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.

Humans ; Diagnosis, Differential ; Constriction, Pathologic/diagnosis* ; Bile Duct Neoplasms/diagnosis* ; Endoscopy, Digestive System

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. Methods: 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. Results: 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. Conclusion 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.
Common Bile Duct ; Cholecystolithiasis

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. Methods: 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. Results: 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. Conclusion 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.
phenobarbital ; cholestasis ; scintigraphy ; radionuclide imaging ; pruritus

BACKGROUND: Gallbladder cancer (GBC) is the most common malignant tumor of biliary tract. Isoliquiritigenin (ISL) is a natural compound with chalcone structure extracted from the roots of licorice and other plants. Relevant studies have shown that ISL has a strong anti-tumor ability in various types of tumors. However, the research of ISL against GBC has not been reported, which needs to be further investigated. METHODS: The effects of ISL against GBC cells in vitro and in vivo were characterized by cytotoxicity test, RNA-sequencing, quantitative real-time polymerase chain reaction, reactive oxygen species (ROS) detection, lipid peroxidation detection, ferrous ion detection, glutathione disulphide/glutathione (GSSG/GSH) detection, lentivirus transfection, nude mice tumorigenesis experiment and immunohistochemistry. RESULTS: ISL significantly inhibited the proliferation of GBC cells in vitro . The results of transcriptome sequencing and bioinformatics analysis showed that ferroptosis was the main pathway of ISL inhibiting the proliferation of GBC, and HMOX1 and GPX4 were the key molecules of ISL-induced ferroptosis. Knockdown of HMOX1 or overexpression of GPX4 can reduce the sensitivity of GBC cells to ISL-induced ferroptosis and significantly restore the viability of GBC cells. Moreover, ISL significantly reversed the iron content, ROS level, lipid peroxidation level and GSSG/GSH ratio of GBC cells. Finally, ISL significantly inhibited the growth of GBC in vivo and regulated the ferroptosis of GBC by mediating HMOX1 and GPX4 . CONCLUSION ISL induced ferroptosis in GBC mainly by activating p62-Keap1-Nrf2-HMOX1 signaling pathway and down-regulating GPX4 in vitro and in vivo . This evidence may provide a new direction for the treatment of GBC.
Animals ; Mice ; Carcinoma in Situ ; Chalcones/pharmacology* ; Ferroptosis ; Gallbladder Neoplasms/genetics* ; Glutathione Disulfide ; Kelch-Like ECH-Associated Protein 1 ; Mice, Nude ; NF-E2-Related Factor 2/genetics* ; Reactive Oxygen Species ; Humans

Humans ; Infant ; Biliary Atresia/diagnosis* ; Choledochal Cyst/diagnosis* ; RNA, Circular ; Diagnosis, Differential

Gallbladder cancer(GBC)is one common type of bile tract cancers with poor prognosis. This review summarizes the recent development of studies about somatic mutation, molecular subtype, microenvironment heterogeneity, organoid, orthotopic model, patient-derived xenograft and clinical translation on GBC in aspects of genomic,transcriptome,single cell omics and clinical translation. We expect this review will provide new ideas on dissecting molecular mechanisms underlying the development and emerging chemoresistance of GBC following therapy and promote GBC precision medicine.
Humans ; Gallbladder Neoplasms/genetics* ; Prognosis ; Tumor Microenvironment