Role of β-glucuronidase in the formation of primary intrahepatic stones / 临床肝胆病杂志

Primary intrahepatic stones （PIS） is a refractory disease with a high incidence rate in Southwest China， which greatly affects the life of patients. Metabolites， such as β-glucuronidase produced by chronic biliary tract infection， play an important role in the formation of pigmented stones. In addition to exogenous β-glucuronidase produced by bacteria， endogenous β-glucuronidase produced by intrahepatic bile duct cells also plays an important role in the formation of stones. This article analyzes the research advances in the role of β-glucuronidase in the pathogenesis of PIS， in order to provide a possible method for the prevention and treatment of PIS.

Development of percutaneous transhepatic cholangioscopy and comparison of different techniques in treatment of cholelithiasis / 临床肝胆病杂志

Intrahepatic bile duct stone is a type of biliary system disease characterized by complex conditions and frequent recurrence， and traditional surgical treatment methods tend to cause various complications and have high requirements for surgical standards. Percutaneous transhepatic cholangioscopy （PTCS） is highly efficient in removing stones and is widely used in clinical practice， but there are also other medical techniques for the treatment of cholelithiasis. This article mainly discusses the constant development of PTCS and compares the efficacy of PTCS and other techniques in the treatment of cholelithiasis.

ABCB4 gene mutation-associated liver cirrhosis with gallstones： A case report / 临床肝胆病杂志

The disease spectrum of ABCB4 gene mutation involves various diseases such as progressive familial intrahepatic cholestasis type 3 （PFIC3）， gallstone disease， intrahepatic cholestasis of pregnancy， portal hypertension， liver cirrhosis， and even primary hepatic and biliary malignancies. A young male patient was admitted to Department of Hepatobiliary Medicine， Eastern Hepatobiliary Surgery Hospital， and was initially diagnosed with liver cirrhosis and gallstones， and he was planned to receive laparoscopic cholecystectomy. Preoperative examination showed abnormal liver function， liver cirrhosis， splenomegaly， and mild esophageal varices， and next-generation sequencing was performed to make a confirmed diagnosis of ABCB4 gene mutation-associated liver cirrhosis with gallstones. The liver function of the patient gradually returned to normal after cholagogic treatment with ursodeoxycholic acid capsules.

Oclusión intestinal mecánica por íleo biliar. Reporte de caso

La obstrucción de la luz del intestino delgado por un cálculo biliar ubicado de forma anómala, denominada incorrectamente íleo biliar, representa del 1 al 3 % de los síndromes obstructivos intestinales. Se define como una entidad inusual, caracterizada por la obstrucción intestinal mecánica, causada por el impacto de uno o varios cálculos biliares en la luz intestinal, por lo general en el ilion terminal. El objetivo es describir el presente caso por lo infrecuente de esta entidad, describir la sistemática diagnóstica y conducta tomada, así como realizar el análisis de la literatura relacionada. Se trata de una paciente femenina de 87 años de edad, que acude por cuadro de vómitos y distensión abdominal de 20 días de evolución, con muy mal estado general. Se realiza laparotomía exploradora, donde se observa en el ilion proximal gran cálculo de aproximadamente 4 cm, que obstruye la luz en su totalidad. Se realiza enterolitotomía y resección intestinal sin intervención en la vesícula biliar o la vía biliar. Fallece al tercer día del postoperatorio mediato por descompensación de su enfermedad cardiovascular. Se concluye que el íleo biliar es una entidad infrecuente sin estudios que estandaricen un tratamiento específico, y que requiere de intervención quirúrgica. La enterotomía para extracción de cálculos es una técnica segura y eficaz, sin necesidad de intervención en la vía biliar en un primer tiempo.

Obstruction of the lumen of the small intestine by an abnormally located gallstone, incorrectly called gallstone ileus, accounts for 1% to 3% of all obstructive bowel syndromes. It is defined as an unusual entity characterized by mechanical intestinal obstruction, caused by the impact of one or several gallstones in the intestinal lumen, usually in the terminal ilium. The objective is to describe the present case due to the infrequency of this entity, to describe the diagnostic system and conduct taken, as well as to carry out the analysis of the related literature. An 87-year-old female patient presented with symptoms of vomiting and abdominal distension of 20 days of evolution, with an unusual, very poor general condition, characterized by mechanical intestinal obstruction caused by the impact of one or several gallstones in the intestinal lumen, usually in the terminal ilium. An exploratory laparotomy was performed, where a large stone of approximately 4 cm was observed in the proximal ileum which completely obstructed the lumen. Enterolithotomy and bowel resection were performed without intervention in the gallbladder or bile duct. She died on the third day of the immediate postoperative period due to decompensation of her cardiovascular disease. It is concluded that gallstone ileus is a rare entity without studies that standardize a specific treatment and that it requires surgical intervention. Enterotomy for stone removal is a safe and effective technique without the need for intervention in the bile duct in the first time.

