The actual five-year survival rate of hepatocellular carcinoma patients after curative resection

The five-year survival rate of patients after curative resection of hepatocellular carcinoma (HCC) has been reported to be 30 to 50%, however the actual survival rate may be different. We analyzed the actual 5-year survival rate and prognostic factors after curative resection of HCC. Retrospective analysis was performed on 63 HCC patients who underwent curative resection from 1998 to 1999. A total of 63 cases were reviewed, consisting of 53 men and 10 women, with a median age of 49 years. These cases included all four pathologic T stages (pT stage) and had the following representation: stage 1 (1 case), stage 2 (17 cases), stage 3 (38 cases), and stage 4 (7 cases). In our study, the actual 5-year survival rate was 57.0% and the median survival time was 60 months. In addition, the patients in our study had an actual 5-year disease-free survival rate of 50.2% and a median disease-free survival time of 46 months. Thirty-one patients had recurrences, with a majority occurring within one year (65%). These patients with early recurrences had a poor actual 5-year survival rate of 5%. A univariate analysis showed that the prognostic factors influencing survival rate were the presence of satellite nodules, increased pT stage, HCC recurrence, and the time to recurrence (within one year). Interestingly, microvascular invasion made a difference in survival rate but was not statistically significant (p = 0.08). Furthermore, factors influencing the disease free survival rate include the presence of satellite nodules, microvascular invasion, and pT stage. Multivariate analysis identified pT stage as the only statistically related factor in determining the disease-free survival rate. The most important prognostic factor of HCC is recurrence. Moreover, the major risk factor for recurrence is an advanced pT stage. Therefore, performing prospective studies of postoperative adjuvant therapy is necessary to prevent recurrences after hepatic resection. Furthermore, active preventative treatment and early diagnosis of recurrences should be of the highest priority in the care of high-risk patient groups that have an advanced pT stage.     

TAK-242 can be the potential agents for preventing invasion and metastasis of hepatocellular carcinoma

The long-term prognosis of hepatocellular carcinoma (HCC) remains unsatisfactory even after surgical resection and chemoembolization because of a high recurrence rate. However, fewer agents are currently available to block or postpone HCC progression.     

Resection of metachronous lymph node metastases from hepatocellular carcinoma after hepatectomy: report of four cases

We report 4 cases of surgical resection of metachronous lymph node (LN) metastases from hepatocellular carcinoma (HCC) following hepatectomy. Clinicopathological features and results of LN dissection were investigated in the 4 patients. One patient was found to have a single metastasis in the mediastinal LNs, another had multiple metastases in the mediastinal and abdominal LNs, and the other 2 had single metastases in the abdominal LN. The locations of the abdominal LN metastases were behind the pancreas head in 2 patients and around the abdominal aorta in 1 patient. They all underwent surgical resection of metastatic LNs and had no postoperative complications. The 3 patients whose LN metastases were solitary have been alive for more than 2 years after LN resection, and one of them is free from recurrence. The patient with multiple LN metastases died 13 months after LN resection due to carcinomatosis. With the expectation of long-term survival, a single metachronous LN metastasis from HCC after hepatectomy should be resected in patients without uncontrollable intrahepatic or extrahepatic tumors.     

Lack of association between hepatitis B virus pre‐S mutations and recurrence after surgical resection in hepatocellular carcinoma

Pre‐S mutation of hepatitis B virus (HBV) is known to be a risk factor for hepatocarcinogenesis. A previous study suggested that pre‐S mutation(s) may associate with increased recurrence after surgical resection. In the present study, 64 patients with HBV‐related hepatocellular carcinoma (HCC) were categorized into two groups according to the presence or absence of pre‐S mutation(s). The clinicopathological variables of the two groups were analyzed to assess the relationship between pre‐S mutations and postoperative recurrence. Nineteen patients (29.7%) had pre‐S mutations;13 had a pre‐S deletion, three had a pre‐S2 start codon mutation, two patients had both a pre‐S deletion, and a pre‐S2 start codon mutation, and one patient had a pre‐S2 insertion. The two groups did not differ in terms of baseline clinicopathological parameters. Cirrhosis and satellite lesion(s) were predictive factors for postoperative recurrence and poor overall survival. Recurrence‐free survival (P = 0.320) and overall survival (P = 0.238) did not differ significantly when pre‐S mutations were present. In conclusion, this study did not find evidence supporting the notion that pre‐S mutation(s) are associated with postoperative recurrence after surgical resection. J. Med. Virol. 85:589–596, 2013. © 2013 Wiley Periodicals, Inc.     

