胸腺内移植脾细胞延长大鼠移植肝存活的研究

探讨大鼠胸腺内移植供体脾细胞在建立特异性供体不反应性中的作用。TJR/1大鼠作供体,SD大鼠为受体。切取供体鼠脾脏制成睥细胞悬液,注入到受体鼠胸腺内,此前两天受体鼠口服环孢素40mg·kg^(-1)·d^(-1),胸腺内脾细胞移植前皮下注射地塞米松25mg/kg。10天后取同一供体肝脏进行原位肝移植,术后不用免疫抑制剂。处理组半数以上大鼠存活超过100天,对照组存活9±1.51天。胸腺内移植了第3品系大鼠脾细胞的受体鼠,在接受了JR/1大鼠的移植肝后也短期死亡。表明这种供体不反应性是特异的。组织病理学及超微结构也证实脾细胞预处理的移植肝受损轻,排斥反应不明显。本研究提示了肝移植抗排斥反应的新途径。

B超诊断肝内外胆管蛔虫同时存活1例

患者,女性,46岁.无明显诱因突发右上腹痛,持续性存在,向背部放射,伴呕吐胃内容物,无畏寒、发热,无腹胀腹泻,曾在我院急诊,肌注杜冷丁、阿托品后,腹痛明显缓解,并收入院进一步诊治.既往有类似病史9年,曾拟"胆管蛔虫症"住院治疗,每年多次应用肠虫清、左旋米唑驱虫.入院后立即行B超检查:胆总管及右肝管、肝内胆管右前支扩张,并于胆总管及肝内胆管右前支内各见一条平行管状结构(图1),且可见蠕动,影像清晰生动,虫体蠕动时,病人出现剧烈的钻顶样痛,持续约半分钟后缓解.B超诊断:胆管蛔虫(存活).

解毒化瘀颗粒对急性肝衰竭小鼠肝细胞FLIP蛋白表达影响的研究

目的:探讨解毒化瘀颗粒对急性肝衰竭小鼠肝细胞凋亡及凋亡抑制蛋白FLIP的影响,进而揭示其治疗肝衰竭的分子机制。方法:将昆明小鼠随机分为空白组、模型组、解毒化瘀颗粒组、安宫牛黄丸组、乳果糖组,用D-GalN+LPS腹腔注射构建急性肝衰竭的小鼠模型,观察各组小鼠存活率;HE染色法和TUNEL法观察肝组织的病理变化及检测肝细胞凋亡情况;免疫组化法检测FLIP蛋白在肝组织中表达。结果:成模后48h存活率解毒化瘀颗粒组高于其他药物组;肝组织HE染色镜下所见的坏死细胞以点状坏死为主,程度比模型组及其它药物干预组轻微;TUNEL法检测结果显示:解毒化瘀颗粒组肝细胞凋亡指数明显减少,与其余药物干预组及模型组比较有显著性差异(P<0.01或P<0.05);免疫组织化学染色结果显示:凋亡抑制蛋白FLIP在解毒化瘀颗粒组肝组织中表达量明显升高,而在其他药物干预组及模型组中则呈低表达(P<0.01或P<0.05)。结论:解毒化瘀颗粒能上调内毒素肝衰竭模型肝细胞浆中FLIP的表达,并发挥抑制凋亡效应。提示阻断FADD凋亡信号传递,有可能是解毒化瘀颗粒防治急性肝衰竭的机制之一。

Science Letters:A novel way of liver preservation improves rat liver viability upon reperfusion

Background/aim： Currently, the liver is cold-preserved at 0-4 ℃ for experimental and clinical purposes. Here, we investigated whether milder hypothermia during the initial phase of the preservation period was beneficial for liver viability upon reperfusion. Methods： In the first set of experiments, rat livers were preserved either conventionally in clinically used histidine-trypthopan-ketoglutarate （HTK） solution （Group A： 45 min and Group B： 24 h） or by slow cooling HTK solution （from 13 ℃ to 3 ℃） during the initial 45 min of preservation （Group C： 24 h）. In the second set of experiments, additional groups of livers were evaluated： Group BB-preservation according to Group B and Group CC-preservation according to Group C. Further, some livers were preserved at 13 ℃ for 24 h. Livers were then reperfused using a blood-free perfusion model. Results： Bile production was approximately 2-fold greater in Group C compared to Group B. Alanine transaminase （ALT） and aspartate transaminase （AST） release into perfusate were 2-3-fold higher in Group B compared to Group C. No significant differences were found in ALT and AST release between Group C and Group A. Livers in Group CC compared to Group BB exhibited significantly lower portal resistance, greater oxygen consumption and bromosulfophthalein excretion into bile and lower lactate dehydrogenase （LDH） release into perfusate. Histological evaluation of tissue sections in Group BB showed parenchymal dystrophy of hepatocytes, while dystrophy ofhepatocytes was absent in Group CC. Livers preserved at 13 ℃ for 24 h exhibited severe ischemic injury Conclusion： These results suggest that the conventional way of liver preservation is not suitable at least for rat livers and that slow cooling of HTK solution during the initial phase of cold storage can improve liver viability during reperfusion.