Íleo biliar complicado con infección con SARS-CoV-2. Reporte de caso / Gallstone ileus: a challenge in the management of bile duct pathology. Case Report

Introducción: El Íleo biliar (IB) es una obstrucción intestinal mecánica muy poco frecuente, del 1 al 4 % de todas las obstrucciones intestinales, y es más común en pacientes de edad avanzada. Se produce a través de una fístula bilioentérica en el intestino delgado, sobre todo en el íleon distal. Luego de tener un enfoque diagnóstico mediante imagenología, en su gran mayoría, se opta por el tratamiento quirúrgico para eliminar el o los cálculos impactados. El éxito de esta intervención depende en gran medida del tamaño del cálculo biliar, de la ubicación de la obstrucción intestinal y comorbilidades preexistentes. Caso clínico: Mujer de 78 años con cuadro clínico de obstrucción intestinal, emesis de contenido fecaloide y sintomática respiratoria; se evidenció una masa concéntrica a nivel de íleon distal y proceso neumónico concomitante por tomografía toracoabdominal. Se realizó laparotomía exploratoria con enterolitotomía, extracción de cálculo y anastomosis íleo-ileal y fue trasladada a la UCI en donde presentó falla ventilatoria y requerimiento de ventilación mecánica; se confirmó infección viral por SARS-CoV-2 mediante RT - PCR. Discusión: El IB es una obstrucción intestinal que ocurre con mayor frecuencia en pacientes de edad avanzada. Se habla de la fisiopatología y mecanismo de producción de la fístula entérica y se presentan opciones diagnósticas, terapéuticas y quirúrgicas para dirigir el manejo clínico más apropiado. Conclusión: El IB es difícil de diagnosticar. Debido a su baja incidencia, no existe un consenso que paute el manejo a seguir en los pacientes con diagnóstico de IB. Aunque el tratamiento estándar es la intervención quirúrgica, hay diversas opiniones en cuanto al tipo de cirugía a realizar.

Introduction: Biliary ileus (BI) is a very rare mechanical intestinal obstruction, responsible for 1-4% of all intestinal obstructions and more frequent in elderly patients. It occurs through a bilioenteric fistula in the small bowel, mainly in the distal ileum. After a diagnostic imaging approach, the vast majority opt for surgical treatment to remove the impacted stone or stones. The success of this intervention depends largely on the size of the stone, the location of the bowel obstruction and pre-existing comorbidities. Case report: 78-year-old woman with clinical symptoms of intestinal obstruction, fecaloid emesis, respiratory symptoms, concentric mass at the level of the distal ileum and concomitant pneumonic process in the thoraco-abdominal CT scan. Exploratory laparotomy was performed, with total lithotomy, extraction of the calculus and ileo-ileal anastomosis, and she was transferred to the ICU, where she presented ventilatory failure and required mechanical ventilation. SARS-CoV-2 infection was confirmed with RT-PCR. Discussion: IB is an intestinal obstruction that occurs more frequently in elderly patients. The pathophysiology and the mechanism of production of enteric fistula are discussed and diagnostic, therapeutic and surgical options are presented to guide the most appropriate clinical management. Conclusion: Enteric fistula is difficult to diagnose. Due to its low incidence, there is no consensus on the management of patients diagnosed with IB. Although the standard treatment is surgical intervention, there are divergent opinions as to the type of surgery to be performed.

Íleo biliar: descripción de dos casos / Gallstone ileus: Description of two cases

Introducción. El íleo biliar es una complicación rara de la colelitiasis y su incidencia varía del 1 al 4 %. Consiste en la migración de un cálculo de la vesicular biliar al tracto gastrointestinal, generando obstrucción intestinal. Presenta síntomas inespecíficos dependiendo del nivel de la obstrucción, lo que hace que su diagnóstico no suela ser precoz, repercutiendo en el deterioro clínico del paciente. Es especialmente grave en pacientes de edad avanzada y con comorbilidades. Casos clínicos. Se reportan los casos de dos pacientes con dolor abdominal difuso, en quienes se diagnosticó íleo biliar por tomografía. Se realizó manejo quirúrgico, el primero mediante técnica abierta y estrategia de dos pasos, y el otro mediante técnica laparoscópica. Discusión. El íleo biliar es una etiología rara de obstrucción intestinal. El cálculo migra debido a una fistula colecisto-entérica y el nivel de obstrucción es con mayor frecuencia la válvula ileocecal. Los síntomas son inespecíficos y dependen del nivel de obstrucción: dolor abdominal difuso mal caracterizado, náuseas, vómito, ausencia de flatos. El diagnóstico se hace mediante tomografía abdominal, en la cual se evidencia la tríada de Rigler. El manejo es quirúrgico, con enterotomía para extraer el cálculo y resolver la obstrucción. Conclusión. El íleo biliar es una patología que debe ser considerada en el abordaje de la obstrucción intestinal, aunque sea poco frecuente. El manejo quirúrgico es clave para resolver el cuadro de obstrucción intestinal; aún así genera importante morbimortalidad en especial en pacientes de avanzada edad.

