首页 | 本学科首页   官方微博 | 高级检索  
相似文献
 共查询到20条相似文献,搜索用时 0 毫秒
1.
Tumor recurrence after liver transplantation still remains a significant problem in patients with hepatocellular carcinoma. The small GTPase Rho/Rho-associated kinase (ROCK) pathway is involved in the motility and invasiveness of cancer cells. We investigated whether tacrolimus activated the Rho/ROCK signal pathway to promote the invasiveness of rat hepatocellular carcinoma cells. We also investigated whether the ROCK inhibitor Y-27632 suppressed tumor recurrence after experimental liver transplantation in a rat hepatocellular carcinoma model. Orthotopic liver transplantation was performed in hepatocellular carcinoma cell line McA-RH7777-bearing rats. Tacrolimus was administered to liver transplant rats and these rats were divided into two groups: the Y-27632-treated (10 mg/kg, for 28 days) group and the Y-27632-untreated group. Tacrolimus enhanced the cancer cell migration and stimulated phosphorylation of the myosin light chain (MLC), a downstream effector of Rho/ROCK signaling. Y-27632 suppressed the cancer cell migration and tacrolimus-induced MLC phosphorylation. Suppression of tumor recurrence after liver transplantation and significant prolongation of survival were observed in the Y-27632-treated rats in comparison with theY-27632-untreated rats. Tacrolimus stimulates the Rho/ROCK signal pathway to enhance the invasiveness of hepatocellular carcinoma, and the ROCK inhibitor Y-27632 can be used as a new antimetastatic agent for the prevention of tumor recurrence after liver transplantation.  相似文献   

2.
The purpose of this study was to evaluate the impact of tumor-positive hilar lymph nodes (LN) on tumor recurrence and survival in patients with hepatocellular carcinoma (HCC) undergoing liver transplantation (LT). A computer search of the Medline database was carried out. The outcome of patients with positive hilar LN (study group) was compared with that of patients with negative LN (reference group). Five clinical studies evaluating tumor recurrence after LT for HCC according to hilar LN status were identified. Five further clinical studies evaluated patients' survival in reference to LN metastases. The test of heterogeneity for each comparison revealed no significant differences (exact P=0.4638). A significant correlation between tumor-positive LN and tumor recurrence was shown (exact estimation of common odds ratio by 10.44, 95% confidence interval of 3.431-38.59). Furthermore, data analyses using the Fisher-combination test regarding patient survival in the two groups showed a statistical difference (P<0.0001). The negative prognostic value of hilar LN metastasis for both tumor recurrence and survival was confirmed by this analysis. Given the ever-present diagnostic dilemma associated with enlarged hilar LN, especially in hepatitis C-positive patients, hilar LN sampling during LT for HCC could better define patients at risk.  相似文献   

3.
ABSTRACT

Previous studies have indicated that sirolimus (SRL) may be effective for HCC patients undergoing liver transplantation (LT). However, the following results are still contradictory and do not have a clear conclusion. Therefore, we conducted an updated meta-analysis by retrieving published data in EMBASE, PubMed, and the Cochrane Library up to October 2017. Both efficiency and safety of SRL were analyzed using pooled odds ratio (ORs) with 95% confidence interval (CIs). A total of 11 studies involving 7,695 HCC patients were included. Compared with control group, SRL prolonged 1-year (OR = 2.44; CI = 1.66–3.59), 3 year (OR = 1.67; CI = 1.08–2.58) and 5-year (OR = 1.68; CI = 1.21–2.33) overall survival, as well as 1-year (OR = 2.13; CI = 1.19–3.81) disease-free survival. Pooled results found that SRL-treated patients had lower recurrence (OR = 0.60; CI = 0.37–0.98), lower recurrence-related mortality (OR = 0.58; CI = 0.42–0.81) and lower overall mortality (OR = 0.62; CI = 0.44–0.89). Moreover, fewer SRL-treated patients suffered from portal vein thrombosis (OR = 0.29; CI, 0.09–0.91) and diabetes (OR = 0.23; CI = 0.12–0.47), while SRL-treated patients were more vulnerable to acne compared with the control group (OR = 4.44; CI = 1.56–12.60). No significant differences in other adverse effects were found between two groups. Taken together, SRL-based immunosuppression is safe and effective in improving survival, as well as reducing recurrence and mortality for HCC patients following LT.  相似文献   

