVE

Phenobarbital is an inductor of microsomal hepatic enzyme and used as choleretic for cholestatic liver disease to enhance bile flow. It is also used as a premedication for hepatobiliary scintigraphy (HIDA) scan to improve diagnostic accuracy for an obstructive liver disease. We reviewed the available literature on the use of Phenobarbital for treatment of cholestasis and its utility as a premedication for HIDA scan.

All published studies before June 30, 2023 that investigated the efficacy, effectiveness or safety of Phenobarbital in cholestatic jaundice and its effect on the accuracy of hepatobiliary scintigraphy in diagnosis of obstructive jaundice were included. Electronic databases were searched including MEDLINE via PubMed, Cochrane Library, medRxIV, BioRxIV, as well as the following registries for ongoing and completed trials: ClinicalTrials.gov (USA); ChiCTR.org. (China); and the WHO International Clinical Trials Registry Platform. We screened abstracts, reviewed full texts, and extracted relevant information on study design, settings, population and outcomes. There was no age and language restriction. Two reviewers independently rated the quality of included studies using: Joanna Briggs Institute critical appraisal tool for case reports, case series, and diagnostic accuracy; Newcastle – Ottawa Quality Assessment Scale for cohort studies, and Cochrane Risk of Bias for Randomized Trials. Risk of bias was appraised and GRADE certainty of evidence was judged. Pooled analysis was done using Stata 14 and reported as sensitivity and specificity.

Included were nine reports on Phenobarbital as treatment for cholestasis (one case report, five case series, one cohort and two randomized studies) and seven studies (four diagnostics, two cohorts, one randomized trial) on its use as a premedication for HIDA scan. The quality of case report and case series were considered fair; cohort studies as good; and diagnostic studies were included based on overall assessment. The randomized studies had some or high risk for bias due to concerns in randomization process, measurement of outcome, and risk in the selection of reported results.

There were 31 patients (16 adults and 15 children) from case reports and case series. Of the 16 adults, serum total bilirubin concentrations declined from 4 to 70% from baseline in 13 of 15 (87%) patients after Phenobarbital was given at 120 to 250 mg per day from 22 days to f ive months. Eleven of 14 with pruritus at onset also had improvement in intensity of itching. Of the 15 pediatric patients, ten (67%) showed a decrease from 10 to 60% of the baseline total bilirubin but not a normalization with Phenobarbital intake at a dose of 3 to 12 mg/kg/day from one to 21 months. Five of 14 children also had relief of itching after treatment.

Phenobarbital compared to Ursodeoxycholic acid had limited efficacy in reducing the bilirubin levels in neonates and young infants with cholestasis.

Phenobarbital compared to Ursodeoxycholic acid had limited efficacy in reducing the bilirubin levels in neonates and young infants with cholestasis.

Moderate certainty evidence showed that with Phenobarbital pretreatment, the hepatobiliary scan done on patients with neonatal cholestasis had 100% (CI 99.2, 100; I2 = 0.0%) sensitivity and 80.2% (CI 65.4, 92.1; I2 = 76.6%) specificity while no Phenobarbital pretreatment had 100% (94.9, 100; I2 = 0.0%) sensitivity and 89.5% (CI 77.0, 98.1; I2 = 11.4%) specificity. Adverse effects of Phenobarbital were drowsiness, lethargy, poor feeding, and irritability.

There was limited effectiveness of Phenobarbital in decreasing bilirubin levels in cholestatic liver disease. Moderate certainty evidence demonstrated that premedication with Phenobarbital did not improve the specificity of HIDA scan in the diagnosis of obstructive jaundice of infancy. Neurologic symptoms were observed with Phenobarbital intake.

BACKGROUND: Growing evidence suggests that long non-coding RNAs (lncRNAs) exert pivotal roles in fostering chemoresistance across diverse tumors. Nevertheless, the precise involvement of lncRNAs in modulating chemoresistance within the context of gallbladder cancer (GBC) remains obscure. This study aimed to uncover how lncRNAs regulate chemoresistance in gallbladder cancer, offering potential targets to overcome drug resistance. METHODS: To elucidate the relationship between gemcitabine sensitivity and small nucleolar RNA host gene 1 ( SNHG1 ) expression, we utilized publicly available GBC databases, GBC tissues from Renji Hospital collected between January 2017 and December 2019, as well as GBC cell lines. The assessment of SNHG1, miR-23b-3p, and phosphatase and tensin homolog (PTEN) expression was performed using in situ  hybridization, quantitative real-time polymerase chain reaction, and western blotting. The cell counting kit-8 (CCK-8) assay was used to quantify the cell viability. Furthermore, a GBC xenograft model was employed to evaluate the impact of SNHG1 on the therapeutic efficacy of gemcitabine. Receiver operating characteristic (ROC) curve analyses were executed to assess the specificity and sensitivity of SNHG1. RESULTS: Our analyses revealed an inverse correlation between the lncRNA SNHG1 and gemcitabine resistance across genomics of drug sensitivity in cancer (GDSC) and Gene Expression Omnibus (GEO) datasets, GBC cell lines, and patients. Gain-of-function investigations underscored that SNHG1 heightened the gemcitabine sensitivity of GBC cells in both in vitro and in vivo  settings. Mechanistic explorations illuminated that SNHG1 could activate PTEN -a commonly suppressed tumor suppressor gene in cancers-thereby curbing the development of gemcitabine resistance in GBC cells. Notably, microRNA (miRNA) target prediction algorithms unveiled the presence of miR-23b-3p binding sites within SNHG1 and the 3'-untranslated region (UTR) of PTEN . Moreover, SNHG1 acted as a sponge for miR-23b-3p, competitively binding to the 3'-UTR of PTEN , thereby amplifying PTEN expression and heightening the susceptibility of GBC cells to gemcitabine. CONCLUSION The SNHG1/miR-23b-3p/PTEN axis emerges as a pivotal regulator of gemcitabine sensitivity in GBC cells, holding potential as a promising therapeutic target for managing GBC patients.
Humans ; Deoxycytidine/pharmacology* ; PTEN Phosphohydrolase/genetics* ; Gemcitabine ; RNA, Long Noncoding/metabolism* ; MicroRNAs/genetics* ; Gallbladder Neoplasms/genetics* ; Cell Line, Tumor ; Animals ; Mice ; Drug Resistance, Neoplasm/genetics* ; Mice, Nude ; Antimetabolites, Antineoplastic ; Gene Expression Regulation, Neoplastic