Introduction. Gallstone ileus is a rare complication of cholelithiasis, its incidence varies from 1% to 4%. It consists of the migration of a stone from the gallbladder to the gastrointestinal tract, causing intestinal obstruction. It presents with non-specific symptoms depending on the level of the obstruction, which means that its diagnosis is not usually early, with repercussions on the clinical deterioration of the patient, being serious especially in elderly patients and with comorbidities. Clinical cases. Two patients with diffuse abdominal pain are reported. A tomographic diagnosis was made showing gallstone ileus. Surgeries were performed, in the first case using an open technique and a 2-step strategy, and on the second one using a laparoscopic technique. Discussion. Gallstone ileus is a rare etiology of intestinal obstruction. Symptoms are usually poorly characterized: diffuse abdominal pain, nausea, vomiting, absence of flatus. The diagnosis is made by abdominal tomography in which Rigler's triad is evident. Management is surgical through enterotomy to remove the stone and resolve the obstruction. Conclusion. Gallstone ileus is a rare pathology that should be considered in the approach to intestinal obstruction. Surgical management is key to resolving intestinal obstruction. Even so, it generates significant morbidity and mortality, especially in elderly patients.

Íleo biliar: análisis de 21 casos / Gallstone ileus: analysis of 21 cases

RESUMEN Antecedentes : el íleo biliar es una complicación infrecuente de la litiasis vesicular, observada más comúnmente en mujeres añosas. Es causada por la migración, a través de una fístula bilioentérica, de un cálculo que produce la obstrucción del tránsito intestinal, que requiere tratamiento quirúrgico. Objetivo : describir las variables preoperatorias, intraoperatorias y posoperatorias de una serie de casos de íleo biliar y la incidencia de íleo biliar recurrente. Material y métodos: se realizó un estudio retrospectivo observacional de pacientes operados con abdomen agudo obstructivo por íleo biliar entre enero de 2009 y diciembre de 2021. Las variables estudiadas fueron: estudios por imágenes, comorbilidades, vías de abordaje quirúrgico, tipo de cirugía, morbimortalidad y recurrencia del íleo. Resultados : sobre 667 pacientes que ingresaron con obstrucción intestinal, 21 tenían íleo biliar (3,1%). El diagnóstico se realizó por tomografía en el 80% de los casos. El abordaje quirúrgico fue por laparotomía en 20 casos y 1 por laparoscopia convertida. La cirugía más utilizada fue la enterotomía con enterorrafia en 18 casos. El tratamiento de la obstrucción fue la cirugía inmediata, mientras que el de la fístula biliar fue diferido en la mayoría de las oportunidades, debido a que el riesgo de tratarla en el momento era muy elevado. La morbilidad fue del 38% y la recurrencia del íleo biliar 4,7%. No se registró mortalidad. Conclusión : el íleo biliar fue una patología infrecuente, que pudo ser correcta y oportunamente diagnosticada y tratada con cirugía, con una baja incidencia de íleo biliar recurrente.

ABSTRACT Background : Gallstone ileus is a rare complication of cholelithiasis and mainly affects elder women. It is caused by gallstone migration through a cholecystoenteric fistula producing bowel obstruction, with the need for surgical treatment. Objective : The aim of this work was to describe the preoperative, intraoperative and postoperative variables of a case series of gallstone ileus and the incidence of recurrent gallstone ileus. Material and methods : We conducted an observational and retrospective study of patients undergoing surgery due to acute bowel obstruction caused by gallstone ileus between January 2009 and December 2021. The variables analyzed were imaging tests, comorbidities, surgical approach, type of surgery, morbidity and mortality and recurrent ileus. Results : Of 667 patients admitted with bowel obstruction, 21 had gallstone ileus (3.1%). The diagnosis was made by computed tomography scan in 80% of the cases. The surgical approach was laparotomy in 20 cases and 1 patient undergoing laparoscopy required conversion. Enterotomy with enterorrhaphy was the most common procedure used in 18 cases. The obstruction was treated by immediate surgery, while the biliary fistula was deferred in most cases because the risk of immediate treatment was very high. Morbidity was 38% and recurrence of gallstone ileus 4.7%. No deaths were reported. Conclusion : Gallstone ileus was a rare condition that was correctly diagnosed and timely treated with surgery, with a low incidence of recurrent gallstone ileus.