4.
We performed a randomized trial to compare two regimens of low-risk kidney allograft recipients in the first year after transplantation. Both regimens initially included sirolimus, tacrolimus and steroids; one with long-term maintenance with these drugs vs. tacrolimus withdrawal. Group I: sirolimus levels of 4-8 ng/mL, plus tacrolimus 8-12 ng/mL for 3 months, and 5-10 ng/mL after month 3. Group II: sirolimus concentration of 8-16 ng/mL, plus tacrolimus 3-8 ng/mL with tacrolimus elimination from month 3 onwards. Owing to difficulties in achieving target levels, the protocol was amended to increase the doses. Eighty-seven patients were recruited. In the intention-to-treat analysis, glomerular filtration rate (GFR) at 12 months, adjusted to zero for graft loss, was similar in both groups (58.8 and 59.9 mL/min). Analysis of patients remaining on protocol showed that GFR was higher in group II only in the patients postamendment (58.4 and 72.9 mL/min, p = 0.03). Rates of biopsy-confirmed rejection (BCAR) were 9.3% and 22.7% in groups I and II, respectively (p = NS). After amendment, BCAR rates were 10.3% and 11.1% (p = NS). Diastolic blood pressure was significantly lower in patients who eliminated tacrolimus (80.4 vs. 75.6 mmHg) (p = 0.03). Combining sirolimus and tacrolimus with adequate loading doses was associated with a low incidence of BCAR, and allowed tacrolimus elimination in a high proportion of patients, which may be followed by amelioration in renal function and blood pressure.  相似文献   

5.
目的 通过活体肝移植(LDLT)与尸体肝移植(DDLT)治疗原发性肝癌(HCC)的比较,探讨LDLT治疗HCC的疗效.方法 分析2007年1月至2008年12月间我院实施的105例肝癌肝移植手术(其中LDLT38例,DDLT67例)的临床资料和随访结果.结果 LDLT患者1年及3年生存率分别为92.1%及78.9%,...  相似文献   

6.
Hepatocellular carcinoma (HCC) remains a significant disease worldwide and its incidence is expected to increase. In selected patients, liver transplantation offers a 5‐year patient survival between 48% and 75%. However, HCC recurrence occurs in approximately 20% of transplant recipients. No therapy has proven efficacious in decreasing the risk of recurrence after transplantation. Sorafenib, a multitargeted tyrosine kinase inhibitor, has been shown to improve survival in patients with advanced HCC that have no history of liver transplantation. We report complete remission of HCC in a 54‐year‐old man who developed biopsy‐proven lung metastasis after liver transplantation treated with sorafenib.  相似文献   

7.
Abstract Orthotopic liver transplantation (OLT) for liver cirrhosis in the presence of hepatocellular carcinoma (HCC) is based on tumour number and size. The high incidence of undetected HCC before OLT has been reported previously. The object of this work to report the results of OLT for liver cirrhosis in the presence of incidental and/or undetected HCC and tumour characteristics. From 1985 to 1996, 334 patients received OLT. Two groups of patients were studied; group 1 (G1) where HCC was diagnosed on radiological examination before OLT ( n = 13, mean age 53.8 ± 8.1 years), and group 2 (G2), where HCC was diagnosed on pathological review ( n = 13, mean age 53.3 ± 6.1 years). Indications for OLT were (G1/G2) hepatitis C = 6/8, hepatitis B = 5/2, alcoholic = 2/3. There was no statistically significant difference in α-foetoprotein levels between both groups. Pathological review showed 26 and 30 HCC with a mean size of 1.6 ± 0.8 and 1.6 ± 1.2 cm ( P > 0.05) in G1 and G2, respectively. Tumour stagings were (G1/G2) stage I = 6/2, stage II = 4/6, stage III = 2/3, stage IVa = 1/2. We had two (G2) hospital and three (G1) later mortalities; none had HCC recurrence. The other patients are alive and recurrence free. Reinforced immunosuppression related to acute or chronic rejection treatment was not associated with HCC recurrence. The 5-year actuarial survival rates were 76% for G1 and 85% for G2 ( P > 0.05). Our study revealed that long-term survival can be achieved with liver transplantation in the presence of HCC in carefully selected patients.  相似文献   