The role of splenectomy in patients with hepatocellular carcinoma and secondary hypersplenism

Hypersplenism, secondary to portal hypertension, is common in hepatocellular carcinoma (HCC) with liver cirrhosis. Hepatic resection in the patient with hypersplenic thrombocytopenia (HSTC) may cause a perioperative bleeding episode and sometimes, liver failure. In order to investigate the effect of concomitant splenectomy in HCC patients with HSTC, clinical parameters are retrospectively reviewed for 18 HCC patients who underwent hepatic resection with or without splenectomy. Among 581 HCC patients who underwent hepatic resection during the past 17 years, 18 patients with HSTC were investigated. Twelve of them underwent hepatic resection for HCC and had a concomitant splenectomy and the remaining 6 patients underwent hepatic resection for HCC only. The clinical outcomes and postoperative changes in platelet count, serum albumin level, serum total bilirubin levels, prothrombin time and clinical staging (Child-Pugh Classification) were reviewed. The resected spleen mean weight was 350.7 +/- 102.9 g. Postoperative platelet counts were significantly increased with albumin levels and clinical staging scores also improved after the splenectomy. Among the 12 patients who had a splenectomy, 6 patients had postoperative complications and one died of recurrent variceal bleeding. According to this data, it is not harmful to perform a concomitant splenectomy and hepatectomy for the HCC patient with severe HSTC, it can even be beneficial in improving both the platelet count and clinical staging.     

Hepatocellular carcinoma and liver transplantation: clinical perspective on molecular targeted strategies

Hepatocellular carcinoma (HCC) has an aggressive clinical course with frequent recurrence and metastasis. Orthotopic liver transplantation has been the only curative tool for unresectable HCC; therefore, recent advances in molecular targeted therapy may improve the prognosis of HCC. The multiple kinase inhibitor sorafenib and the macrolide antibiotic rapamycin are currently the most promising agents for treating unresectable HCC. A large population-based clinical trial revealed that sorafenib significantly prolonged the overall survival of HCC patients. However, subsequent clinical studies showed that sorafenib rarely reduced tumor volume and inadequately prolonged survival of patients with severe liver damage. To improve its therapeutic effect, the development of a predictive biomarker and a sorafenib-based combination is awaited. Another molecular targeting agent, rapamycin, has now been considered as a putative agent for preventing tumor recurrence in post-liver transplantation HCC patients, because it not only has immunosuppressive activity but also exerts an anti-tumor effect. In the near future, a combination of molecular targeting agents, such as sorafenib and rapamycin, may become a standard protocol for treating unresectable HCC. For specifying cases with more effective and less harmful modalities, further investigation in clinical and basic research to identify unexpected effects are needed.     

Solitary extrahepatic intraabdominal metastasis from hepatocellular carcinoma after liver transplantation

A liver transplantation is a treatment option in selected patients with hepatocellular carcinoma (HCC). Despite the adequate selection of candidates, recurrences of HCC may still develop. Solitary extrahepatic metastasis from HCC after a liver transplantation is rare. Here we report two cases of HCC demonstrated extrahepatic recurrence to the adrenal gland and spleen, respectively, within one year after a liver transplantation. Since the treatment of solitary extrahepatic metastasis from HCC after a liver transplantation is not standardized, surgical resection was performed. In the case of HCC adrenal metastasis, innumerable intrahepatic metastases were found two months after the adrenalectomy. And 16 months after adrenalectomy, the patient expired due to tumor progression and hepatic failure. In the case of HCC splenic metastasis, postoperative radiation therapy was performed. However, two recurrent HCC nodules were found 15 months after the splenectomy and received transarterial chemoembolization (TACE). And 29 month after the splenectomy, the patient also expired as same causes of former patient.     

