Sirolimus to treat chronic and steroid-resistant allograft rejection-related fibrosis in pediatric liver transplantation.

This study aimed to report our experience with the use of sirolimus in pediatric liver transplant patients with chronic rejection or steroid-resistant rejection with hepatic fibrosis, focusing on their histological evolution. All pediatric liver transplant recipients who received off-label treatment with sirolimus for chronic ductopenic rejection or cortico-resistant rejection between July 2003 and July 2022 were included in the study. All nine patients included in the study showed improvement in liver enzymes and cholestasis parameters as soon as 1-month after postsirolimus introduction. A decrease in fibrosis stage was observed in 7/9 (77.7%) patients at 36 months. All but one patient experienced an improvement in the Rejection Activity Index and ductopenia at 12 months. A single patient had to discontinue sirolimus treatment owing to nephrotic proteinuria. In conclusion, sirolimus may be a safe and effective treatment for chronic and steroid-resistant rejection and may improve allograft rejection-related fibrosis and ductal damage.

Biliary Viability Assessment and Treatment Options of Biliary Injury During Normothermic Liver Perfusion-A Systematic Review.

In recent years, significant progress has been made in the field of liver machine perfusion. Many large transplant centers have implemented machine perfusion strategies in their clinical routine. Normothermic machine perfusion (NMP) is primarily used to determine the quality of extended criteria donor (ECD) organs and for logistical reasons. The vast majority of studies, which assessed the viability of perfused grafts, focused on hepatocellular injury. However, biliary complications are still a leading cause of post-transplant morbidity and the need for re-transplantation. To evaluate the extent of biliary injury during NMP, reliable criteria that consider cholangiocellular damage are needed. In this review, different approaches to assess damage to the biliary tree and the current literature on the possible effects of NMP on the biliary system and biliary injury have been summarized. Additionally, it provides an overview of novel biomarkers and therapeutic strategies that are currently being investigated. Although expectations of NMP to adequately assess biliary injury are high, scant literature is available. There are several biomarkers that can be measured in bile that have been associated with outcomes after transplantation, mainly including pH and electrolytes. However, proper validation of those and other novel markers and investigation of the pathophysiological effect of NMP on the biliary tree is still warranted.

The Role of Magnetic Resonance in Evaluating Abdominopelvic Trauma - Part 1: Pancreatic and Hepatobiliary Injuries.

Trauma is an important cause of mortality, particularly in the young. While computed tomography (CT) is the mainstay of body imaging in the setting of trauma, magnetic resonance (MR) imaging can be useful in stable patients. Although more commonly used in spinal and musculoskeletal trauma, MR also has a role in abdominopelvic trauma. Broadly, its uses include clarification of equivocal cases, monitoring complications of trauma, particularly with solid organ injury, or as a primary imaging modality for patients with low suspicion for injury for whom avoiding ionizing radiation is a priority-namely, in pediatric and pregnant patients. In this two-part review article, we will review clinical scenarios where this may be encountered, utilizing case examples. This first installment will focus on pancreatic and hepatobiliary injuries. Pancreatic trauma may be difficult to diagnose on CT, and MR may aid in demonstrating pancreatic duct disruption, allowing for accurate grading according to American Association for the Surgery of Trauma (AAST) criteria. It may also be a useful modality for monitoring evolution of pancreatic injuries and/or pseudocyst development, guiding potential stenting, and/or drainage. Biliary injuries are also optimally evaluated with MR, particularly when aided by the use of hepatobiliary contrast material. This can allow for accurate delineation of biliary ductal anatomy and aid in planning percutaneous or endoscopic treatment of bile leaks.

The segment IV approach: a useful method for achieving the critical view of safety during laparoscopic cholecystectomy in patients with anomalous bile duct.

