Risk factors of intrahepatic recurrence after curative resection of hepatocellular carcinoma

BACKGROUND/AIMS: Although the risk factors for the development of intrahepatic recurrence after hepatectomy for hepatocellular carcinoma (HCC) have been widely studied, little attention has been given to the prognostic factors affecting such patients. METHODOLOGY: Intrahepatic recurrence occurred in 105 (56%) of 188 patients who underwent curative hepatic resection of HCC and were discharged from the hospital. Among them, 17 (16%) also had simultaneous extrahepatic recurrence. Independent prognostic factors were evaluated by multivariate analysis using Cox's proportional hazards model. RESULTS: Multivariate analysis revealed that presence of extrahepatic recurrence, hepatitis B, and non-surgical treatments for recurrence were independent predictors of poor overall survival after initial hepatic resection or after recurrence. Risk factors of extrahepatic recurrence were young age, solitary and large HCC, high hepatitis activity, and large amount of intraoperative blood loss and blood transfusion. CONCLUSIONS: Survival of patients with intrahepatic recurrent HCC after resection should be stratified by the type of recurrence, type of hepatitis, and type of treatment for recurrence.     

Risk factors of recurrence after curative resection of hepatocellular carcinoma in Taiwan

IntroductionThe purpose of this study was to explore the potential risk factors of hepatocellular carcinoma (HCC) recurrence after curative resection of primary HCC.MethodsThis was a hospital-based retrospective cohort study. The authors analyzed the medical records of all the subjects with HCC initially treated by hepatic resection at a medical center in Taiwan from 1995 to 2006. In all, 222 subjects were enrolled in this study. The total observational period was 3 years.resultsThere were 172 men (77.5%) and 50 women (22.5%). The mean age was 57.0 ± 13.7 years (range, 15–79 years). Among 222 subjects, the overall recurrence rates were 28.8% (64/222), 42.3% (94/222) and 47.7% (106/222) at 1, 2 and 3 years, respectively. Multivariate logistic regression analysis exhibited that tumor size ≥ 5 cm [odds ratio (OR) = 2.31, 95% confidence interval (CI) = 1.27–4.17], liver cirrhosis (OR = 2.11, 95% CI = 1.18–3.79) and preoperative aspartate aminotransferase level ≥ 34IU/L (OR = 2.02, 95% CI = 1.01–4.04) were independent risk factors of HCC recurrence.conclusionPatients who have larger tumor size, liver cirrhosis and higher preoperative aspartate aminotransferase level should be carefully followed up because they are at high risk of HCC recurrence postoperatively.     

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 (2...     

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

AIM:To investigate the clinicopathological riskfactors for immediate post-operative fatal recurrenceof hepatocellular carcinoma (HCC),which may havepractical implication and contribute to establishinghigh risk patients for pre-or post-operative preventivemeasures against HCC recurrence.METHODS:From June 1994 to May 2004,269 patientswho received curative resection for HCC were reviewed.Of these patients,those who demonstrated diffuse intra-hepatic or multiple systemic recurrent lesions within 6mo after surgery were investigated (fatal recurrencegroup).The remaining patients were designated as thecontrol group,and the two groups were compared forclinicopathologic risk factors.RESULTS:Among the 269 patients reviewed,30patients were enrolled in the fatal recurrence group.Among the latter,20 patients showed diffuse intra-hepatic recurrence type and 10 showed multiple systemicrecurrence type.Multivariate analysis between the fatalrecurrence group and control group showed that pre-operative serum alpha-fetoprotein (AFP) level wasgreater than 1000 μg/L (P=0.02; odds ratio=2.98),tumor size greater than 6.5 cm (P=0.03; OR=2.98),and presence of microvascular invasion (P=0.01;OR=4.89) were the risk factors in the fatal recurrencegroup.The 48.1% of the patients who had all the threerisk factors and the 22% of those who had two riskfactors experienced fatal recurrence within 6 mo aftersurgery.CONCLUSION:Three distinct risk factors for immediatepost-operative fatal recurrence of HCC after curativeresection are pre-operative serum AFP level>1000 μg/L, tumor size>6.5 cm,and microvascular invasion.Thehigh risk patients with two or more risk factors should bethe candidates for various adjuvant clinical trials.     