Combined therapy of transcatheter hepatic arterial embolization with intratumoral dendritic cell infusion for hepatocellular carcinoma: clinical safety

The curative treatments for hepatocellular carcinoma (HCC), including surgical resection and radiofrequency ablation (RFA), do not prevent tumour recurrence effectively. Dendritic cell (DC)-based immunotherapies are believed to contribute to the eradication of the residual and recurrent tumour cells. The current study was designed to assess the safety and bioactivity of DC infusion into tumour tissues following transcatheter hepatic arterial embolization (TAE) for patients with cirrhosis and HCC. Peripheral blood mononuclear cells (PBMCs) were differentiated into phenotypically confirmed DCs. Ten patients were administered autologous DCs through an arterial catheter during TAE treatment. Shortly thereafter, some HCC nodules were treated additionally to achieve the curative local therapeutic effects. There was no clinical or serological evidence of adverse events, including hepatic failure or autoimmune responses in any patients, in addition to those due to TAE. Following the infusion of (111)Indium-labelled DCs, DCs were detectable inside and around the HCC nodules for up to 17 days, and were associated with lymphocyte and monocyte infiltration. Interestingly, T lymphocyte responses were induced against peptides derived from the tumour antigens, Her-2/neu, MRP3, hTERT and AFP, 4 weeks after the infusion in some patients. The cumulative survival rates were not significantly changed by this strategy. These results demonstrate that transcatheter arterial DC infusion into tumour tissues following TAE treatment is feasible and safe for patients with cirrhosis and HCC. Furthermore, the antigen-non-specific, immature DC infusion may induce immune responses to unprimed tumour antigens, providing a plausible strategy to enhance tumour immunity.     

Effect of Previous Interferon-based Therapy on Recurrence after Curative Treatment of Hepatitis C Virus-related Hepatocellular Carcinoma

Previous reports have shown that interferon (IFN)-based therapy decreases the risk of development of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C virus (HCV) infection. However, it remains to be fully elucidated whether elimination of HCV by IFN-based therapy inhibits HCC recurrence after curative treatment, such as surgical resection and local ablation therapies. In this study, we aimed to clarify the influence of a sustained virological response (SVR) after IFN-based therapy on recurrence and survival after curative treatment of HCC. Fifty-one patients who underwent curative treatment of HCV-related HCC after receiving IFN-based therapy were analyzed retrospectively. They were classified into SVR (N = 14) and non-SVR groups (N = 37). In the SVR group, serum levels of aspartate aminotransferase and alanine aminotransferase, the indocyanine green retention rate at 15 min, and the percentages of patients with liver cirrhosis and HCV serotype 1 were significantly lower, whereas serum albumin level and platelet count were significantly higher upon HCC occurrence. Recurrence-free survival (RFS) for the first recurrence was significantly higher in the SVR group (P < 0.01). Multivariate analysis showed that SVR at initial HCC treatment (P < 0.01) and multiple tumors (P < 0.01) are prognostic factors for RFS. Moreover, RFS for the second recurrence showed a similar trend to that for the first recurrence. In conclusion, patients who underwent IFN-based therapy before initial curative treatment of HCC had a favorable clinical outcome compared with non-SVR patients.     

肝癌肝移植后亚砷酸化疗的应用

背景：移植后肿瘤复发是影响肝癌肝移植疗效的主要因素,如何防止肝癌肝移植后肿瘤复发是目前肝移植研究的热点问题之一。亚砷酸全身化疗被认为对中晚期肝癌具有一定作用,但在肝移植后的应用还未见报道。 目的：观察超出米兰标准的肝癌患者肝移植后应用亚砷酸全身化疗的对肿瘤复发的干预效果。 方法：对23例超出米兰标准的肝癌患者肝移植后采用亚砷酸行预防性化疗：静脉滴注10 mg/d,连续使用7 d后间隔7 d,重复4次为1个疗程,患者接受1~4个疗程。观察以上使用亚砷酸化疗患者的生存、肿瘤复发情况,以及化疗不良反应,并与同期16例未使用化疗的肝癌肝移植患者相比较。 结果与结论：经过3~32个月随访,共30例患者出现肝癌复发,化疗组16例,非化疗组14例,复发部位最常见于肺部、移植肝及骨骼。化疗组与非化疗组肿瘤复发率差异无显著性意义,但化疗组复发时间明显延迟(P=0.026);两组6个月、1年生存率差异无显著性意义,化疗组2年生存率显著高于非化疗组(P=0.037);两组6个月无瘤生存率差异无显著性意义,1年、2年无瘤生存率化疗组显著高于明显非化疗组(P=0.030,0.023)。亚砷酸使用过程中未发现严重不良反应。提示肝癌肝移植患者静脉使用亚砷酸化疗可以延迟肿瘤复发,提高生存率。     

