Objective:A novel bile duct end-to-end anastomosis and percutaneous transhepatic cholangial drainage (PTCD) were designed to treat iatrogenic bile duct injuries, and the clinical efficacy and technical advantage of this combined treatment were analyzed.Methods:Clinical data from 11 patients with iatrogenic bile duct injuries treated between February 2012 to July 2021 was retrospectively analyzed. There were 4 females and 7 males, with age of (47.5±15.3) years old. The types of bile duct injuries were: Bismuth type 1 ( n=7), Bismuth type Ⅱ ( n=1), Bismuth type Ⅲ type ( n=1), combined Bismuth type 1 and type 2 ( n=1), and Bismuth type Ⅳ ( n=1). Repair operations were performed at the time of the initial surgical procedures in 8 patients. The remaining 3 patients had their repair done 2 days, 9 days and 5 months, respectively, after the initial operations. All patients underwent successful bile duct end-to-end anastomosis and PTCD without use of T-tubes. Results:All biliary injuries were successfully repaired with no operative mortalities. Two patients who underwent end-to-end anastomosis of common hepatic duct developed anastomotic bile leakage. The amount of bile leakage was small and bile leakage resolved with conservative treatment in 1 patients 3 days after surgery, and was treated successfully by percutaneous peritoneal drainage for 2 weeks in the other patient. There were no other complications, including stricture formation or cholangitis which developed in other patients. All patients’ liver functions recovered well. The percutaneous biliary drainage tube was removed 6 months after operation in 1 patient. The remaining patients had their drainage tubes removed 3 months after operation. On follow-up, all patients had no history suggestive of cholangitis, jaundice and other symptoms. The liver functions were normal on laboratory examinations. No stricture or dilatation of intrahepatic bile ducts were detected on imaging examinations. The cure rate was 100% (11/11).Conclusion:Surgical repair of biliary tract injuries should aim to preserve sphincter of Oddi function and maintain normal physiological pathway of bile excretion. PTCD helped smooth recovery of an end-to-end anastomosis, lowered severity of physical disability of patients and minimized occurrence of medical disputes.

Background/Aims: The pathogenesis of nonalcoholic fatty liver disease (NAFLD) has not be fully elucidated, and the lack of therapeutic strategies for NAFLD is an urgent health problem. Guanine nucleotide binding protein, alpha inhibiting activity polypeptide 3 (GNAI3) participates in several biological processes, but its relationship with lipid metabolism and NAFLD has not yet been reported. We aimed to determine the function of GNAI3 in the development of NAFLD. Methods: Mice were fed a methionine and choline-deficient diet to induce NAFLD. An NAFLD model in HepG2 cells was induced by free fatty acid treatment. GNAI3 levels in HepG2 cells were downregulated by shRNA. Protein levels of related proteins were evaluated by Western blotting, and mRNA levels were determined by quantitative reverse transcription polymerase chain reaction. Hematoxylin and eosin and Oil Red O staining were used to observe histological changes in liver tissue. Results: The dysregulated hepatic lipid metabolism in the NAFLD mouse model was enhanced by GNAI3 knockout, which also provoked worse liver damage. In the NAFLD model in HepG2 cells, the downregulation of GNAI3 promoted cellular lipid accumulation and enhanced the changes in lipid metabolic enzyme levels. Conclusions This study demonstrates that GNAI3 participates in the development of NAFLD in both cellular and mouse models. The data indicate that GNAI3 is a potential new target for the treatment of NAFLD in humans.

Objective To evaluate the efficacyof the first line chemotherapy FOLFIRINOX (5-Fu,Leucovorin calcium,Irinotecan,Oxaliplatin) as the treatment of pancreatic cancer.Methods Pertinent studies were identified from the PubMed,Cochrane Library and EMBASE.The outcomes were resection rate and radical (R0) resection rate were analyzed.Data were expressed as weighted pooled proportions with 95％ confidence intervals (95％ CI).Results There were thirteen studies with 408 patients with LAPC and BRPC included.After the treatment,42.0％ (95％ CI:28.0％ ～56.0％) tumorswere resected and 41.0％ (95％ CI:37.0％ ～45.0％) were underwentR0 resection,and median overall survival ranged from 15.5 to 34.5 months,median progression-free survival ranged from 10.0 to 17.8 months.Conclusion The meta-analysis shows that down-staging after first line FOLFIRINOX-based therapy is noticeable in patients with borderline resectable/unresectable PC,and the adverse events were in control.

The treatment for severe pancreatitis includes surgical and non-surgical methods,and the key points of treatment include surgical timing,surgical method selection and the management of postoperative complications.Hepatic artery thrombosis after surgery for severe pancreatitis is rarely seen,and few experiences in the diagnosis and treatment for this disease have been summarized.A patient with the course of severe pancreatitis of 10 years and suffered from 3 different kinds of diseases including thrombosis of right hepatic artery was cured by open surgery for 2 times and intervention therapy in the Affiliated Hospital of Hainan Medical College in October 2011.The treatment experience was summarized based on the clinical data of this patient.