Clinical characteristics, treatments, and outcomes of dificult biliary stones in a reference hospital in Colombia

The local experience and the success rate of different available treatments for dificult biliary stones in Colombia are poorly described. We made an observational study reporting patients treated for dificult biliary stones, at Hospital Universitario San Ignacio in Bogotá, Colombia between January 2015, and November 2021. Clinical characteristics, endoscopic retrograde cholangiopancreatography (ERCP) findings, and outcomes are presented. Additionally, the success rates of Endoscopic Sphincterotomy Plus Large Balloon Dilation (ESLBD), Mechanical Lithotripsy (ML), temporary stenting (TS), cholangioscopy-guided laser lithotripsy (CGLL), and surgery are described. A total of 146 patients were included (median age 69 years, IQR 58.5-78.5, 33.8% men). The median stone diameter was 15 mm (IQR 10 - 18 mm). One stone was presented in 39.9%, two stones in 18.2%, and ≥3 stones in the remaining stone. A 67.6% disproportion rate was observed between the stone and distal common bile duct. Successful stone extraction was achieved in 56.2% in the first procedure, 22.6% in the second, 17.1% in the third, 3.4% in the fourth, and 0.7% in the fifth procedures. The successful extraction rates were 56.8% for ESLBD, 75% for ML, 23.4% for TS, 57.7% for CGLL, and 100% for surgery. Endoscopic management of dificult stones is usually successful, although it usually requires 2 or more ERCPs procedures. The surgical requirements were low. ESLBD is an effective technique unlike TS. Few patients required advanced techniques such as ML or CGLL. Endoscopic procedures are associated with a low rate of complications.

La tasa de éxito de diferentes tratamientos de Cálculo Biliar Difícil (CBD) en Colombia no está descrita. Hemos realizado un estudio descriptivo observacional sobre el tratamiento de CBD en el Hospital Universitario San Ignacio en Bogotá, Colombia entre enero 2015 y noviembre 2021. Se presentan las características clínicas, hallazgos en la Colangiopancreatografía Retrógrada Endoscópica (CPRE) y desenlaces asociados. Adicionalmente, se describe la tasa de éxito de los pacientes tratados mediante esfinterotomía asociada a dilatación endoscópica con balón grande (EDEBG), litotripsia mecánica (LM), stent temporal (ST), litotripsia con láser guiada por colangioscopia (LLGC) y cirugía. 146 pacientes fueron incluidos (Mediana de edad 69 años, RIC 58,6-78,5). 33,8% eran hombres. La mediana del tamaño del CBD fue de 15 mm (RIC 10-18 mm). 39,9% tenían un solo cálculo, 18,2% tenían 2 y el resto ≥3 cálculos. 67,6% tenían desproporción entre el cálculo y el colédoco distal. La extracción exitosa se logró en 56,2% en el primer procedimiento, 22,6% en el segundo, 17,1% en el tercero, 3,4% en el cuarto y 0,7% en el quinto procedimiento. La tasa de extracción exitosa fue de 56,8% con EDEBG, 75% con LM, 23,4% con ST, 57,7% con LLGC y 100% con cirugía. El manejo endoscópico del CBD es usualmente exitoso. Sin embargo, requiere usualmente ≥2 CPRE. El tratamiento quirúrgico no es común. EDEBG es una técnica efectiva a diferencia del ST. Pocos pacientes requirieron técnicas avanzadas como LM o LLGC. Los métodos endoscópicos presentan una baja tasa de complicaciones.

A meta-analysis of cholelithiasis after metabolic and bariatric surgery / 国际外科学杂志

Objective:To analyze the incidence of gallstone formation after Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) by meta-analysis.Methods:English terms for this meta-analysis included "bariatric surgery, gastric bypass, Roux-n-Y gastric bypass, RYGB, sleeve gastrectomy, SG, cholelithiasis, cholecystectomy, gallstone". Researched articles in Pubmed, Medline and Embase databases were searched up to February 2023 and retrieved for further analysis. The quality of each article was evaluated with Newcastle-Ottawa Scale (NOS). Generated data were analyzed with Revman 5.4.Results:Nine relevant cohort studies were retrieved for this meta-analysis, including a total of 24 255 RYGB patients and 4 500 SG patients. All articles met the requirements after the quality evaluation of NOS. The meta-analysis results showed that the incidence of postoperative gallstones in RYGB group was higher than that in SG group ( P<0.001). In subgroup analysis, by administering ursodeoxycholic acid (UDCA) for gallstone prevention, the incidence had no difference between the two groups ( P=0.090), while in the study without UDCA, the incidence of gallstones after RYGB was higher than SG ( P=0.005). In the studies with follow-up time no more than 24 months, the incidence of postoperative gallstones in RYGB group was higher than that in SG group ( P=0.050), but there was no statistical difference when following-up beyond 24 months ( P=0.240). Conclusions:Within 2 years after surgery, RYGB patients have more chances to develop gallstones than SG patients. However, beyond 2-year follow-up, there is no difference between the two procedures. Prophylactical utilization of UDCA after RYGB can effectively reduce the incidence of gallstone formation.