8.
Hepatitis B virus (HBV) recurrence following orthotopic liver transplantation (OLT) is generally preventable by prophylaxis with hepatitis B immunoglobulin (HBIG) and lamivudine (LAM). However, HBV recurrence sometimes develops despite prophylaxis. This study assessed posttransplant outcomes and identified predictors of HBV recurrence. We analyzed the outcomes of 209 consecutive patients positive for hepatitis B surface antigen who underwent OLT, who received either combination prophylaxis with HBIG and LAM (89.0%) or HBIG monoprophylaxis (11.0%). The median follow‐up was 36.8 months (range, 1.0–84.4). Posttransplant HBV recurrence occurred in 22 patients (10.5%), including 13 patients with drug‐resistant mutations. HBV recurrence was observed in six patients after hepatocellular carcinoma (HCC) recurrence. Independent predictors of HBV recurrence were recurrent HCC (p < 0.001), LAM therapy >1.5 years (p = 0.001) and high HBV DNA titers (≥105 copies/mL) at OLT (p = 0.036). In conclusion, high viremia at OLT and prolonged exposure to LAM should be further stressed as main predictors of HBV recurrence.  相似文献   

9.
Recurrence of primary biliary cirrhosis (PBC) after liver transplantation has been shown to negatively affect graft and patient survival. Recently, protective effects of cyclosporine A against PBC recurrence after liver transplantation have been reported. Participants were 4 patients who underwent living-donor liver transplantation (LDLT) for end-stage liver disease due to PBC. Tacrolimus was used for initial immunosuppression, and this was switched to cyclosporine A at least 3 months after liver transplantation. Targeted trough level of cyclosporine A was 20 times that of tacrolimus. We assessed liver and renal function, as well as antimitochondrial M2 antibody for recipients prior to LDLT, as well as before and after switching immunosuppressive agents. Patients were 1 man and 3 women, and they were ages 45 to 47 years at LDLT. Timing of switching from tacrolimus to cyclosporine A was 13, 3, 7, and 4 months respectively after liver transplantation, and all 4 patients have been on cyclosporine A without adverse effects at 20 to 46 months after transplantation. In 2 of 4 patients who had high titers of antimitochondrial M2 antibody before transplantation, antibody titer did not elevate after LDLT. In the other 2 patients without elevation of antimitochondrial M2 antibody, the titer did not turn positive. Switching from tacrolimus to cyclosporine A was possible without medical problems, and all patients exhibit no recurrence of PBC. Cyclosporine A may be useful for prevention of PBC recurrence after LDLT.  相似文献   

10.
11.
The treatment for hepatocellular carcinoma (HCC) relies on liver resection, which is, however, burdened by a high rate of recurrence after surgery, up to 60% at 5 years. No pre-operative tools are currently available to assess the recurrence risk tailored to every single patient. Recently liquid biopsy has shown interesting results in diagnosis, prognosis and treatment allocation strategies in other types of cancers, since its ability to identify circulating tumor cells (CTCs) derived from the primary tumor. Those cells were advocated to be responsible for the majority of cases of recurrence and cancer-related deaths for HCC. In fact, after being modified by the epithelial-mesenchymal transition, CTCs circulate as “seeds” in peripheral blood, then reach the target organ as dormant cells which could be subsequently “awakened” and activated, and then initiate metastasis. Their presence may justify the disagreement registered in terms of efficacy of anatomic vs non-anatomic resections, particularly in the case of microvascular invasion, which has been recently pointed as a histological sign of the spread of those cells. Thus, their presence, also in the early stages, may justify the recurrence event also in the contest of liver transplant. Understanding the mechanism behind the tumor progression may allow improving the treatment selection according to the biological patient-based characteristics. Moreover, it may drive the development of novel biological tailored tests which could address a specific patient to neoadjuvant or adjuvant strategies, and in perspective, it could also become a new method to allocate organs for transplantation, according to the risk of relapse after liver transplant. The present paper will describe the most recent evidence on the role of CTCs in determining the relapse of HCC, highlighting their potential clinical implication as novel tumor behavior biomarkers able to influence the surgical choice.  相似文献   