Prognosis of hepatocellular carcinoma accompanied by microscopic portal vein invasion

AIM:To investigate the prognostic factors in patients with hepatocellular carcinoma(HCC) accompanied by microscopic portal vein invasion(PVI).METHODS:Of the 267 patients with HCC undergoing hepatic resection at Aso Iizuka Hospital,71 had PVI.After excluding 16 patients with HCC that invaded the main trunk and the first and second branches of the portal vein,55 patients with microscopic PVI were enrolled.RESULTS:The patients with HCC accompanied by microscopic invasion were divided into two groups:solitary PVI(PVI-S:n = 44),and multiple PVIs(PVI-M:n = 11).The number of portal vein branches invaded by tumor thrombi was 5.4 ± 3.8(2-16) in patients with PVI-M.In cumulative survival,PVI-M was found to be a significantly poor prognostic factor(P = 0.0019);while PVI-M and non-anatomical resection were significantly poor prognostic factors in disease-free survival(P = 0.0213,and 0.0115,respectively).In patients with PVI-M,multiple intrahepatic recurrence was more common than in the patients with PVI-S(P = 0.0049).In patients with PVI-S,non-anatomical resection was a significantly poor prognostic factor in disease-free survival(P = 0.0370).Operative procedure was not a significant prognostic factor in patients with PVI-M.CONCLUSION:The presence of PVI-M was a poor prognostic factor in patients with HCC,accompanied by microscopic PVI.Anatomical resection is recommended in these patients with HCC.Patients with HCC and PVI-M may also be good candidates for adjuvant chemotherapy.

Clinical benefit of radiation therapy and metallic stenting for unresectable hilar cholangiocarcinoma

AIM： To determine the efficacy of external beam radiotherapy （EBRT）, with or without intraluminal brachytherapy （ILBT）, in patients with non-resected locally advanced hilar cholangiocarcinoma.METHODS： We analyzed 64 patients with locally advanced hilar cholangiocarcinoma, including 25 who underwent resection （17 curative and 8 non-curative）, 28 treated with radiotherapy, and 11 who received best supportive care （BSC）. The radiotherapy group received EBRT （50 Gy, 30 fractions）, with 11 receiving an ad- ditional 24 Gy （4 fractions） ILBT by iridium-192 with remote after loading. ILBT was performed using percu-taneous transhepatic biliary drainage （PTBD） route. Uncovered metallic stents （UMS） were inserted into nonresected patients with obstructive jaundice, with the exception of four patients who received percutaneous transhepatic biliary drainage only. UMS were placed endoscopically or percutaneously, depending on the initial drainage procedure. The primary endpoints were patient death or stent occlusion. Survival time of patients in the radiotherapy group was compared with that of patients in the resection and BSC groups. Stent patency was compared in the radiotherapy and BSC groups.RESULTS： No statistically significant differences in patient characteristics were found among the resection, radiotherapy, and BSC groups. Three patients in the radiotherapy group and one in the BSC group did not receive UMS insertion but received PTBD alone; cholangitis occurred after endoscopic stenting, and patients were treated with PTBD. A total of 16 patients were administered additional systemic chemotherapy （5-fluorouracil-based regimen in 9, S-1 in 6, and gemcitabine in 1）. Overall survival varied significantly among groups, with median survival times of 48.7 mo in the surgery group, 22.1 mo in the radiotherapy group, and 5.7 mo in the BSC group. Patients who underwent curative resection survived significantly longer than those who were not candidates for surgery （P = 0.0076）. Cumulative survival in the radiotherapy group was significantly longer than in the BSC group （P = 0.0031）, but did not differ significantly from those in the non-resection group. Furthermore, the median survival time of patients in the radiotherapy group who were considered for possible resection （excluding the seven patients who were not candidates for surgery due to comorbid disease or age） was 25.9 mo. Stent patency was evaluated only in the 24 patients who received a metallic stent. Stent patency was significantly longer in the radiotherapy than in the BSC group （P = 0.0165）. Biliary drainage was not eliminated in any patient. To determine the efficacy of ILBT, we compared

Hepatocellular carcinoma in cirrhotic patients with portal hypertension:Is liver resection always contraindicated?

