预后营养指数在原发性肝癌肝切除患者预后评估中的价值

目的：评价预后营养指数（PNI）在接受根治性肝切除的原发性肝癌患者预后评估中的意义及价值。方法：回顾性分析西安交通大学第一附属医院肝胆外科2002年12月至2011年12月间接受肝切除的原发性肝癌患者病例及随访资料,根据患者术前的血清白蛋白和总的淋巴细胞计数算出 PNI 值,分析 PNI 与患者临床病理特征及预后的关系。结果：预后危险因素分析显示：PNI 是影响肝癌切除术后患者生存率的独立危险因素（P ＜0．05）,高 PNI 组患者的5年累计生存率为56．20％,而低 PNI 组仅为36．10％,差异显著（P ＝0．01）。分层分析发现在早期肝癌患者中,PNI 亚组间的总体生存存在显著差异（P ＜0．05）,而在晚期患者中差异不明显（P ＞0．05）。结论：PNI 是影响原发性肝癌切除术后患者生存情况的独立危险因素,但对术后肿瘤的复发作用不明显。     

Peritumoral Cbl is a strong independent prognostic marker after curative resection of hepatocellular carcinoma

Growing evidences support the concept that peritumoral microenvironment gene expression is an important element for physicians to make an accurate prognosis. Nonetheless, the correlation between peritumoral ubiquitin ligases and the hepatocellular carcinoma (HCC) survival remains unclear till this present. The expression of intratumoral and peritumoral Casitas B-lineage Lymphoma (cb1) and epidermal growth factor receptor (EGFR) in hepatocellular carcinomas (HCCs) followed by curative resection was assessed by tissue microarray-based immune-histochemistry in two independent cohorts (n = 352). Their respective prognostic values and other clinicopathologic factors were then evaluated. The peritumoral cbl density, much higher than that in intratumoral tissue, was an independent prognostic factor for overall survival (P < 0.001) and time to recurrence (P < 0.001) of HCCs after curative resection. The hazard ratio were 1.587 and 1.689, respectively. However, there was no correlation between intratumoral Cbl and prognosis. The peritumoral Cbl was also associated with prognosis even in HCC subgroups with small tumor size, negative AFP, without microvascular invasion and negative HBeAg. After a thorough analysis pertaining to the key role of Cb1 on ubiquitination and degradation of activated receptor tyrosine kinases, we eventually discovered the negative correlation between peritumoral Cbl and EGFR (P = 0.015). Furthermore, the combination of peritumoral Cbl and EGFR serves as a much stronger indicator to make an accurate prognosis, especially during early recurrence (P < 0.001). These findings suggest that low expression of peritumoral Cbl and EGFR were positively associated with tumor size, microvascular invasion and patients survival after hepatectomy, highlighting the key role of peritumoral liver milieu in HCC progression.     

Thioredoxin reductase: A novel,independent prognostic marker in patients with hepatocellular carcinoma

Here we found that hepatocellular carcinoma (HCC) patients with recurrence outcome and nonsurvivors had significantly increased thioredoxin reductase (TrxR) serum levels on reoperation (P < 0.0001 and P < 0.0001). Multivariate regression analysis adjusted for common risk factors showed that TrxR was an independent predictor of recurrence (hazard ratios [HR] = 4.19; 95% confidence intervals [CI]: 3.21–7.08) and overall survival (HR = 5.56; 95% CI: 3.42–10.21). The area under the receiver operating characteristic curve of TrxR was 0.837 (95% CI, 0.794–0.881) for recurrence outcome and 0.901 (95% CI, 0.869–0.933) for mortality, which was superior to high-sensitivity-C-reactive protein and a-fetoprotein (P < 0.001). The preoperative serum TrxR level is an independent and significant indicator predictive of poor prognosis and early recurrence in patients with HCC, which offering reliable information for predicting survival.     

HIWI is associated with prognosis in patients with hepatocellular carcinoma after curative resection

BACKGROUND:

PIWI protein family was found to play an important role in stem cell self‐renewal. Overexpression of HIWI, the human homolog of PIWI family proteins, was found in several solid tumors, although the role of HIWI in hepatocellular carcinoma (HCC) and its prognostic value remain unclear.

