Role of TGF-β1 in hepatic fibrosis induced by echinococcus multilocular infection / 医学研究生学报

ObjectiveTo investigate the role of transforming growth factor (TGF-β1) in hepatic fibrosis induced by echinococcus multilocular infection and its possible mechanisms in this process.Methods Forty-five C57BL/6 mice were randomly divided into the model group（30）and the control group (15). Protoscolece suspension of echinococcus multilocular was infused through portal vein in the model group (4000/each). Mice in the control group was injected the same volume of normal saline solution. Six mice in the model group and 3 mice in the control group were sacrificed at 1, 2, 4, 8 and 12 weeks after infection. The liver tissues were observed the histopathological changes by using hematoxylin-eosin (H&E) staining. The fibrosis degree and glycogen synthesis function of liver tissue were observed by Sirius-red staining and Periodic acid schiff (PAS), respectively. The expression levels of TGF-β1 and a-smooth muscle actin (α-SMA) were measured by immunohistochemical staining.ResultsThe obvious abnormal changes were not observed in 1 week after model setup. The diffuse distribution of multiple white spots began to appear at 2 weeks, but the amount of white plaques decreased after 8 weeks. Meanwhile, forming small lesions were not obviously observed the boundary with the surrounding normal liver tissue. Clear echinococcal vesicles were seen at week 12. H&E staining showed that hepatic tissue structure of control group was normal. In the model group, the number of lesions with worms decreased gradually and amount of granulomas were increased. The inflammatory lesions did not change significantly. Sirius-red staining demonstrated that collagen deposition in the control group was mainly around the bile duct and blood vessels. However, the deposition in the model group was mainly around the lesion and the degree of fibrosis became more serious with time. PAS staining displayed that the content of glycogen in the liver tissues of the control group was rich, evenly distributed and stained uniformly. However, the glycogen staining positive area decreased with the time of infection and the staining became lighter in the model group. Immunohistochemical staining indicated that the positive expression of α-SMA and TGF- β1 in the control group were mainly found in the bile ducts and perivascular areas. The positive areas in the model group were mostly granulomatous areas around the metacercariae and fibroblasts. Expression of α-SMA and TGF- β1 increased over time after infection with the expression peak at 12 weeks(16.80±2.09、4.10±2.14).ConclusionThe degree of fibrosis in liver tissues at different time points was consistent with the expression trend of TGF- β1 and α-SMA. TGF-β1 may promote collagen deposition and lead to fibrosis by activating hepatic stellate cells.

Exhaustion of CD8 T cell immune functions in spleen of mice with different doses of Echinococcus multilocularis infections / 中国血吸虫病防治杂志

