1.Effect and mechanism of endoclip papilloplasty in reducing the incidence of cholelithiasis.
Yao LI ; Xiaofang LU ; Yingchun WANG ; Hong CHANG ; Yaopeng ZHANG ; Wenzheng LIU ; Wei ZHENG ; Xiue YAN ; Yonghui HUANG
Chinese Medical Journal 2025;138(20):2596-2603
BACKGROUND:
Endoscopic sphincterotomy (EST) is widely used to treat common bile duct stones (CBDS); however, long-term studies have revealed the increasing incidence of recurrent CBDS after EST. Loss of sphincter of Oddi function after EST was the main cause of recurrent CBDS. Reparation of the sphincter of Oddi is therefore crucial. This study aims to investigate the effectiveness and safety of endoclip papilloplasty (ECPP) for repairing the sphincter of Oddi and elucidate its mechanism.
METHODS:
Eight healthy Bama minipigs were randomly divided into the EST group and the ECPP group at a 1:1 ratio, and bile samples were collected before endoscopy and 6 months later. All minipigs underwent transabdominal biliary ultrasonography for the diagnosis of cholelithiasis 6 months after endoscopy. The biliary microbiota composition and alpha and beta diversity were analyzed by 16S ribosomal RNA gene sequencing. Differential metabolites were analyzed by bile acid metabolomics to explore the predictive indicators of cholelithiasis.
RESULTS:
Three minipigs were diagnosed with cholelithiasis in the EST group, while none in the ECPP group showed cholelithiasis. The biliary Firmicutes/Bacteroidota (F/B) ratio was increased after EST and decreased after ECPP. The Chao1 and observed species index significantly decreased 6 months after EST ( P = 0.017 and 0.018, respectively); however, the biliary α-diversity was similar before and 6 months after ECPP. The β-diversity significantly differed in the EST group before and 6 months after EST, as well as in the ECPP group before and 6 months after ECPP (analysis of similarities [ANOSIM]: R = 0.917, P = 0.040; R = 0.740, P = 0.035; respectively). Glycolithocholic acid (GLCA) and taurolithocholic acid (TLCA) accumulated in bile 6 months after EST.
CONCLUSIONS
ECPP has less impact on the biliary microenvironment than EST and prevents duodenobiliary reflux by repairing the sphincter of Oddi. The bile levels of GLCA and TLCA may be used to predict the risk of cholelithiasis.
Animals
;
Swine, Miniature
;
Swine
;
Cholelithiasis/prevention & control*
;
Sphincterotomy, Endoscopic/methods*
;
Sphincter of Oddi/surgery*
;
Female
;
Male
2.Small nucleolar RNA host gene 1 (SNHG1) facilitates gemcitabine chemosensitivity in gallbladder cancer by regulating the miR-23b-3p/phosphatase and tensin homolog (PTEN) pathway.
Hui WANG ; Yixiang GU ; Miaomiao GUO ; Ming ZHAN ; Min HE ; Yang ZHANG ; Linhua YANG ; Yingbin LIU
Chinese Medical Journal 2025;138(21):2783-2792
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
3.Expert consensus on conversion therapy of biliary tract cancer (2025).
Chinese Journal of Surgery 2025;63(6):453-460
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
4.Clinicopathologic profile and outcomes of pediatric patients managed with open and laparoscopic cholecystectomy: A two-center experience
Monica Bianca C. Balictar ; Patrick U. Avellano ; Pia Cerise V. Creencia ; Franco Antonio C. Catangui ; Jose Modesto B. Abellera ; Nino P. Isabedra ; Russel Alegarbes ; Dorothy Anne D. Lopez
Philippine Journal of Surgical Specialties 2025;80(1):8-19
OBJECTIVE
This seven-year, two-center retrospective cross-sectional study aimed to describe the demographic, clinical characteristics and surgical indications of patients managed with open or laparoscopic cholecystectomy in the pediatric age group, and determine these variables’ associations with patient outcomes.
