Hepatocellular carcinoma recurrence after liver transplantation: Risk factors, screening and clinical presentation

Liver transplantation is the best treatment option for cirrhotic patients with earlystage hepatocellular carcinoma, but it faces the problem of scarcity of donors and the risk of tumor recurrence, which affects between 15% and 20% of the cases,despite the use of restrictive criteria. The risk of recurrence depends on a number of factors, related to the tumor, the patient, and the treatment, which are discussed in this review. Some of these factors are already well established, such as the histopathological characteristics of the tumor, Alpha-fetoprotein(AFP)levels, and waiting time. Other factors related to the biological behavior of the tumor and treatment should be recognized because they can be used in the refinement of the selection criteria of transplant candidates and in an attempt to reduce recurrence. This review also discusses the clinical presentation of recurrence and its prognosis, contributing to the identification of a subgroup of patients who may have better survival, if they are timely identified and treated.Development of recurrence after the first year, with AFP levels ≤ 100 ng/mL, and single site capable of locoregional therapy are associated with better survival after recurrence.

Computed tomography-based radiomics to predict early recurrence of hepatocellular carcinoma post-hepatectomy in patients background on cirrhosis

BACKGROUND The prognosis for hepatocellular carcinoma(HCC)in the presence of cirrhosis is unfavourable,primarily attributable to the high incidence of recurrence.AIM To develop a machine learning model for predicting early recurrence(ER)of posthepatectomy HCC in patients with cirrhosis and to stratify patients’overall survival(OS)based on the predicted risk of recurrence.METHODS In this retrospective study,214 HCC patients with cirrhosis who underwent curative hepatectomy were examined.Radiomics feature selection was conducted using the least absolute shrinkage and selection operator and recursive feature elimination methods.Clinical-radiologic features were selected through univariate and multivariate logistic regression analyses.Five machine learning methods were used for model comparison,aiming to identify the optimal model.The model’s performance was evaluated using the receiver operating characteristic curve[area under the curve(AUC)],calibration,and decision curve analysis.Additionally,the Kaplan-Meier(K-M)curve was used to evaluate the stratification effect of the model on patient OS.RESULTS Within this study,the most effective predictive performance for ER of post-hepatectomy HCC in the background of cirrhosis was demonstrated by a model that integrated radiomics features and clinical-radiologic features.In the training cohort,this model attained an AUC of 0.844,while in the validation cohort,it achieved a value of 0.790.The K-M curves illustrated that the combined model not only facilitated risk stratification but also exhibited significant discriminatory ability concerning patients’OS.CONCLUSION The combined model,integrating both radiomics and clinical-radiologic characteristics,exhibited excellent performance in HCC with cirrhosis.The K-M curves assessing OS revealed statistically significant differences.

Development of a machine learning-based model for predicting risk of early postoperative recurrence of hepatocellular carcinoma

BACKGROUND Surgical resection is the primary treatment for hepatocellular carcinoma(HCC).However,studies indicate that nearly 70%of patients experience HCC recurrence within five years following hepatectomy.The earlier the recurrence,the worse the prognosis.Current studies on postoperative recurrence primarily rely on postoperative pathology and patient clinical data,which are lagging.Hence,developing a new pre-operative prediction model for postoperative recurrence is crucial for guiding individualized treatment of HCC patients and enhancing their prognosis.AIM To identify key variables in pre-operative clinical and imaging data using machine learning algorithms to construct multiple risk prediction models for early postoperative recurrence of HCC.METHODS The demographic and clinical data of 371 HCC patients were collected for this retrospective study.These data were randomly divided into training and test sets at a ratio of 8:2.The training set was analyzed,and key feature variables with predictive value for early HCC recurrence were selected to construct six different machine learning prediction models.Each model was evaluated,and the bestperforming model was selected for interpreting the importance of each variable.Finally,an online calculator based on the model was generated for daily clinical practice.RESULTS Following machine learning analysis,eight key feature variables(age,intratumoral arteries,alpha-fetoprotein,preoperative blood glucose,number of tumors,glucose-to-lymphocyte ratio,liver cirrhosis,and pre-operative platelets)were selected to construct six different prediction models.The XGBoost model outperformed other models,with the area under the receiver operating characteristic curve in the training,validation,and test datasets being 0.993(95%confidence interval:0.982-1.000),0.734(0.601-0.867),and 0.706(0.585-0.827),respectively.Calibration curve and decision curve analysis indicated that the XGBoost model also had good predictive performance and clinical application value.CONCLUSION The XGBoost model exhibits superior performance and is a reliable tool for predicting early postoperative HCC recurrence.This model may guide surgical strategies and postoperative individualized medicine.