Disputes and thinking on the clinical diagnosis and treatment of asymptomatic gallstones / 国际外科学杂志

Cholecystolithiasis is a common clinical disease, which can be secondary to cholecystitis, cholangitis, pancreatitis and gallbladder cancer. Many patients with gallstone have no obvious clinical symptoms such as biliary colic. Some patients are indeed asymptomatic because there are not obstruction and inflammation. However, some patients have no symptoms due to ignorance, mistaken for stomach pain, enteritis, etc. Some patients have no symptoms because of insensitivity and insufficient perception. For other patients with abnormal gallbladder morphology and structure, non-functional gallbladder must be no pain. To clarify the concept, diagnosis and classification of asymptomatic gallstones according to pathophysiological stages is conducive to the development of personalized management strategies. According to guidelines formulated by different periods, different regions and different medical institutions, there are many controversies regarding the management of asymptomatic gallstones, including regular follow-up, drug treatment, surgical resection or gallblades-saving lithotomy. Reasonable personalized diagnosis and treatment requires more in-depth basic research evidence.

Analysis on mechanisms of Jindan Tablets, Xiaoyan Lidan Tablets and ursodeoxycholic acid in the treatment of gallstones and cholecystitis based on network pharmacology / 国际中医中药杂志

Objective:To analyze the mechanism of Jindan Tablets, Xiaoyan Lidan Tablets and ursodeoxycholic acid in the treatment of gallstone and cholecystitis based on network pharmacology; To conduct a comparative analysis.Methods:The chemical components of Jindan Tablets, Xiaoyan Lidan Tablets and ursodeoxycholic acid and their drug targets were collected from Traditional Chinese Medicine Database and Analysis Platform (TCMSP). DAVID 6.8 database was used to search for the associated diseases of the drug targets. The disease targets of gallstone and cholecystitis were collected from GeneCards and other databases. The protein-protein interactions network was established based on the intersecting targets of three drugs and two diseases. KEGG enrichment analysis was performed based on the DAVID 6.8 database. Cytoscape 3.7.1 software was used to construct a complex network and topology analysis of component- target- disease between three drugs and diseases.Results:222 chemical components and 3 133 drug targets were collected for Jindan Tablets. 104 chemical components and 1 425 action targets were collected for Xiaoyan Lidan Tablets. 1 chemical component and 119 action targets were collected for ursodeoxycholic acid. The three drugs were associated with 31 diseases. 1 382 disease targets for gallstones and cholecystitis were collected. There were 237, 163 and 33 targets for gallstones and cholecystitis in the three drugs, of which 17 were shared by the three drugs and 20 were shared by Jindan Tablets and Xiaoyan Lidan Tablets. Based on the DAVID database, 113, 74 and 10 significant KEGG enrichment pathways were obtained for the three drugs respectively.Conclusions:The three drugs shared many targets and pathways in the treatment of gallstones and cholecystitis, which all had the function of regulating metabolism and inhibiting inflammatory response, while participating in apoptosis, oxidative stress and cancer pathology process. However, they had their own special effects, with Jindan Tablets favoring involving in the cancer process and inhibition of inflammation, and promoting angiogenesis. Xiaoyan Lidan Tablets and ursodeoxycholic acid focused on regulating cholesterol metabolism, and Xiaoyan Lidan Tablets also regulated steroid metabolism and inhibit inflammation, while ursodeoxycholic acid regulated bile acid metabolism.