Cholangiocarcinoma (CCA) is a fatal malignancy with steadily increasing incidence and poor prognosis. Since most CCA cases are diagnosed at an advanced stage, systemic therapies, including chemotherapy, radiotherapy, targeted therapy, and immunotherapy, play a crucial role in the management of unresectable CCA. The recent advances in targeted therapies and immunotherapies brought more options in the clinical management of unresectable CCA. This review depicts the advances of targeted therapies and immunotherapies for unresectable CCA, summarizes crucial clinical trials, and describes the efficacy and safety of different drugs, which may help further develop precision and individualization in the clinical treatment of unresectable CCA.
Humans ; Cholangiocarcinoma/drug therapy* ; Immunotherapy/methods* ; Bile Duct Neoplasms/drug therapy* ; Molecular Targeted Therapy/methods*

Most patients with biliary tract cancer are diagnosed at advanced stage and lose the opportunity for radical surgery,resulting in dismal prognosis. In recent years,with advances in therapeutic approaches,conversion therapy has gradually been implemented in some cases of initially unresectable biliary tract cancer, enabling a subset of patients to achieve opportunities for curative surgery. To further standardize conversion therapy of biliary tract cancer and improve the overall efficacy, the Branch of Biliary Surgery, Chinese Society of Surgery, Chinese Medical Association and Working Group of Biliary Surgeons,Chinese College of Surgeons,Chinese Medical Doctor Association, based on the latest evidence-based medical evidence and specific practices in the treatment of biliary tract cancer in China,organized discussion among experts in the field. Following the discussion,the "Expert consensus on conversion therapy of biliary tract cancer（2025）" was developed. This consensus aims to address key issues in the field of biliary tract cancer conversion therapy, standardize diagnostic and therapeutic procedures and protocols, and lay the foundation for further advancing research and practice in this area.
Humans ; Biliary Tract Neoplasms/surgery* ; Consensus

Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive malignant tumor with poor prognosis, and lymph node metastasis constitutes one of the critical risk factors contributing to unfavorable patient outcomes. Lymph node dissection holds significant value in accurately staging ICC, guiding prognostic evaluation, and determining adjuvant therapeutic strategies. In recent years, both domestic and international scholars have conducted extensive research on lymph node metastasis and dissection in ICC. However, discrepancies persist among various research findings and consensus guidelines domestically and internationally regarding the understanding and recommendations for lymph node dissection in ICC. Furthermore, substantial variations exist in the extent of lymph node dissection, the minimum number of lymph nodes required for retrieval, and surgical dissection techniques, which have consequently led to divergent research conclusions. To standardize the clinical practice of lymph node dissection for ICC in China and enhance the level of ICC diagnosis and treatment, the Branch of Biliary Surgery, Chinese Society of Surgery, Chinese Medical Association and Working Group of Biliary Surgeons, Chinese College of Surgeons, Chinese Medical Doctor Association, convened relevant experts to develop this expert consensus. This consensus document has been formulated based on the latest evidence-based medical research and accumulated clinical experience.
Humans ; Cholangiocarcinoma/pathology* ; Lymph Node Excision ; Bile Duct Neoplasms/pathology* ; Lymphatic Metastasis ; Consensus ; Prognosis

OBJECTIVES: To develop and validate a preoperative clinical-radiomics model for predicting overall survival (OS) and disease-free survival (DFS) in patients with extrahepatic cholangiocarcinoma (eCCA) undergoing radical resection. METHODS: In this retrospective study, consecutive patients with pathologically-confirmed eCCA who underwent radical resection at our institution from 2015 to 2022 were included. The patients were divided into a training cohort and a validation cohort according to the chronological order of their CT examinations. Least absolute shrinkage and selection operator (LASSO)-Cox regression was employed to select predictive radiomic features and clinical variables. The selected features and variables were incorporated into a Cox regression model. Model performance for 1-year OS and DFS prediction was assessed using calibration curves, area under receiver operating characteristic curve (AUC), and concordance index (C-index). RESULTS: This study included 123 patients (mean age 64.0 ± 8.4 years, 85 males/38 females), with 86 in the training cohort and 37 in the validation cohort. The OS-predicting model included four clinical variables and four radiomic features. It achieved a training cohort AUC of 0.858 (C-index = 0.800) and a validation cohort AUC of 0.649 (C-index = 0.605). The DFS-predicting model included four clinical variables and four other radiomic features. It achieved a training cohort AUC of 0.830 (C-index = 0.760) and a validation cohort AUC of 0.717 (C-index = 0.616). CONCLUSIONS The preoperative clinical-radiomics models show promise as a tool for predicting 1-year OS and DFS in eCCA patients after radical surgery.
Humans ; Male ; Female ; Retrospective Studies ; Middle Aged ; Cholangiocarcinoma/mortality* ; Prognosis ; Bile Duct Neoplasms/mortality* ; Tomography, X-Ray Computed/methods* ; Aged ; Radiomics