12.
目的 探讨挽救性肝移植(SLT)的手术安全性及对患者预后的影响.方法 回顾性分析复旦大学附属中山医院肝外科2001年6月至2008年12月期间连续289例肝癌肝移植(符合UCSF标准)患者的临床资料,其中242例患者行初始肝移植(PLT),即PLT组,47例患者行SLT,即SLT组,比较2组患者围手术期及长期生存情况的差异.结果 2组患者的平均年龄、性别构成及肿瘤情况差异均无统计学意义(P>0.05).SLT组的手术时间要长于PLT组[(7.1±1.8)h比(6.4±1.4)h,P=0.004],但2组患者的术中出血量[(2 560.5±2 683.6)ml比(2 042.9±2 006.2)ml,P=0.173]及术中输血量[(13.8±12.9)U比(9.9±12.6)U,P=0.087]比较差异均无统计学意义,SLT组患者从第1次手术切除至行肝移植的间隔时间为(32.8±32.4)个月.截至2009年12月,2组患者中位随访时间为38.7个月,SLT组与PLT组患者的3年生存率(82.3%比75.5%,P=0.312)和3年无瘤生存率(78.8%比70.1%,P=0.755)之间比较差异均无统计学意义.但按意向性治疗分析,SLT组患者的3年生存率明显优于PLT组(88.4%比76.2%,P=0.047).结论 SLT并不增加移植手术的风险,也不影响患者的长期预后,对部分病例,先行手术切除再行肝移植可作为肝癌治疗的一种有效策略.  相似文献   

13.
We previously suggested that in patients with heptocellular carcinoma (HCC), the conventional Milan criteria (T1/T2) for orthotopic liver transplantation (OLT) could be modestly expanded based on pathology (UCSF criteria). The present study was undertaken to prospectively validate the UCSF criteria based on pretransplant imaging. Over a 5-year period, the UCSF criteria were used as selection guidelines for OLT in 168 patients, including 38 patients exceeding Milan but meeting UCSF criteria (T3A). The 1- and 5-year recurrence-free probabilities were 95.9% and 90.9%, and the respective survivals without recurrence were 92.1% and 80.7%. Patients with preoperative T1/T2 HCC had 1- and 5-year recurrence-free probabilities of 95.7% and 90.1%, respectively, versus 96.9% and 93.6%, respectively, for preoperative T3A stage (p = 0.58). Under-staging was observed in 20% of T2 and 29% of T3A HCC (p = 0.26). When explant tumor exceeded UCSF criteria (15%), the 1- and 5-year recurrence-free probabilities were 80.4% and 59.5%, versus 98.6% and 96.7%, respectively, for those within UCSF criteria (p < 0.0001). In conclusion, our results validated the ability of the UCSF criteria to discriminate prognosis after OLT and to serve as selection criteria for OLT, with a similar risk of tumor recurrence and under-staging when compared to the Milan criteria.  相似文献   

14.
目的分析影响肝癌肝移植术后生存率和无瘤生存率的危险因素,探讨国内肝移植治疗肝癌的选择标准。方法对67例接受同种异位原位肝移植治疗的原发性肝癌病人的基本资料和肿瘤相关资料包括术前病情分级、血清AFP水平、术前辅助治疗以及肝癌大小、数目、pTNM分期、肿瘤恶性程度分级等因素进行单因素和多因素分析。结果术后1年、2年累积生存率为77%、67%,6个月和12个月无瘤生存率为66%和58%。单因素分析显示对肝癌肝移植术后累积生存率影响有统计学意义的因素为CHILD分级(MELD积分)和肝外大血管侵犯;多因素分析影响肝癌肝移植术后无瘤生存率有统计学义的因素是肿瘤大小、大血管侵犯和肿瘤分化程度。结论影响肝癌肝移植术后生存率的因素仍是术前患者肝功能状态。对存在大血管侵犯的肝癌患者需严格控制肝移植术适应证,而无血管侵犯的患者在选择肝移植治疗时肿瘤大小指标可较米兰标准适当放宽。  相似文献   