METHODSRecords of all patients less than 19 years old who underwent laparoscopic or open cholecystectomy at Jose R. Reyes Memorial Medical Center (JRRMMC) and National Children’s Hospital (NCH) from January 2015 to December 2021 were reviewed. The gathered data were organized, described and analyzed using univariate and multivariate statistics.
RESULTSA total of 32 patients underwent open or laparoscopic cholecystectomy at the two institutions. Majority were female (78.1%). The diagnoses included chronic calculous cholecystitis (62.5%), acute calculous cholecystitis (21.9%), choledocholithiasis (12.5%). One (3.1%) patient had empyema of the gallbladder. The 15 – 18 year age group made up 78.1%, with the rest (21.9%) from the 10 – 14 year age group. By BMI percentile, 62.5% were normal, 15.6% were overweight, and 12.5% were obese. Most patients across all conditions (96.9%) had no known hemolytic disorder. Underweight patients (9.4% of the cohort) had statistically higher lengths of stay [F(3,28) = 3.444, p = .030]. No significant associations were found between the categorical outcomes (discharged well, morbidity, mortality) and patient variables (age group, sex, BMI percentile, presence of co-morbidities, symptoms, indication for surgery, operation done).
CONCLUSIONIn pediatric patients undergoing laparoscopic or open cholecystectomy, BMI percentile is inversely related to the length of hospital stay.
Human ; Cholecystectomy ; Gallbladder Diseases ; Demography
5.Surgical manifestations of hepatobiliarypancreatic tuberculosis (HBPTB)
Apolinario Ericson B. Berberabe ; Daniel Ernest L. Florendo
Acta Medica Philippina 2025;59(Early Access 2025):1-6
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.
METHODSThis 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.
RESULTSAmong 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).
CONCLUSIONSThis 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.
Human ; Tuberculosis, Extrapulmonary ; Biliary Tract Diseases ; General Surgery ; Acute Care Surgery ; Liver Diseases ; Pancreas
6.The diameter of the normal extrahepatic bile duct among patients diagnosed with cholecystolithiasis managed at the Philippine General Hospital
Dante G. Ang ; Teressa Mae D. Bacaro ; Juan Carlos R. Abon ; Jose Miguel P. Verde
Acta Medica Philippina 2025;59(2):50-54
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.
METHODSThis 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.
RESULTSThe 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.
CONCLUSIONIn 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.
Human ; Male ; Female ; Common Bile Duct ; Cholecystolithiasis
7.Precision medicine for advanced biliary tract cancer in China: current status and future perspectives.
Zhen HUANG ; Wen ZHANG ; Yongkun SUN ; Dong YAN ; Xijie ZHANG ; Lu LIANG ; Hong ZHAO
Frontiers of Medicine 2025;19(5):743-768
Biliary tract cancer (BTC) is a rare group of malignancies that develop from the epithelial lining of the biliary tree and have a poor prognosis. Although chemotherapy is the standard of care for patients with advanced BTC in China, its clinical benefits are moderate. In recent years, the approval of targeted therapies and immunotherapies has provided new avenues for the management of advanced BTC. Nonetheless, the increasing number of personalized medicine approaches has created a challenge for clinicians choosing individualized treatment strategies based on tumor characteristics. In this article, we discuss recent progress in implementing precision medicine approaches for advanced BTC in China and examine genomic profiling studies in Chinese patients with advanced BTC. We also discuss the challenges and opportunities of using precision medicine approaches, as well as the importance of considering population-specific factors and tailoring treatment approaches to improve outcomes for patients with BTC. In addition to providing a comprehensive overview of current and emerging precision medicine approaches for the management of advanced BTC in China, this review article will support clinicians outside of China by serving as a reference regarding the role of patient- and population-specific factors in clinical decision-making for patients with this rare malignancy.
Humans
;
Precision Medicine/methods*
;
Biliary Tract Neoplasms/genetics*
;
China
;
Molecular Targeted Therapy
;
Immunotherapy/methods*
8.Effects of autophagy on myocardial injury in rats with common bile duct ligation.
Xiaoyu WANG ; Lin LYU ; Aijie LIU ; Lei LUN ; Wenli BI ; He DONG
Chinese Critical Care Medicine 2025;37(1):59-64
OBJECTIVE:
To investigate the impact of autophagy on cardiac tissue injury following common bile duct ligation (CBDL) in rats.
