Congenital hepatic fibrosis, liver cell carcinoma and adult polycystic kidneys.

In reviewing the literature, we found no liver cell carcinoma (LCC) or well-documented adult polycystic kidneys (APK) associated with congenital hepatic fibrosis (CHF). We report a 69-year-old man with CHF, LCC, APK, duplication cyst of distal portion of stomach, two calcified splenic artery aneurysms, myocardial fibrosis and muscular hypertrophy of esophagus. The LCC was grossly predunculated and microscopically showed prominent fibrosis and hyaline intracytoplasmic inclusions in the tumor cells.     

Relation of type II transforming growth factor-beta receptor to hepatic fibrosis and hepatocellular carcinoma

Hepatocarcinogenesis is closely related to hepatic fibrosis. In this study, we investigated the relationship of type II transforming growth factor-beta receptor (T beta RII) to hepatic fibrosis and hepatocellular carcinoma (HCC). In vivo: liver tissues were obtained from 30 patients (10 chronic hepatitis, 7 cirrhosis, 13 HCC). Protein expression and immunolocalization of T beta RII were examined by Western blot analysis and immunohistochemistry. In vitro: T beta RII protein expression in hepatoma cell lines (HepG2, Hep3B, HLE, HLF and Huh7) was examined by Western blot analysis. Next, we transfected T beta RII cDNA to Huh7, and compared the change of cell number and observed the induction of apoptosis after TGF-beta1 treatment using a FACScan flow cytometer. In vivo: T beta RII immunolocalization in liver tissues was significantly decreased in patients with HCC compared with that of patients with chronic hepatitis or liver cirrhosis. In Western blot analysis, T beta RII expression in tissues attenuated in comparison with that in non-tumor tissues in some patients with HCC. In vitro: T beta RII protein expression in HLE, HLF and Huh7 cells was weaker than that in HepG2 and Hep3B cells. In Huh7 cells transfected T beta RII cDNA, cell arrest and apoptosis were obviously induced. These results indicated that human HCC has a reduced expression of T beta RII for TGF-beta1. This may provide a selective growth advantage to HCC to escape the inhibitory growth signals of TGF-beta1, and may be linked with critical steps in the growth of hepatoma cells.     

Regression of hepatic metastases from gastrointestinal leiomyosarcoma after hepatic arterial chemoembolization

Two patients with gastrointestinal leiomyosarcoma metastatic to the liver were treated by hepatic chemoembolization with cisplatin and polyvinyl sponge followed by hepatic arterial infusion of vinblastine. Effective palliation in terms of durable tumor regression was achieved in both patients after two chemoembolization-infusion procedures. These results suggest that regional therapy may offer new hope for the subset of sarcoma patients who have liver metastases resistant to combination systemic chemotherapy.     

术前肝纤维化指数对肝癌手术疗效及预后的影响

目的探讨术前肝纤维化指数(HFI)对肝癌手术疗效及预后的影响。方法 2011年4月至2015年4月,将北京大学深圳医院接受肝癌切除术的65例患者分为低指数组(HFI≤5.4)与高指数组(HFI5.4)。分析两组术后疗效及预后情况。结果术前资料,两组性别、年龄、谷氨酰转肽酶、透明质酸、血小板、肝功能分级、HBV-DNA拷贝量比较,差异有统计学意义(均P0.05)。术中、术后资料,两组肿瘤数目、肿瘤最大径、肝纤维化类型、术后血管侵犯情况、切缘情况、肝门静脉癌栓和HBVDNA变化比较,差异有统计学意义(均P0.05)。低指数组并发症发生率20.0%,复发率23.3%,1、3、5年生存率分别为93.0%、53.0%、53.0%;高指数组并发症发生率22.9%,复发率25.7%,1、3、5年生存率分别为72.0%、29.0%、25.7%,两组生存率比较,差异有统计学意义(P0.05)。肿瘤数目3、HFI5.4、肝、门静脉癌栓是肝癌术后复发的独立危险因素。结论术前肝纤维化指数对手术疗效及预后均有显著影响,是术后复发的独立危险因素。     

