Íleo biliar complicado con infección con SARS-CoV-2. Reporte de caso

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.

Colangiopatía hipertensiva portal por transformación portal cavernomatosa de origen no cirrótica: a propósito de un caso

La colangiopatía portal hace referencia a anomalías colangiográficas que se producen en pacientes con cavernomatosis portal, siendo progresiva, cursando con enfermedad biliar sintomática y anomalías graves de las vías biliares. Y, representa una complicación infrecuente de la hipertensión portal. Se describe el caso de un hombre de 53 años, con historia de larga data de hipertensión portal nocirrótica y cavernomatosis portal, quien presentó un episodio de enfermedad biliar obstructiva sintomática, y en estudios se documentó tejido fibrótico de extensión periportal ascendente con compresión extrínseca del colédoco distal y dilatación de la vía biliar extra e intrahepática. Por lo que se procedió a colangiopancreatografía retrógrada endoscópica, realizándose tratamiento paliativo, con papilotomía pequeña y colocación de endoprótesis biliar plástica, siendo exitoso por ausencia de complicaciones procedimentales, y mejoría clínica y parámetros bioquímicos. Finalmente, recibiendo de alta con indicación de seguimiento prioritario para recambios periódicos de endoprótesis biliares, y valoración por hepatología. La colangiopatía portal es una entidad rara que debe sospecharse en sujetos con hipertensión portal de origen no-cirrótico, con hallazgos imagenológicos de estenosis, angulaciones o dilataciones segmentarias, su tratamiento debe ser individualizado, y la terapia endoscópica es de elección en enfermedad biliar sintomática.

Portal cholangiopathy refers to cholangiographic abnormalities occurring in patients with portal cavernomatosis, being progressive, presenting with symptomatic biliary disease and severe biliary tract abnormalities. And, it represents an infrequent complication of portal hypertension. We describe the case of a 53-year-old man with a long history of non-cirrhotic portal hypertension and portal cavernomatosis, who presented an episode of symptomatic obstructive biliary disease, and studies documented fibrotic tissue of ascending periportal extension with extrinsic compression of the distal common bile duct and dilatation of the extra and intrahepatic biliary tract. Therefore, endoscopic retrograde cholangiopancreatography was performed, and palliative treatment with small papillotomy and placement of a plastic biliary endoprosthesis was successful due to the absence of procedural complications, and clinical improvement and biochemical parameters. Finally, the patient was discharged with indication of priority follow-up for periodic replacement of biliary stents, and evaluation by hepatology. Portal cholangiopathy is a rare entity that should be suspected in subjects with portal hypertension of non-cirrhotic origin, with imaging findings of stenosis, angulations or segmental dilatations, its treatment should be individualized, and endoscopic therapy is of choice in symptomatic biliary disease.

Fases del desarrollo de biomarcadores para la detección temprana del cáncer / Phases of the development of biomarkers for early detection of cancer

Introducción. Un biomarcador se define como una alteración molecular presente en el desarrollo de la patogénesis del cáncer, que puede ser utilizada para el diagnóstico temprano de la enfermedad. La medición del biomarcador se hace por medio de diversas técnicas, como bioquímica, inmunohistoquímica o biología molecular, en diferentes tipos de muestras, como tejido, sangre periférica y orina. El biomarcador ideal será aquel que sea válido y específico a la vez, que sea no invasivo, barato y fácilmente detectable. El uso de biomarcadores para la detección temprana del cáncer debe seguir un desarrollo ordenado y sistemático antes de introducirlos en la práctica clínica. Métodos. Se realizó una búsqueda exhaustiva en las bases de datos de PubMed y Embase, seleccionando los artículos pertinentes para revisarlos acorde a la temática específica de interés. Resultados. Se propone la sistematización del desarrollo de biomarcadores en cinco grandes fases, las cuales tienen la característica de ser ordenadas desde las evidencias más tempranas hasta las fases finales de su estudio. Conclusiones. El correcto desarrollo de biomarcadores hace posible la introducción de intervenciones terapéuticas en el ámbito de la prevención secundaria del cáncer.