BACKGROUND: The critical view of safety (CVS) method can be achieved by avoiding vasculo-biliary injury resulting from misidentification during laparoscopic cholecystectomy (LC). Although achieving the CVS has become popular worldwide, there is no established standardized technique to achieve the CVS in patients with an anomalous bile duct (ABD). We recently reported our original approach for securing the CVS using a new landmark, the diagonal line of the segment IV of the liver (D-line). The D-line is an imaginary line that lies on the right border of the hilar plate. The cystic structure can be securely isolated along the D-line without any misidentification, regardless of the existence of an ABD. We named this approach the segment IV approach in LC. METHODS: In this study, we adopted the segment IV approach in patients with an ABD. RESULTS: From October 2015 to June 2020, 209 patients underwent LC using the segment IV approach. Among them, three (1.4%) were preoperatively diagnosed with an ABD. The branching point of the cystic duct was the posterior sectional duct, anterior sectional duct, or left hepatic duct in each patient. The CVS was achieved in all cases without any complications. CONCLUSION: It is a promising technique, especially even for patients with an ABD during LC.

Transjejunal Laparoscopic Assisted ERCP in a Patient with Roux-en-Y Hepaticojejunostomy.

Background and Objectives: Nowadays, with the increasing laparoscopic expertise and accessibility to modern surgical tools, laparoscopic assisted ERCP (LAERCP) has become an effective approach for the management of bile stone disease in patients with modified gastrointestinal anatomy. In contrast to patients with gastric bypass in whom a transgastric LAERCP approach is usually performed, the resultant anatomy of Roux-en-Y hepaticojejunostomy precludes a gastric approach as the newly formed bilioenteric anastomosis is not reachable through the stomach. Therefore, a transjejunal approach has been described as an alternative LAERCP technique. To the best of our knowledge this is the tenth case of transjejunal LAERCP reported worldwide. Materials and Methods: We present the case of a 50-year-old female with history of biliary injury during a cholecystectomy corrected with Roux-en-Y hepaticojejunostomy who presented to our center with manifestations of acute abdomen. After laboratory and image analysis, diagnosis of intrahepatic lithiasis was confirmed. The decision to perform a transjejunal LAERCP was made due to the complex anatomy in this patient. No complications were found during surgery and in the follow up period. Conclusions: Transjejunal LAERCP is an effective approach for endoscopic management of biliary complications in patients with Roux-en-Y hepaticojejunostomy and other modified gastrointestinal anatomy. Previous recommendations by more experienced teams have been reported, nonetheless, there are too few cases reported to make definitive recommendations and conclusions. In limited settings, such as ours, some of these recommendations may not be applicable. We are certain that, with the increasing expertise and innovations in laparoscopy surgery for the management of complications that cannot be addressed by endoscopic or noninvasive measures, more cases will be reported.

Animal models of biliary injury and altered bile acid metabolism.

In the last 25years, a number of animal models, mainly rodents, have been generated with the goal to mimic cholestatic liver injuries and, thus, to provide in vivo tools to investigate the mechanisms of biliary repair and, eventually, to test the efficacy of innovative treatments. Despite fundamental limitations applying to these models, such as the distinct immune system and the different metabolism regulating liver homeostasis in rodents when compared to humans, multiple approaches, such as surgery (bile duct ligation), chemical-induced (3,5-diethoxycarbonyl-1,4-dihydrocollidine, DDC, α-naphthylisothiocyanate, ANIT), viral infections (Rhesus rotavirustype A, RRV-A), and genetic manipulation (Mdr2, Cftr, Pkd1, Pkd2, Prkcsh, Sec63, Pkhd1) have been developed. Overall, they have led to a range of liver phenotypes recapitulating the main features of biliary injury and altered bile acid metabolisms, such as ductular reaction, peribiliary inflammation and fibrosis, obstructive cholestasis and biliary dysgenesis. Although with a limited translability to the human setting, these mouse models have provided us with the ability to probe over time the fundamental mechanisms promoting cholestatic disease progression. Moreover, recent studies from genetically engineered mice have unveiled 'core' pathways that make the cholangiocyte a pivotal player in liver repair. In this review, we will highlight the main phenotypic features, the more interesting peculiarities and the different drawbacks of these mouse models. This article is part of a Special Issue entitled: Cholangiocytes in Health and Disease edited by Jesus Banales, Marco Marzioni, Nicholas LaRusso and Peter Jansen.