METHODS:

HIWI expression was measured in stepwise metastatic HCC cell lines (HCCLM3, MHCC97H, MHCC97L, SMMC7721, and HepG2), the normal liver cell line (L02), and HCC tissue samples (n = 20). Proliferation and invasion were investigated in HCC cell lines undergoing HIWI target small interfering RNA transfection. Also explored was HIWI expression in HCC tissue microarrays (n = 168) for survival analysis.

RESULTS:

Levels of HIWI protein and mRNA were up‐regulated in highly metastatic HCC cell lines (HCCLM3, MHCC97H, and MHCC97L), whereas their proliferation and invasion significantly decreased after depletion of HIWI. Intratumoral HIWI expression was higher than that of peritumoral tissue (P < .001) and positively associated with proliferating cell nuclear antigen expression (P < .001). Positive expression of intratumoral HIWI was associated with larger tumor size (P = .047) and intrahepatic metastasis (P = .027) and was an independent risk factor for overall survival (P = .007) and recurrence‐free survival (P = .036), particularly in patients with low serum α‐fetoprotein and low Edmondson‐Steiner grade.

CONCLUSIONS:

HIWI may play a key role in HCC proliferation and metastasis and can be a potential prognostic factor for HCC after curative resection, particularly with well‐differentiated HCC. Cancer 2011. © 2011 American Cancer Society.     

MiR-21/miR-375 ratio is an independent prognostic factor in patients with laryngeal squamous cell carcinoma

We sought to identify microRNAs that exhibit altered expression in laryngeal squamous cell carcinoma (SCC) and to determine whether microRNA expression is predictive of disease. This study was divided into three steps: (1) The expression of six miRNAs, such as up-regulated miR-223, miR-142-3p, miR-21, miR-16, miR-23a and down-regulated miR-375, was evaluated using total RNA isolated from freshly-frozen primary tumors and non-cancerous laryngeal squamous epithelial tissues and analyzed using quantitative real-time polymerase chain reaction (qRT-PCR). (2) We also investigated the mRNA expression levels of processing elements (RNASEN, DGCR8, and DICER1) that participate in miRNA-biogenesis pathway. (3) We analyzed the relationships between the expression levels of these miRNAs and the clinicopathologic parameters of laryngeal SCC patients. In this study, we found that: (1) A marked difference in the microRNA expression pattern was observed between tumors and non-cancerous tissue. With regard to miRNA-processing elements, the expression level of RNASEN was higher in laryngeal SCC than in normal epithelium (P<0.01). (2) The miR-21/miR-375 expression ratio was highly sensitive and specific for disease prediction. Kaplan-Meier analysis revealed a significant association between high expression of miR-21/miR-375 in cancerous tissue and a worse prognosis (p=0.032). (3) Furthermore, the expression ratio of miR-21/mir-375 in patients with stage (III-IV) tumors was significantly higher than that in those with stage (I-II) tumors (p=0.006). These data suggest that the pattern of microRNA expression in primary laryngeal SCC tissues is exhibiting strong predictive potential.     

The derived neutrophil to lymphocyte ratio is an independent prognostic factor in patients with diffuse large B-cell lymphoma

Background:

With growing evidence on the role of inflammation in cancer biology, the systemic inflammatory response has been postulated as having prognostic significance in a wide range of different cancer types. Recently, the derived neutrophil to lymphocyte ratio (dNLR) has been proposed as an easily determinable prognostic factor in cancer patients. Nevertheless, its prognostic significance in diffuse large B-cell lymphoma (DLBCL) patients has never been explored.

Methods:

Data from 290 consecutive DLBCL patients, diagnosed between 2004 and 2013 at a single Austrian centre, were evaluated retrospectively. The prognostic influence of the dNLR and other clinico-pathological factors including age, lactate dehydrogenase, cell of origin category and Ann Arbor stage on 5-year overall- (OS) and disease-free (DFS) survival was studied by Kaplan–Meier curves. To evaluate the independent prognostic relevance of dNLR, univariate and multivariate Cox regression models were applied.