15.
影响原发性肝癌肝移植治疗的预后因素分析   总被引:3,自引:0,他引:3  
目的分析影响肝癌肝移植术后生存率和无瘤生存率的危险因素,探讨国内肝移植治疗肝癌的选择标准。方法对67例接受同种异位原位肝移植治疗的原发性肝癌病人的基本资料和肿瘤相关资料包括术前病情分级、血清AFP水平、术前辅助治疗以及肝癌大小、数目、pTNM分期、肿瘤恶性程度分级等因素进行单因素和多因素分析。结果术后1年、2年累积生存率为77%、67%,6个月和12个月无瘤生存率为66%和58%。单因素分析显示对肝癌肝移植术后累积生存率影响有统计学意义的因素为CHILD分级(MELD积分)和肝外大血管侵犯;多因素分析影响肝癌肝移植术后无瘤生存率有统计学义的因素是肿瘤大小、大血管侵犯和肿瘤分化程度。结论影响肝癌肝移植术后生存率的因素仍是术前患者肝功能状态。对存在大血管侵犯的肝癌患者需严格控制肝移植术适应证,而无血管侵犯的患者在选择肝移植治疗时肿瘤大小指标可较米兰标准适当放宽。  相似文献   

16.
Microvascular invasion affects survival after orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC). We sought to identify preoperative predictors of microvascular invasion in patients with HCC who were candidates for OLT. A cohort of 245 patients who underwent resection for HCC and fulfilled the criteria for OLT (i.e., single tumors ≤5 cm or no more than three tumors S3 cm) were identified from a multi-institutional database. Thirty-three percent of the patients had pathologic evidence of microvascular invasion. Thirty percent of patients with single tumors and 47% with multiple tumors had microvascular invasion (P = 0.04). Only 25% of patients with tumors smaller than ≤2 cm had microvascular invasion, compared to 31% and 50% with tumors greater than 2 to 4 cm or larger than 4 cm, respectively (P = 0.01). Tumor grade was highly correlated with microvascular invasion: 12% of patients with well-differentiated tumors had microvascular invasion, compared to 29% and 50% with moderately or poorly differentiated tumors, respectively (P < 0.001). The independent predictors of microvascular invasion were tumor size greater than 4 cm (odds ratio [OR], 3.0, 95% confidence interval [CI], 1.2 to 7.1), and high tumor grade (OR, 6.3; 95% CI, 2.0 to 19.9). Tumor size and grade are strong predictors of microvascular invasion. A tumor biopsy with pathologic grading at the time of pretransplantation ablative therapy could improve selection of patients with HCC for OLT. Presented at the Forty-Second Annual Meeting of The Society for Surgery of the Alimentary Tract, Atlanta, Georgia, May 20–23, 2001. Supported by a T-32 Surgical Oncology Training Grant from the National Institutes of Health (N.F.E).  相似文献   

17.
BACKGROUND AND AIMS: Liver transplantation (OLT) for hepatocellular carcinoma (HCC) improves patient survival when tumor size and number are limited according to the Milan criteria. However, the impact of tumor size vs. the number of lesions for tumor recurrence after OLT is unclear. Microvascular invasion appears to be a significant risk factor for tumor recurrence. Therefore, it was the aim of this study to investigate tumor differentiation and microvascular invasion in relation to tumor number and size and their impact on survival after transplantation. PATIENTS AND METHODS: In 97 adult HCC patients who underwent OLT between June 1985 and December 2005 the incidence of microvascular invasion, tumor differentiation, and the number and size of tumor lesions were analyzed retrospectively. Their impact on survival was studied by multivariate analysis. RESULTS: Microvascular invasion was the only independent negative predictor of survival after OLT for HCC (p = 0.025). Tumor size > 5 cm was predictive for microvascular invasion (p = 0.007). In contrast, tumor number did not affect the incidence of microvascular invasion or cumulative survival. CONCLUSION: The size of the largest HCC lesion, but not the number of tumors, determined microvascular invasion, a predictor of the outcome following OLT for HCC. Thus, the number of HCC lesions should not be applied to patient selection prior to OLT. These data support the extension of the Milan criteria for the selection of HCC patients for OLT with regard to tumor number, but not tumor size.  相似文献   

