Diagnosis and treatment of hepatic cholangiocarcinoma:report of 52 cases

OBJECTIVE: To summarize the experience in diagnosis and surgical treatment of hepaticcholangiocarcinoma.METHODS: Clinical features, diagnosis, surgical treatment and prognosis of 52 patients with hepaticcholangiocarcinoma treated at our hospital from 1993 to 2001 were retrospectively reviewed.RESULTS: The patients with hepatic cholangiocarcinoma accounted for 4.1% (52/1261) of the totalpatients with primary, liver carcinoma encountered at this hospital. The ratio of male to female was 1.36:1in this group. Some patients were complicated by hepatitis B (32.7%), hepatolith (34.6%), liver abscess(13.5%), cirrhosis (53.8%), and serum positivity for alpha-fetaprotein (21.2%). No typical clinicalmanifestations were present in all patients. The diagnostic rates of ultrasound examination and CT were80.8% and 94.2%, respectively. The resection rate of hepatic cholangiocarcinoma was 48.1%; and the1-, 3-, 5-year survival rates were 48.1% (25/52), 30.8% (16/52), and 19.2% (10/52) respectivelyin this group. In resectable cases, the 1-, 3-, 5-year survival rates were 80.0% (20/25), 48.0% (12/25),28.0% (7/25) respectively. Seven patients without cirrhosis who had received radical resection andintra-arterial chemotherapy survived for more than 5 years. In unresectable 27 cases, only 5 survivedover one year even if selective hepatic arterial embolism and perfusion chemotherapy were employed.CONCLUSIONS: No specific, serum marker is found for hepatic cholangiocarcinoma. CT diagnosis issuperior to ultrasonography. When a patient has already diagnosed as having hepatolith or liver abscessbefore operation and occupying lesion is seen intraoperatively, rapid pathological examination should bedone for a fair judgement of the nature of the mass and a decision-making of operative protocol. Thepatient can survive well after curative resection. No matter whether hepatic cholangiocarcinoma isresectable or not, both selective hepatic arterial embolism and perfusion chemotherapy are valuable.

Antitumor and antiangiogenic activities of anti-vascular endothelial growth factor hairpin ribozyme in human hepatocellular carcinoma cell cultures and xenografts

AIM: To study the effectiveness and mechanisms of anti-human vascular endothelial growth factor (hVEGF) hairpin ribozyme on angiogenesis,oncogenicity and tumor growth in a hepatocarcinoma cell line and a xenografted model. METHODS: The artificial anti-hVEGF hairpin ribozyme was transfected into hepatocarcinoma cell line SMMC-7721 and,subsequently,polymerase chain reaction (PCR) and reverse transcription polymerase chain reaction (RT-PCR) were performed to confirm the ribozyme gene integration and transcription. To determine the effects of ribozyme ,VEGF expression was detected by semiquantitative RT-PCR and enzyme liked immunosorbent assay (ELISA). MTT assay was carried out to measure the cell proliferation. Furthermore,the transfected and control cells were inoculated into nude mice respectively,the growth of cells in nude mice and angiogenesis were observed. RESULTS: VEGF expression was down-regulated sharply by ribozyme in transfected SMMC-7721 cells and xenografted tumor. Compared to the control group,the transfected cells grew slower in cell cultures and xenografts,and the xenograft formation was delayed as well. In addition,the microvessel density of the xenografted tumor was obviously declined in the transfected group. As demonstratedby microscopy,reduction of VEGF production induced by ribozyme resulted in a significantly higher cell differentiation and less proliferation vigor in xenografted tumor. CONCLUSION: Anti-hVEGF hairpin ribozyme can effectively inhibit VEGF expression and growth of hepatocarcinoma in vitro and in vivo. VEGF is functionally related to cell proliferation,differentiation and tumori-genesis in hepatocarcinoma.

CXC CHEMOKINE RECEPTOR 3 MODULATES BLEOMYCIN-INDUCED PULMONARY INJURY VIA INVOLVING INFLAMMATORY PROCESS

Objective To investigate the role of CXC chemokine receptor 3 (CXCR3) in bleomycin-induced lung injury by using CXCR3 gene deficient mice. Methods Sex-, age-, and weight-matched C57BL/6 CXCR3 gene knockout mice and C57BL/6 wide type mice were challenged by injection of bleomycin via trachea. Lung tissue was stained with HE method. Airway resistance was measured. Bronchoalveolar lavage (BAL) was performed using phosphate buffered saline twice, cell number and differentials were counted by Diff-Quick staining. Interleukin(IL)-4, IL-5, IL-12p40, and interfon-γ in BAL fluid and lung homogenate were measured by enzyme-linked immunosorbent assay. Unpaired t test was explored to compare the difference between two groups. Results On day 7 after bleomycin injection via trachea, CXCR3 knockout mice were protected from bleomycin-induced lung injury as evidenced by fewer accumulation of inflammatory cells in the airway and lung interstitium compared with their wild type littermates (P<0.05). Airway resistance was also lower in CXCR3 knockout mice compared with wild type mice (P<0.01). Significantly lower level of inflammatory cytokines release, including the altered production of IL-4 and IL-5 both in BAL fluid and lung tissue was seen in CXCR3 knockout mice than in wild type mice (both P<0.05).Conclusion CXCR3 signaling promotes inflammatory cells recruiting and initiates inflammatory cytokines cascade following endotracheal bleomycin administration, indicating that CXCR3 might be a therapeutic target for pulmonary injury.

Vascular endothelial growth factor concentration in vitreous humor of patients with severe proliferative diabetic retinopathy after intravitreal injection of conbercept as an adjunctive therapy for vitrectomy

Background:Proliferative diabetic retinopathy(PDR)is a progressive stage of diabetic retinopathy featured by the formation of neovascular and proliferative membrane.Vascular endothelial growth factor(VEGF)acts as a pivot factor in the development of neovascularization.This study was to investigate the changes of intravitreal VEGF concentrations of severe PDR after intravitreal injection of conbercept(IVC)and its potential advantages to the following vitrectomy.Methods:This was a prospective,interventional,randomized controlled study.Sixty eyes(60 patients)with severe PDR and 20 eyes from 20 patients with rhegmatogenous retinal detachment complicated with proliferative vitreoretinopathy were enrolled in this study.PDR eyes were randomly assigned to three groups by sortation randomization method with 20 eyes in each based on the interval of preoperative IVC(group A:7 days,group B:14 days,group C:non-IVC).Another 20 eyes without diabetes were enrolled as the non-diabetic control group(group D),receiving PPV directly.Vitreous specimens of all 80 patients were collected and evaluated afterwards.The intravitreal VEGF concentration of the four groups,and the total surgical time and the intraoperative bleeding rate of the PDR groups were recorded.Results:The mean intravitreal VEGF concentrations of groups A-D were 66.6±43.3,93.1±52.3,161.4±106.1 and 1.8±1.2 pg/mL,respectively.It increased significantly in PDR patients(groups A,B and C)(P=0.002,<0.001,and<0.001,respectively).PDR patients with preoperative IVC(groups A and B)presented significantly lower VEGF concentrations(P<0.001 and 0.001),intraoperative bleeding rates(P=0.004)and total surgical time(P<0.001,P=0.003)compared with group C.No statistical differences were presented between groups A and B on the three parameters.Conclusion:Seven days and 14 days of preoperative IVC are equally efficient and safe for the vitrectomy of severe PDR patients through decreasing vitreous VEGF concentrations,intraoperative bleeding rate and total surgical times.