谷氨酰转肽酶与血小板比值在评估肝细胞癌肝纤维化分期中的价值

目的 探讨谷氨酰转肽酶与血小板比值（gamma-glutamy transpeptidase to platelet ratio,GPR）在评估肝细胞癌（hepatocellular carcinoma,HCC）患者肝纤维化分期中的价值。方法 收集2015年8月至2016年8月在广西医科大学附属肿瘤医院肝胆外科行肝切除术的HCC患者的临床资料,计算GPR、天门冬氨酸氨基转移酶与血小板比值指数（amino- transferase to platelet ratio index,APRI）、FIB4指数（index based on the 4 factors,FIB4）,用ROC曲线下面积比较GPR、APRI、FIB4诊断肝纤维化不同分期（S0期、S1期、S2期、S3期、S4期）的效能。结果 GPR、APRI、FIB4、谷丙转氨酶（alanine transaminase,ALT）与肝纤维化分期呈正相关（P＜0.05）,而血小板计数（blood platelet count,PLT）与肝纤维化分期呈负相关（r=-0.360,P＜0.001）;肝纤维化不同分期（S0期、S1期、S2期、S3期、S4期）中,GPR、APRI、FIB4、PLT值差异均有统计学意义（P＜0.05）;肝纤维化＞S0期,GPR曲线下面积分别与APRI、FIB4、PLT曲线下面积比较,差异均无统计学意义（P＞0.05）;肝纤维化＞S1期和＞S3期中,GPR曲线下面积分别相应与APRI、PLT曲线下面积比较,差异均无统计学意义（P＞0.05）,但高于FIB4曲线下面积,差异有统计学意义（P＜0.05）;肝纤维化＞S2期,GPR曲线下面积分别相应与APRI、PLT曲线下面积比较,差异均有统计学意义（P＜0.05）。结论 GPR诊断肝纤维化分期具有较高的准确性,可作为评估HCC患者术前肝纤维化分期的无创性指标。     

Adjuvant hepatic arterial infusion after resection of hepatic metastasis from colorectal cancer

We examined retrospectively the efficacy of hepatic arterial infusion (HAI) chemotherapy comparing systemic treatment as adjuvant therapy after the curative resection of hepatic metastasis from colorectal cancer. Seventeen cases of HAI and 8 of the systemic treatment were enrolled in this study. We compared the pattern of recurrent sites and the overall survival rate between the two groups. There was no difference in a patients' background. Intrahepatic recurrence rate was lower and extrahepatic recurrence rate was higher in the HAI group, but not significant. The 1-, 3-, and 5-year overall survival rate was 94, 72, and 49% in the HAI group and 100, 100, and 50% in the systemic treatment group (p = 0.29), respectively. HAI chemotherapy did not contribute to the elongation of survival time in comparison with systemic treatment. This study indicates that there is no efficacy of HAI alone after the resection of hepatic metastasis from colorectal cancer and that there is need to use systemic chemotherapy together with HAI to prevent an extrahepatic recurrence.     

Chronic peripheral arteriopathy is associated with seropositivity to Chlamydia pneumoniae

The study was carried out to clarify the correlation between Chlamydia pneumoniae infection and peripheral arterial disease (PAD). The level of specific antibodies of the 133 consecutive patients suffering from PAD at 2nd stage of Leriche's classification were compared with 60 healthy controls by using a commercial Micro-IF Test. A higher incidence of serological evidence of C. pneumoniae infection was found in the patients (106/133) than in controls (6/60). These results are in agreement with other findings that measured the infection in atheromasic plaques. A strong cause-effect relationship between bacterial infection and peripheral arterial disease was not found, but the raised seropositivity level could be considered as a target for medical therapy of PAD.     

Lessons from the Atomic Bomb About Secondary MDS

Myelodysplastic syndromes (MDSs) is a hematological neoplasm defined by ineffective hematopoiesis, dysplasia of hematopoietic cells, and risk of progression to acute leukemia. MDS occurs as de novo or secondary, and chemoradiotherapy for cancers is thought to increase the risk of MDS among patients. Recently, an epidemiological study for MDS among A-bomb survivors was performed, and it clearly demonstrated that the exposure to external radiation significantly increased the risk of MDS. Precise epidemiological data among survivors have revealed important clinical factors related to the risk of leukemias. In this review, by comparing data for secondary MDS and leukemia/MDS among survivors, several factors which would affect the risk of MDS, especially secondary MDS, are discussed.     