Assessing recent recurrence after hepatectomy for hepatitis Brelated hepatocellular carcinoma by a predictive model based on sarcopenia

BACKGROUND Sarcopenia may be associated with hepatocellular carcinoma(HCC)following hepatectomy.But traditional single clinical variables are still insufficient to predict recurrence.We still lack effective prediction models for recent recurrence(time to recurrence<2 years)after hepatectomy for HCC.AIM To establish an interventable prediction model to estimate recurrence-free survival(RFS)after hepatectomy for HCC based on sarcopenia.METHODS We retrospectively analyzed 283 hepatitis B-related HCC patients who underwent curative hepatectomy for the first time,and the skeletal muscle index at the third lumbar spine was measured by preoperative computed tomography.94 of these patients were enrolled for external validation.Cox multivariate analysis was per-formed to identify the risk factors of postoperative recurrence in training cohort.A nomogram model was developed to predict the RFS of HCC patients,and its predictive performance was validated.The predictive efficacy of this model was evaluated using the receiver operating characteristic curve.RESULTS Multivariate analysis showed that sarcopenia[Hazard ratio(HR)=1.767,95%CI:1.166-2.678,P<0.05],alpha-fetoprotein≥40 ng/mL(HR=1.984,95%CI:1.307-3.011,P<0.05),the maximum diameter of tumor>5 cm(HR=2.222,95%CI:1.285-3.842,P<0.05),and hepatitis B virus DNA level≥2000 IU/mL(HR=2.1,95%CI:1.407-3.135,P<0.05)were independent risk factors associated with postoperative recurrence of HCC.Based on the sarcopenia to assess the RFS model of hepatectomy with hepatitis B-related liver cancer disease(SAMD)was established combined with other the above risk factors.The area under the curve of the SAMD model was 0.782(95%CI:0.705-0.858)in the training cohort(sensitivity 81%,specificity 63%)and 0.773(95%CI:0.707-0.838)in the validation cohort.Besides,a SAMD score≥110 was better to distinguish the high-risk group of postoperative recurrence of HCC.CONCLUSION Sarcopenia is associated with recent recurrence after hepatectomy for hepatitis B-related HCC.A nutritional status-based prediction model is first established for postoperative recurrence of hepatitis B-related HCC,which is superior to other models and contributes to prognosis prediction.

Risk factors associated with early and late recurrence after curative resection of hepatocellular carcinoma: a single institution's experience with 398 consecutive patients

BACKGROUND: Surgical resection is an important curative treatment for hepatocellular carcinoma (HCC); however, some patients experience an unexpected recurrence even after hepatectomy. The present study aimed to investigate risk factors and predictive criteria for early and late recurrence of HCC after resection.METHODS: A retrospective analysis of 398 Chinese patients who received curative resection for HCC was conducted. Patients were divided into three groups: without recurrence, early recurrence and late recurrence. Prognostic factors and predictive criteria for early and late recurrence were statistically analyzed. RESULTS: The cumulative recurrence-free survival rates at1, 2, 3, 4, and 5 years were 75.5%, 58.2%, 54.1%, 40.5%, and28.7%, respectively. The distribution of the time to recurrence suggested that recurrence could be divided into early phase(before 2 years; n=164) and late phase (after 2 years; n=83)Cox’s multivariate proportional hazard model analysis revealed that multiplicity of tumors (P=0.004) and venous infiltration(P=0.002) were independent risk factors associated with early recurrence. In contrast, indocyanine green retention rate at 15minutes (P=0.007), serum albumin level (P=0.045), and HBeAg status ( =0.028) proved to be significant independent adverse prognostic factors for late recurrence. Patients with at least 1of the 2 early recurrence risk factors (multiplicity of tumors ≥2and venous infiltration) or with 2 or more late recurrence risk factors are often susceptible to recurrence (P=1.36e-4 and 1.0e-6respectively).CONCLUSIONS: Early and late recurrences correlate with different risk factors and predictive criteria. Early recurrence primarily results from intrahepatic metastases, while late recurrence may be multicentric in origin.