Intraductal Cooling via a Nasobiliary Tube During Radiofrequency Ablation of Central Liver Tumors Reduces Biliary Injuries.

OBJECTIVE: The objective of our study was to determine the safety and efficacy of intraductal perfusion of chilled 5% dextrose in water (D5W) via an endoscopic nasobiliary tube (NBT) for the prevention of thermal bile duct injury in patients undergoing percutaneous radiofrequency ablation (RFA) of central liver tumors. MATERIALS AND METHODS: We performed a retrospective study comparing outcomes of 32 consecutive patients who underwent percutaneous RFA of central liver tumors without intraductal perfusion of chilled D5W (control cohort) and 14 consecutive patients who underwent temporary intraductal perfusion of chilled D5W at 2 mL/s via endoscopic NBT placement before RFA (endoscopic NBT cohort). The primary and secondary outcomes were the rate of biliary complications and local tumor progression, respectively. RESULTS: All patients tolerated the procedures well. There was a significantly lower rate of biliary complications in the endoscopic NBT cohort (0/14 patients, 0%) than in the control cohort (10/32 patients, 31%) (p < 0.03) with a trend toward improved preservation of liver function in the endoscopic NBT cohort (12/14 patients, 86%) compared with the control cohort (20/32 patients, 62%) (p = 0.05). There was no difference in the rate of local tumor progression between the endoscopic NBT cohort (4/19 tumors, 21%) and the control cohort (9/39 tumors, 23%) (p = 1.0). CONCLUSION: Perfusion of chilled water through an endoscopic NBT helps prevent thermal biliary injury during RFA of central liver tumors without increasing rates of local tumor progression.

Delayed rearterialization unlikely leads to nonanastomotic stricture but causes temporary injury on bile duct after liver transplantation.

Nonanastomotic strictures (NAS) are common biliary complications after liver transplantation (LT). Delayed rearterialization induces biliary injury in several hours. However, whether this injury can be prolonged remains unknown. The correlation of this injury with NAS occurrence remains obscure. Different delayed rearterialization times were compared using a porcine LT model. Morphological and functional changes in bile canaliculus were evaluated by transmission electron microscopy and real-time PCR. Immunohistochemistry and TUNEL were performed to validate intrahepatic bile duct injury. Three months after LT was performed, biliary duct stricture was determined by cholangiography; the tissue of common bile duct was detected by real-time PCR. Bile canaliculi were impaired in early postoperative stage and then exacerbated as delayed rearterialization time was prolonged. Nevertheless, damaged bile canaliculi could fully recover in subsequent months. TNF-α and TGF-ß expressions and apoptosis cell ratio increased in the intrahepatic bile duct only during early postoperative period in a time-dependent manner. No abnormality was observed by cholangiography and common bile duct examination after 3 months. Delayed rearterialization caused temporary injury to bile canaliculi and intrahepatic bile duct in a time-dependent manner. Injury could be fully treated in succeeding months. Solo delayed rearterialization cannot induce NAS after LT.

Biliary peritonitis following percutaneous nephrolithotomy: Minimally invasive management.

Percutaneous nephrolithotomy (PCNL) is a standard procedure for large renal calculi but has potential for complications. Rarely, biliary tract injury can occur during PCNL that can lead to biliary peritonitis with sepsis. Such cases are usually managed by emergent cholecystectomy. We present a case of biliary peritonitis resulting from gall bladder injury during PCNL, managed minimally invasively with an abdominal drain and endoscopic retrograde cholangiography with common bile duct stenting.

Injury to peribiliary glands and vascular plexus before liver transplantation predicts formation of non-anastomotic biliary strictures.