麦默通微创旋切术治疗乳腺炎性病灶的临床分析

目的 分析麦默通微创旋切术治疗乳腺炎性病灶的临床疗效。方法 选择2016年5月~2019年5月在我院诊治的乳腺炎性病灶患者74例,采用随机数字表法分为对照组和观察组,各37例。对照组采用切开引流术治疗,观察组采用麦默通微创旋切术治疗,比较两组临床治愈率、手术指标（术后VAS评分、切口长度、切口治愈时间、手术时间、术中出血量）、复发率及并发症发生率。结果 观察组临床治愈率（97.30%）与对照组（94.59%）比较,差异无统计学意义（P＞0.05）;观察组术后VAS评分、切口长度、切口治愈时间、手术时间、术中出血量均低于对照组（P＜0.05）;观察组复发率、并发症发生率均低于对照组（P＜0.05）。结论 麦默通微创旋切术治疗乳腺炎性病灶疗效确切,且术后疼痛轻,创伤小,复发率低,并发症少,安全可行,值得临床应用。     

肝癌肝移植患者外周血中AFP mRNA和MXR7 mRNA的表达及其与预后的关系

目的： 探讨甲胎蛋白（ɑ-fetoprotein,AFP）mRNA和米托蒽醌抗性基因（Mitoxantrone-resistant 7，MXR7）mRNA作为游离癌细胞（isolated tumor cells,ITC）的标志物在肝癌肝移植患者外周血中的表达情况及其与术后肿瘤复发和转移的关系。方法: 以2002年4月至2003年12月期间的53例肝癌肝移植患者为对象，通过建立稳定可靠的实时荧光定量RT-PCR检测方法来定量检测肝癌患者外周血全细胞中AFP mRNA和MXR7 mRNA在整个肝移植术围手术期的表达和动态变化情况，并与术后肝癌复发和转移进行相关分析。 结果: 将研究对象分为肝癌移植组（53例）、晚期肝癌组（8例）、良性肝病组（26例）、正常对照组（10例），检测发现在肝移植术前，晚期肝癌组的AFP mRNA和MXR7 mRNA其表达率均达到100％,在肝癌移植组中表达率分别为57.7%和53.6%。2者均明显高于在良性肝病组（表达率为19.2%和0）和正常对照组（表达率均为0）（P<0.05）。同时在2者的阳性结果表达水平上，晚期肝癌组和肝癌组要明显高于良性肝病组和正常对照组(P<0.05)，前2者阳性结果定量水平达到1×10¹²copies/g RNA，是后2者定量水平的100－200倍。围手术期AFP mRNA和MXR7 mRNA的表达无论是表达率还是阳性结果表达水平，均以在术中的检测标本为最高，而术后1周为次之。术后出现2次以上的持续性的AFP mRNA和MXR7 mRNA的表达往往提示肝癌的复发和转移，较之移植术后没表达或一过性升高的病例，其差异有统计学意义（P<0.05），而术前和术中单次的AFP mRNA和MXR7 mRNA的表达与否则对术后肝癌复发和转移无明显影响（P>0.05）。结论: AFP mRNA和MXR7 mRNA可以作为肝癌ITC细胞的标志物，具有较好的特异性。术后血全细胞检测出现2次以上的持续性的AFP mRNA和MXR7 mRNA的表达可以有效预测肝癌肝移植术后肿瘤复发和转移。     

A case of hepatocellular carcinoma in the caudate lobe successfully treated by transcatheter arterial chemoembolization using drug-eluting beads

