[Double extrahepatic bile duct with pancreaticobiliary maljunction:a case report].

A 76-year-old woman with a suspected double extrahepatic bile duct was referred to our hospital. MRCP revealed that the left hepatic and posterior ducts combined to form the ventral bile duct and that the anterior duct formed the dorsal bile duct. ERCP demonstrated that the ventral bile duct was linked with the Wirsung duct. Amylase levels in the bile were unusually high. Based on these findings, we diagnosed a double extrahepatic bile duct with pancreaticobiliary maljunction and choledocholithiasis. Duplicate bile duct resection and bile duct jejunal anastomosis were performed considering the risk of biliary cancer due to pancreaticobiliary maljunction. The resected bile duct epithelium demonstrated no atypia or hyperplastic changes.

Diseases of bile duct in children.

Several diseases originate from bile duct pathology. Despite studies on these diseases, certain etiologies of some of them still cannot be concluded. The most common disease of the bile duct in newborns is biliary atresia, whose prognosis varies according to the age of surgical correction. Other diseases such as Alagille syndrome, inspissated bile duct syndrome, and choledochal cysts are also time-sensitive because they can cause severe liver damage due to obstruction. The majority of these diseases present with cholestatic jaundice in the newborn or infant period, which is quite difficult to differentiate regarding clinical acumen and initial investigations. Intraoperative cholangiography is potentially necessary to make an accurate diagnosis, and further treatment will be performed synchronously or planned as findings suggest. This article provides a concise review of bile duct diseases, with interesting cases.

Modified technique of Hepatojejunostomy for biliary tract reconstruction after resection of tumors affecting the perihilar region: a case series.

BACKGROUNDS: Radical resection is the most effective treatment for perihilar tumors. Biliary tract reconstruction after resection is one of the key steps in this surgery. Mucosa-to-mucosa cholangiojejunostomy is traditionally performed, in which the bile ducts at the resection margin are separately anastomosed to the jejunum. However, this approach is associated with long operative time and high risk of postoperative complications. The present study presents a modified technique of hepatojejunostomy and its outcomes. METHODS: The data of patients who underwent hepatojejunostomy using the modified technique at the Department of Hepatobiliary Surgery, Daping Hospital, Army Medical University, Chongqing, China, from January 2016 to December 2021, were retrospectively analyzed. RESULTS: A total of 13 patients with perihilar tumors underwent R0 resection and bilioenteric reconstruction using the modified hepatojejunostomy technique during the study period. During the operation, the alignment of the bile duct stumps was improved, the posterior wall of the anastomosis was reinforced, internal stents were placed in the smaller bile ducts, external stents were placed in the larger bile ducts, and hepatojejunostomy was performed using 4 - 0 prolene. No serious postoperative complications, such as death or bile leakage, occurred during the hospitalization. Furthermore, there were no cases of biliary stricture or cholangitis after the six-month follow-up period. CONCLUSION: The modified hepatojejunostomy technique is a safe and effective technique of biliary reconstruction after the resection of perihilar tumors. This can be easily performed for difficult cases with multiple bile ducts that require reconstruction after resection.

BILE DUCT INJURY REPAIR IN A PATIENT WITH SITUS INVERSUS TOTALIS.

BACKGROUND: Bile duct injury (BDI) causes significant sequelae for the patient in terms of morbidity, mortality, and long-term quality of life, and should be managed in centers with expertise. Anatomical variants may contribute to a higher risk of BDI during cholecystectomy. AIMS: To report a case of bile duct injury in a patient with situs inversus totalis. METHODS: A 42-year-old female patient with a previous history of situs inversus totalis and a BDI was initially operated on simultaneously to the lesion ten years ago by a non-specialized surgeon. She was referred to a specialized center due to recurrent episodes of cholangitis and a cholestatic laboratory pattern. Cholangioresonance revealed a severe anastomotic stricture. Due to her young age and recurrent cholangitis, she was submitted to a redo hepaticojejunostomy with the Hepp-Couinaud technique. To the best of our knowledge, this is the first report of BDI repair in a patient with situs inversus totalis. RESULTS: The previous hepaticojejunostomy was undone and remade with the Hepp-Couinaud technique high in the hilar plate with a wide opening in the hepatic confluence of the bile ducts towards the left hepatic duct. The previous Roux limb was maintained. Postoperative recovery was uneventful, the drain was removed on the seventh post-operative day, and the patient is now asymptomatic, with normal bilirubin and canalicular enzymes, and no further episodes of cholestasis or cholangitis. CONCLUSIONS: Anatomical variants may increase the difficulty of both cholecystectomy and BDI repair. BDI repair should be performed in a specialized center by formal hepato-pancreato-biliary surgeons to assure a safe perioperative management and a good long-term outcome.