Introduction. A biomarker can be defined as a molecular alteration present in the development of cancer pathogenesis which can be used for early diagnosis of the disease. The measurement of the biomarker can be carried out through various techniques such as biochemistry, immunohistochemistry, molecular biology, in different types of samples such as tissue, peripheral blood, and urine. The ideal biomarker will be one that is valid and specific while is non-invasive, cheap, and easily detectable. The use of biomarkers for the early detection of cancer must follow an orderly and systematic development before introducing them into clinical practice. Methods. An exhaustive search was performed in PubMed and Embase databases, selecting the relevant articles according to the specific topic of interest. Results. Systematization of the development of biomarkers in five large phases is proposed, which has the characteristic of being ordered from the earliest evidence to the final phases of their study. Conclusions. The correct development of biomarkers makes possible the introduction of therapeutic interventions in the field of secondary prevention of cancer.

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.

Cost-utility analysis of pembrolizumab combined with chemotherapy in the first-line treatment of advanced or unresectable biliary tract carcinoma / 中国药房

OBJECTIVE To evaluate the cost-effectiveness of pembrolizumab combined with chemotherapy versus placebo combined with chemotherapy in the first-line treatment of advanced or unresectable biliary tract carcinoma （BTC） from the perspective of China’s health system. METHODS A partitioned survival model was constructed based on the KEYNOTE-966 study data. The simulation period was 21 days， and the simulation time was the patient’s whole life. Using quality-adjusted life year （QALY） as the output indicator， the cost-utility analysis method was used to evaluate the cost-effectiveness of the two schemes mentioned above. Univariate and probabilistic sensitivity analyses were performed to verify the results of the basic analysis， and to explore the cost-effectiveness under the scenario of drug donation scheme. RESULTS The basic analysis showed that both the cost and effectiveness of the pembrolizumab group were higher than those of the placebo group， and the incremental cost-effectiveness ratio （ICER） was 3 909 359.78 yuan/QALY， which was higher than the willingness-to-pay （WTP） threshold of 3 times 2022 gross domestic product （GDP） per capita （257 094 yuan）， indicating no cost-effectiveness. The results of univariate sensitivity analysis showed that the utility discount rate， the utility value of progression-free survival （PFS） status， the cost discount rate， and the cost of pembrolizumab had a great influence on ICER. Probabilistic sensitivity analysis verified the robustness of the results of basic analysis， and concluded that when the WTP threshold was greater than 1 500 000 yuan/QALY， the pembrolizumab group became cost-effective. The results of the scenario analysis showed that considering the drug donation scheme of pembrolizumab for low-income people， although its treatment cost was significantly reduced， it was still not cost-effective. CONCLUSIONS At the WTP threshold of 3 times China’s GDP per capita in 2022， pembrolizumab combined with chemotherapy is not cost-effective compared with placebo combined with chemotherapy for advanced or unresectable BTC.

Clinical features of portal biliopathy / 临床肝胆病杂志

ObjectiveThis article aims to investigate the clinical features of portal biliopathy （PB） patients， in order to improve the understanding of PB. MethodsClinical data were collected from 22 patients who were diagnosed with PB in recent years in The First Hospital of Jilin University， and an analysis was performed for their clinical manifestations， liver function， abdominal color Doppler ultrasound， abdominal CT， and hepatobiliary magnetic resonance imaging. The imaging manifestations of biliary tract abnormalities were described， as well as the type of collateral circulation and the location of thrombosis. ResultsAs for the initial symptom in these 22 patients， three were 11 patients with gastrointestinal bleeding， 5 with abdominal distension， 3 with abdominal pain， 1 with fever， 1 with abdominal discomfort， and 1 with gingival bleeding. There were 3 patients with an increase in aspartate aminotransferase， 4 with an increase in alanine aminotransferase， 4 with an increase in gamma-glutamyl transpeptidase， 7 with an increase in alkaline phosphatase， 8 with a reduction in cholinesterase， 9 with a reduction in albumin， 2 with an increase in globulin， and 5 with an increase in total bilirubin. Among the 22 patients， 20 had cavernous transformation of the portal vein， and 2 had portal vein thrombosis without cavernous transformation. All 22 patients had bile duct abnormalities， among whom 2 had extrahepatic bile duct abnormalities alone， 12 had intrahepatic bile duct dilatation alone， and 8 had dilatation of both intrahepatic and extrahepatic bile ducts. Varices at different sites were observed in 20 patients， among whom 19 had esophageal and gastric varices and 1 had peri-gallbladder varices， and no varices was observed in the superior mesenteric vein or the splenic vein. ConclusionThere are no typical clinical symptoms and changes in liver function parameters in patients with PB， but radiological examination may show dilatation， stenosis， or malformation of the bile ducts at different parts. Therefore， it is necessary to expand the sample size to further explore the diagnosis and treatment of PB.