ObjectiveTo examine the changes in the immune functions of CD8+ T cells in the spleen of mice following Echinococcus multilocularis infections at various doses and at different time points. MethodsThe E. multilocularis protoscoleces were collected, and E. multilocularis infection was modeled in mice via the hepatic portal vein at doses of 50 (low-dose), 500 (medium-dose) and 2 000 protoscoleces (high-dose), while physiological saline served as controls. Mouse spleen was isolated 2 (earlystage), 12 (middle-stage) and 24 weeks post-infection (late-stage), and spleen lymphocytes were harvested. The phenotype of memory CD8+ T cells and 2B4 expression were quantified in the mouse spleen, and the secretion of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-17A and IL-10 was measured. Results A central-memory phenotype was predominant in the CD8+ T cells in the spleen of mice at the early stage of high-dose protoscolece infections, and the proportion of central-memory CD8+ T cells was significantly greater in the high-dose group than in the control group (35.50% ± 2.00% vs. 25.90% ± 2.46%, P < 0.01), while a effector- memory phenotype was predominant in the CD8+ T cells in the spleen of mice at the late stage of medium- and high-dose protoscolece infections, and the proportions of effector-memory CD8+ T cells were significantly greater in the medium- (25.70% ± 4.12%) and high-dose group (28.40% ± 4.12%) than in the control group (10.50% ± 6.45%) (P < 0.05). The proportions of the central-memory CD8+ T cells were significantly higher in the high-dose group than at middle and late stages than at the early stage (P < 0.01), and the proportion of effector-memory CD8+ T cells was significantly greater in the high-dose group at the late stage than at early and middle stages (P < 0.05). The secretion of IFN-γ and IL-17A by spleen CD8+ T cells was elevated in the low- and medium-dose groups at the early stage of infection, and high-dose protoscolece infection promoted the secretion of IFN-γ and TNF-α by spleen CD8+ T cells; however, the levels of IFN-γ and TNF-α were significantly lower at the late stage than at the early and middle stages (P < 0.05). In addition, high 2B4 expression was detected in spleen CD8+ T cells in the middle- and high-dose groups at the late stage of infection, and the 2B4 expression was significantly higher in the medium(4.73% ± 1.56%) and high-dose groups (4.94% ± 1.90%) than in the low-dose group (2.49% ± 0.58%) and the control group (2.92% ± 0.60%) (P < 0.05). Conclusions E. multilocularis may be killed and eliminated through the host immune responses at the middle and late stages of low- and medium-dose protoscolece infections, while high-dose protoscolece infections may trigger the upregulation of 2B4 expression in mouse spleen CD8+ T cells at the late stage, which leads to immune exhaustion and the resultant chronic infections.

Alveolar echinococcosis of the adrenal gland: brief review of two cases / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Alveolar echinococcosis located in the adrenal gland can be considered a rare and aggressive infestation that radiologically and macroscopically mimics a malignant neoplasm. Its pathogenesis is poorly understood. This paper describes its clinical and radiological aspects and discusses its proper management.</p><p><b>METHODS</b>The records of two patients with adrenal gland alveolar echinococcosis who were diagnosed and treated in our center in 2009 were evaluated.</p><p><b>RESULTS</b>Neither patient showed any signs of recurrence following radical surgical treatment and postoperative oral anthelmintic therapy.</p><p><b>CONCLUSION</b>Radical surgery can be a feasible, effective management option that results in a good prospective outcome.</p>

Application of a digital three-dimensional reconstruction technique in the diagnosis and treatment of hepatic alveolar echinococcosis / 中华消化外科杂志

ObjectiveTo investigate the value of a digital three-dimensional reconstruction technique in the treatment of hepatic alveolar echinococcosis (HAE).MethodsThe computed tomography scan data for 13 patients with HAE who were admitted to the First Affiliated Hospital of Xinjiang Medical University from February 2011 to October 2011 were reconstructed and analyzed by a three-dimensional reconstruction system to assess resectability,and to facilitate surgical planning and individualized virtual surgery.The results of preoperative analysis were compared with the results of actual operations.ResultsThe three-dimensional models of the liver were reconstructed successfully,and intrahepatie lesions and vessels were clearly displayed.One patient received an autologous liver transplantation,10 underwent hepatectomy,and 2 received percutaneous transhepatic cholangial drainage.Virtual operation planning was carried out for 11 patients using the three-dimensional reconstruction system.The mean volume of the liver to be resected was predicted to be 920 ml (range,339-2678 ml),and the mean percentage of liver to be resected to the total liver volume was predicted to be 45％ ( range,23％ -68％ ).The mean volume o[ the actual liver resection was 834 ml (range,315-2250 m[),and the mean percentage of actual liver resected to the total liver volume was 42％ (range,22％ -70％ ),which was consistent with the results of preoperative three-dimensional reconstruction.All patients were followed up for 2-8 months,and no severe complications such as liver failure,hemorrhage and bile leakage were detected.ConclusionDigital three-dimen-sional reconstruction is helpful in the diagnosis and treatment of HAE and effectively reduces surgical risks.