Clinical analysis of the risk factors for recurrence of HCC and its relationship with HBV

AIM: To comprehend the risk factors of recurrence of hepatocellular carcinoma (HCC) and its relationship with the infection patterns of hepatitis B virus (HBV). METHODS: All materials of 270 cases of postoperative HCC were statistically analyzed by SPSS software. Recurrence and metastasis were classified into early (≤2 years) and late phase (＞2 years). Risk factors for recurrence and metastasis after surgery in each group were analyzed.RESULTS: Out of 270 cases of HCC, 162 cases were followed up in which recurrence and metastasis occurred in 136 cases. There were a lot of risk factors related to recurrence and metastasis of HCC; risk factors contributing to early phase recurrence were serum AFP level, vascular invasion, incisal margin and operative transfusion, gross tumor classification and number of intrahepatic node to late phase recurrence. The HBV infective rate of recurrent HCC was 94.1%, in which 'HBsAg, HBeAb, HBcAb' positive pattern reached 45.6%. The proportion of HBV infection in solitary large hepatocellular carcinoma (SLHCC) evidently decreased compared to nodular hepatocellular carcinoma (NHCC) (P＜0.05).CONCLUSION: The early and late recurrence and metastasis after hepatectomy of HCC were associated with different risk factors. The early recurrence may be mediated by vascular invasion and remnant lesion, the late recurrence by tumor's clinical pathology propert, as multicentric carcinogenesis or intrahepatic carcinoma denovo. HBV replication takes a great role in this process. From this study, we found that SLHCC has more satisfactory neoplasm biological behavior than NHCC.

Risk factors for early recurrence of small hepatocellular carcinoma after curative resection

BACKGROUND: Poorer prognosis is seen in patients with hepatocellular carcinoma (HCC) after curative hepatic resection with early recurrence (<= 1 year) than in those with late recurrence (>1 year). This study aimed to identify risk factors for postoperative early recurrence of small HCC (<= 3 cm in diameter). METHODS: The study population consisted of 158 patients who underwent curative resection for small HCC between January 2002 and July 2004. Risk factors for early recurrence were analyzed. RESULTS: Thirty-three (20.8%) patients developed early recurrence after surgery. Univariate analysis showed the following significant risk factors for early recurrence in small HCC: serum alpha-fetoprotein (AFP) level >100 ng/ml, lack of tumor capsule formation, microscopic vascular invasion, high Edmonson-Steiner grades, and cytokeratin-19 (CK-19) expression (P<0.05). Multivariate stepwise logistic regression analysis showed that serum AFP level >100 ng/ml (odds ratio 2.561, 95% confidence interval 1.057 to 6.206, P=0.037) and microscopic vascular invasion (odds ratio 4.549, 95% confidence interval 1.865 to 11.097, P=0.001) were independent factors. CONCLUSIONS: Postoperative early recurrence is related to serum AFP level >100 ng/ml and microscopic vascular invasion in patients with small HCC. Adjuvant therapy and careful follow-up are required for patients with these risk factors.