Effects of nicotine on microRNA-124 expression in bile duct ligation-induced liver fibrosis in rats.

BACKGROUND: Nicotine, the main compound of smoking may exert its effects by changing the expression of microRNAs (miRNAs). This study was conducted to further investigate the molecular mechanisms of miRNA-dependent effects of nicotine in an animal model of liver fibrosis. METHODS: The bile duct ligation (BDL) approach was used to create a model of liver fibrosis. Twenty-four male Wistar rats were used in the study. The effects of nicotine administration on miRNA-124 expression, as well as alpha-smooth muscle actin (liver fibrosis marker) and chemokine ligand 2 (an inflammatory chemokine), were investigated using RT-qPCR. In addition, the mRNA and protein expression of signal transducer and activator of transcription 3 (STAT-3; as a potential target for miRNA-124) were investigated by RT-qPCR and immunofluorescence, respectively. Liver enzyme activity levels were measured using a colorimetric assay. In addition, the effects of nicotine on the process of liver fibrosis were investigated with histological studies. RESULTS: The development of liver fibrosis in BDL rats and nicotine administration led to a decrease in miRNA-124 expression. The decrease in the expression is accompanied by the increase in the expression of fibrotic and proinflammatory genes. Also, an increase in STAT-3 mRNA and protein expression was observed in the fibrotic rats that received nicotine. In addition, the significant increase in bilirubin and liver enzymes in fibrotic rats worsens with nicotine administration. The results of histological studies also confirm these results. CONCLUSION: Considering that miRNA-124 is an anti-inflammatory miRNA, it can be concluded that the decrease in its expression due to nicotine exposure leads to an increase in inflammatory processes and subsequently to an increase in liver fibrosis.

Reparación laparoscópica de las lesiones quirúrgicas de la vía biliar: factibilidad y evaluación de resultados / Laparoscopic repair of bile duct injuries: Feasibility and outcomes

Introducción: Las lesiones quirúrgicas de la vía biliar (LQVB) posteriores a la colecistectomía videolaparoscópica tienen una incidencia de 0,6% aproximadamente, siendo por lo general más graves y complejas. La hepaticoyeyunoanastomosis (HYA) en Y de Roux es la mejor opción terapéutica (tasas de éxito entre 75-98%). Algunas series demostraron factible el abordaje laparoscópico en la resolución de esta patología. El objetivo es describir nuestra experiencia en la reparación laparoscópica de las LQVB. Métodos: Estudio retrospectivo y descriptivo. Se incluyeron pacientes sometidos a reparación laparoscópica posterior a LQVB. Se analizaron variables demográficas, clínicas, quirúrgicas y posoperatorias. Se aplicaron análisis estadísticos descriptivos. Resultados: Se evaluaron 92 pacientes con LQVB; 81 se sometieron a reparación quirúrgica, ocho fueron candidatos a HYA laparoscópica (aplicabilidad 9,88%). En 75% (seis) se logró una reparación laparoscópica completa. La mayoría eran mujeres (75%). Edad promedio de 40,8 ± 16,61 años (rango 19-65). Las lesiones Strasberg-Bismuth ≥ E3 afectaron a 25% (dos). En la mitad se realizó una HYA laterolateral según la técnica de Hepp-Couinaud; tres usuarios recibieron una HYA terminolateral y otro una bi-HYA terminolateral en Y de Roux. El tiempo operatorio promedio fue de 260 min (rango 120-360). La morbilidad global fue de 37,5% (tres casos): dos complicaciones menores (bilirragia grado A y hemorragia por drenajes) y una mayor (bilirragia grado C). No se registró mortalidad. El seguimiento máximo fue de 26 meses (rango 6-26). Conclusiones: Nuestro estudio muestra que, en un grupo seleccionado de pacientes, la HYA laparoscópica es factible, con los beneficios de un abordaje miniinvasivo.(AU)