Angiotensin II induces tumor progression and fibrosis in intrahepatic cholangiocarcinoma through an interaction with hepatic stellate cells

Intrahepatic cholangiocarcinoma (ICC) is characterized as a highly fatal tumor with poor prognosis because of its strong progression, early invasion, widespread metastasis and rich cancerous stroma. Although it is widely accepted that fibroblasts facilitate stromal fibrosis and tumor progression, the mechanisms of the interaction between cancer cells and activated fibroblasts have not been fully elucidated thus far. In this study, we demonstrate the presence of angiotensin II (AngII) in ICC tissues and explore the interaction between hepatic stellate cells (HSCs) and ICC cells as one of the sources of stromal fibrosis and tumor progression through the interaction of the AngII/AngII type 1 receptor (AT-1) axis. The concentrations of AngII in ICC tissues were significantly higher than those of HCC and normal liver. Two human ICC cell lines (HuCCT-1, CCKS-1) and a human HSC cell line (LI-90) expressed AT-1 mRNA and protein. The proliferative activity of ICC cells and HSCs to which AngII was added dose-dependently increased and AT-1 antagonist inhibited the proliferative effects. HSCs to which AngII was added showed a higher expression of α-smooth muscle actin (α-SMA, a marker of activated HSCs and myofibroblasts), glial fibrillary acidic protein (GFAP, a specific marker of HSCs) and collagen type I than control cells. AT-1 antagonist also inhibited the activation and transformation of HSCs stimulated by AngII. These findings suggested that locally formed AngII in ICC tissues plays a role in the proliferation and activation of ICC cells and HSCs expressing AT-1 as a growth factor in autocrine and paracrine fashions. Our mechanistic findings provide the first insight into an autocrine and paracrine AngII-initiated signaling pathway that regulates ICC proliferation and fibrosis.     

Acyclic retinoid targets platelet-derived growth factor signaling in the prevention of hepatic fibrosis and hepatocellular carcinoma development

Hepatocellular carcinoma (HCC) often develops in association with liver cirrhosis, and its high recurrence rate leads to poor patient prognosis. Although recent evidence suggests that peretinoin, a member of the acyclic retinoid family, may be an effective chemopreventive drug for HCC, published data about its effects on hepatic mesenchymal cells, such as stellate cells and endothelial cells, remain limited. Using a mouse model in which platelet-derived growth factor (PDGF)-C is overexpressed (Pdgf-c Tg), resulting in hepatic fibrosis, steatosis, and eventually, HCC development, we show that peretinoin significantly represses the development of hepatic fibrosis and tumors. Peretinoin inhibited the signaling pathways of fibrogenesis, angiogenesis, and Wnt/β-catenin in Pdgf-c transgenic mice. In vitro, peretinoin repressed the expression of PDGF receptors α/β in primary mouse hepatic stellate cells (HSC), hepatoma cells, fibroblasts, and endothelial cells. Peretinoin also inhibited PDGF-C-activated transformation of HSCs into myofibroblasts. Together, our findings show that PDGF signaling is a target of peretinoin in preventing the development of hepatic fibrosis and HCC. Cancer Res; 72(17); 4459-71. ?2012 AACR.     

Microcirculation of hepatic nodules from diethylnitrosamine-treated rats

The microcirculation of nodules (0.5 to 10 mm in diameter) from diethylnitrosamine-treated rats was studied in perfused livers. Microlight guides were placed on nodules and surrounding tissue on the capsular surface of the liver to measure fluorescence due to fluorescein-dextran (12 microM), a dye confined to the vascular space, infused via the hepatic artery and portal vein separately or simultaneously. The fluorescence increase due to fluorescein-dextran infusion via the artery and vein simultaneously was used to compare vascular space in nodules with that of surrounding tissue. The vascular space of nodules less than 1 mm in diameter was only about one-half as large as that of surrounding tissue. In contrast, in nodules 1 to 2 mm in diameter, the vascular space was similar to values from surrounding tissue. This was largely due to an increase in the fluid entering via the artery. As nodules grew from 2 to 10 mm in diameter, the vascular space decreased as a function of nodule size to 40% of surrounding tissue. The sum of fluorescence increases due to fluorescein-dextran infused via the artery and vein separately always equalled values obtained from simultaneous infusions. From these measurements, the fraction of vascular fluid observed by the microlight guide that entered the liver via the artery was calculated. In tissue surrounding nodules, fluid entering from the artery was 19% of the total, a value approximating the fraction of fluid pumped into the liver via the artery (25%). The percentage of fluid in the nodule that entered the liver via the hepatic artery increased progressively to 100% of the total as nodules grew from 2 to 10 mm in diameter. Thus, nodules become increasingly dependent on the hepatic artery and less dependent on blood supply via the portal vein as they grow.     