Results:

An independent significant association between high dNLR and poor clinical outcome in multivariate analysis for OS (HR=2.02, confidence interval (CI) 95%=1.17–3.50, P=0.011), as well as DFS (HR=2.15, CI 95%=1.04–4.47, P=0.038), was identified.

Conclusion:

In the present study, we showed that a high dNLR at diagnosis of DLBCL represents an independent poor prognostic factor for clinical outcome. Our data encourage the further validation of this easily available parameter in prospective studies and as a potential stratification tool in clinical trials.     

合并门静脉癌栓的原发性肝癌的手术治疗及预后分析

目的:评价手术治疗合并门静脉癌栓(PVTT)的原发性肝癌(PHCC)的疗效和影响患者术后生存的预后因素。方法:对26例在我院行手术治疗的PHCC合并PVTT患者的资料进行回顾性分析并进行随访,计算术后生存率和中位生存时间,单因素分析11项临床病理因素对术后生存时间的影响。结果:手术采用肝癌切除术联合门静脉癌栓摘除术。术后总的1,2,3年生存率为50%,16.7%和8.3%,中位生存时间为13个月。术后定期行门静脉或肝动脉灌注化疗,患者的中位生存时间为16.1个月,而单纯手术者为7.2个月,两者差异有显著性(P=0.001)。单因素分析提示术后是否化疗和肿瘤大小(以10cm为界限)对术后生存有影响。结论:手术治疗可明显提高PHCC合并PVTT患者的生存时间,对没有禁忌证者应为首选。术后是否化疗和肿瘤大小影响术后生存时间,术后应常规进行化疗。     

术中出血400 ml以上是BCLC B期肝癌患者预后不良的独立危险因素

目的 探讨BCLC B期肝癌患者进行手术治疗的预后及危险因素.方法 回顾性分析经手术治疗的805例BCLC A期和B期肝癌患者的临床资料及预后情况,对比BCLC A期及BCLC B期患者的预后差异,应用Kaplan-Meier法及Cox回归法分析BCLC B期患者的生存相关因素,并对相关因素进行危险分级.结果 365例BCLC B期肝癌患者中位随访时间为26.0个月(2.0~135.0个月);中位生存时间为50.8个月,1、3、5年生存率分别为76%、54%和40%;中位无病生存时间为25.8月,1、3、5年无病生存率分别为53%、38%和31%.单因素分析提示脉管瘤栓、肿瘤多发、术中出血≥400 ml为患者总生存时间的预后不良因素;肿瘤多发、术中出血≥400 ml是患者无病生存时间的危险因素.多因素分析显示术中出血≥400 ml是影响BCLC B期患者总生存时间及无病生存时间的独立危险因素.结论 大部分BCLC B期肝癌患者能够从手术治疗中获益,术中出血≥400 ml是提示预后不良的独立危险因素.     

术前外周血中性粒细胞与淋巴细胞比值评估肝细胞癌根治性切除术后预后的临床价值

目的 探讨肝细胞癌(HCC)患者术前外周血中性粒细胞与淋巴细胞的比值(NLR)对根治性切除术后预后评估的临床价值.方法 收集行HCC根治性切除术的161例HCC患者的临床资料,根据患者术前NLR值情况,将患者分为高NLR组(NLR≥2.60,n=52)及低NLR组(NLR﹤2.60,n=109).应用Kaplan-Meier方法分析患者的生存率,并采用Log-rank检验差异;采用Cox回归模型分析影响HCC患者总体生存率的预后因素.结果161例HCC患者的中位随访时间为29个月,高NLR组的1、3、5年总体生存率分别为79.6%、70.8%、41.1%,中位肿瘤复发时间14.9个月;低NLR组的1、3、5年总体生存率分别为90.4%、79.6%、48.7%,中位肿瘤复发时间为20.1个月,高NLR组的1、3、5年总体生存率均低于低NLR组(P﹤0.05),中位肿瘤复发时间短于低NLR组(P﹤0.05);单因素分析结果显示:肿瘤包膜、TNM分期、术前AFP、术前高NLR、淋巴结转移、肿瘤大小与HCC根治性切除术后预后生存时间有关,差异有统计学意义(P﹤0.05);Cox多因素分析结果显示:TNM分期为Ⅲ~Ⅳ期、术前AFP﹤400 ng/ml、术前NLR≥2.60、淋巴结转移、肿瘤大小≥10 mm为影响HCC患者根治性切除术后预后的独立危险因素(P﹤0.001).结论 术前NLR是影响HCC患者根治性切除术后预后的独立危险因素,可作为评估患者预后的指标,术前高NLR者其预后较差.     