Comparing one-step common bile duct exploration plus cholecystectomy with two-step endoscopic sphincterotomy plus cholecystectomy in patients over 80 years with concomitant gallbladder and common bile duct stones / 中华肝胆外科杂志

Objective:To compare safety and efficacy of one-stage laparoscopic common bile duct exploration plus laparoscopic cholecystectomy (LCBDE+ LC) with endoscopic retrodrade cholangiopancreatography plus laparoscopic cholecystectomy (ERCP+ LC) in elderly patients with concomitant gallbladder and common bile duct (CBD) stones.Methods:This is a two-center retrospective study with clinical data on 492 patients aged over 80 years diagnosed with concomitant gallbladder and CBD stones treated between January, 2014 and December, 2020 at The First Affiliated Hospital of Wenzhou Medical University and Quzhou Hospital Affiliated to Wenzhou Medical University. There were 254 males and 238 females, aged (83.9±3.0) years. These patients were divided into two groups based on their operative methods: the one-stage group (LCBDE+ LC, n=186) and the two-stage group (ERCP+ LC, n=306). Differences in surgery, stones and hospitalization costs were compared between the two groups. Results:When compared with the ERCP+ LC group, the LCBDE+ LC group had significantly higher incidences of previous gastrectomy [21.5%(40/186) vs 4.2%(13/306)], multiple stones [77.4%(144/186) vs 49.3%(151/306)], larger stone diameter [13.7(6.4, 18.6)mm vs 10.9(5.7, 16.1) mm], and increased hospitalization expenditure [(2.37±0.31) Wanyuan vs (3.26±0.44) Wanyuan] (all P<0.05). However, the rates of residual stone [2.7%(5/186) vs 1.3%(4/306)], stone recurrence [2.2%(4/186) vs 5.2%(16/306)], postoperatively overall complications [3.2%(6/186) vs 1.3%(4/306)], and total hospital stay [(10.7±6.2) d vs (11.3±5.4) d] were not significantly different between the two groups (all P>0.05). Conclusions:Allowing for the similar safety and effectiveness, and lower hospitalization expenditure, LCBDE+ LC was a preferred choice for patients aged over 80 year, especially in patients who had previous gastrectomy, multiple large CBD stones, or who could not accept endoscopic procedures for treatment of CBD stones.

Effect of tert-butyl acetate and ethyl butyrate on the dissolution of gallbladder cholesterol stones / 中华肝胆外科杂志

Objective:To compare the effect and biotoxicity of tert-butyl acetate (TBA) and ethyl butyrate (EB) on stone dissolution in vitro.Methods:Ten gallstone samples from patients with multiple gallbladder stones were selected and the cholesterol content was analyzed by HPLC. Stone dissolution tests of TBA and EB were performed on cholesterol gallstone in vitro, and the weight of stone at each time point was recorded, meanwhile, methyl tert-butyl ether (MTBE) was used as the control. The inhibitory effects of MTBE, TBA and EB on proliferation of human normal liver cell line LO2 were analyzed by cell proliferation inhibition assay. Flow cytometry was used to analyze the effects of MTBE, TBA and EB on the early and late apoptosis of LO2 cells, and the changes of reactive oxygen species level in LO2 cells were also analyzed.Results:Of the 10 gallbladder gallstones, 6 were cholesterol gallstones and 4 were non-cholesterol gallstones. Stone dissolution experiment showed that the remaining stones of MTBE, TBA and EB groups were (47.83±3.84)%, (58.12±4.53)% and (75.75±4.61)% 30 minutes later. The remaining stones were (18.38±6.47)%, (33.82±6.22)% and (56.38±3.91)% 90 minutes later. MTBE had the best stone dissolution effect in vitro, the stone dissolution effect of TBA was slightly weaker than MTBE, and the stone dissolution effect of EB was relatively weak in all ( P<0.05). The cell proliferation inhibition experiment showed that the cell viability of the control group, MTBE group and TBA group were (100.00±4.46)%, (96.79±4.32)% and (93.72±3.51)%, respectively, and there were no significant differences among the three groups ( P>0.05). However, the cell viability of EB group (87.57±5.29)% was lower than the above three groups, and the differences were statistically significant ( P<0.001). The early apoptosis and late apoptosis of the control group were (1.67±0.15)% and (1.27±0.06)%, respectively. EB induced early apoptosis (15.90±0.53)% ( P<0.001) and late apoptosis (5.13±0.76)% ( P<0.05). However, MTBE and TBA had no significant effect on cell apoptosis ( P>0.05). Compared with control group, MTBE, TBA and EB all significantly inhibited the level of reactive oxygen species ( P<0.05), and the inhibitory effect of EB was the most obvious. Conclusions:TBA has good stone dissolution effect and biosafety for gallbladder cholesterol stones in vitro, while EB has relatively poor performance. TBA is a potential drug for gallstone dissolution.