BACKGROUND & AIMS: The peribiliary glands of large bile ducts have been identified as a niche of progenitor cells that contribute to regeneration of biliary epithelium after injury. We aimed to determine whether injury to the peribiliary glands of donor livers is a risk factor for development of non-anastomotic biliary strictures (NAS) after liver transplantation. METHODS: In 128 liver transplant procedures, biopsies were taken from the donor bile duct and injury was assessed using an established histological grading system. Histological severity of injury was subsequently compared in liver grafts that later developed biliary structures vs. uncomplicated liver grafts. RESULTS: Luminal biliary epithelial loss >50% was observed in 91.8% of the grafts before transplantation, yet NAS occurred in only 16.4%. Periluminal peribiliary glands were more severely injured than deep peribiliary glands located near the fibromuscular layer (>50% loss in 56.9% vs. 17.5%, respectively; p<0.001). Injury of deep peribiliary glands was more prevalent and more severe in livers that later developed NAS, compared to grafts without NAS (>50% loss in 50.0% vs. 9.8%, respectively; p=0.004). In parallel, injury of the peribiliary vascular plexus was more severe in livers that developed NAS, compared to grafts without NAS (>50% vascular changes in 57.1% vs. 20.3%; p=0.006). CONCLUSION: Injury of peribiliary glands and vascular plexus before transplantation is strongly associated with the occurrence of biliary strictures after transplantation. This suggests that insufficient regeneration due to loss of peribiliary glands or impaired blood supply may explain the development of biliary strictures.

The retrospective documentation of legal cases with bile duct injury that were submitted for consideration to Istanbul Forensic Medicine Institute by the courts between 2008-2012.

OBJECTIVE: The aim was to evaluate the parameters that were considered by Forensic Medicine in bile duct injury as well as the issues that the physicians were found to be faulty. MATERIAL AND METHODS: The following parameters were investigated in 21 files that were referred to Istanbul Forensic Medicine Institute with request of expert opinion between 2008-2012; expert decisions, patient's age, gender, written patient consent, diagnosis, type of first surgery, surgical complications, timing of complication diagnosis within the scope of complication management, patient's referral timing, troubleshooting procedures and mortality rate. RESULTS: Physicians were found to be faulty in all files. The reason for physician fault was failure to show the necessary professional care and attention in one (4.7%) file, late recognition of injury and late transfer of the patient in 20 (95.3%) files. Written consent had not been obtained in any of the files. Thirteen patients were female (61.9%) and 8 (30.1%) were male, with a mean age of 43.3 years. Nineteen patients had cholelithiasis (90.4%), and two patients (9.5%) had a mass in the head of the pancreas. Cholecystectomy was performed laparoscopically in 15 patients (78.9%), and with open surgery in 4 patients (21.1%). The Whipple procedure was performed in two patients. The diagnosis was made during the operation in one patient (4.7%), and in the post-operative period in 20 patients (95.3%). The time to diagnosis after surgery was between 3-6 days. All of the patients had been referred to third level health care facilities. The timing of transfer was 1 day in the patient who was diagnosed during the operation, and ranged between 4-10 days in those who were diagnosed postoperatively. Reasons for late referral were delays related to pending test results in 12 patients, vague signs in 3 patients, and following-up patients with the thought that the biliary fistula will heal by itself in 5 patients. Mortality was not observed in any of the examined files. CONCLUSION: The issues where physicians were most frequently found to be faulty were failure to obtain written patient consent, late recognition of injury and late transfer of the patient.

Biliary Complications Post Transjugular Intrahepatic Portosystemic Shunt in a Child With Portal Vein Cavernous Transformation.

The transjugular intrahepatic portosystemic shunt is a rising interventional procedure with multiple indications and high technical success but with risks of biliary injuries, an underreported scenario. We present an 11-year-old patient with biliary injury with a leak, biloma formation, and biliary obstruction caused by the percutaneous procedure. Interventional radiology drainages addressed these complications by resolving the leak and biloma. These biliary complications in percutaneous procedures and their management are rarely reported in the medical literature, making their management not standard. We highlight drainage management and the importance of sharing it to add experience to this clinical scenario and encourage sharing cases with similar diagnoses.

Hypothermic oxygenated perfusion (HOPE) protects from biliary injury in a rodent model of DCD liver transplantation.