18F-Fluorodeoxyglucose positron-emission tomography could have a prognostic role in patients with advanced hepatocellular carcinoma

Introduction

We set out to evaluate the prognostic value of ¹⁸F-fluorodeoxyglucose positron-emission tomography (pet) in patients with advanced (non-transplant-eligible) hepatocellular carcinoma (hcc) and to evaluate the correlation between standardized uptake values (suvs) and survival outcomes.

Methods

We identified patients with hcc who, from 2005 to 2013, underwent pet imaging before any treatment. This retrospective study from our hcc database obtained complete follow-up data for the 63 identified patients.

Results

Of the 63 patients, 10 underwent surgical resection, and 59 underwent locoregional therapy. In this cohort, 28 patients were pet-positive (defined as any lesion with a suv ≥ 4.0) before any therapy was given, and 35 patients were pet negative (all lesions with a suv < 4.0). On survival analysis, median survival was greater for the pet-negative than for the pet-positive patients: 29 months (range: 16.3–41.1 months) versus 12 months (range: 4.0–22.1 months) respectively, p = 0.0241. The pet-positive patients more often had large tumours (≥5 cm), poor differentiation, and extrahepatic disease, reflecting more aggressive tumours. On multivariate analysis, only pet positivity was associated with poor survival (p = 0.049).

Conclusions

Compared with pet-positive patients, pet-negative patients with hcc experienced longer survival. Imaging by pet can be of value in early prognostication for patients with hcc, especially patients receiving locoregional therapy for whom pathologic tumour differentiation is rarely available. This potential role for pet requires further validation in a prospective study.     

术后复发性肝癌的介入治疗疗效分析

目的分析肝动脉化疗栓塞(TACE)治疗术后复发性肝细胞肝癌的生存率及影响因素。方法对行TACE治疗的130例术后复发性肝细胞肝癌患者进行回顾性分析,计算此类患者治疗后的生存率及生存时间,分析影响其生存的相关因素。结果全组130例总的1,3,5年生存率为83.0%、45.5%和17.6%,中位生存时间2.4年。单纯TACE治疗94例,其1,3年生存率分别为76.4%和37.1%,中位生存期2.1年;TACE联合瘤内无水酒精注射(PEI)治疗36例,1,3年生存率分别为100.0%和66.5%,中位生存期为3.5年。TACE联合PEI治疗组的生存率和生存期均显著优于单纯TACE治疗组(P<0.05),死亡风险显著低于单纯TACE治疗组(P<0.05);复发瘤直径>5cm和有远处转移者的死亡风险,显著高于肿瘤直径≤5cm和无远处转移者(P<0.05)。结论TACE联合PEI治疗,可显著提高术后复发性肝癌患者的生存率,延长生存期。     

Extent of hepatic resection as a prognostic factor for small,solitary hepatocellular carcinomas

The prognostic factors for solitary hepatocellular carcinomas with a maximum tumor diameter of ?3 cm were investigated in 59 of 231 patients who underwent curative hepatic resections at the Department of Surgery II, Nagoya University Hospital between January 1981 and December 1991. The 3- and 5-year survival rates of these 59 patients were 61% and 41%, respectively. As prognostic factors, tumor maximum diameter, vascular invasion, capsule formation, cell differentiation, tumor localization, hepatic functional reserve, extent of hepatic resection, and macroscopic surgical margin were selected in this study. Of the patients with a tumor size > 1.5 cm, those who underwent major hepatic resections (hepatic lobectomy or segmentectomy) tended to have better survival than patients who received minor hepatic resections (hepatic subsegmentectomy or limited resection). Although most patients with a tumor size ?1.5 cm underwent minor hepatic resections, they had a good survival rate. According to Cox's multivariate analysis, the extent of hepatic resection was significantly correlated with long-term prognosis of patients with a solitary hepatocellular carcinoma ?3 cm in diameter, but the macroscopic surgical margin was not. Cell differentiation, vascular invasion, capsule formation, and tumor localization were all correlated with the long survival. These results suggest that the selection of an adequate operative procedure is an important factor for the long-term prognosis of patients with small, solitary hepatocellular carcinomas. © 1993 Wiley-Liss, Inc.     