Current research status of biliary stents / 临床肝胆病杂志

Biliary tract diseases are a common type of hepatobiliary diseases in China and have a relatively high incidence rate， and related complications are important influencing factors for the health of Chinese patients. Biliary stents are mainly used to alleviate and relieve benign or malignant biliary stricture and obstruction， with the features of little trauma， high safety， and in line with the physiological and anatomical structure of biliary tract， and it has become the preferred palliative treatment method for biliary obstruction caused by unresectable pancreaticobiliary tumors. However， there is still a lack of satisfactory treatment outcomes since commonly used biliary stents have the shortcomings such as bacterial adhesion， cholestasis， stent obstruction， and stent migration. In recent years， scholars have conducted extensive and in－depth studies on the causes of biliary stent obstruction， the improvement of stent design， and the extension of drainage duration and have made certain progress. This article reviews the types， advantages and disadvantages， and development history of biliary stents and proposes the future research directions and application value of biliary stents.

Analysis of bacterial spectrum and variability of drug resistance of bile in patients with common bile duct stones and biliary tract infections / 中华消化杂志

Objective:To analyze the distribution of pathogenic bacteria in bile culture in patients with common bile duct stones and biliary tract infections, in order to guide clinical optimization of antibiotics application.Methods:From March 30, 2017 to December 31, 2021, at Affiliated Hospital of Qingdao University, 753 patients with common bile duct stones and biliary tract infections and received endoscopic retrograde cholangiopancreatography were selected. Bile samples were obtained for bacterial culture, strain type identification and drug sensitivity test in order to analyze bile pathogenic bacteria distribution, change trend and drug resistance. Chi-square test was used for statistical analysis.Results:From 2017 to 2021, the total positive rate of bile culture in 753 patients with choledocholithiasis complicated with biliary tract infection was 90.17% (679/753). From 2017 to 2021, the positive rates of bile culture were 82.05% (64/78), 88.81% (119/134), 88.03% (125/142), 93.87% (199/212), and 91.98% (172/187), respectively, and the difference was statistically significant ( χ2=10.78, P=0.029). The positive rate of bile culture in 2017 was lower than those in 2020 and 2021, and the differences were statistically significant ( χ2=9.43 and 5.57, P=0.002 and 0.018). There were no significant differences in the positive rates of bile culture among the other years (all P>0.05). A total of 1 033 pathogenic bacteria were detected in the 679 bile specimens with positive bile culture results. Among which the total proportion of Gram-negative bacilli was 57.02% (589/1 033), and from 2017 to 2021 the proportions were 66.38% (77/116), 66.47% (111/167), 59.43% (104/175), 54.75% (173/316), and 47.88% (124/259), respectively. The total proportion of Gram-positive cocci was 41.05% (424/1 033), and from 2017 to 2021 the proportions were 31.90% (37/116), 31.74% (53/167), 38.86% (68/175), 44.30% (140/316), and 48.65% (126/259), respectively. The total proportion of fungus was 1.94% (20/1 033), and from 2017 to 2021 the proportions were 1.72% (2/116), 1.80% (3/167), 1.71% (3/175), 0.95% (3/316), and 3.47% (9/259), respectively. From 2017 to 2021, the proportion of Gram-negative bacilli gradually decreased, while the proportion of Gram-positive cocci gradually increased, and the differences were statistically significant ( χ2=20.14 and 17.91, P<0.001 and =0.001). From 2017 to 2021, the change in the proportion of fungus was not statistically significant ( P>0.05). The main Gram-negative bacilli in the bile culture were Escherichia coli (31.36%, 324/1 033) and Klebsiella pneumoniae (12.68%, 131/1 033); the main Gram-positive cocci were Enterococcus faecalis (14.04%, 145/1 033) and Streptococcus salivarius (4.36%, 45/1 033). From 2017 to 2021, the proportions of Escherichia coli were 39.66% (46/116), 38.92% (65/167), 33.14% (58/175), 28.48% (90/316), and 25.10% (65/259), respectively, with gradual decrease and the difference was statistically significant ( χ2=14.34, P=0.006). From 2017 to 2021 the detection rates of extended-spectrum β-lactamase (ESBL) in Escherichia coli and Klebsiella pneumoniae were 30.43% (14/46), 26.15% (17/65), 29.31% (17/58), 38.89% (35/90), 40.00% (26/65), and 4/15, 20.00% (5/25), 20% (5/25), 24.32% (9/37), and 31.03% (9/29), and there were no significant differences in the detection rates of ESBL between different years (both P>0.05). Conclusions:From 2017 to 2021, the positive rate of bile culture in patients with choledocholithiasis complicated with biliary tract infection showed an overall increasing trend. Gram-negative bacilli were still dominated in bile pathogenic bacteria, while the proportion of Gram-positive cocci remarkably increased, and the bile bacterial spectrum significantly changed. Clinicians should adjust the antibiotic dosing regimens according to the variation of bacterial spectrum and drug resistance.