Clinical effect and safety of liposomal-albendazole and tablet-albendazole for the treatment of human cystic echinococcosis / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To explore and compare the clinical effect and safety of liposomal albendazole (L-ABZ) and tablet-albendazole (T-ABZ) in the treatment of cystic echinococcosis (CE1, CE2, and CE3).</p><p><b>METHODS</b>A total of 269 cases treated with cystic echinococcosis (CE) in Xinjiang Medical University the First Affiliated Hospital from 1998 to 2008 were reviewed. 51 cases were excluded and 218 cases were enrolled in this research by retrospective case-control method. Among 110 cases were treated with L-ABZ and 108 cases were treated with T-ABZ for short-term (3 months) and long-term courses (6 months) respectively. The effects and safety of the two medicines were compared by analyzing the clinical symptoms, imaging check and serologic test results.</p><p><b>RESULTS</b>In short-term effect evaluation, the total effective rates and curative rates of L-ABZ group and T-ABZ group were 77.9% and 49.1% vs 28.4% and 13.9%, respectively. The effects of L-ABZ group was better than that of T-ABZ group, with remarkable difference in total effective rates and curative rates (x2 value was 19.581, 6.877, respectively, P is less than 0.05). In long-term effect evaluation, the total effective rates and curative rates of L-ABZ and T-ABZ group were 81.7% and 49.0% vs 47.6% and 20.6%, respectively. There was significant difference between L-ABZ group and T-ABZ group in total effective rates and curative rates (x2 value was 20.977, 15.049, respectively, P is less than 0.05). In T-ABZ group the short-term curative rates were 50.0% (15/30), 8.8% (8/91) and 33.3% (7/21) respectively in CE1, CE2, and CE3, the short-term total effective rates were 56.7% (17/30), 35.2% (32/91) and 61.9% (13/21) respectively in CE1, CE2, and CE3. The long-term curative rates were 58.3% (7/12), 28.6% (12/42) and 70.0% (7/10) respectively in CE1, CE2 and CE3, the long-term total effective rates were 75.0% (9/12), 69.0% (29/42) and 100.0% (10/10) respectively in CE1, CE2, and CE3. When compared with CE2, differences existed in CE1 (x2 = 24.887, 4.329; P is less than 0.05) and CE3 groups (x2 = 8.860, 5.076; P is less than 0.05) in terms of short-term effects. In L-ABZ group, the short-term curative rates were 47.4% (18/38), 12.2% (12/98) and 61.5% (8/13) respectively in CE1, CE2 and CE3, the short-term total effective rates were 92.1% (35/38), 65.3% (64/98) and 92.3% (12/13) respectively in CE1, CE2 and CE3, the long-term curative rates were 79.3% (23/29), 35.9% (23/64) and 50.0% (3/6) respectively in CE1, CE2 and CE3, the long-term total effective rates were 96.6% (28/29), 84.4% (54/64) and 100% (6/6) respectively in CE1, CE2 and CE3. When compared with CE2, there were significant differences in CE1 (x2 = 19.648, 9.930; P is less than 0.05) and CE3 groups (x2 = 18.880, 3.876; P is less than 0.05) in terms of short-term effect. In L-ABZ and T-ABZ groups, the drug-related adverse effects were 11.1% (12/108) and 12.7% (14/110) respectively without significant difference (x2 = 0.155, P is more than 0.05).</p><p><b>CONCLUSION</b>L-ABZ and T-ABZ were both effective anti-echinococcosis drugs without dominant side-effects. The clinical effect of L-ABZ was better than that of T-ABZ.</p>