Introduction: Bile duct injuries (BDI) following laparoscopic cholecystectomy occurs in approximately 0.6% of the cases, often being more severe and complex. Roux-en-Y hepaticojejunostomy (RYHJ) is considered the optimal therapeutic option, with success rates ranging from 75% to 98%. Several series have demonstrated the advancements of the laparoscopic approach for resolving this condition. The objective of this study is to describe our experience in the laparoscopic repair of BDI. Methods: A retrospective, descriptive study was conducted, including patients who underwent laparoscopic repair after BDI. Demographic, clinical, surgical, and postoperative variables were analyzed using descriptive statistical analyses. Results: Eight patients with BDI underwent laparoscopic repair (out of 81 surgically repaired patients). Women comprised 75% of the sample. A complete laparoscopic repair was achieved in 75% (6) of cases. The mean age was 40.8 ± 16.61 years (range 19–65). Injuries at or above the confluence (Strasberg–Bismuth ≥ E3) occurred in 25% of cases (2). Primary repair was performed in two cases. Half of the cases underwent a Hepp-Couinaud laterolateral RYHJ, while three patients received a terminolateral RYHJ, and one underwent a bi-terminolateral RYH. The mean operative time was 260 min (range 120–360). Overall morbidity was 37.5% (three cases): two minor complications (bile leak grade A and drainage-related bleeding) and one major complication (bile leak grade C). No mortality was recorded. The maximum follow-up period reached 26 months (range 6–26). Conclusions: Our study demonstrates the feasibility of laparoscopic RYHJ in a selected group of patients, offering the benefits of a minimally invasive approach.(AU)

A case report of carcinoma of the papilla of Vater associated with a hyperplasia-dysplasia-carcinoma sequence by pancreaticobiliary maljunction.

BACKGROUND: Pancreaticobiliary maljunction (PBM) is a known risk factor for biliary tract cancer. However, its association with carcinoma of the papilla of Vater (PVca) remains unknown. We report a case with PVca that was thought to be caused by the hyperplasia-dysplasia-carcinoma sequence, which is considered a mechanism underlying PBM-induced biliary tract cancer. CASE PRESENTATION: A 70-year-old woman presented with white stool and had a history of cholecystectomy for the diagnosis of a non-dilated biliary tract with PBM. Esophagogastroduodenoscopy revealed a tumor in the papilla of Vater, and PVca was histologically proven by biopsy. We finally diagnosed her with PVca concurrent with non-biliary dilated PBM (cT1aN0M0, cStage IA, according to the Union for International Cancer Control, 8th edition), and subsequently performed subtotal stomach-preserving pancreaticoduodenectomy. Pathological findings of the resected specimen revealed no adenomas and dysplastic and hyperplastic mucosae in the common channel slightly upstream of the main tumor, suggesting a PBM related carcinogenic pathway with hyperplasia-dysplasia-carcinoma sequence. Immunostaining revealed positivity for CEA. CK7 positivity, CK20 negativity, and MUC2 negativity indicated that this PVca was of the pancreatobiliary type. Genetic mutations were exclusively detected in tumors and not in normal tissues, and bile ducts from formalin-fixed paraffin-embedded samples included mutated-ERBB2 (Mutant allele frequency, 81.95%). Moreover, of the cell-free deoxyribonucleic acid (cfDNA) extracted from liquid biopsy mutated-ERBB2 was considered the circulating-tumor deoxyribonucleic acid (ctDNA) of this tumor. CONCLUSIONS: Herein, we report the first case of PVca with PBM potentially caused by a "hyperplasia-dysplasia-carcinoma sequence" detected using immunostaining and next-generation sequencing. Careful follow-up is required if pancreaticobiliary reflux persists, considering the possible development of PVca.

Impact of Liver Sympathetic Nervous System on Liver Fibrosis and Regeneration After Bile Duct Ligation in Rats.