Analysis of biliary microbiota in experimental pigs before and after enteral extended biliary stents implantation / 中华消化内镜杂志

Objective:To compare the changes of biliary microbiota after enteral extended biliary stents (EEBS) implantation with that of conventional plastic stents in animal experiment, and to preliminarily investigate its possible mechanism in preventing stents occlusion.Methods:A total of 12 healthy Bama minipigs were randomly assigned to the conventional plastic stent group ( n=6) and the EEBS group ( n=6) using simple random method. The bile samples of all pigs were collected before stents implantation and 4 weeks after stents placement. The biliary microbiota composition and diversity before and after different stents implantation were analyzed by 16S rRNA gene sequencing and compared. Results:No complications including acute cholangitis, perforation, bleeding, or death occurred in 12 pigs. Eight days after stents implantation, stents were out of bile duct in all pigs under endoscopy, while the bile samples were collected again for analysis. The main composition of biliary microbiota at the phylum level were Proteobacteria, Firmicutes and Bacteroidota. Alpha-diversities revealed the Shannon ( P=0.004) and Simpson index ( P=0.008) significantly decreased in the conventional stent group after stents placement, and Bata diversity analysis also showed a significant difference in microbial composition (Anosim: R=0.514 8, P=0.011). There was no significant difference in Observed species index ( P=0.095), Chao1 index ( P=0.136), Shannon index ( P=0.353), Simpson index ( P=0.227) or Bata diversity (Anosim: R=0.059 3, P=0.187) in the EEBS group before and after stents placement. LEfSe algorithm indicated Bacteroides_ fragilis and Proteobacteria- Gammaproteobacteria- Enterobacterales- Enterobacteriaceae- scherichia_ Shigella- Escherichia_ coli significantly increased in the conventional stent group, and Desulfobacterota- Desulfovibrionia- Desulfovibrionales- Desulfovibrionaceae- Bilophila significantly increased in the EEBS group after stents placement. Conclusion:The biliary microbiota change slightly after EEBS implantation in the short-term, and EEBS may prevent duodenobiliary reflux by prolonging the reflux path.

Safety and efficacy of endoscopic ultrasound-guided hepaticogastrostomy for the treatment of hilar and distal biliary obstruction: a retrospective cohort study / 中华消化内镜杂志

Objective:To compare the safety and efficacy of endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) for the treatment of biliary obstruction at different locations.Methods:From January 2016 to June 2021 data of 82 patients with obstructive jaundice treated with EUS-HGS in Nanjing Drum Tower Hospital were reviewed in this retrospective cohort study. According to the location of biliary obstruction,patients were divided into hilar biliary obstruction group ( n=30) and distal biliary obstruction group ( n=52). Univariate and multivariate logistic regression analyses were conducted adjusting covariates to compare the technical success rate, the clinical success rate, the adverse reaction incidence, hospital stay and cost of the two groups. Results:The technical success rates were 93.3% (28/30) and 94.2% (49/52) in the hilar biliary obstruction group and the distal biliary obstruction group with no significant difference between the two groups ( P=0.870, OR=1.17, 95% CI: 0.18-7.41). The clinical success rates were 83.3% (25/30) and 88.5% (46/52) in the hilar biliary obstruction group and the distal biliary obstruction group with no significant difference between the two groups ( P=0.514, OR=1.53, 95% CI: 0.43-5.53). The incidence of adverse events in hilar biliary obstruction group was 10.0% (3/30), including cholangitis 3.3% (1/30), biliary fistula 6.7% (2/30), biliary peritonitis 6.7% (2/30). The incidence of adverse events in patients with distal biliary obstruction was 17.3% (9/52), including cholangitis 9.6% (5/52), biliary fistula 7.7% (4/52) and biliary peritonitis 5.8% (3/52). There was no significant difference in the incidence of adverse events between the two groups ( P>0.05). Conclusion:There is no significant difference in safety or efficacy of EUS-HGS for hilar biliary obstruction and distal biliary obstruction.