AIM:To analyze the outcome of hepatocellular car-cinoma(HCC)resection in cirrhosis patients,related to presence of portal hypertension(PH)and extent of hepatectomy.METHODS:A retrospective analysis of 135 patients with HCC on a background of cirrhosis was submitted to curative liver resection.RESULTS:PH was present in 44(32.5%)patients.Overall mortality and morbidity were 2.2% and 33.7%,respectively.Median survival time in patients with or without PH was 31.6 and 65.1 mo,respectively(P=0.047);in the subgroup with Child-Pugh class A cirrhosis,median survival was 65.1 mo and 60.5 mo,respectively(P=0.257).Survival for patients submitted to limited liver resection was not significantly different in presence or absence of PH.Conversely,median survival for patients after resection of 2 or more segments with or without PH was 64.4 mo and 163.9 mo,respectively(P=0.035).CONCLUSION:PH is not an absolute contraindication to liver resection in Child-Pugh class A cirrhotic patients,but resection of 2 or more segments should not be recommended in patients with PH.

Clinicopathological and prognostic analysis of 429 patients with intrahepatic cholangiocarcinoma

AIM:To understand the clinicopathological characteristics and treatment selections and improve survival and provide valuable information for patients with intrahepatic cholangiocarcinoma(ICC). METHODS:We retrospectively evaluated 5311 liver cancer patients who received resection between October 1999 and December 2003.Of these,429(8.1%)patients were diagnosed with ICC,and their clinicopathological, surgical,and survival characteristics were analyzed. RESULTS:Upper abdominal discomfort or pain(65.0%), no symptoms(12.1%),and hypodynamia(8.2%)were the major causes for medical attention.Laboratory tests showed 198(46.4%)patients were HBsAg positive, 90(21.3%)hadα-fetoprotein>20μg/L,50(11.9%) carcinoembryonic antigen>10μg/L,and 242(57.5%) carbohydrate antigen 19-9(CA19-9)>37 U/mL.Survival data was available for 329(76.7%)patients and their mean survival time was 12.4 mo.The overall survival of the patients with R0,R1 resection and punching exploration were 18.3,6.6 and 5.6 mo,respectively. Additionally,CA19-9>37 U/mL was associated with lymph node metastases,but inversely associated withcirrhosis.Multivariate analysis indicated that radical resection,lymph node metastases,macroscopic tumor thrombi and size,and CA19-9 were associated with prognosis. CONCLUSION:Surgical radical resection is still the most effective means to cure ICC.Certain laboratory tests(such as CA19-9)can effectively predict the survival of the patients with ICC.

Sorafenib in hepatocellular carcinoma:efficacy and predictive factors

Objective:To evaluate the efficacy and safety in patients with hepatocellular carcinoma treated with sorafenib and determine the predictive factors for survival.Methods:From April 2009 to December 2010,all patients with hepatocellular carcinoma treated with sorafenib were included in the study.Clinical data and survival time were collected.Survival analysis was conducted using the Kaplan-Meier method,and predictive factors for survival were analysed using the Cox's model.Results:A total of 51 patients were included in the study,the median time of follow-up was 10 months(range 1-22).All the 51 patients had one or more adverse events,of which 2 patients died of upper gastrointestinal bleeding and 6 patients discontinued treatment.The mean survival time was 11 months and 1-year survival was 60.8%.On univariate analysis,the median survival time of patients with tumors of BCLC A,B and C were 17,12.5 and 8.5 months,and 1-year survival were 71.4%,61.1%,and 23.1%, respectively(P=0.006).Compared with those with mild and poor arterial supply tumors,patients with good arterial supply tumors had longer median survival time(12 months vs 8 months and 9 months) and higher 1-year survival(52.0%vs 30.8%and 38.5%)(P=0.037).Patients with portal invasion had shorter median survival time and lower 1-year survival(8.5 months vs 13 months and 57.6%vs 16.7%,respectively) than those without(P=0.012).Patients with prealbumin≥170 mg/L had longer median survival time and higher 1-year survival(13.5 months vs 9 months and 55.6%vs 36.4%,respectively) than those with prealbumin<170 mg/L(P=0.016).Early tumor BCLC staging and high level of prealbumin were independent predictive factors for survival on multivariate analysis using Cox's regression model,the hazard ratio were 3.69(95%CI:1.30-10.53,P=0.015) and 3.53(95%CI:1.40-8.91,P=0.008) respectively.Conclusion:Upper gastrointestinal bleeding was a severe event need to be concerned in patients with hepatocellular carcinoma treated with sorafenib.Patients with high level of prealbumin could benefit more from sorafenib treatment,and prealbumin could be a predictor for survival in HCC patients treated with sorafenib.

肝移植术后胆道并发症的内镜治疗

胆道并发症是影响肝移植受者和提高移植肝存活率的主要原因,目前常见的胆道并发症主要有胆管狭窄、胆漏、胆管结石、胆管炎、乳头肌功能紊乱等.现对我院肝移植术后出现胆道并发症的16例患者进行回顾性分析,总结内镜治疗肝移植术后胆道并发症的疗效,报道如下.