The sympathetic nervous system (SNS) affects many functions of the body. SNS fibers regulate many aspects of liver function, repair, and regeneration. However, in the model of bile duct ligation (BDL) in rats, the kind of impact caused by the regulation of liver SNS on liver fibrosis and liver regeneration is unclear. The main research objective of this experiment is to examine the effect of SNS on liver fibrosis and liver regeneration. Twenty-four male Sprague-Dawley (SD) rats were assigned randomly to four groups. These groups included the sham surgery group (sham), model group (BDL), 6-hydroxydopamine group (BDL+6-OHDA), and spinal cord injury group (BDL+SCI). In the sham group, only exploratory laparotomy was performed without BDL. In the 6-OHDA group, 6-OHDA was used to remove sympathetic nerves after BDL. In the spinal cord injury group, rats underwent simultaneous BDL and spinal cord injury. After 3 weeks of feeding, four groups of rats were euthanized using high-dose anesthesia without pain. Moreover, liver tissue and blood were taken to detect liver fibrosis and regeneration indicators. After intraperitoneal injection of 6-OHDA into BDL rats, liver fibrosis indicators decreased. The administration of the injection effectively alleviated liver fibrosis and inhibited liver regeneration. However, after SCI surgery in BDL rats, liver fibrosis indicators increased. This resulted in exacerbating liver fibrosis and activating liver regeneration. The SNS plays a role in contributing to the liver injury process in the rat BDL model. Therefore, regulating the SNS may become a novel method for liver injury treatment.

Variations in the cystic duct: frequency and the relationship among insertion sides and heights on the bile duct.

BACKGROUND: Evaluation of the cystic duct anatomy prior to bile duct or gallbladder surgery is important, to decrease the risk of bile duct injury. This study aimed to clarify the frequency of cystic duct variations and the relationship between them. METHODS: Data of 205 patients who underwent cholecystectomy after imaging at Sada Hospital, Japan, were analyzed. The Chi-square test was used to analyze the relationships among variations. RESULTS: The lateral and posterior sides of the bile duct were the two most common insertion points (92 patients, 44.9%), and the middle height was the most common insertion height (135 patients, 65.9%). Clinically important variations (spiral courses, parallel courses, low insertions, and right hepatic duct draining) relating to the risk of bile duct injury were observed in 24 patients (11.7%). Regarding the relationship between the insertion sides and heights, we noticed that the posterior insertion frequently existed in low insertions (75.0%, P < 0.001) and did not exist in high insertions. In contrast, the anterior insertion coexisted with high and never low insertions. Spiral courses have two courses: anterior and posterior, and anterior ones were only found in high insertion cases. CONCLUSIONS: The insertion point of the cystic duct and the spiral courses tended to be anterior or lateral superiorly and posterior inferiorly. Clinically significant variations in cystic duct insertions are common and surgeons should be cautious about these variations to avoid complications.

Exploring the impact of naltrexone on the THBS1/eNOS/NO pathway in osteoporotic bile duct-ligated rats.

Hepatic osteodystrophy, a prevalent manifestation of metabolic bone disease, can arise in the context of chronic liver disease. The THBS1-eNOS-NO signaling pathway plays a pivotal role in the maturation of osteoclast precursors. This study aimed to investigate the impact of Naltrexone (NTX) on bone loss by examining the THBS1-eNOS-NO signaling pathways in bile duct ligated (BDL) rats. Male Wistar rats were randomly divided into five groups (n = 10 per group): control, sham-operated + normal saline, BDL + normal saline, sham-operated + NTX (10 mg/kg), and BDL + NTX. Parameters related to liver injury were measured at the study's conclusion, and Masson-trichrome staining was employed to evaluate collagen deposition in liver tissue. Bone THBS-1 and endothelial nitric oxide synthase (eNOS) expression levels were measured using real-time PCR, while the level of bone nitric oxide (NO) was assessed through a colorimetric assay. NTX treatment significantly attenuated the BDL-induced increase in circulating levels of liver enzymes and bilirubin. THBS-1 expression levels, elevated after BDL, were significantly suppressed following NTX administration in the BDL + NTX group. Despite no alterations in eNOS expression between groups, the bone NO level, significantly decreased in the BDL group, was significantly reduced by NTX in the BDL + NTX group. This study partly provides insights into the possible molecular mechanisms in BDL-induced osteoporosis and highlights the modulating effect of NTX on these pathways. Further research is needed to establish the impact of NTX on histomorphometric indexes.

Bile duct ligation elevates 5-HT levels in cerebral cortex of rats partly due to impairment of brain UGT1A6 expression and activity via ammonia accumulation.