Clinicopathologic risk factors and prognostic evaluation in hepatocellular carcinoma recurrence after surgery

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Risk factors for immediate post-operative fatal recurrence after curative resection of hepatocellular carcinoma

瞄准：调查 clinicopathological 风险因素因为肝细胞癌(HCC ) 的立即的手术后的致命的复发，它可以有实际牵连并且贡献高建立对 HCC 复发为外科手术前或手术后的预防措施冒病人的风险。方法：从 1994 年 6 月到 2004 年 5 月，为 HCC 收到了药品切除术的 269 个病人被考察。这些病人，在外科以后在 6 瞬间以内表明了弥漫的 intra 肝或多重的全身的周期性的损害的那些被调查(致命的复发组) 。留下的病人被指定为控制组，并且二个组为临床病理风险因素被比较。结果：在考察的 269 个病人之中， 30 个病人在致命的复发组被注册。在后者之中， 20 个病人证明弥漫的 intra 肝的复发类型和 10 显示出的多重全身的复发打字。在致命的复发组和控制组之间的 Multivariate 分析证明那外科手术前的浆液 alpha-fetoprotein (法新社) 水平比 1,000 microg/L 大(P = 0.02；机会比率 = 2.98 ) ，比 6.5 厘米大的肿瘤尺寸(P = 0.03；或 = 2.98 ) ，并且微脉管的侵略的存在(P = 0.01；或 = 4.89 ) 是在致命的复发组的风险因素。有所有三个风险因素的 48.1% 病人和有二个风险因素的 22% 那些在外科以后在 6 瞬间以内经历了致命的复发。结论：为在药品切除术以后的 HCC 的立即的手术后的致命的复发的三个不同风险因素是外科手术前的浆液法新社水平 】 1,000 microg/L，肿瘤尺寸 】 6.5 厘米，和微脉管的侵略。有二的高风险病人或更多的风险因素应该是各种各样的辅助临床的试用的候选人。

Predictors of Recurrence of Hepatocellular Carcinoma after Transarterial Chemoembolization: Role of Hepatocyte Growth Factor

Background: Hepatocellular carcinoma is the third leading cause of tumor related mortality and develops mostly in patients with chronic liver disease and liver cirrhosis. Human hepatocyte growth factor (HGF) is produced in various organs of the body and is characterized as a multifunctional factor with various biologic activities. Aim: Our aim was to investigate the predictive factors of recurrence specially the role of HGF in patients with HCC treated with TACE. Patients and Methods: one hundred HCC patients treated by TACE who achieved complete response were included and divided into two groups according to disease free survival (DFS) status at 1 year: the non-early recurrence (NER) group (1) and the early recurrence (ER) group (2). Univariate binary logistic regression analysis for the possible risk factors of recurrence showed that AFP, multinodularity and HGF level were significant. Conclusion: high AFP, multinodularity and high HGF were inter-related possible risk factors for 1-year recurrence of HCC in patients with initial remission following TACE.

Diabetes mellitus: a “true” independent risk factor for hepatocellular carcinoma?

BACKGROUND:Diabetes mellitus(DM)is thought to be associated with an increased risk of hepatocellular carcinoma(HCC)in some published studies.However,can we draw the conclusion that DM is a'true'independent risk factor for HCC based on these references? DATA SOURCES:MEDLINE and PubMed searches were conducted for published studies(between January 1966 and June 2009)to identify relevant articles using the keywords 'diabetes','insulin resistance'and'hepatocellular carcinoma',including'primary liver cancer'.Because of the very limited number of relevant articles most were reviewed. RESULTS:This systematic review was conducted from 4 aspects:(1)the significant synergy between DM,hepatitis virus infection,and heavy alcohol consumption in HCC; (2)the role of DM independently in HCC cases while other identified risk factors were controlled or excluded; (3)obesity,DM,and nonalcoholic fatty liver disease in HCC patients;and(4)the impact of DM for the prognosis or surgical treatment in HCC patients with DM.No consensus has been reached among these studies and it is too early to draw the conclusion that DM is a'true' independent risk factor for HCC. CONCLUSIONS:DM can be regarded as a risk factor for HCC.However,whether DM itself directly predisposes to HCC or whether it is a'true'independent risk factor remains unclear.Related issues should be clarified by more research.