Hepatocellular carcinoma (HCC) in the caudate lobe remains one of the most intricate locations where various treatments tend to pose problems with regard to the optimal approach. Surgical resection has been regarded as the most effective treatment; however, isolated resection of the caudate lobe is strenuous and associated with a high rate of early recurrence. Percutaneous ablation might be technically difficult or impossible to perform due to the deep location of tumors and adjacent large vessels. Treatment with drug-eluting beads (DEB) can potentially enhance the therapeutic efficacy for patients with unresectable HCC by drawing on the slower, more consistent drug delivery process. We described a case of a 62-year-old man with HCC in the caudate lobe who was successfully treated by DEB.     

Molecular techniques for identifying HCC origin and biology after orthotopic liver transplantation.

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world. Liver transplantation represents the potentially curative treatment for small HCC. Recurrence after surgical resection and liver transplantation remains one of the major obstacles in further prolonging survival of patients with HCC. In the new liver, HCC might be of recipient or donor origin. One approach for investigating this question is by performing human identification and/or engraftment analysis. Distinction between recurrent and de novo HCC after orthotopic liver transplantation could allow for the development of important clinical and therapeutic strategies. Polymerase chain reaction amplification of highly polymorphic short tandem repeat DNA sequences, gene expression profiling, and fluorescence in situ hybridization were applied in a patient who developed a second HCC after orthotopic liver transplantation from an opposite gender donor. These techniques provided consistent evidence that the second HCC was a recurrence of the primary tumor.     

Posthepatectomy hepatitis shortens tumor-free intervals in hepatitis C virus-associated hepatocellular carcinoma patients

In hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCC), serum alanine aminotransferase (ALT) is frequently sustained on a high level after hepatectomy, with the formation of recurrent HCC tumors during follow-up periods. We investigated whether or not postoperative serum ALT level affects the interval before recurrence in hepatitis C virus-associated HCC. The subjects studied were 50 hepatectomized HCC patients who were HCV-Ab(+), and underwent a curable surgery in our Hospital from June 1990 to December 1999. We assessed the significance of the postoperative serum ALT level affecting tumor-free survival rates, as compared with other clinicopathological parameters, using univariate and multivariate Cox proportional hazard analysis. Thereafter, tumor-free and overall survival rates after hepatectomy were compared between high and low ALT groups, using Kaplan-Meier plotting and a log-rank test. The factor of ALT levels (a high or low ALT group) was most strongly associated with a tumor-free survival rate. Both tumor-free and overall survival rates were significantly poorer in the high ALT group than in the low ALT group among HCV-associated HCC cases (p<0.05). The results in this study suggest that postoperative hepatitis, which is indicated by sustained high ALT levels, may shorten the interval before recurrence in HCV-associated HCC. We should take care to control postoperative hepatitis to improve the prognoses of HCV-associated HCC cases.     

Antimetastatic efficacy of adjuvant gemcitabine in a pancreatic cancer orthotopic model

Gemcitabine is a promising new agent that has been recently studied for palliation of advanced (stage IV) unresectable pancreatic cancer. We hypothesized that adjuvant gemcitabine would reduce recurrence and metastases following surgical resection of pancreatic cancer. To test this hypothesis, we evaluated gemcitabine on a green fluorescent protein (GFP) transductant of the human pancreatic cancer cell line BxPC-3 (BxPC-3-GFP) using surgical orthotopic implantation (SOI) in nude mice. GFP enabled high resolution fluorescent visualization of primary and metastatic growth. Five weeks after SOI, the mice were randomized into three groups: Group I received exploratory laparotomy only. Group II underwent surgical resection of the pancreatic tumor without further treatment. Group III underwent tumor resection followed by adjuvant treatment with gemcitabine, 100 mg/kg every three days for a total of four doses, starting two days after resection. The mice were sacrificed at thirteen weeks following implantation and the presence and location of recurrent tumor was recorded. Gemcitabine reduced the recurrence rate to 28.6% compared to 70.6% with resection only (P=0.02) and reduced metastatic events 58% in the adjuvant group compared to resection only. This study, demonstrating that gemcitabine is effective as adjuvant chemotherapy post-pancreatectomy, suggests this new indication of the drug clinically. This revised version was published online in July 2006 with corrections to the Cover Date.     