Hepatic encephalopathy (HE) is often associated with endogenous serotonin (5-HT) disorders. However, the reason for elevated brain 5-HT levels due to liver failure remains unclear. This study aimed to investigate the mechanism by which liver failure increases brain 5-HT levels and the role in behavioral abnormalities in HE. Using bile duct ligation (BDL) rats as a HE model, we verified the elevated 5-HT levels in the cortex but not in the hippocampus and striatum, and found that this cortical 5-HT overload may be caused by BDL-mediated inhibition of UDP-glucuronosyltransferase 1A6 (UGT1A6) expression and activity in the cortex. The intraventricular injection of the UGT1A6 inhibitor diclofenac into rats demonstrated that the inhibition of brain UGT1A6 activity significantly increased cerebral 5-HT levels and induced HE-like behaviors. Co-immunofluorescence experiments demonstrated that UGT1A6 is primarily expressed in astrocytes. In vitro studies confirmed that NH4Cl activates the ROS-ERK pathway to downregulate UGT1A6 activity and expression in U251 cells, which can be reversed by the oxidative stress antagonist N-acetyl-l-cysteine and the ERK inhibitor U0126. Silencing Hepatocyte Nuclear Factor 4α (HNF4α) suppressed UGT1A6 expression whilst overexpressing HNF4α increased Ugt1a6 promotor activity. Meanwhile, both NH4Cl and the ERK activator TBHQ downregulated HNF4α and UGT1A6 expression. In the cortex of hyperammonemic rats, we also found activation of the ROS-ERK pathway, decreases in HNF4α and UGT1A6 expression, and increases in brain 5-HT content. These results prove that the ammonia-mediated ROS-ERK pathway activation inhibits HNF4α expression to downregulate UGT1A6 expression and activity, thereby increasing cerebral 5-HT content and inducing manic-like HE symptoms. This is the first study to reveal the mechanism of elevated cortical 5-HT concentration in a state of liver failure and elucidate its association with manic-like behaviors in HE.

Golexanolone improves fatigue, motor incoordination and gait and memory in rats with bile duct ligation.

BACKGROUND AND AIMS: Many patients with the chronic cholestatic liver disease primary biliary cholangitis (PBC) show fatigue and cognitive impairment that reduces their quality of life. Likewise, rats with bile duct ligation (BDL) are a model of cholestatic liver disease. Current PBC treatments do not improve symptomatic alterations such as fatigue or cognitive impairment and new, more effective treatments are therefore required. Golexanolone reduces the potentiation of GABAA receptors activation by neurosteroids. Golexanolone reduces peripheral inflammation and neuroinflammation and improves cognitive and motor function in rats with chronic hyperammonemia. The aims of the present study were to assess if golexanolone treatment improves fatigue and cognitive and motor function in cholestatic BDL rats and if this is associated with improvement of peripheral inflammation, neuroinflammation, and GABAergic neurotransmission in the cerebellum. METHODS: Rats were subjected to bile duct ligation. One week after surgery, oral golexanolone was administered daily to BDL and sham-operated controls. Fatigue was analysed in the treadmill, motor coordination in the motorater, locomotor gait in the Catwalk, and short-term memory in the Y-maze. We also analysed peripheral inflammation, neuroinflammation, and GABAergic neurotransmission markers by immunohistochemistry and Western blot. RESULTS: BDL induces fatigue, impairs memory and motor coordination, and alters locomotor gait in cholestatic rats. Golexanolone improves these alterations, and this was associated with improvement of peripheral inflammation, neuroinflammation, and GABAergic neurotransmission in the cerebellum. CONCLUSION: Golexanolone may have beneficial effects to treat fatigue, and motor and cognitive impairment in patients with the chronic cholestatic liver disease PBC.

Endoscopic ultrasound-rendezvous versus percutaneous-endoscopic rendezvous endoscopic retrograde cholangiopancreatography for bile duct access: Systematic review and meta-analysis.