Hepatocellular carcinoma: Epidemiology, risk factors and pathogenesis

Hepatocellular carcinoma (HCC) is the commonest primary malignant cancer of the liver in the world. Given that the burden of chronic liver disease is expected to rise owing to increasing rates of alcoholism, hepatitis B and C prevalence and obesity-related fatty liver disease, it is expected that the incidence of HCC will also increase in the foreseeable future. This article summarizes the international epidemiology, the risk factors and the pathogenesis of HCC, including the roles of viral hepatitis, toxins, such as alcohol and aflatoxin, and insulin resistance.

Evaluation of prognostic factors on recurrence after curative resections for hepatocellular carcinoma

AIM:To select appropriate patients before surgical resection for hepatocellular carcinoma(HCC),especially those with advanced tumors.METHODS:From January 2000 to December 2012,we retrospectively analyzed the medical records of 298 patients who had undergone surgical resections for HCC with curative intent at our hospital.We evaluated preoperative prognostic factors associated with histologic grade of tumor,recurrence and survival,especially the findings of pre-operative imaging studies such as positron emission tomography-computed tomography(PETCT)and magnetic resonance imaging(MRI).And then,we established a scoring system to predict recurrence and survival after surgery dividing the patients into two groups based on a tumor size of 5 cm.RESULTS:Of the 298 patients,129(43.3%)developed recurrence during the follow-up period.The 5 year disease free survival and overall survival were 47.0%and58.7%respectively.In multivariate analysis,a serum alpha-fetoprotein(AFP)level of>100 ng/m L and a standardized uptake value(SUV)of PET-CT of>3.5 were predictive factors for histologic grade of tumor,recurrence,and survival.Tumor size of>5 cm and a relative enhancement ratio(RER)calculated from preoperative MRI were also significantly associated with prognosis in univariate analysis.We established a scoring system to predict prognosis using AFP,SUV,and RER.In those with tumors of>5 cm,it showed predicted both recurrence(P=0.005)and survival(P=0.001).CONCLUSION:The AFP,tumor size,SUV and RER are useful for prognosis preoperatively.An accurate prediction of prognosis is possible using our scoring system in large size tumors.

Hepatocellular Carcinoma: Risk Factors, Diagnosis, Staging and Treatment in a Referral Centre

Introduction: Hepatocellular carcinoma is the most common primary neoplasm of the liver and a significant cause of mortality in patients with cirrhosis. A retrospective cross-sectional study was performed to analyze epidemiological aspects related to risk factors, diagnosis, staging and first-line treatment in a closed population. Methods: The medical records of patients seen between November 1998 and May 2011 were revisited. Results: Of the 272 patients included in this study, 229 (84.2%) were male and the average age was 57.1 years (standard deviation 10.9 years). The most common etiology was hepatitis C virus infection in 145 (55.1%) patients, with this being the single cause in 88 (33.4%) patients. The largest masses ranged from 6 mm to 260 mm in diameter with a mean of 61.4 mm (standard deviation 41.5 mm). Only one mass was found in 145 (64.2%) cases, two masses in 26 (11.5%), three masses in 9 (4%) and 46 patients (20.3%) had multifocal disease. Early stage disease was diagnosed in 47 patients (22.0%), advanced stage in 65 (30.4%) and terminal stage in 32 (14.9%). Hepatocellular carcinoma was found by chance in 11%. Diagnosis was by means of imaging in 175 (68.1%) cases. The level of alpha-fetoprotein was measured in 209 patients, with 29.2% having levels lower than 20 ng/mL and 34.9% having levels above 400 ng/mL. Specific treatment was administered in 236 patients (86.8%) with hepatic chemoembolization in 127 (46.7%) and liver transplantation in 72 (26.5%);of these 33 (45.8%) received hepatic chemoembolization as a bridge to transplantation. Thirty-four patients (12.5%) received only supportive therapy. Conclusions: Patients are chiefly male and disease involvement generally occurs in the 5th decade of life. Cirrhosis was present in most patients and hepatitis C virus infection was the commonest etiologic agent. Only one imaging examination was required for diagnosis in most patients. The measurement of alpha-fetoprotein levels did not prove to be a good tool in the diagnosis of hepatocellular carcinoma. Intermediate, advanced and terminal stages predominated compared to early stages. Treatment was based on non-curative therapies.