Application value of modified through-suture T-tube in laparoscopic biliary tract surgery / 中华消化外科杂志

Objective:To investigate the application value of modified through-suture T-tube in laparoscopic biliary tract surgery.Methods:The retrospective and descriptive study was constructed. The clinical data of 15 patients with cholecystolithiasis and choledocholithiasis who underwent laparoscopic biliary tract surgery in China-Japan Friendship Hospital of Jilin University from January to December 2022 were collected. There were 8 males and 7 females, aged (49± 14)years. Of 15 patients, 8 cases undergoing laparoscopic cholecystectomy + common bile duct exploration and lithotomy+conventional T-tube drainage were set as conventional group and 7 cases undergoing laparoscopic cholecystectomy + common bile duct exploration and lithotomy+modified through-suture T-tube drainage were set as modified group. Observation indicators: (1) intraoperative and postoperative conditions; (2) follow-up. Measurement data with normal distribution were expressed as Mean± SD, and comparison between groups was conducted using the t test. Count data were described as absolute numbers, and comparison between groups was conducted using Fisher exact probability. Results:(1) Intraoperative and postoperative conditions. Both groups of patients successfully completed the operation, with postoperative vital signs as stable, and no discomfort symptoms. There was no significant difference in duration of postoperative hospital stay between the coventional group and the modified group ( P>0.05). (2) Follow-up. Both groups of patients completed 30 days of postoperative outpatient follow-up. There was a significant difference in the sinus wall thickness between the coventional group and the modified group ( P<0.05). Among the 8 patie-nts in the conventional group, T tube was removed in the first 2 cases of patients after T tube angio-graphy 30 days after operation, and biliary fistula occurred in 1 of them and the drainage tube was re-indurated. For the other 6 cases, the time of T tube retention was extended to 6 weeks after surgery. After T tube angiography, the T tube was removed and no biliary fistula occurred. Among the 7 patients in the modified group, 2 cases with residual choledocholithiasis were found by T tube angiography 30 days after operation. After removal of T tube, percutaneous choledochoscopy was performed, in which the sinus wall was well formed and stone removal was smooth. The other 5 pati-ents were confirmed no residual calculi by T-tube angiography, and then the T-tube was removed, with no biliary fistula. Conclusion:Modified through-suture T-tube can be used in laparoscopic biliary tract surgery.

Targeted bile acids metabolomics in cholesterol gallbladder polyps and gallstones:From analytical method development towards application to clinical samples / 药物分析学报

Bile acids(BAs)are synthesized by the liver from cholesterol through several complementary pathways and aberrant cholesterol metabolism plays pivotal roles in the pathogeneses of cholesterol gallbladder polyps(CGP)and cholesterol gallstones(CGS).To date,there is neither systematic study on BAs profile of CGP or CGS,nor the relationship between them.To explore the metabolomics profile of plasma BAs in healthy volunteers,CGP and CGS patients,an ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)method was developed and validated for simultaneous determination of 42 free and conjugated BAs in human plasma.The developed method was sensitive and reproducible to be applied for the quantification of BAs in the investigation of plasma samples.The results show that,compared to healthy volunteers,CGP and CGS were both characterized by the significant decrease in plasma BAs pool size,furthermore CGP and CGS shared aberrant BAs metabolic characteristics.Cheno-deoxycholic acid,glycochenodeoxycholic acid,λ-muricholic acid,deoxycholic acid,and 7-ketolithocholic acid were shared potential markers of these two cholesterol gallbladder diseases.Subsequent analysis showed that clinical characteristics including cysteine,ornithine and body mass index might be closely related to metabolisms of certain BA modules.This work provides metabolomic information for the study of gallbladder diseases and analytical methodologies for clinical target analysis and efficacy evaluation related to BAs in medical institutions.

Efficacy of laparoscopic choledochoscopy combined with holmium laser lithotripsy versus traditional laparotomy in treatment of bile duct stones： A Meta－analysis / 临床肝胆病杂志

ObjectiveTo systematically review the efficacy and safety of laparoscopic choledochoscopy combined with holmium laser lithotripsy through a meta－analysis. MethodsThis study was conducted based on PRISMA guidelines， with a PROSPERO registration number of CRD42023406221. Chinese databases including CNKI， Wanfang Data， and VIP and foreign language databases such as PubMed， Embase， the Cochrane Library， and Web of Science were searched for original articles on traditional laparotomy versus laparoscopic choledochoscopy combined with holmium laser lithotripsy in the treatment of bile duct stones. Dichotomous variables were assessed by odds ratio （OR） and 95% confidence interval （CI）， while continuous variables were assessed by weighted mean difference （WMD） and 95%CI， and a sensitivity analysis was performed for outcome measures with relatively high heterogeneity. The Begg test and Egger test were used to evaluate publication bias. Stata 15.0 and Review Manager 5.3 were used to perform the statistical analysis. ResultsA total of 26 retrospective studies from China were included in this study， with 2 238 patients in total. The meta－analysis showed that compared with traditional laparotomy for the treatment of bile duct stones， laparoscopic choledochoscopy combined with holmium laser lithotripsy had significantly shorter time of operation （WMD＝－1.26， 95%CI： －1.36 to －1.16， P<0.001）， length of hospital stay （WMD＝－1.93， 95%CI： －2.64 to －1.12， P <0.001）， and time to bowel function recovery （WMD＝－1.52， 95%CI： －1.68 to －1.35， P<0.001）， significantly less intraoperative blood loss （WMD＝－1.79， 95%CI： －1.93 to －1.66， P<0.001）， a significantly lower rate of intraoperative residual stone （OR＝0.15， 95%CI： 0.11－0.20， P<0.001）， and significantly fewer complications （OR＝0.17， 95%CI： 0.13－0.23， P<0.001）. ConclusionCompared with traditional laparotomy， laparoscopic choledochoscopy combined with holmium laser lithotripsy shows better efficacy in the treatment of bile duct stones.