Elevated preoperative neutrophil to lymphocyte ratio predicts survival following hepatic resection for colorectal liver metastases

Background

The neutrophil–lymphocyte ratio (NLR) provides an indicator of inflammatory status. An elevated NLR has been shown to be a prognostic indicator in primary colorectal malignancy. The aim of this study was to establish whether NLR predicts outcome in patients undergoing resection for colorectal liver metastasis.

Design

Retrospective analysis of the white cell and differential counts for 440 patients undergoing liver resections for colorectal liver metastasis between January 1996 and January 2006. An NLR ≥ 5 was considered to be elevated.

Results

Two hundred and eighty-nine males and 151 females were included. Seventy-eight patients (18%) had an elevated NLR, 55 of whom died, giving elevated NLR a positive predictive value (PPV) for death of 71%. Sixty of the 78 patients had recurrent disease giving raised NLR an PPV for recurrence of 78%. The 5-year survival for patients undergoing resection with high NLR was significantly worse than that for patients with normal NLR (22% vs. 43%, p < 0.0001). Univariate analysis of factors affecting survival revealed raised NLR, number of metastases >8, tumour size >5 cm and age >70 significantly affected outcome. All factors except tumour size remained significant predictors of term survival on multivariate analysis (NLR:HR = 2.261, CI = 1.654–3.129, p < 0.0001, metastases >8:HR = 1.611, CI = 1.006–2.579, p = 0.047, age >70:HR = 1.418, CI = 1.049–1.930, p = 0.027). Elevated NLR was found to be the sole positive predictor of recurrence on univariate analysis (HR = 4.521, CI = 2.475–8.257, p < 0.0001).

Conclusion

Elevated NLR increases both risk of death and the risk of recurrence in patients who undergo surgery for CRLM. Preoperative NLR measurement may therefore provide a simple method of identifying patients with a poorer prognosis.     

A novel, externally validated inflammation-based prognostic algorithm in hepatocellular carcinoma: the prognostic nutritional index (PNI)

Background:

There is increasing evidence that the presence of an ongoing systemic inflammatory response is a stage-independent predictor of poor outcome in patients with cancer. The aim of this study was to investigate whether an inflammation-based prognostic score, the prognostic nutritional index (PNI), is associated with overall survival (OS) in patients with hepatocellular carcinoma (HCC).

Methods:

All patients with a new diagnosis of HCC presenting to the Medical Oncology Department, Hammersmith Hospital between 1993 and 2011 (n=112) were included. Demographic and clinical data were collected. Patients in whom the combined albumin (g l⁻¹) × total lymphocyte count × 10⁹ l⁻¹ was ⩾45, at presentation, were allocated a PNI score of 0. Patients in whom this total score was <45 were allocated a score of 1. Univariate and multivariate analyses were performed to identify clinicopathological variables associated with OS. Independent predictors of survival identified on multivariate analysis were validated in an independent, stage-matched cohort of 68 patients.

Results:

Univariate analyses showed that PNI (P=0.003), intrahepatic spread (P<0.001), the presence of extrahepatic disease (P=0.006), portal vein thrombosis (P=0.02), tumour multifocality (P=0.003), alfa-fetoprotein >400 ng ml⁻¹ (P<0.001) and Barcelona Clinic Liver Cancer score (P<0.01) were all predictors of OS in the training set. Multivariate analysis revealed the PNI (P=0.05), presence of extrahepatic disease (P<0.001) and degree of intrahepatic spread (P<0.001) as independent predictors of worse OS in this population. The PNI retained independent prognostic value in the validation set (P<0.001).