Viral Genotypes and Associated Risk Factors of Hepatocellular Carcinoma in India

Objective This study aims to investigate the etiological relationship among hepatitis B virus(HBV),hepatitis C virus(HCV),and alcohol as risk factors in a cohort of hepatocellular carcinoma(HCC) patients from India.The clinical and biochemical profiles and tumor characteristics in the HCC cases were also evaluated. Methods A total of 357 consecutive cases of HCC fulfilling the diagnostic criteria from the Barcelona-2000 EASL conference were included in the study.The blood samples were evaluated for serological evidence of HBV and HCV infection,viral load,and genotypes using serological tests,reverse transcription-polymerase chain reaction,and restriction fragment length polymorphism. Results The male/female ratio for the HCC cases was 5.87:1.Majority of the HCC patients(33.9% ) were 50 to 59 years of age,with a mean age of 4±13.23 years.More than half the cases(60.8% ) had underlying cirrhosis at presentation.Among the HCC patients,68.9% were HBV related,21.3% were HCV related,18.8% were alcoholic,and 18.2% were of cryptogenic origin.The presence of any marker positive for HBV increased the risk for developing HCC by almost 27 times[OR:27.33;(12.87-60.0)].An increased risk of 10.6 times was observed for HCC development for cases positive for any HCV marker[OR:10.55;(3.13-42.73)].Heavy alcohol consumption along with HCV RNA positivity in cirrhotic patients was found to be a risk for developing HCC by 3 folds[OR:3.17;(0.37-70.71)]. Conclusions Patients of chronic HBV infection followed by chronic HCV infection were at higher risk of developing HCC in India. Chronic alcohol consumption was found to be a risk factor in cirrhotic cases only when it was associated with HCV RNA positivity. Most of the patients had a large tumor size(>5 cm) with multiple liver nodules,indicating an advanced stage of the disease thus making curative therapies difficult.

Differences in characteristics of patients with and without known risk factors for hepatocellular carcinoma in the United States

AIM: To examine the clinical characteristics of a subgroup of patients with hepatocellular carcinoma (HCC) and compare them to those with known risk factors.METHODS: We used the HCC database of 306 patients seen at our institution from January 1, 1995 to December 31, 2001. Of the 306 patients, 63 (20%, group 1) had no known risk factors (hepatitis C virus, hepatitis B virus, alcohol, hemochromatosis or cirrhosis from any cause) and 243 (group 2) had one or more risk factors.RESULTS: The median age was similar in both groups, but there were disproportionate numbers of younger (< 30 years old), older (> 80 years) patients, women (33% vs 18%), and Caucasians (81% vs 52%) in group 1 as compared to group 2. There were fewer Asians (2% vs 11%) and African Americans (13% vs 27%) in group 1. Abdominal pain (70% vs 37%) was more common while gastrointestinal bleeding (0% vs 11%) and ascites (4% vs 17%) were less common in group 1 compared to group 2. Group 1 had larger tumor burden (median size 9.4 cm vs 5.7 cm) at the time of presentation, but there were no differences in the site (right, left or bilateral lesions), or number of tumors between the two groups.CONCLUSION: HCC patients without identifiable risk factors have different characteristics and clinical presentation compared to those with known risk factors.Absence of cirrhosis and larger tumor burden may explain the differences in the presenting symptoms.

Predictors of disease recurrence after radical resection and adjuvant chemotherapy in patients with stage IIb-IIIa squamous cell lung cancer:A retrospective analysis