Ex vivo liver resection followed by autotransplantation for end-stage hepatic alveolar echinococcosis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>For patients with end-stage hepatic alveolar echinococcosis (AE), in vivo resection of the involved parts of the liver is usually very difficult, therefore, allogenic liver transplantation is indicated. However, we hypothesize that for selected patents, ex vivo liver resection for thorough elimination of the involved tissues and liver autotransplantation may offer a chance for clinical cure.</p><p><b>METHODS</b>We presented a 24-year-old women with a giant hepatic AE lesion who was treated with hepatectomy, ex vivo resection of the involved tissue and hepatic autotransplantation. The patient had moderate jaundice and advanced hepatic AE lesion which involved segments I, IV, V, VI, VII, VIII and retrohepatic inferior vena cava. The lateral segments (II and III) of the left liver remained normal with over 1000 ml in its volume. No extrahepatic metastases (such as to the lung or brain) could be found. As the first step of treatment, X-ray guided percutaneous transhepatic cholangiodrainage (PTCD) was performed twice for bile drainage in segment III and II separately until her serum total bilirubin decreased gradually from 236 to 88 µmol/L. Total liver resection was then performed, followed by extended right hepatic trisegmentectomy and the entire retrohepatic vena cava was surgically removed en bloc while her hemodynamics parameters were stable. Neither veino-veinous bypass nor temporary intracorporeal cavo-caval or porto-caval shunt was used during the 5.7-hour anhepatic phase. The remained AE-free lateral segments of the left liver were re-implanted in situ. The left hepatic vein was directly anastomosed end-to-end to the suprahepatic inferior vena cava due to the lack of the retrohepatic inferior vena cava with AE total infiltration. Because compensatory retroperitoneal porto-caval collateral circulation developed, we enclosed remained infrahepatic inferior vena cava at renal vein level without any haemodynamics problems.</p><p><b>RESULTS</b>During a 60-day following-up after operation, the patient had a good recovery except for a mildly elevated serum total bilirubin.</p><p><b>CONCLUSIONS</b>As a radical approach, ex vivo liver resection and liver autotransplantation in a case has shown a optimal potential for treatment of the end-stage hepatic AE. Strict compliance with its indications, evaluation of vessels of patients pre-operatively, and precise surgical techniques are the keys to improve the prognosis of patients.</p>

Diagnosis and treatment for biliary complications of hepatic cystic echinococcosis / 中华肝胆外科杂志

Objective To evaluate the diagnosis and treatment of hepatic cystic echinococcosis with biliary complications. Methods 284 patients with hepatic cystic echinococcosis (CE) with biliary complications were surgically treated from January 2002 to January 2009 in our hospital. A summary of the surgical procedures was categorized and compared in the current study. Results (1) Intrabiliary rupture of CE with obstructive jaundice and (or) inflammation of bile duct (51 patients). The diagnosis of biliary complications of hepatic hydatid cyst was difficult on ultrasound and CT, with sensitivity rates of 78.4% and 85.7%, respectively. MRCP was an effective, noninvasive and useful diagnostic tool in difficult cases; ERCP was used as the gold standard in confirmation. Biliary fistulae were seen in 3 patients (10.7%) treated by suturing the rupture site. In the non-sutured group, 17 patients (74%) developed biliary fistulae after surgery (P＜0.01). In three patients the fistula was a high-output type (the fistula output was greater than 250 ml/d). (2) CE communicated with the bile duct and (or) infection (210 patients): The cavity-related problems and draining time in group C (no bile duct exploration and decompression) were significantly higher than group A (biliary system explored and decompressed through the cystic duct) and group B (biliary system explored and decompressed through the common bile duct), while cavity-related problems and draining time between the A and B groups showed no significant difference. Biliary tract-related problems in group A was significantly lower than group B (P＜0. 05). Conclusions (1) MRCP was an effective, noninvasive and useful diagnostic tool; ERCP was used only as the gold standard in confirming intrabiliary rupture of liver cystic hydatid disease, and also as an effective technique for treating extended postoperative external biliary fistula. (2) This study indicated that suturing the communication at the rupture site and biliary decompression were effective with low morbidity and mortality rates. (3) Cholangiography and common bile duct exploration through the cystic duct could solve the cavity-related problems while avoiding the T-tube related problems.