OBJECTIVES: Endoscopic ultrasound (EUS) or percutaneous-assisted antegrade guidewire insertion can be used to achieve biliary access when standard endoscopic retrograde cholangiopancreatography (ERCP) fails. We conducted a systematic review and meta-analysis to evaluate and compare the effectiveness and safety of EUS-assisted rendezvous (EUS-RV) and percutaneous rendezvous (PERC-RV) ERCP. METHODS: We searched multiple databases from inception to September 2022 to identify studies reporting on EUS-RV and PERC-RV in failed ERCP. A random-effects model was used to summarize the pooled rates of technical success and adverse events with 95% confidence interval (CI). RESULTS: In total, 524 patients (19 studies) and 591 patients (12 studies) were managed by EUS-RV and PERC-RV, respectively. The pooled technical successes were 88.7% (95% CI 84.6-92.8%, I2 = 70.5%) for EUS-RV and 94.1% (95% CI 91.1-97.1%, I2 = 59.2%) for PERC-RV (P = 0.088). The technical success rates of EUS-RV and PERC-RV were comparable in subgroups of benign diseases (89.2% vs. 95.8%, P = 0.068), malignant diseases (90.3% vs. 95.5%, P = 0.193), and normal anatomy (90.7% vs. 95.9%, P = 0.240). However, patients with surgically altered anatomy had poorer technical success after EUS-RV than after PERC-RV (58.7% vs. 93.1%, P = 0.036). The pooled rates of overall adverse events were 9.8% for EUS-RV and 13.4% for PERC-RV (P = 0.686). CONCLUSIONS: Both EUS-RV and PERC-RV have exhibited high technical success rates. When standard ERCP fails, EUS-RV and PERC-RV are comparably effective rescue techniques if adequate expertise and facilities are feasible. However, in patients with surgically altered anatomy, PERC-RV might be the preferred choice over EUS-RV because of its higher technical success rate.

Prediction of Biliary Complications After Human Liver Transplantation Using Hyperspectral Imaging and Convolutional Neural Networks: A Proof-of-concept Study.

BACKGROUND: Biliary complications (BCs) negatively impact the outcome after liver transplantation. We herein tested whether hyperspectral imaging (HSI) generated data from bile ducts (BD) on reperfusion and machine learning techniques for data readout may serve as a novel approach for predicting BC. METHODS: Tissue-specific data from 136 HSI liver images were integrated into a convolutional neural network (CNN). Fourteen patients undergoing liver transplantation after normothermic machine preservation served as a validation cohort. Assessment of oxygen saturation, organ hemoglobin, and tissue water levels through HSI was performed after completing the biliary anastomosis. Resected BD segments were analyzed by immunohistochemistry and real-time confocal microscopy. RESULTS: Immunohistochemistry and real-time confocal microscopy revealed mild (grade I: 1%-40%) BD damage in 8 patients and moderate (grade II: 40%-80%) injury in 1 patient. Donor and recipient data alone had no predictive capacity toward BC. Deep learning-based analysis of HSI data resulted in >90% accuracy of automated detection of BD. The CNN-based analysis yielded a correct classification in 72% and 69% for BC/no BC. The combination of HSI with donor and recipient factors showed 94% accuracy in predicting BC. CONCLUSIONS: Deep learning-based modeling using CNN of HSI-based tissue property data represents a noninvasive technique for predicting postoperative BC.

Melatonin and metformin co-loaded nanoliposomes efficiently attenuate liver damage induced by bile duct ligation in rats.

In the current study, the therapeutic effectiveness of the metformin (Met) and melatonin (Mel) co-loaded liposomes was investigated on cholestasis induced by bile duct ligation (BDL) in male rats. Histopathological analysis, biochemical analysis, and oxidative stress markers were assayed to determine the therapeutic effect of Met and Mel co-loaded liposomes on cholestasis. Histopathological analysis revealed that the simultaneous administration of Met and Mel, whether in the free (C-Mel-Met) or liposomal (C-Lipo-Mel-Met) forms, reduced inflammation as well as proliferation of bile ducts; however, results were more prominent in the liposomal form of Mel and Met. Additionaly, serum levels of aspartate aminotransferase (AST) were significantly (p < 0.001) higher in (C-Mel-Met) treated rats compared with (BDL) rats; however, (C-Lipo-Mel-Met) treated rats exhibited significant (p < 0.05) lower AST rates in comparison to (BDL) rats. Moreover, a significant (p < 0.0001) drop in bilirubin levels was detected in (C-Lipo-Mel-Met) treated rats in comparison to (BDL) rats; it is noteworthy mentioning that bilirubin levels in (C-Lipo-Mel-Met) treated rats were insignificant in comparison to sham-control (SC) rats. Furthermore, rats concomitantly administered Met and Mel, exhibited significant downregulation in the expression levels of inflammatory cytokine genes such as TNF-α and IL-1 gene expression, where the downregulation was more prominent in the liposomal from. Our findings demonestrate that the concomitant administration of metformin and melatonin in the liposomal form had more therapeutic effect on liver injury than their free forms through improving histological changes, reducing biochemical markers and favoring oxidant- antioxidant balance.