Exploration of critical values of monitoring indexes for perioperative major adverse cardiac events in elderly patients with biliary diseases / 中华老年医学杂志

Objective:The purpose of this study was to explore the critical values of monitored indexes of perioperative major adverse cardiac events(MACE), so as to take effective prevention and treatment measures in time to maintain the stability of perioperative cardiac function to further improve the perioperative safety of elderly patients with biliary diseases.Methods:The clinical data of 246 elderly patients with biliary diseases in our hospital from May 2016 to February 2022 were collected.According to whether MACE occurred during the perioperative period, they were divided into the MACE group and the non-MACE group.The differences of clinical data, the monitoring indexes of postoperative cardiac function, and the coagulation function between the two groups were compared and analyzed.Logistic regression was used to analyze the independent risk factors of perioperative MACE, the cut-off value of the receiver operating characteristic(ROC)curve was calculated, and the Logistic multivariate prediction model was established.Results:In the MACE compared with the non-MACE group, age, postoperative complications and mortality, postoperative hospital stay, and the levels of postoperative high sensitivity troponin-I(Hs-TnI), creatine kinase isoenzyme(CK-MB), myoglobin(MYO), B-type natriuretic peptide(BNP), and D-dimer(D-D)were significantly increased(all P<0.05). Multivariate Logistic regression showed that postoperative BNP and D-D were two independent risk factors for perioperative MACE, and their cut-off values in the ROC curve were 382.65 pg/mL and 0.975mg/L respectively.The Logistic multivariate prediction model established by the Logistic regression equation was P= ex/(1+ ex), X=-5.710+ 0.003X 1+ 0.811X 2, where X 1 was the postoperative BNP level and X 2 was the postoperative D-D level.The accuracy, specificity and sensitivity of this prediction model for predicting perioperative MACE were 96.3%(237/246), 100.0%(235/235), and 18.2%(2/11). Conclusions:The Logistic multivariate prediction model established in this study can effectively predict the occurrence of perioperative MACE in elderly patients.Postoperative BNP and D-D were two independent risk factors for perioperative MACE.The cut-off values of BNP and D-D in the ROC curve could be used as critical values for monitoring perioperative MACE.Therefore, it is of great clinical significance to take effective prevention and treatment measures in time to maintain the stability of perioperative cardiac function, and further improve the perioperative safety of elderly patients with biliary diseases.

Diagnostic and prognostic value of 68Ga-FAPI PET for malignant tumors of the liver and biliary tract / 中华核医学与分子影像杂志

Objective:To investigate the diagnostic and prognostic value of 68Ga-fibroblast activation protein inhibitor (FAPI) PET for hepatobiliary malignancies. Methods:From July 2020 to February 2023, 33 patients (23 males, 10 females; age (55.4±13.5) years) with suspected or confirmed liver or biliary tract malignancies who underwent 68Ga-FAPI PET in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology were retrospectively analyzed. PET images were evaluated by 3 experienced nuclear medicine physicians, and the results of biopsy or postoperative pathology, clinical and imaging follow-up were used as the gold standard. One-way analysis of variance and least significant difference t test were used to compare the differences among groups. Survival analysis was performed using Kaplan-Meier curves and the log-rank test. Results:Of 33 patients, 14 performed PET for initial diagnosis and staging, and 19 for restaging. There were 14 patients with hepatocellular carcinoma (HCC), 13 patients with cholangiocarcinoma (CCA), and 6 patients with gallbladder carcinoma (GBC). The primary tumor of HCC, CCA and GBC all showed significant 68Ga-FAPI uptake, with no statistically significant difference in SUV max among groups ( F=1.58, P=0.250). The sensitivities of 68Ga-FAPI PET for initial diagnosis and restaging of hepatobiliary malignancies were 14/14 and 15/15, respectively. Compared with conventional imaging, 68Ga-FAPI PET changed the diagnosis and staging in 29.2%(7/24) patients. The treatment strategy was changed in 30.3%(10/33) patients with malignant tumors due to 68Ga-FAPI PET findings. Follow-up showed 22 cases survived and 11 cases died, with the overall survival of 355.56(80.00, 516.97) d, and 1- and 2-year survival rates were 68.2% and 57.9%, respectively. Semi-quantitative 68Ga-FAPI PET parameters such as SUV max, target-liver ratio (TLR), and target-blood ratio (TBR) had no significant prognostic value, but the prognosis of the group without distant metastases diagnosed by 68Ga-FAPI PET was significantly better than that of the group with distant metastasis ( P=0.032). Conclusion:68Ga-FAPI PET has high sensitivity for the diagnosis of hepatobiliary malignancies, which can help guide treatment decisions and prognosis evaluation.