BACKGROUND Lung cancer(LC)is a global medical,social and economic problem and is one of the most common cancers and the leading cause of mortality from malignant neoplasms.LC is characterized by an aggressive course,and in the presence of disease recurrence risk factors,patients,even at an early stage,may be indicated for adjuvant therapy to improve survival.However,combined treatment does not always guarantee a favorable prognosis.In this regard,establishing predictors of LC recurrence is highly important both for determining the optimal treatment plan for the patients and for evaluating its effectiveness.AIM To establish predictors of disease recurrence after radical resection and adjuvant chemotherapy in patients with stage IIb-IIIa lung squamous cell carcinoma(LSCC).METHODS A retrospective case-control cohort study included 69 patients with LSCC who underwent radical surgery at the Orenburg Regional Clinical Oncology Center from 2009 to 2018.Postoperatively,all patients received adjuvant chemotherapy.Histological samples of the resected lung were stained with Mayer's hematoxylin and eosin and examined under a light microscope.Univariate and multivariate analyses were used to identify predictors associated with the risk of disease recurrence.Receiver operating characteristic curves were constructed to discriminate between patients with a high risk of disease recurrence and those with a low risk of disease recurrence.Survival was analyzed using the Kaplan-Meier method.The log-rank test was used to compare survival curves between patient subgroups.Differences were considered to be significant at P<0.05.RESULTS The following predictors of a high risk of disease recurrence in patients with stage IIb-IIa LSCC were established:a low degree of tumor differentiation[odds ratio(OR)=7.94,95%CI=1.08-135.81,P=0.049];metastases in regional lymph nodes(OR=5.67,95%CI=1.09-36.54,P=0.048);the presence of loose,fine-fiber connective tissue in the tumor stroma(OR=21.70,95%CI=4.27-110.38,P=0.0002);and fragmentation of the tumor solid component(OR=2.53,95%CI=1.01-12.23,P=0.049).The area under the curve of the predictive model was 0.846(95%CI=0.73-0.96,P<0.0001).The sensitivity,accuracy and specificity of the method were 91.8%,86.9%and 75.0%,respectively.In the group of patients with a low risk of LSCC recurrence,the 1-,2-and 5-year disease-free survival(DFS)rates were 84.2%,84.2%and 75.8%,respectively,while in the group with a high risk of LSCC recurrence the DFS rates were 71.7%,40.1%and 8.2%,respectively(P<0.00001).Accordingly,in the first group of patients,the 1-,2-and 5-year overall survival(OS)rates were 94.7%,82.5%and 82.5%,respectively,while in the second group of patients,the OS rates were 89.8%,80.1%and 10.3%,respectively(P<0.00001).CONCLUSION The developed method allows us to identify a group of patients at high risk of disease recurrence and to adjust to ongoing treatment.

Expression of Cyclooxygenase-2 and Transforming Growth Factor-Beta 1 in Patients with the Early Recurrence of Hepatocellular Carcinoma Following Hepatectomy

Background: Cyclooxygenase-2 (COX-2) and transforming growth factor-beta1 (TGF-β1) are modulated in variety cancers including Hepatocellular carcinoma (HCC). However, there is a paucity of data concerning their role in the pathologic process of recurrence of HCC following hepatectomy. We herein assessed the role of the hepatic expression of COX-2 and TGF-β as predictors for patients with early recurrence within 2 years of HCC diagnosis. Methods: Sixty patients with HCC who underwent curative hepatectomy between 2000 and 2003 were entered in the present study. The immunoreactivity and distribution patterns of COX-2 and TGF-β1 were examined in both the HCC and the adjacent nonHCC tissues of the liver. Risk factors of tumor recurrence within 2 years, including COX-2 and TGF-β1 expression, were investigated by univariate and multivariate analyses. Results: Among 60 patients, 31 patients had early recurrences within 2 years and 14 patients recurred after 2 years following surgery. Patients with low COX-2 expression in the HCC tissues and adjacent nonHCC tissues had favorable disease-free survival (p = 0.002 and p β1 expression in the nonHCC tissues had also longer disease-free survival (p = 0.045). Based on the expression patterns of COX-2 and TGF-β1, patients with low COX-2 and positive TGF-β1 expression in the nonHCC tissues had favorable overall and disease-free survival (p β1 signaling in nontumor tissues suggested high risk of recurrence and poor survival to the HCC patients following hepatectomy.