METHODS:
Twenty-four SPF grade healthy adult male Sprague-Dawley (SD) rats were randomly divided into four groups, with 6 rats in each group. The sham-operated (Sham) group underwent only dissection of the common bile duct without ligation. The CBDL group underwent CBDL to simulate jaundice-induced myocardial injury. The autophagy inhibitor 3-methyladenine (3-MA)+CBDL group was intraperitoneally injected with 15 mg/kg 3-MA 2 hours before modeling, and then injected once every other day. The CBDL+autophagy enhancer rapamycin (Rapa) group was intraperitoneally injected with Rapa 1 mg/kg 0.5 hour after modeling, and then injected once every other day. The rats in each group were sacrificed 2 weeks after surgery, and blood was taken from the inferior vena cava. Serum total bilirubin (TBil), alanine transaminase (ALT), aspartate transaminase (AST), lactate dehydrogenase (LDH), and MB isoenzyme of creatine kinase (CK-MB) were detected by using a fully automated animal biochemical analyzer. Serum oxidative stress marker superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were detected by colorimetric assay. The heart tissues of rats were taken and pathological changes were observed under a light microscope after hematoxylin-eosin (HE) staining. Transmission electron microscope was used to observe autophagosomes after double staining with uranyl acetate and lead citrate. The expressions of autophagy-related proteins were detected using Western blotting.
RESULTS:
Compared with the Sham group, the serum SOD activity of rats in the CBDL group was significantly decreased, while the serum MDA, TBil, ALT, AST, LDH, and CK-MB were significantly increased; the expressions of autophagy-related proteins Beclin-1 and microtubule-associated protein 1 light chain 3-II/I (LC3-II/I) were significantly increased, and p62 protein expression was significantly decreased. Autophagosomes were seen under electron microscopy in the CBDL group, and cardiac histopathological morphology showed focal necrosis in the myocardium as well as infiltration of inflammatory cells, dilatation of small interstitial blood vessels, and myocardial fiber degeneration. Compared with the CBDL group, cardiac tissue injury in rats was attenuated by pretreatment with the autophagy inhibitor 3-MA, with a decrease in inflammatory cell infiltration in myocardial tissue, a reduction in interstitial vasodilatation, and a decrease in the area of myocardial fibrosis; a decrease in the number of autophagosomes by electron microscopy; and a further rise in the viability of serum TBil, ALT, and AST [TBil (μmol/L): 184.40±6.74 vs. 120.70±16.93, ALT (U/L): 501.10±62.18 vs. 178.80±22.30, AST (U/L): 806.50±76.92 vs. 275.50±55.81, all P < 0.01], as well as a decrease in the levels of serum SOD, MDA, LDH, and CK-MB [SOD (kU/L): 85.00±5.29 vs. 107.50±7.86, MDA (μmol/L): 10.72±0.93 vs. 15.06±1.88, LDH (U/L): 387.40±119.50 vs. 831.30±84.35, CK-MB (U/L): 320.10±14.04 vs. 814.70±75.66, all P < 0.05]. The expressions of the autophagy-related proteins Beclin-1 and LC3-II/I in cardiac tissues were significantly decreased [Beclin-1 protein (Beclin-1/GAPDH): 0.67±0.04 vs. 0.89±0.01, LC3-II/I ratio: 0.93±0.03 vs. 1.09±0.01, both P < 0.01], and p62 protein expression was significantly increased (p62/GAPDH: 0.99±0.01 vs. 0.60±0.01, P < 0.01). In contrast, compared with the CBDL group, after administration of the autophagy enhancer Rapa, the rats showed increased cardiac tissue injury, increased inflammatory cell infiltration in myocardial tissues, increased interstitial vasodilatation, and increased area of myocardial fibrosis; an increase in autophagosomes was seen by electron microscopy; the change tendency of serum biochemical indicators and proteins in myocardial tissues were opposite with autophagy inhibition group with a decrease in serum TBil, ALT, and AST [TBil (μmol/L): 22.00±3.21 vs. 120.70±16.93, ALT (U/L): 72.13±5.97 vs. 178.80±22.30, AST (U/L): 135.20±12.95 vs. 275.50±55.81, all P < 0.05], as well as a increase in the levels of serum SOD, MDA, LDH, and CK-MB [SOD (kU/L): 208.00±2.65 vs. 107.50±7.86, MDA (μmol/L): 20.38±0.40 vs. 15.06±1.88, LDH (U/L): 1 268.00±210.90 vs. 831.30±84.35, CK-MB (U/L): 1 150.00±158.70 vs. 814.70±75.66, all P < 0.05]. The protein expressions of Beclin-1 and LC3-II/I in cardiac tissues were significantly increased [Beclin-1 protein (Beclin-1/GAPDH): 0.96±0.01 vs. 0.89±0.01, LC3-II/I ratio: 1.19±0.01 vs. 1.09±0.01, both P < 0.05], and p62 protein expression was significantly decreased (p62/GAPDH: 0.19±0.02 vs. 0.60±0.01, P < 0.01).