Objective To explore the treatment of primary hepatic neuroendocrine tumors (PHNET).Methods The therapeutic treatments of 9 PHNET patients from January 2003 to January 2010 in 3 hospitals were retrospective analyzed and followed up.Results Diagnosis of PHNET was confirmed immunohistochemically and by excluding extrahepatic primary sites.The survival is significantly dependent on tumor resectability.One patient received only radiotherapy and one with only chemotherapy,one with radiofrequency ablation.Six patients received R0 resection,one received postoperative radiotherapy,one with TACE perioperatively and internal radiotherapy.Two patients were lost to follow up 3 patients died and 4 were alive.Intrahepatic recurrence was found in 1 patient and metastasis to bone in 2 patients.Survival time ranged from 11 days to 66 months.Conclusions PHNET is an extremely rare entity with difficulty in early diagnosis.Curative liver resection integrated with transarterial chemoembolization or radiotherapy is considered to be an effective modality.

Anatomic hepatic resection not only enables enough tumor-free resection margin,but also guarantee the maximal remnant of normal liver tissue.A 61-year-old male patient with hepatic cancer was admitted to the Affiliated Hospital of Hainan Medical College in February 2012.Multiple space-occupying lesions were found in segment Ⅵ,Ⅶ and Ⅷ by computed tomography (CT).The results of CT volumetry analysis showed that the left hemihepatic volume was lesser than the minimal limit of survival,so anatomic hepatic segmentectomy of Ⅵ,Ⅶ and Ⅷ with preservation of segment Ⅴ was designed to guarantee the maximal remaining of normal liver tissue.Glisson's pedicle transection was used twice to divide the right hemihepatic Glisson's pedicle,segment Ⅵ and Ⅶ Glisson's pedicle,respectivley,then the resection line was determined,and anatomical hepatic segmentectomy of Ⅵ,Ⅶ and Ⅷ was completed.With the procedures adopted,the hepatic ischemia reperfusion injury and hemodynamic instability were maximally reduced during operation.

AIM: To study the molecular mechanism of EGCG on inhibiting the growth of hepatic carcinoma. METHODS: The proliferation of hepatic cell line HepG2 cultured with different doses of EGCG was studied by MTT and suspension/adherence methods. The effect of EGCG on the expression of HIF-1α/VEGF at mRNA and protein levels in vitro and in vivo was evaluated by RT-PCR and Western blotting, respectively. The inhibition of EGCG on the growth of tumor implanted into athymic nude mice was also observed. RESULTS: The proliferation of hepatic cell line HepG2 was inhibited by EGCG in a dose-dependent manner. The expression of HIF-1α/VEGF was suppressed markedly by EGCG at protein level. However, the inhibitory effect of EGCG on the mRNA expression was only observed on VEGF, not on HIF-1α. In the animal experiment, the implanted tumor growth was inhibited by 39.8%±5.1%. CONCLUSION: EGCG suppresses the hepatic carcinoma cell growth, and interrupts the HIF-1α/VEGF signaling pathway significantly, indicating a fundamental mechanism of EGCG for inhibiting tumor growth.

OBJECTIVETo study the effects of liver specific antigen (LSA) on liver allotransplantation rejection.

METHODSOrthotopic liver transplantation was performed in this study. Group I: syngeneic control (Wistar-to-Wistar); Group II: acute rejection (SD-to-Wistar). Group III: thymic inoculation of SD rat LSA day 7 before transplantation. The observation of general condition and survival time, rejection grades and the NF-kappaB activity of splenocytes were used to analyze severity of acute rejection and immune state of animals in different groups.

RESULTSThe general condition of group I was fair post transplantation with no sign of rejection. All recipients of group II died within days 9 to 13 post transplantation with median survival time of 10.7 +/- 1.37 days. As for group III, 5 out of 6 recipients survived for a long period with remarkably better general condition than that of group II. Its rejection grades were significantly lower than group II (P<0.05). NF-kappaB activity was only detected in group I between days 5 and 7 after transplantation, whereas high activity of NF-kappaB was detected at all points in group II and low NF-kappaB activity was detected in group III which was significantly lower than that of group II (P<0.05).

CONCLUSIONSLSA is an important transplantation antigen directly involved in the immunorejection of liver transplantation. Intrathymic inoculation of LSA can alleviate the rejection of liver allotransplantation, grafts survive for a period of time thereby, allowing a novel way to liver transplantation immunotolerance.

Animals ; Cell Separation ; Graft Rejection ; metabolism ; pathology ; Isoantigens ; administration & dosage ; pharmacology ; Liver ; pathology ; Liver Transplantation ; Male ; NF-kappa B ; metabolism ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar ; Spleen ; cytology ; metabolism ; Thymus Gland ; physiology

OBJECTIVETo investigate the gene expression of 4-1BB in peripheral blood mononuclear cells (PBMCs) and the possible significance of the 4-1BB pathway after clinical orthotopic liver transplantation (OLT).