Surgical treatment of punctal-canalicular fibrosis from 5-fluorouracil therapy

5-Fluorouracil (5-FU) has been reported to cause punctal-canalicular fibrosis with resultant severe epiphora. It is reported that the epiphora will often resolve when treatment ceases or is decreased. However, this report describes a case of punctal-canalicular fibrosis so severe that bilateral conjunctivodacryocystorhinostomies were necessary. This has not been previously reported to the best of the authors' knowledge. It is recommended that ophthalmic consultation be obtained for patients in whom long-term 5-FU therapy is anticipated or who develop tearing while on therapy.     

柴胡疏肝散对早期肝纤维化大鼠JAK2/STAT3信号通路的影响

目的: 研究柴胡疏肝散对早期肝纤维化大鼠JAK2/STAT3信号通路的影响。方法: 以CCl₄诱导造模,将SD大鼠50只按随机数字表法分为正常组(腹腔注射橄榄油+蒸馏水灌胃),模型组(腹腔注射40% CCl₄橄榄油溶液,蒸馏水灌胃),柴胡疏肝散低、中、高剂量组(腹腔注射40% CCl₄橄榄油溶液,同时分别按生药3.5,6.3,12.6 g/kg灌胃)。柴胡疏肝散给药至第10周,观察大鼠大体形态,计算肝系数;全自动生化分析仪测定血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST),酶联免疫吸附法(ELISA)检测血清透明质酸(HA)、Ⅲ型前胶原(PCⅢ)、Ⅳ型胶原(Ⅳ-C)变化;HE染色观察各组大鼠肝脏纤维化程度;荧光定量PCR(qPCR)法检测肝组织中的JAK2、STAT3 mRNA表达;Western blot法检测肝组织中JAK2和STAT3蛋白表达。结果: 与正常组比较,模型组大鼠血清ALT、AST、HA、PCⅢ、Ⅳ-C的含量均明显升高(P<0.01),HE染色显示模型组大鼠肝细胞出现明显水肿、坏死、炎性细胞浸润。与模型组比较,柴胡疏肝散低、中、高剂量组能抑制肝细胞坏死、炎性细胞浸润,且血清中ALT、AST、HA、PCⅢ、Ⅳ-C水平均显著降低(P<0.05或P<0.01);柴胡疏肝散中、高剂量组大鼠的肝系数显著降低(P<0.05);柴胡疏肝散各剂量组不同程度抑制肝组织中JAK2、STAT3 mRNA及蛋白的表达(P<0.05或P<0.01)。结论: 柴胡疏肝散对早期肝纤维化大鼠的保护作用可能与抑制JAK2/STAT3信号通路相关。     

A case report of hepatic metastasis from leiomyosarcoma of the rectum with right hepatic lobectomy

A case of hepatic metastasis from leiomyosarcoma of the rectum submitted to right hepatic lobectomy is presented. Surgery for hepatic metastasis from intestinal leiomyosarcoma is rarely possible. The patient was a 67-year-old woman who was diagnosed as leiomyosarcoma of the rectum and underwent abdominoperineal excision of the rectum in fifteen months. Hepatic metastasis was detected by US, CT and angiography. Right hepatic lobectomy was performed, and the resected hepatic lesions were histologically identified as metastasis from leiomyosarcoma of the rectum. The patient is still alive 10 months after the second operation with no lesions of the liver.     

Transcatheter treatment of hepatic metastasis from stomach cancer

The data on arterial chemo-infusion (14) and chemoembolization (10) were compared in the treatment of 24 patients with unresectable metastases of gastric cancer into the liver. Decrease in or stabilization of tumor growth were found in 80 and 50%, respectively. Mean survival after chemo-infusion was 15.8 months, chemoembolization--9.6 months (p = 0.06); one-year survival--71 and 44%, respectively. These results match the literature data on resection of the liver. Therapy should start with chemo-infusion and should not be followed by chemoembolization unless the former fails.