Progress of Research on Relationship Between Intestinal Flora, Immunity and Gallstone / 胃肠病学

Gallstone disease is a common and frequently seen disease of digestive system, and is a common cause of inflammation of gallbladder and bile duct, biliary tract tumor and obstructive jaundice, however, its pathogenesis is not yet fully understood. Recent studies have revealed that intestinal flora and immunity play important roles in the formation of gallstones. This paper reviewed the relationship between the abundance and composition of intestinal flora, immuno - globulins, mucins and immune cells, as well as the interactions between intestinal flora and biliary immunity and gallstone formation for providing new ideas and methods for gallstone prevention and treatment.

Research advances in the risk factors for recurrence of common bile duct stone after choledocholithotomy / 临床肝胆病杂志

Cholelithiasis is a common and frequent disease of the digestive system, and its incidence rate tends to increase with the improvement of living standards. Patients suffering from both gallbladder stones and common bile duct stones account for 5%-15%. Choledocholithiasis can cause a series of serious complications such as acute cholangitis and biliary pancreatitis. Choledocholithotomy is the main method for the treatment of choledocholithiasis, but there is still a high recurrence rate after surgery. The recurrence of choledocholithiasis seriously affects the life of patients and increases their economic burden. With reference to the latest published clinical studies, this article summarizes the influencing factors for the recurrence of choledocholithiasis from the aspects of anatomical factors, stone-related factors, biliary factors, and surgical factors, so as to provide a reference for the treatment of choledocholithiasis and the prevention of its recurrence.

Effect of Dahuang Lingxian prescription on the scf/c-kit signaling pathway in gallbladder interstitial cells of Cajal in a guinea pig model of cholesterol gallstone / 临床肝胆病杂志

Objective To investigate the expression levels of scf and c-kit under the regulation of Dahuang Lingxian prescription and the possible mechanism of its effect on gallbladder dynamics, and to provide a theoretical basis for Dahuang Lingxian prescription in preventing the development and recurrence of cholesterol gallstone. Methods A total of 45 specific pathogen-free healthy male guinea pigs were randomly divided into normal group, model group, and traditional Chinese medicine (TCM) group. The guinea pigs in the normal group were fed with normal diet, and those in the model group and the TCM group were fed with high-fat lithogenic diet. After 8 weeks of feeding, 5 guinea pigs were randomly selected from each group, and successful modeling was determined if gallstone was observed with the naked eye in more than 4 guinea pigs. After successful modeling, the guinea pigs in the TCM group were given Dahuang Lingxian prescription by gavage, and those in the model group were given an equal volume of normal saline by gavage. After 8 consecutive weeks of administration by gavage, gallbladder tissue samples were collected, and HE staining was used to observe the pathological changes of gallbladder tissue; Western blot was used to measure the expression level of tumor necrosis factor-α (TNF-α) in gallbladder tissue; immunohistochemistry was used to measure the protein expression levels of scf and c-kit in gallbladder smooth muscle tissue. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the least significant difference multiple comparison method was used for further comparison between two groups. Results HE staining showed marked inflammation of gallbladder tissue in the model group, and compared with the model group, the TCM group had a significantly lower degree of inflammation. Western blot showed that the model group had the highest expression level of TNF-α in gallbladder tissue, followed by the TCM group and the normal group ( P < 0.05); immunohistochemistry showed that compared with the model group, the normal group and the TCM group had significantly higher protein expression levels of scf and c-kit in gallbladder smooth muscle tissue ( P < 0.05). Conclusion Dahuang Lingxian prescription can enhance the dynamic function of the gallbladder, possibly by upregulating the scf/c-kit signaling pathway in interstitial cells of Cajal in gallbladder.