Predictive factors of advanced recurrence after curative resection of small hepatocellular carcinoma

Background: The tumour recurrence rate after resection is still high even in patients with small hepatocellular carcinoma (HCC). The advanced patterns of recurrence occasionally occur after resection. In this study, we analysed the clinical and histological characteristics of small HCC and evaluated the predictive factors of advanced tumour recurrence. Methods: One hundred and sixty‐five patients underwent resection of small HCC measuring 3 cm or less in greatest dimension. Patterns of tumour recurrences were classified into advanced recurrence and minor recurrence based on size, number, vascular invasion and extrahepatic metastasis of recurrent tumour. We created a simple index to closely evaluate the malignant potential of small HCC, named α‐foetoprotein–size ratio index (ASRI). Results: Overall tumour recurrence was significantly associated with tumour multiplicity (P<0.001) and ASRI (P=0.001). Tumour multiplicity, ASRI and tumour differentiation were independent and significant predictive factors of advanced recurrences. The overall survival rates were lower in the advanced recurrence group than the minor recurrence or the no recurrence group. Conclusions: Patients with advanced recurrences have a poor prognosis, although they have undergone curative resection of small HCC. On the other hand, patients with minor recurrences have a relatively good prognosis. ASRI was a useful index to predict advanced recurrence after curative resection of small HCC. The therapeutic management to prevent advanced recurrences is needed.     

Risk factors and management for early and late intrahepatic recurrence of solitary hepatocellular carcinoma after curative resection

Background

Intrahepatic recurrence is a significant problem for patients who have undergone a hepatic resection for hepatocellular carcinoma (HCC). The objective of the present study was to identify risk factors and evaluate the management of early and late recurrence of solitary HCC after curative resection.

Methods

Included in this study were 816 patients with solitary HCC who underwent a curative partial hepatectomy. Intrahepatic recurrence in these patients was followed up retrospectively. Prognosis and therapy for the recurrence were investigated and analysed.

Results

Early and late intrahepatic recurrence occurred in 423 patients and 199 patients, respectively. Multivariate analysis showed that a tumour diameter >5 cm, the absence of a tumour capsule and the presence of microvascular invasion were correlated with early recurrence, whereas cirrhosis and alpha-fetal protein >400 μg/l were independent risk factors contributing to late recurrence. The 5-year survival of HCC patients with early recurrence was significantly lower than that of patients with late recurrence. Further curative treatment for intrahepatic recurrence offered a 5-year overall survival of 56.0%, which was better than alternative management.

Conclusion

Early and late recurrences of solitary HCC after curative resection are associated with different predictive factors. The time to recurrence and further curative treatment after recurrence were the best predictors of survival post recurrence.     

Patterns of intrahepatic recurrence after curative resection of hepatocellular carcinoma

Using selective angiograms of the liver, we analyzed the patterns of intrahepatic recurrence of hepatocellular carcinomas following curative surgery. In 33 patients with intrahepatic recurrences, seven patients (21%) had a recurrence near the resected hepatic stump. The remaining 26 had either a nodular recurrence in segments away from the resected margin or a widespread multinodular recurrence in the liver remnant. There was a recurrence within the first postoperative year in five of 16 patients with a nodular recurrence and in eight of 10 patients with a widespread multinodular recurrence. In these patients, particularly those with a widespread multinodular recurrence, tumor thrombi in the portal vein present before the operation and/or disseminated during operation from such an advanced main tumor seemed to be the most important and significant factor related to the early recurrence in the remnant liver. This evidence suggests that in cases of surgery for hepatocellular carcinoma it is important to establish a technique to prevent dissemination of cancer cells due to operative manipulation and also adequate adjuvant therapy rather than attempting to obtain an ample resection margin.     