18.
目的分析影响肝细胞癌(HCC)患者肝移植后肿瘤复发和预后的相关因素,总结HCC患者肝移植的选择标准。方法回顾性分析118例HCC肝移植受者的临床资料,应用单因素和多因素的分析方法,分析临床和病理等相关因素对HCC患者肝移植后肿瘤复发及预后的影响,筛选出影响肿瘤复发和预后的危险因素,并结合国际HCC肝移植受者选择标准运用于临床。结果HCC患者肝移植围手术期死亡8例,对存活的110例随访1~32个月,其中有41例肿瘤复发(37.3%),死亡39例(35.5%);12、18和24个月的累积存活率分别是84.55%、70.30%和62.24%;12、18和24个月的无瘤存活率分别是69.05%、66.93%和61.38%。单因素分析结果显示癌栓形成、米兰标准、肿瘤大小、肿瘤分化程度以及pTNM分期对HCE患者肝移植后肿瘤复发有显著影响;癌栓形成、米兰标准、术前血清甲胎蛋白(AFP)水平、肿瘤分化程度以及pTNM分期对患者预后有显著影响;多因素分析显示,癌栓形成和肿瘤分化程度是肿瘤复发的独立影响因素,癌栓形成和术前AFP水平则是影响预后的独立危险因素。结论癌栓形成和肿瘤分化程度是影响HCC患者肝移植后肿瘤复发的独立因素,而癌栓形成和术前AFP水平是影响预后的独立危险因素。  相似文献   

19.
We investigated the efficacy of nonresective ablation techniques and the tumor-free survival of cirrhotic patients undergoing liver transplantation for hepatocellular carcinoma (HCC). In group 1, 11 HCC patients were treated with these techniques and transplanted. On the waiting list, patients were treated to complete ablation, judged by gadolinium-enhanced MRI and alpha-fetoprotein (AFP) levels. Group 1 was compared with a concurrent group of 10 liver transplant patients (group 2) with incidental HCC (stages T1 three patients, T2 seven patients). The group 1 patients received 36 procedures (4 alcohol ablations, 14 trans -hepatic artery chemo-embolizations, 15 trans -hepatic chemo-infusions, and 3 radio frequency ablations) for treatment of 13 liver masses. Tumor-node-metastasis (TNM) stage was reduced in eight patients (72.7%), unchanged in two patients and increased in one patient before transplantation. The mean waiting time for transplantation was 12.9 7.6 months. Both groups had a tumor-free survival of 100%, at 30 12 months post transplant. On pathology, 54.5% of explanted livers had residual viable HCC after tumor treatment, and 36.4% (4/11) explants had synchronous lesions. Non-resective ablation therapy is safe and effective in reducing the HCC progression in cirrhotic patients awaiting liver transplantation. The cancer-free survival rate in this treatment group is equal to that for incidental T1-T2 HCCs.  相似文献   

20.
目的探讨采用补救性肝移植(salvage liver transplantation,SLT)治疗原发性肝细胞癌(肝癌)切除术后肝内复发或肝功能衰竭的疗效及手术体会。方法肝癌切除术后肝内复发16例,肝癌切除术后肝功能衰竭3例,其中合并肾功能异常2例,均接受SLT。术前充分评估病情。手术方式采用附加腔静脉整形的改良背驮式原位肝移植,其中肾功能异常的2例采用股静脉-颈内静脉转流术。肝动脉的重建采用供肝腹腔干动脉与受者肝固有动脉行端端吻合17例,采用供肝腹腔干动脉通过供者髂动脉间置搭桥与受者腹主动脉行端侧吻合2例。胆道的重建全部采用胆道端端吻合。术程始终遵循精细的无瘤操作,术后常规抗排斥和抗感染治疗,并对患者进行了长期随访。结果围手术期19例SLT患者无死亡。术后1、3、5年累积生存率分别为100%、84%、84%;1、3、5年无瘤生存率分别为100%、89%、89%。结论采用SLT治疗肝癌切除术后肝内复发或肝功能衰竭患者的疗效较好。采用腔静脉整形的改良背驮式肝移植术式、充分的术前评估以及遵循精细的无瘤操作是手术成功的关键。  相似文献   

设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号