BACKGROUND & AIMS: The use of livers from donors after cardiac arrest (DCD) is increasing in many countries to overcome organ shortage. Due to additional warm ischemia before preservation, those grafts are at higher risk of failure and bile duct injury. Several competing rescue strategies by machine perfusion techniques have been developed with, however, unclear effects on biliary injury. We analyze the impact of an end-ischemic Hypothermic Oxygenated PErfusion (HOPE) approach applied only through the portal vein for 1h before graft implantation. METHODS: Rat livers were subjected to 30-min in situ warm ischemia, followed by subsequent 4-h cold storage, mimicking DCD-organ procurement and conventional organ transport. Livers in the HOPE group underwent also passive cold storage for 4h, but were subsequently machine perfused for 1h before implantation. Outcome was tested by liver transplantation (LT) at 12h after implantation (n=10 each group) and after 4 weeks (n=10 each group), focusing on early reperfusion injury, immune response, and later intrahepatic biliary injury. RESULTS: All animals survived after LT. However, reperfusion injury was significantly decreased by HOPE treatment as tested by hepatocyte injury, Kupffer cell activation, and endothelial cell activation. Recipients receiving non-perfused DCD livers disclosed less body weight gain, increased bilirubin, and severe intrahepatic biliary fibrosis. In contrast, HOPE treated DCD livers were protected from biliary injury, as detected by cholestasis parameter and histology. CONCLUSIONS: We demonstrate in a DCD liver transplant model that end-ischemic hypothermic oxygenated perfusion is a powerful strategy for protection against biliary injury.

Gallbladder perforation following trauma in an 18-month-old child with a common bile duct cyst.

Gallbladder rupture caused by blunt abdominal trauma is an uncommon injury, particularly in children. This condition occurs even less frequently in children with common bile duct cysts. The history is difficult to obtain, the clinical symptoms are indistinct, and their assessment is obscured by a slew of other lesions. Radiography cannot produce clear images. Thus, the diagnosis is frequently delayed and confirmed only during surgery. Case reports of gallbladder injury after abdominal trauma are relatively rare and there are only 50 case reports in literature for 100 years. Herein, we present the case of an 18-month-old girl who had a ruptured gallbladder funnel due to blunt abdominal trauma caused by domestic violence, with an early clinical presentation of septic shock and chylous effusion. The patient underwent surgery after being diagnosed with chylous ascites that had not responded to medical treatment. Based on the findings, single-stage laparoscopic surgery is confirmed to aid in the diagnosis and treatment of gallbladder injury in the presence of a common bile duct cyst.

Modeling bile duct ischemia and reoxygenation injury in human cholangiocyte organoids for screening of novel cholangio-protective agents.

BACKGROUND: Ischemia of the bile duct is a common feature in liver disease and transplantation, which represents a major cause of morbidity and mortality, especially after liver transplantation. Detailed knowledge of its pathogenesis remains incomplete due to the lack of appropriate in vitro models. METHODS: To recapitulate biliary damage induced by ischemia and reperfusion in vitro, human intrahepatic cholangiocyte organoids (ICOs) were grown at low oxygen levels of 1% up to 72 h, followed by re-oxygenation at normal levels. FINDINGS: ICOs stressed by ischemia and subsequent re-oxygenation represented the dynamic change in biliary cell proliferation, upregulation of epithelial-mesenchymal transition (EMT)-associated markers, and the evocation of phase-dependent cell death programs similar to what is described in patients. Clinical-grade alpha-1 antitrypsin was identified as a potent inhibitor of both ischemia-induced apoptosis and necroptosis. INTERPRETATION: These findings demonstrate that ICOs recapitulate ischemic cholangiopathy in vitro and enable drug assessment studies for the discovery of new therapeutics for ischemic cholangiopathies. FUNDING: Dutch Digestive FoundationMLDS D16-26; TKI-LSH (Topconsortium Kennis en Innovatie-Life Sciences & Health) grant RELOAD, EMC-LSH19002; Medical Delta program "Regenerative Medicine 4D"; China Scholarship Council No. 201706230252.