Risk factors for local recurrence of middle and lower rectal carcinoma after curative resection

AIM： To explore the risk factors for local recurrence of middle and lower rectal carcinoma after curative resection. METHODS： Specimens of middle and lower rectal carcinoma from 56 patients who received curative resection at the Department of General Surgery of Guangdong Provincial People＇s Hospital were studied. A large slice technique was used to detect mesorectal metastasis and evaluate circumferential resection margin status. The relations between clinicopathologic characteristics, mesorectal metastasis and circumferential resection margin status were identified in patients with local recurrence of middle and lower rectal carcinoma. RESULTS： Local recurrence of middle and lower rectal carcinoma after curative resection occurred in 7 of the 56 patients （12.5%）, and was significantly associated with family history （Х^2= 3.929, P = 0.047）, high CEA level （Х^2 = 4.964, P = 0.026）, cancerous perforation （Х^2 = 8.503, P = 0.004）, tumor differentiation （Х^2 = 9.315, P = 0.009） and vessel cancerous emboli （Х^2 = 11.879, P = 0.001）. In contrast, no significant correlation was found between local recurrence of rectal carcinoma and other variables such as age （Х^2 = 0.506, P = 0.477）, gender （Х^2 = 0.102, Z2 = 0.749）, tumor diameter （Х^2 = 0.421, P = 0.516）,tumor infiltration （Х^2 = 5.052, P = 0.168）, depth of tumor invasion （Х^2 = 4.588, P = 0.101）, lymph node metastases （Х^2 = 3.688, P = 0.055） and TNM staging system （Х^2 = 3.765, P = 0.152）. The local recurrence rate of middle and lower rectal carcinoma was 33.3% （4/12） in patients with positive circumferential resection margin and 6.8% （3/44） in those with negative circumferential resection margin. There was a significant difference between the two groups （Х^2 = 6.061, P = 0.014）. Local recurrence of rectal carcinoma occurred in 6 of 36 patients （16.7%） with mesorectal metastasis, and in 1 of 20 patients （5.0%） without mesorectal metastasis. However, there was no significant     

Risk factors linked to tumor recurrence of human hepatocellular carcinoma after hepatic resection.

A total of 238 patients who received curative hepatic resections during the last 10 yr were observed to search for the risk factors linked to early tumor recurrence of human hepatocellular carcinoma after hepatectomy. The results revealed that tumor size, tumor appearance and DNA ploidy were the factors in predicting tumor recurrence after resection for hepatocellular carcinoma. Patients with a tumor size less than or equal to 5 cm or a tumor appearance of the solitary type had better disease-free survival than did those with a tumor size greater than 5 cm or a tumor appearance of multiple/daughter nodule types (p < 0.05). Although patients with pattern III (aneuploid with > or = 2 G0/G1 peaks) hepatoma had fewer statistically significant differences (p = 0.19) than did those with pattern I (diploid) or pattern II (aneuploid with single G0/G1 peak) tumors in predicting tumor recurrence, they did have poorer results in terms of the overall survival rate (p < 0.05). We conclude that patients with hepatocellular carcinoma having the aforementioned risk factors should be observed closely.     

Lymphocyte-to-monocyte ratio predicts survival of patients with hepatocellular carcinoma after curative resection