Conclusion:

The presence of a systemic inflammatory response, as measured by the PNI, is an independent and externally validated predictor of poor OS in patients with HCC.     

Smoking as an independent risk factor for hepatocellular carcinoma: the Singapore Chinese Health Study

Background:

Given the close correlation between smoking and alcohol intake in most epidemiologic studies, it is difficult to exclude the residual confounding effect of alcohol in the association between smoking and hepatocellular carcinoma (HCC).

Method:

We evaluated the association between smoking and risk of HCC in the Singapore Chinese Health Study, a prospective cohort with a low prevalence of alcohol intake. Information on cigarette smoking and alcohol consumption was obtained through in-person interviews conducted at enrolment.

Results:

After a mean of 11.5 years of follow-up, there were 394 incident cases of HCC. Participants who consumed more than two alcoholic drinks per day showed an increased risk for HCC (hazard ratio (HR)=2.24; 95% confidence interval (CI)=1.46–3.41). After adjusting for alcohol consumption and other potential confounders, current vs never smokers had a statistically significant, increased risk of HCC (HR=1.63; 95% CI=1.27–2.10) that was dose-dependent (number of cigarettes per day, P for trend<0.001). The observed tobacco–HCC association also was duration-dependent (years of smoking in ever smokers, P for trend=0.002). When we excluded daily drinkers from the analysis, all risk estimates remained essentially the same and statistically significant.

Conclusion:

Our findings strongly implicate tobacco smoke as a causal factor of HCC development.     

Age as an independent prognostic factor for survival of localised synovial sarcoma patients

Background:

We performed a retrospective nationwide study to explore age as a prognostic factor in synovial sarcoma patients.

Methods:

Data on 613 synovial sarcoma patients were obtained from the Netherlands Cancer Registry. The prognostic relevance of age groups (children, adolescent and young adults (AYAs), adults, and elderly) was estimated by Kaplan–Meier survival curves and multivariable Cox-proportional hazards modelling.

Results:

A total of 461 patients had localised disease at diagnosis. The 5-year overall survival (OS) was 89.3±4.6%, 73.0±3.8%, 54.7±3.6%, and 43.0±7.0% in children (n=54), AYAs (n=148), adults (n=204), and elderly (n=55), respectively. Treatment modalities had no significant effect on survival in the univariable analysis. Multivariable analysis identified age at diagnosis, tumour localisation, and tumour size as significant factors affecting OS. Both tumour localisation and size were equally distributed over the age groups.

Conclusions:

We show that outcome of synovial sarcoma patients significantly decreases with age regardless of primary tumour site, size, and treatment.     

Identification of the resection severity index as a significant independent prognostic factor for early mortality and observed survival >5 and >10 years after liver resection for hepatocellular carcinoma

Background and objectives

This study evaluates predictive factors for observed long-term survival of more than 5 and 10 years for patients after liver resection for hepatocellular carcinoma and compares their life expectancy to the normal national population matched for sex, year of birth and age at resection.

肝癌切除术中肝动脉留置化疗泵的临床意义

目的　探讨肝癌切除术中肝动脉留置化疗泵对复发的监测、预防和治疗价值。方法　 3 4例行肝癌根治性切除者 ,术中肝动脉留置化疗泵 ,定期经化疗泵肝动脉灌注化疗和CO2 超声造影。结果　 1)直径≤ 3cm 2 4个肝癌复发灶 ,CO2 超声造影检出率 95 .8% ,而常规超声为 5 0 % (P <0 .0 1)。 2 ) 2 0例单纯肝切除和 3 4例肝切除加肝动脉化疗者 ,其1、3年的复发率分别是 40 %、75 %和 2 9.4%、64 .7% (P <0 .0 5 ) ,1、3年的生存率分别是 70 %、3 0 %和 91.2 %、47.1% (P<0 .0 5 )。结论　肝癌术中肝动脉留置化疗泵 ,术后行肝动脉CO2 超声造影和化疗对于复发的监测、预防和治疗具有重要价值。