Laparoscopic repair of bile duct injuries: Feasibility and outcomes.

INTRODUCTION: Bile duct injuries (BDI) following laparoscopic cholecystectomy occurs in approximately 0.6% of the cases, often being more severe and complex. Roux-en-Y hepaticojejunostomy (RYHJ) is considered the optimal therapeutic option, with success rates ranging from 75% to 98%. Several series have demonstrated the advancements of the laparoscopic approach for resolving this condition. The objective of this study is to describe our experience in the laparoscopic repair of BDI. METHODS: A retrospective, descriptive study was conducted, including patients who underwent laparoscopic repair after BDI. Demographic, clinical, surgical, and postoperative variables were analysed using descriptive statistical analyses. RESULTS: Eight patients with BDI underwent laparoscopic repair (out of 81 surgically repaired patients). Women comprised 75% of the sample. A complete laparoscopic repair was achieved in 75% (6) of cases. The mean age was 40.8 ± 16.61 years (range 19-65). Injuries at or above the confluence (Strasberg-Bismuth ≥ E3) occurred in 25% of cases (2). Primary repair was performed in two cases. Half of the cases underwent a Hepp-Couinaud laterolateral RYHJ, while three patients received a terminolateral RYHJ, and one underwent a bi-terminolateral RYH. The mean operative time was 260 min (range 120-360). Overall morbidity was 37.5% (3 cases): two minor complications (bile leak grade A and drainage-related bleeding) and one major complication (bile leak grade C). No mortality was recorded. The maximum follow-up period reached 26 months (range 6-26). CONCLUSIONS: Our study demonstrates the feasibility of laparoscopic RYHJ in a selected group of patients, offering the benefits of a minimally invasive approach.

The Effect of Intrahepatic and Intrasplenic Administration of Mesenchymal Stem Cell to Liver Function and Degree of Liver Fibrosis in Common Bile Duct Ligation Model in Rabbit.

BACKGROUND: Mesenchymal stem cells (MSC) is a promising alternative method in liver cirrhosis management. Several administration routes of MSC have been studied, but few studies compared one to another. The purpose of this study is to compare the intrahepatic and intrasplenic route of MSC administration in terms of liver function and degree of liver fibrosis in the bile duct ligation model in rabbits. METHOD: Experimental study was conducted using rabbits (Oryctolagus cuniculus) model undergoing bile duct ligation (BDL). The subjects were randomized into 4 groups: sham surgery; bile duct ligation; bile duct ligation followed by intrahepatic route of MSC (BDL + IH MSC), and bile duct ligation followed by intrasplenic route of MSC (BDL + IS MSC). Umbilical cord mesenchymal stem cell (UC MSC) was administered on the fifth day after bile duct ligation, and the subjects were observed until the fourteenth day after bile duct ligation. The liver function was evaluated with alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total and direct bilirubin. The degree of fibrosis was evaluated with Laennec score, fibrosis area fraction, the number of viable and necrosis hepatocytes, and the number of hepatic progenitor cells. RESULT: The subjects were randomized into 4 groups: 2 in sham surgery group, and 7 in each of the following groups: BDL, BDL + IH MSC and BDL + IS MSC groups. The mortality rate in BDL group was 57.1 %, while mortality in BDL + IH MSC and BDL + IS MSC groups were 14.3 % and 28.6 % respectively. No significant difference was found regarding liver function in each group, such as AST, ALT, total, and direct bilirubin. Histopathology examination in almost every subject undergone bile duct ligation (regardless of MSC administration) showed degree of fibrosis of Laennec 4B. Fibrosis area fraction, the number of viable and necrotic hepatocytes, and progenitor cells were analyzed; no significant difference was found between BDL + IH MSC and BDL + IS MSC groups, but the groups administered with MSC showed a larger number of viable hepatocytes compared to BDL group. No difference was found between BDL + IH MSC and BDL + IS MSC groups in terms of liver function and histologic parameters. CONCLUSION: Administration of MSC increases the number of viable hepatocytes, but no difference was found in terms of liver function and degree of liver fibrosis between the intrahepatic route and intrasplenic route of administration. TYPE OF STUDY: Animal Research, Randomized Controlled Study. LEVEL OF EVIDENCE: Level I? (animal research is not indicated in the levels of evidence table in the journal website).