AIM: To investigate the prognostic value of preoperative lymphocyte-to-monocyte ratio(LMR) in patients with hepatocellular carcinoma(HCC) undergoing curative hepatectomy.METHODS: Clinicopathological data of 210 hepatitis B virus(HBV)-associated HCC patients who were treated by radical hepatic resection between 2003 and 2010 were retrospectively analyzed. None of the patients received any preoperative anticancer therapyor intraoperative radiofrequency ablation. The diagnosis was confirmed by pathological examination after surgery. Absolute peripheral blood lymphocyte and monocyte counts were derived from serum complete blood cell count before surgery,and LMR was calculated by dividing lymphocyte count by monocyte count. The best cutoff was determined by receiver operating characteristics(ROC) curve analysis. Correlations between LMR levels and clinicopathological features were assessed using the χ2 test. Survival outcomes were estimated using the Kaplan-Meier method and compared by the log-rank test. Univariate and multivariate analyses were performed to evaluate the prognostic impact of LMR and other clinicopathological factors on overall survival(OS) and recurrence-free survival(RFS),using the Cox proportional hazards model.RESULTS: The optimal cutoff value of LMR for survival analysis was 3.23,which resulted in the most appropriate sensitivity of 55.3% and specificity of 74.7%,with the area under the curve(AUC) of 0.66(95%CI: 0.593-0.725). All patients were dichotomized into either a low(≤ 3.23) LMR group(n = 66) or a high( 3.23) LMR group(n = 144). A low preoperative LMR level was significantly correlated with the presence of cirrhosis,elevated levels of total bilirubin and larger tumor size. Patients with a low LMR level had significantly reduced 5-year OS(61.9% vs 83.2%,P 0.001) and RFS(27.8% vs 47.6%,P = 0.009) compared to those with a high LMR level. Multivariate analyses indicated that a lower LMR level was a significantly independent predictor of inferior OS(P = 0.003) and RFS(P = 0.006). Subgroup analysis indicated that survival outcome was significantly more favorable in cirrhotic patients with LMR 3.23. However,there were no differences between low and high LMR groups for OS and RFS in non-cirrhotic patients.CONCLUSION: Preoperative LMR was demonstrated for the first time to serve as an independent prognostic factor in HBV-associated HCC patients after curative resection. Prospective studies with larger cohorts for validation are warranted.     

Persistent hepatitis B viral replication affects recurrence of hepatocellular carcinoma after curative resection

Background: Elevated serum hepatitis B virus (HBV) DNA increases the development of hepatocellular carcinoma (HCC). Rather than instantaneous DNA level, the duration of persistent HBV replication is more important in carcinogenesis. Nevertheless, most investigators evaluated the DNA level at study entry. We assessed the effects of persistently detectable serum HBV DNA on HCC recurrence. Patients and methods: We included 230 consecutive patients undergoing curative resection between 2000 and 2006. Patients who had antiviral therapy (at diagnosis or during follow‐up), fluctuating DNA (cut‐off value: 100 000 copies/ml) or recurrence within 12 months of resection were excluded. Ultimately, 157 were enrolled: 89 (non‐viraemia group) had consistently negative DNA (<100 000 copies/ml), while 68 (viraemia group) had consistently positive DNA (>100 000copies/ml). Serum DNA level, biochemical tests, α‐foetoprotein (AFP) and liver dynamic computed tomography were obtained every 3 months after surgery. Results: There were no significant differences in age, gender, liver function, histology, AFP, tumour stages or follow‐up duration between the two groups. During follow‐up (median: 35 months), patients in the non‐viraemia group had a lower 5‐year cumulative recurrence rate (54.7%) than those in the viraemia group (72.9%; P=0.043). In multivariate analysis, sustained viraemia (P=0.041) increased recurrence independently. Conclusions: Persistent viraemia increased recurrence independently after surgery. To prevent long‐term recurrences, antiviral therapy should be initiated in those with detectable serum HBV DNA.     

Interval dynamics of transplantability for hepatocellular carcinoma after primary curative resection: risk factors for nontransplantable recurrence