Research progress of precise targeted therapy for human epidermal growth factor receptor-2 in biliary tract cancers / 中华肝胆外科杂志

Biliary tract cancers (BTC) are highly heterogeneous tumours. Currently, the global demand for advanced BTC treatment is far from being met, and the survival benefit from advanced chemotherapy is limited. In recent years, with the rise of precision treatment, there are more and more treatment options available for advanced BTC. Human epidermal growth factor receptor-2 (HER2) inhibitors, including monoclonal antibodies, tyrosine kinase inhibitors, antibody drug conjugates, and bispecific antibodies, have been explored in BTC. This article reviews the research progress and prospects of HER2 inhibitors in BTC in recent years, so as to provide a better clinical guidance.

Thought and practice of long-term management for hepatobiliary and pancreatic malignant tumors / 中华肝胆外科杂志

Radical resection is the only measurement to cure patients of hepatobiliary and pancreatic tumors. The comprehensive application of endoscopy, interventional therapy, radiotherapy and systemic therapy can not only significantly improve the early diagnosis rate of the disease, and successfully transform some borderline resectable tumors into radical resectable states, but also reduce the recurrence rate of tumors after surgery, thus prolonging the survival time of patients. In recent years, the continuous emergence of new systemic therapeutic drugs has brought new opportunities for patients with hepatobiliary and pancreatic malignancies, but the number of doctors participating in diagnosis and treatment has also increased accordingly. Therefore, the contradiction between the division system based on treatment methods and the orderly and standardized treatment is becoming more and more prominent. According to the latest progress of hepatobiliary and pancreatic cancer research at home and abroad, and combined with our clinical experience, we proposed a long-term management concept based on hepatobiliary and pancreatic comprehensive multi-technical team. Based on this concept, we have carried out new thought and practice on the diagnosis and treatment of patients with hepatobiliary and pancreatic malignant tumors.

Application status and prospect of biodegradable polymer stents in pancreatobiliary disease / 中华肝胆外科杂志

Endoscopic stent implantation is one of the main methods for the treatment of biliary and pancreatic diseases. At present, the commonly used biliary and pancreatic stents are mainly plastic and metal stents which are still have some deficiencies in clinical applications, and the emergence of the new type of biodegradable polymer materials is expected to achieve the purpose of treatment to overcome these shortcomings. It is a potential hope to break through the bottleneck of endoscopic treatment of choleopancreatic diseases. Previous animal experiments and human clinical studies have preliminarily shown its safety and effectiveness, which can effectively solve some problems of bile and pancreatic duct stenosis and so on. Biodegradable polymer stents have been widely studied, but their clinical application progress is slow and not yet popular, and it has gradually become a research hotspot in recent years . This article discusses the research status and development direction of biodegradable polymer stents in biliary and pancreatic diseases.