CONCLUSIONS
Activation of autophagy in CBDL rats led to myocardial tissue injury and reduced cardiac function. Inhibition of autophagy improved cardiac tissue injury in CBDL rats, while increasing autophagy exacerbated myocardial tissue injury.
Animals
;
Autophagy
;
Rats, Sprague-Dawley
;
Male
;
Ligation
;
Rats
;
Common Bile Duct/surgery*
;
Myocardium/pathology*
;
Adenine/pharmacology*
9.Advances in Construction and Application of Biliary Organoids.
Zhong-Wen LEI ; Yang XIANG ; Yi-Jun YANG
Acta Academiae Medicinae Sinicae 2025;47(4):611-620
Biliary duct injury,congenital biliary atresia,biliary tract tumors,primary sclerosing cholangitis,etc.are common and refractory diseases in the digestive system in clinical practice.The existing surgical operations and drug treatments demonstrate limited effects.Organoids,as an emerging technology,have attracted much attention in recent years for deeply understanding the pathogenesis and development of these diseases and seeking more effective treatment approaches.An organoid,a three-dimensional complex derived from stem/progenitor cells,can simulate the complex structure and physiological function of tissues or organs in vitro.It provides an important platform for studying the pathogenesis of biliary tract diseases and brings new hope for the repair and regeneration of biliary tract injury.The seed cells for constructing biliary organoids are mainly biliary tract epithelial cells,pluripotent stem cells,etc.The conventional technologies for constructing biliary organoids mainly include embedding,rotary culture,and hanging drop culture.In recent years,new culture technologies such as organ chip and three-dimensional and four-dimensional printing are emerging.This article reviews the construction methods of biliary organoids,discusses the application of these organoids in disease model construction,disease mechanism research,drug screening,and tissue/organ repair,and proposes the current problems and future research directions of biliary organoids,which will provide reference for treating common refractory digestive system diseases in clinical practice.
Organoids
;
Humans
;
Tissue Engineering/methods*
;
Biliary Tract/cytology*
10.Gastric-Duodenal Contrast-Enhanced Ultrasound for Diagnosis of Gallbladder-Duodenal Fistula:Report of One Case.
Ya-Jiao GAN ; Qi-Ping HU ; Yi TANG ; Zhi-Kui CHEN
Acta Academiae Medicinae Sinicae 2025;47(5):768-770
Gallbladder-duodenal fistula,a severe complication of cholecystitis caused by gallstones,is clinically rare.Its clinical presentation lacks specificity,and conventional preoperative imaging often fails to establish a definitive diagnosis.This report describes a case where a gallbladder-duodenal fistula was diagnosed using oral microbubble ultrasound contrast agent for gastric-duodenal contrast-enhanced ultrasound,providing a novel approach for diagnosing this condition.
Humans
;
Biliary Fistula/diagnostic imaging*
;
Contrast Media
;
Duodenal Diseases/diagnostic imaging*
;
Gallbladder Diseases/diagnostic imaging*
;
Intestinal Fistula/diagnostic imaging*
;
Ultrasonography


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