Role of long-term lamivudine treatment of hepatitis B virus recurrence after liver transplantation

In this study, the long-term (>3 years) efficacy of combination therapy for hepatitis B virus (HBV) recurrence and the associated factors were investigated. One hundred and sixty-five consecutive HBsAg-positive patients (92 with liver cirrhosis, 73 with hepatocellular carcinoma; HCC) who underwent liver transplantation were assessed with a median follow-up time of 40 months. One hundred and twenty-one patients (121/165, 73.3%) were treated with lamivudine before transplantation for a mean of 8.4 months (range 0.1-72 months). The post-transplantation treatment protocol consisted of a high dose intravenous hepatitis B immunoglobulin (HBIg) followed by a low dose intramuscular HBIg and lamivudine combination therapy. Seven (4.2%, 7/165) recipients experienced HBV recurrence at a median time of 19 months (range 5-36 months) following transplantation. Six of seven cases of HBV recurrence were treated with lamivudine before transplantation for a median period of 15 months (range 0.6-30 months). Eighteen (24.6%, 18/73) patients had HCC recurrences after transplantation. Of the four patients with both HCC and HBV recurrence, three experienced HBV recurrence after recurrence of HCC. The clinical factor associated with HBV recurrence in the total cohort (n = 165) was the duration of antiviral treatment (over 6 months) before transplantation (P = 0.004). In the HCC group, HCC recurrence after transplantation (P = 0.002), tumor burden before transplantation (P = 0.005), and postoperative adjuvant chemotherapy (P = 0.002), were additional factors for HBV recurrence. Combination therapy of HBIg and antiviral drugs was effective over 3 years regardless of the pretransplantation viral load. However, the possible recurrence of HBV needs to be monitored cautiously in patients treated with long-term (over 6 months) lamivudine.     

腹腔镜辅助经肛全直肠系膜切除术在低位直肠癌保肛根治术中的应用研究

目的:探讨腹腔镜辅助经肛全直肠系膜切除术（Lap-TaTME）在低位直肠癌保肛根治手术中的安全性、近期临床疗效。方法:回顾性队列研究。纳入2019年4月—2020年8月蚌埠医学院第一附属医院胃肠外科85例行低位直肠癌根治术患者的临床资料,其中男52例、女33例,年龄40~74岁。患者按照手术方式不同分为Lap-TaTM...     

槐耳颗粒联合术后辅助化疗对结直肠癌肝转移预后的影响

目的　探讨肠癌肝转移术后患者运用槐耳颗粒联合辅助化疗的临床疗效。 方法　回顾性分析2012年1月~2017年12月中山大学附属第六医院行根治性切除的结直肠癌肝转移患者128例。根据术后辅助治疗方案不同分为两组,槐耳颗粒联合辅助化疗共72例,为治疗组,单纯辅助化疗56例,为对照组。统计两组患者临床病理资料,包括性别、年龄、术前癌胚抗原（CEA）、术前病理类型及原发肿瘤分期、肝转移瘤大小及数目、化疗完成情况、复发后局部治疗等。随访至2019年11月,使用随访数据计算生存率,并作影响复发和总生存时间的单因素及多因素分析。 结果　实验组围手术期化疗完成率高于对照组,治疗组及对照组术后3、5年总生存率分别为83.5%、60.7%与65.3%、48.2%,差异有显著性（p=0.015）;两组术后3、5年无复发生存率分别为77.8%、53.5%与59.7%、35.7%,差异有显著性（p=0.003）。多因素分析提示术前CEA水平,淋巴结转移,肝转移瘤个数及完成围手术期化疗影响肠癌肝转移患者术后复发;而原发灶合并淋巴结转移,肝转移瘤个数,完成围手术期化疗及槐耳颗粒维持治疗影响患者总生存时间。 结论　结直肠癌肝转移根治术后复发与肿瘤负荷和化疗相关。肝转移瘤单个、无淋巴结转移、以及槐耳颗粒联合辅助化疗的病人可能获得长期生存。