Patients with early recurrence of hepatocellular carcinoma have poor prognosis

BACKGROUND： Early recurrence （ER） after hepatic resection （HR） is a poor prognostic factor for patients with hepatocellular carcinoma （HCC）. This study aimed to identify the clinico- pathological features, outcomes, and risk factors for ER after HR for small HCC in order to clarify the reasons why ER is a worse recurrence pattern. METHODS： We retrospectively examined 130 patients who underwent HR for small HCC （___30 mm）. Recurrence was clas- sifted into ER （〈2 years） and late recurrence （LR） （_〉2 years）. The clinicopathological features, outcomes, and risk factors for ER were analyzed by multivariate analysis. RESULTS： ER was observed in 39 patients （30.0%）. The sur- vival rate of the ER group was significantly lower than that of the LR group （P〈0.005）, and ER was an independent prognos- tic factor for poor survival （P=0.0001）. The ER group had a significantly higher frequency （P=0.0039） and shorter interval （P=0.027） of development to carcinoma beyond the Milan criteria （DBMC） compared with the LR group, and ER was an independent risk factor for DBMC （P〈0.0001）. Multi-nodularity, non-simple nodular type, and microvascular invasion were independent predictors for ER （P=0.012, 0.010, and 0.019, respectively）.CONCLUSIONS： ER was a highly malignant recurrence pattern associated with DBMC and subsequent poor survival after HR for small HCC. Multi-nodularity, non-simple nodular type, and microvascular invasion predict ER, and taking these factors into consideration may be useful for the decision of the treatment strategy for small HCC after HR.

Comparison of survival between adolescent and young adult vs older patients with hepatocellular carcinoma

BACKGROUND Due to the special clinical features and biologic characteristics of adolescent and young adult(AYA)cancers,AYA cancers are different from cancers in children and elderly individuals.However,there are few reports on AYA hepatocellular carcinoma(HCC).AIM To investigate the overall survival(OS)of AYA(15-39 years)and elderly(40-74 years)patients with HCC.METHODS The data of all the HCC cases were extracted from the Surveillance,Epidemiology,and End Results database from 2004 to 2015 and were then divided into two groups based on age:AYA group(15-39 years)and older group(40-74 years).Kaplan-Meier curves and log-rank tests were used to compare the OS of the two groups.Propensity score matching(PSM)was employed to analyze the OS difference between the two groups.The Cox proportional hazards regression model was used to perform multivariate analysis to explore the risk factors for OS of HCC patients.RESULTS Compared to elderly cancer patients,AYA patients with HCC had a worse Surveillance,Epidemiology,and End Results stage,including the distant stage(22.1%vs 15.4%,P<0.001),and a more advanced American Joint Committee on Cancer(AJCC)stage,including AJCC III and IV(49.2%vs 38.3%,P<0.001),and were more likely to receive surgery(64.5%vs 47.5%,P<0.001).Before PSM,the AYA group had a longer survival in months(median:20.00,interquartile range[IQR]:5.00-62.50)than the older group(median:15.00,IQR:4.00-40.00)(P<0.001).After PSM,the AYA group still had a longer survival in months(median:21.00,IQR:5.00-64.50)than the older group(median:18.00,IQR:6.00-53.00)(P<0.001).The Cox proportional hazards regression model showed that advanced age(hazard ratio[HR]=1.405,95%CI:1.218-1.621,P<0.001)was a risk factor for OS of HCC patients.In the subgroup analysis,the Cox proportional hazards regression model showed that in AJCC I/II HCC patients,advanced age(HR=1.749,95%CI:1.352-2.263,P<0.001)was a risk factor for OS,while it was not a risk factor in AJCC III/IV HCC patients(HR=1.186,95%CI:0.997-1.410,P=0.054)before PSM.After PSM,advanced age(HR=1.891,95%CI:1.356-2.637,P<0.001)was still a risk factor for OS in AJCC I/II HCC patients,but was not a risk factor for OS in AJCC III/IV HCC patients(HR=1.192,95%CI:0.934-1.521,P=0.157)after PSM.CONCLUSION AYA patients with HCC have different clinical characteristics from older adults.In different AJCC stages,the two groups of patients have different OS:In AJCC I/II HCC patients,advanced age is a risk factor for OS,but it is not a risk factor for OS in the AJCC III/IV HCC patient group.