Distribution and drug resistance of pathogenic bacteria of biliary tract infection in patients subjected to hepatobiliary surgery / 中国基层医药

Objective:To study the distribution and drug resistance of pathogenic bacteria of biliary tract infection in patients with hepatobiliary surgery.Methods:A total of 103 patients with biliary tract infection who received treatment in the Department of Hepatobiliary Surgery, Lanxi People's Hospital from May 2020 to October 2022 were included in this study. Their bile was cultured to analyze the distribution and drug resistance of pathogenic bacteria. The data were processed using the WHONET5.5 software system.Results:Fifty-eight pathogenic bacteria-positive samples were cultured from the bile of 103 patients with biliary tract infection, with a pathogenic bacteria-positive rate of 56.31%. Among 58 strains of pathogenic bacteria, 38 strains (65.52%) were gram-negative bacteria, mainly Escherichia coli and Klebsiella pneumonia, and 5 strains (8.62%) were fungal strains. Escherichia coli and Klebsiella pneumoniae were highly resistant to sulfamethoxazole-trimethoprim, ciprofloxacin, and other antibacterial drugs, and were completely sensitive to imipenem and meropenem. Enterococcus faecalis was mainly resistant to ampicillin and penicillin G,and it was completely sensitive to vancomycin and teicoplanin. Staphylococcus aureus was resistant to vancomycin, ciprofloxacin, cefotaxime, and other drugs. A total of 13 strains of ultrabroad-spectrum beta-lactamase bacteria were isolated from 25 strains of Escherichia coli and 7 strains of Klebsiella pneumonia, with the positive detection rate of 40.63%. Conclusion:The main pathogenic bacteria of biliary tract infection are Gram-negative bacteria, which are widely distributed and have serious drug resistance. In clinical practice, antimicrobial drugs should be reasonably selected according to the results of bile drug sensitivity tests.

Function of peribiliary glands as well as its relationship with ischemic-type biliary lesions / 中华消化外科杂志

Peribiliary glands (PBG) is a kind of microscopic structure around the intra-hepatic bile ducts and extrahepatic bile ducts. PBG not only participates in maintaining the normal physiological function of biliary epithelial tissue, but also plays an important role in its damage and repair process. Biliary tree stem/progenitor cells in PBG are important cell sources of biliary epithelial regeneration and repair. PBG and the surrounding peribiliary vascular plexus are key influencing factors for the occurrence of ischemic-type biliary lesions (ITBL) after liver transplantation. Based on relevant literatures and clinical practice, the authors summarize the function of PBG as well as its relationship with ITBL.

Research progress of perineural invasion in gallbladder cancer / 中华消化外科杂志

As a special mode of tumor metastasis, perineural invasion has been paid more and more attention. It is closely related to prognosis, recurrence and metastasis of tumor after surgery. As the most common malignancy of the biliary tract, perineural invasion is also an inde-pendent prognostic risk factor for gallbladder cancer due to its anatomical location, lymphatic reflux, blood perfusion and innervation. However, there are few studies on perineural invasion in gallbla-dder cancer, especially on its mechanism. By analyzing the general situation and recent progress of perineural invasion in gallbladder cancer, the authors mainly introduce the perineural invasion mechanism, perineural invasion rate of gallbladder cancer, relationship between perineural invasion and the clinical pathologic characteristic, the correlation with the prognosis, relationship with surgi-cal procedures and postoperative adjuvant therapy.

Risk factors of acute biliopancreatic complications in patients of pregnancy combined with gallbladder stone and construction of prediction model / 中华消化外科杂志