Percutaneous Management of Hepatic Duct Injury Using Extra-Anatomic Biliary Catheters.

Iatrogenic bile duct injury during laparoscopic cholecystectomy is a known complication of low incidence. The outcome can be devastating if not recognized and managed timely and properly. In cases of iatrogenic biliary injury due to cholecystectomy, the management depends on the level of injury, the timing of discovery (intraoperative or postoperative), and the patient's condition. If discovered intraoperatively, the injury should be managed immediately. In case expertise is lacking, a surgical drain with external biliary drainage can provide a temporary alternative solution to allow for referral to a tertiary care center. If the patient is septic or not fit for surgery, a percutaneous internal-external biliary drainage (PTBD) catheter can be placed until the patient's condition improves. We report a case of complete transection of the common hepatic duct during laparoscopic cholecystectomy managed by extra-anatomic PTBD.

Recapitulating Cholangiopathy-Associated Necroptotic Cell Death In Vitro Using Human Cholangiocyte Organoids.

BACKGROUND & AIMS: Liver and bile duct diseases often are associated with extensive cell death of cholangiocytes. Necroptosis represents a common mode of programmed cell death in cholangiopathy, however, detailed mechanistic knowledge is limited owing to the lack of appropriate in vitro models. To address this void, we investigated whether human intrahepatic cholangiocyte organoids (ICOs) can recapitulate cholangiopathy-associated necroptosis and whether this model can be used for drug screening. METHODS: We evaluated the clinical relevance of necroptosis in end-stage liver diseases and liver transplantation by immunohistochemistry. Cholangiopathy-associated programmed cell death was evoked in ICOs derived from healthy donors or patients with primary sclerosing cholangitis or alcoholic liver diseases by the various stimuli. RESULTS: The expression of key necroptosis mediators, receptor-interacting protein 3 and phosphorylated mixed lineage kinase domain-like, in cholangiocytes during end-stage liver diseases was confirmed. The phosphorylated mixed lineage kinase domain-like expression was etiology-dependent. Gene expression analysis confirmed that primary cholangiocytes are more prone to necroptosis compared with primary hepatocytes. Both apoptosis and necroptosis could be specifically evoked using tumor necrosis factor α and second mitochondrial-derived activator of caspases mimetic, with or without caspase inhibition in healthy and patient-derived ICOs. Necroptosis also was induced by ethanol metabolites or human bile in ICOs from donors and patients. The organoid cultures further uncovered interdonor variable and species-specific drug responses. Dabrafenib was identified as a potent necroptosis inhibitor and showed a protective effect against ethanol metabolite toxicity. CONCLUSIONS: Human ICOs recapitulate cholangiopathy-associated necroptosis and represent a useful in vitro platform for the study of biliary cytotoxicity and preclinical drug evaluation.

Long-term Outcomes of Combined Endoscopic-Radiological Approach for the Management of Complete Transection of the Biliary Tract.

BACKGROUND: Complete transection of the main bile duct (CTMD) is a major complication during hepato-bilio-pancreatic (HBP) surgery and is associated with high morbidity and mortality. In recent years, a combined endoscopic-radiological approach (CERA) for minimally invasive treatment of CTMD has been introduced, but evidence on its long-term outcomes is limited. Our aim is to report efficacy, safety, and long-term outcomes of CERA for the management of post-surgical CTMD in a tertiary referral center. METHODS: All consecutive patients referred for CTMD after HBP surgery between February 2012 and January 2021 were included in this study. CERA was first performed to re-establish biliary tree continuity, and then multiple biliary plastic stents were deployed to guarantee biliary tree reconstruction. Anthropometric, clinical, procedural (endoscopic/radiologic/surgical), and follow-up data were collected and analyzed. Each lesion was classified according to Strasberg classification. RESULTS: Overall, 60 patients (age 60.5 years, range 28-91), 38 F (61.7%), underwent CERA. Mean interval from surgery to endoscopic treatment was 13.2 days. Mean treatment duration was 526 days (SD ± 415) with a median number of 8 endoscopic sessions (range 1-33). Mean length of the biliary defect was 17.6 mm (SD ± 11.5). Long-term clinical success was achieved in 33/49 (67.3%) of patients. Treatment failure was experienced in 16/49 (32.7%) patients, while after an average follow-up of 41 months, stricture recurrence was observed in 3/36 (8.3%) patients. CONCLUSIONS: CERA is a minimally invasive and effective technique to re-establish the continuity of the biliary tract after CTMD, achieving permanent restoration in over half of treated patients.