METHODS4-1BB mRNA levels in PBMCs from 22 OLT patients were analyzed by RT-PCR. 4-1BB protein expressed on the surface of CD(4)(+) and CD(8)(+) T cells were detected by flow cytometry, and visualized with direct immunofluorescence and confocal fluorescence microscopy. Patients with primary liver cancer (PLC) and healthy volunteers served as controls. Six cases of recently performed liver transplantation were also observed in this study.

RESULTS4-1BB mRNA was detected in PBMCs from both liver transplant patients with long-term graft acceptance (22 cases) and from transplant patients on day 1 to day 3 post-transplantation (6 cases), but was not found in PBMCs from transplant patients on day 7 to day 30 post-transplantation (6 cases). 4-1BB mRNA was also not found in samples from 8 of the healthy controls and 7 of the PLC patients, though very low expression was detected in the other 4 healthy volunteers and 6 PLC patients. Simultaneously, 4-1BB protein was expressed at nearly undetectable levels on CD(4)(+) and CD(8)(+) T cells from healthy controls, PLC patients, as well as OLT patients within the first month post-transplantation (6 cases). However, 4-1BB expression was found on the surface of CD(4)(+) and CD(8)(+) T cells from liver transplant patients with long-term graft acceptance. Direct immunofluorescent staining and confocal fluorescence microscopy clearly revealed evidence of 4-1BB protein on cell membranes of CD(4)(+) and CD(8)(+) T cells from liver transplant patients with long-term graft acceptance. Simultaneously, a significantly higher percentage of CD(3)(+) CD(25)(+) T cells were found in liver transplant patients with long-term graft acceptance group as compared with the healthy control group (P < 0.05). The expression of 4-1BB protein on T cells did not correlate with the survival time of OLT patients postoperation.

CONCLUSIONSThis study demonstrates that although patients remain in stable condition after liver transplantation under the treatment of immunosuppressants, activated T cells are present to some extent and 4-1BB protein may be involved in this process. Effector T-cells can exert permanent immunoresponses against grafts under these circumstances. Therefore, we conclude that a new immune response balance is established under the combination of both treatment with immunosuppressants and natural immune responses against alloantigens. Manipulation of the 4-1BB/4-1BBL pathway may provide a therapeutic technique for prolonging graft survival.

Adult ; Antigens, CD ; Female ; Gene Expression ; Humans ; Leukocytes, Mononuclear ; chemistry ; Liver Transplantation ; Male ; Middle Aged ; Receptors, Nerve Growth Factor ; genetics ; physiology ; Receptors, Tumor Necrosis Factor ; genetics ; physiology ; Tumor Necrosis Factor Receptor Superfamily, Member 9

OBJECTIVETo investigate the relationship between NF-kappa B activity and IFN-gamma gene expression, as well as the histopathological changes following liver transplants, both with and without cyclosporin A (CsA) treatment.

METHODSSixty male Wistar and Thirty male SD rats were subjected to orthotopic liver transplants. Fourty-five of the Wistar rats were used as recipients, and were divided into 3 groups: group I, syngeneic control (Wistar-to-Wistar); group II, acute rejection (SD-to-Wistar); and group III: acute rejection treated with cyclosporin A by intramuscular injection (SD-to-Wistar + CSA). After the liver transplants, electrophoretic gel mobility shift assay was used to analyze NF-kappa B activity in the splenocytes of recipient rats, and RT-PCR was used to measure IFN-gamma gene expression in grafted liver specimens. In addition, histopathological examinations were performed to assess the severity of acute liver rejection.

RESULTSIn group I, low levels of NF-kappa B activity were only detectable on day 5 and 7 post-transplant, and only weak IFN-gamma mRNA expression was observed at all time points. By contrast, both high NF-kappa B activity and high expression levels of IFN-gamma mRNA were detected at all time points in group II. In group III, NF-kappa B activity and IFN-gamma mRNA expression were significantly inhibited, as compared to group II (P < 0.05). A good correlation was found between NF-kappa B activity and IFN-gamma mRNA expression (r = 0.815). In addition, NF-kappa B activity and IFN-gamma mRNA expression mirrored histopathological changes in all three experimental groups.

CONCLUSIONSChanges in IFN-gamma mRNA expression levels after liver transplantation are at least partially due to changes in levels of NF-kappa B activity. CsA appears to downregulate NF-kappa B activity, thus inhibiting IFN-gamma gene transcription. Blocking the NF-kappa B mediated transcription pathway may be of benefit in preventing liver transplant rejection.

Animals ; Cyclosporine ; pharmacology ; Down-Regulation ; Gene Expression ; Graft Rejection ; prevention & control ; Interferon-gamma ; analysis ; genetics ; Liver Transplantation ; Male ; NF-kappa B ; physiology ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar ; Transcription, Genetic ; physiology