Objective:To investigate the risk factors of acute biliopancreatic complica-tions in patients of pregnancy combined with gallbladder stone and construction of prediction model.Methods:The retrospective case-control study was constructed. The clinical data of 98 patients of pregnancy combined with gallbladder stone who were admitted to the First Hospital of Lanzhou University from September 2011 to October 2022 and 53 patients of pregnancy combined with gallbladder stone who were admitted to Gansu Provincial Hospital May 2014 to October 2021 were collected. The age of 151 patients was 29(25,32)years. Observation indicators: (1) situations of patients of pregnancy combined with gallbladder stone; (2) risk factors of acute biliopancreatic com-plications in patients of pregnancy combined with gallbladder stone; (3) construction of prediction model for acute biliopancreatic complications in patients of pregnancy combined with gallbladder stone. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data was conducted using the rank sum test. Univariate and multi-variate analyses were conducted using the Logistic regression model. Nomogram prediction model was conducted, and the receiver operating characteristic (ROC) curve was used to evaluate discri-mination of the nomogram predic-tion model. The calibration curve and clinical decision curve were used to evaluate calibration and net clinical benefit of the nomogram prediction model. Internal validation of the prediction model was performed by applying 10-fold cross-validation. Results:(1) Situations of patients of pregnancy combined with gallbladder stone. The total cholesterol, triglyceride, high density lipoprotein cholesterol, low density lipoprotein cholesterol, prepregnancy body mass index (<18.5 kg/m 2, 18.5?24.0 kg/m 2, >24.0 kg/m 2), gesta-tional period (early, mid, late), primipara (positive, negative), stone type (solitary, non solitary), diameter of stone (≤10 mm, >10 mm), gallbladder wall thickness (≥4 mm, <4 mm) were (4.9±1.4)mmol/L, 1.88(1.22,2.93)mmol/L, 1.48(1.22,1.83)mmol/L, (2.8±0.9)mmol/L, 13, 75, 58, 37, 45, 69, 86, 65, 37, 114, 89, 62, 38, 113 in the 151 patients of pregnancy combined with gallbladder stone. Of the 151 patients, the age, prepregnancy body mass index (<18.5 kg/m 2, 18.5?24.0 kg/m 2, >24.0 kg/m 2), primipara (positive, negative), stone type (solitary, non solitary), diameter of stone (≤10 mm, >10 mm), gallbladder wall thickness (≥4 mm, <4 mm) were 31(28,37)years, 3, 30, 36, 29, 40, 32, 37, 26, 43, 4, 65 in 69 cases without symptom, versus 27(24,31)years, 10, 45, 22, 57, 25, 5, 77, 63, 19, 34, 48 in 82 cases combined with acute biliopancreatic complications, showing significant differences in the above indicators between them ( Z=?3.636, ?2.385, χ2=11.544, 32.862, 23.729, 25.310, P<0.05). Five of the 82 patients of pregnancy combined with gallbladder stone missed data of prepregnancy body mass index. Of the 82 patients, there were 42 patients of simple acute cholecystitis, 40 patients of common bile duct stone and/or acute biliary pancreatitis including 18 cases of common bile duct stone, 13 cases of acute biliary pancreatitis and 9 cases of common bile duct stone combined with acute biliary pancreatitis. (2) Risk factors of acute biliopancreatic complications in patients of pregnancy combined with gallbladder stone. Results of multivariate analysis showed that primipara, non solitary stone, diameter of stone ≤10 mm, gallbladder wall thickness ≥4 mm were independent risk factors of acute biliopancreatic complications in patients of pregnancy combined with gallbladder stone ( odds ratio=3.102, 6.305, 3.674, 6.686, 95% confidence interval as 1.280?7.519, 1.886?21.080, 1.457?9.265, 1.984?22.528, P<0.05). Results of multivariate analysis in further analysis showed that primipara, non solitary stone, gallbladder wall thickness ≥4 mm were independent risk factors of simple acute cholecystitis in patients of pregnancy combined with gallbladder stone ( odds ratio=3.671, 8.905, 7.137, 95% confidence interval as 1.386?9.723, 2.332?34.006, 1.902?26.773, P<0.05), and age, non solitary stone, diameter of stone ≤10 mm, gallbladder wall thickness ≥4 mm were independent risk factors of common bile duct stone and/or acute biliary pancreatitis in patients of pregnancy combined with gallbladder stone ( odds ratio=0.883, 5.361, 5.472, 8.895, 95% confidence interval as 0.789?0.988, 1.062?27.071, 1.590?18.827, 2.064?38.325, P<0.05). (3) Construction of prediction model for acute biliopancreatic complications in patients of pregnancy combined with gallbladder stone. The nomogram prediction model for acute biliopancreatic complications in patients of pregnancy combined with gallbladder stone was constructed based on the clinical factors of age, primipara, stone type, diameter of stone and gallbladder wall thickness. The area under the curve (AUC) of ROC curve of prediction model was 0.869 (95% confidence interval as 0.813?0.923), indicating that the prediction model with good predictive ability. Results of Hosmer-Lemeshow test showed a good fit ( χ2=5.680, P>0.05), indicating that the prediction model with good calibration. Results of decision curve analysis showed the prediction model with high net clinical benefit. Results of internal validation of the prediction model based on 10-fold cross-validation showed the AUC of ROC curve for the cross-validation sample was 0.833, indicating that the prediction model with good stability. Conclusions:Primigravida, non solitary stone, diameter of stone ≤10 mm, gallbladder wall thickness ≥4 mm are independent risk factors of acute biliopancreatic complications in patients of pregnancy combined with gallbladder stone. The prediction model for acute biliopancreatic complications has good predictive ability.