BackgroundTo investigate the changes in transplantability between primary and recurrent Hepatocellular carcinoma (HCC) after hepatic resection (HR) and the risk factors for nontransplantable recurrence (NTR).MethodsConsecutive 3122 patients who received HR for primary HCC between 2001 and 2019 were analyzed for changes in transplantability. Predictors of survival and NTR were evaluated using a competing risk analysis.ResultsAfter a median follow-up of 78.3 months, the 5-year overall survival rate was 82.6%. Also, 58.2% of them developed recurrence after a median of 45.6 months. Recurrence occurred in 1205 and 611 patients with primary transplantable and nontransplantable HCC, respectively, of whom 26.1% and 63.2%, respectively, had NTR. Tumor diameter >3 cm [subdistribution hazard ratios (95% CI), 2.00 (1.62–2.48)], major resection [1.20 (1.00–1.43)], pathological grade >2 [1.28 (1.07–1.52)], microvascular invasion [1.74 (1.45–2.08)], and early recurrence (<1 year) [9.22 (7.83–10.87)] were associated with NTR. The overall transplantable pool increased from 72.3% to 77.5%.ConclusionMicrovascular invasion and early recurrence were risk factors for NTR. Nonetheless, the transplantable pool increased after HR, 41.8% of the patients had no recurrence and may not require liver transplantation. If the patient’s liver function is acceptable, HR should be considered the treatment of choice for HCC.     

Prognostic risk factors of survival after resection of hepatocellular carcinoma

BACKGROUND/AIMS: Surgical resection is a standard treatment of hepatocellular carcinoma, but liver cirrhosis is known to be associated to a high tumor recurrence rate. METHODOLOGY: A retrospective study of 55 consecutive patients (37 males, 18 females) suffering from hepatocellular carcinoma having undergone surgical resection. Hepatocellular carcinoma developed in 29 patients with normal liver (group A) and in 26 patients with chronic liver disease (CLD) (group B). Patients were significantly older and at high-risk in Group B. RESULTS: Radical liver resection was achieved in 98% (100% in group A; 96% in group B). Overall 2-month mortality was 2% (0% in group A; 4% in group B). The 5-year overall and disease-free survival was respectively 55% and 35%. However, the 5-year overall and disease-free survival was significantly better in Group A (71% and 59%) compared to Group B (37% and 6%) (p < 0.001), respectively. Multivariate statistical analysis demonstrated that age > 50 years, poor tumor differentiation and presence of satellite nodules were significant independent adverse predictive factors of overall and disease-free survival. CONCLUSIONS: Resection of HCC is safe and effective with satisfactory overall and disease-free survival rates, except when underlying chronic liver disease and poor tumor differentiation are present.     

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.     

肝细胞癌冷冻消融术后早期复发的危险因素

目的:探讨肝细胞癌(hepatocellular carcinoma,HCC)患者冷冻消融术后影响早期复发的相关危险因素.方法:回顾分析90例直径≤5.0 cm的HCC行冷冻消融治疗后复发的患者的临床资料,分析影响冷冻消融术后早期复发的危险因素.结果:本组患者随访8-47(平均随访时间21.9±10.1)mo,共有57...     

Prognostic value of postoperative complication for early recurrence after curative resection of hepatocellular carcinoma

Background: Postoperative complications may adversely affect oncological outcomes. The aim of this study was to evaluate the impact of postoperative complications on early-phase recurrence after curative resection for hepatocellular carcinoma(HCC).Methods: We included 145 HCC patients who underwent initial and curative resection between January2004 and December 2013. Postoperative complications of grade III or higher based on Clavien–Dindo classification were defined as clinically relevant postoperative complications. Recurrence within two years after hepatectomy was defined as early-phase recurrence.Results: Thirty-eight patients(26%) developed postoperative complications. The only predictive factor for postoperative complication was longer operative duration(P = 0.037). The disease-specific survival rate of patients with complication was lower than that of patients without complications(P = 0.015). Earlyphase recurrence was observed in 20/38(53%) patients who suffered postoperative complications and36/107(34%) patients with no complications, which was statistically significant(P = 0.039). Multivariate analysis identified four factors contributing to early-phase recurrence: high serum AFP level(P = 0.042),multiple tumors(P 0.001), poor differentiation(P = 0.036) and presence of postoperative complication(P = 0.039).Conclusions: Postoperative complication is an independent prognostic factor for early-phase recurrence after curative resection of HCC. Close observation of patients with postoperative complications may be a necessary treatment strategy for HCC.