Comparison of Fenestrating and Reconstituting Subtotal Cholecystectomy Techniques in Difficult Cholecystectomy.

Purpose Cholecystectomy is one of the most frequently performed surgeries. Although laparoscopy is considered the gold standard approach, it cannot prevent biliary injuries. Subtotal cholecystectomy has been performed mainly to prevent biliary injuries during difficult cholecystectomies. This study aimed to analyse our subtotal cholecystectomy results for difficult cholecystectomy cases and to evaluate the fenestrating and reconstituting techniques. Methods Retrospective data were collected and analysed statistically for cases that underwent subtotal cholecystectomy in a single referral centre between 2015 and 2020. Comparisons were made of the patients' age, gender, preoperative American Society of Anaesthesiologists (ASA) score, comorbidities, surgical timing, surgical procedure choice, postoperative complications, and mortality. Results The number of patients who underwent subtotal cholecystectomy was 46; 30.4% underwent emergent surgery and 69.6% underwent elective surgery. Twelve patients had subtotal fenestrating cholecystectomy and 34 had subtotal reconstituting cholecystectomy. Wound issues were noted in 17.4% of the patients, while 10.9% had temporary biliary fistulas that resolved spontaneously. Reoperation was performed in one patient due to high-output biliary drainage. Patients with postoperative complications had significantly higher co-morbid conditions (p=0.000), but surgery timing (p=0.192) and type of subtotal cholecystectomy (p=0.409) had no statistically significant effect on complications. Mortality showed a statistically significant correlation with patient comorbidities, surgery timing, and the type of procedure (p<0.05). Postoperative complications showed a statistically significant correlation with mortality (p<0.05). Conclusion Subtotal cholecystectomy prevents major biliary complications after cholecystectomy. Yet, the frequency of postoperative complications after subtotal cholecystectomy is incontrovertible. Intraoperative characteristics and the surgeon's expertise decide the optimal choice of the subtotal cholecystectomy technique.

IL-10 regulates Th17 response to inhibit hepatobiliary injury caused by Clonorchis sinensis infection in C57BL/6J mice.

Clonorchiasis caused by Clonorchis sinensis is a mainly foodborne parasitic disease. It can lead to hepatobiliary duct inflammation, fibrosis, obstructive jaundice, liver cirrhosis, and even cholangiocarcinoma. Interleukin (IL)-10 is an immune-regulatory cytokine which plays an immunosuppressive role during infection. Our previous study found that IL-10 was increased in mice with C. sinensis infection. However, the role and mechanism of IL-10 playing in hepatobiliary injury induced by C. sinensis infection remain unknown. Herein, Il10+/+ mice and Il10+/- C57BL/6J mice were infected with C. sinensis. It was found that IL-10 deficiency aggravated biliary hyperplasia and exacerbated periductal fibrosis induced by C. sinensis infection. Moreover, IL-10 deficiency increased CD4+T cells and CD8+T cells but not macrophages in the liver of mice with infection. There were no apparent differences in Th1 and Treg cells between Il10+/+ and Il10+/- mice infected with C. sinensis. However, the proportion of Th17 cells in CD4+T cells in Il10+/- infected mice was significantly higher than that in Il10+/+ infected mice. IL-10 deficiency also enhanced the increase of Th17 cells induced by ESPs stimulation in vitro. Taken together, our results suggest that IL-10 plays a protective role in hepatobiliary injury in C57BL/6J mice induced by C. sinensis infection via inhibiting Th17 cells, which could deepen our understanding of the immunopathology of clonorchiasis.