| BackgroundIn recent years,the incidence of hepatocellular carcinoma(HCC)has increased in local areas and is the third leading cause of cancer death worldwide.About 75-80% of HCC patients in the world live in Asia-Pacific region,and whose HCC is caused by liver cirrhosis of HBV and/or HCV.In mainland of China,there are a large number of HCC patients with an annual incidence of about 28/100,000 and a mortality rate of 26/100,000.In addition,HCC disease is insidious.So most of the patients are in the middle and late stage when they are hospitalized and the long-term prognosis of those is poor.HCC tumor staging determines the treatment and the long-term curative prognosis of the patients.Barcelona Clinical Liver Cancer(BCLC)is highly praised by scholars both at home and abroad.It is the only HCC staging system recommended by the American Association for the Study of Liver Diseases(AASLD)and the European Association for the Study of the Liver(EASL).The BCLC staging system only recommended hepatectomy for HCC patients with phase A,and the patient should meet the Milan standards:(a)only a singletumor and diameter of tumor <5cm,or less than 3 nodules,and the maximum diameter of tumor is less than 3cm;(b)hepatic functional reserve is child-pugh A or level b;(c)It has no major vascular invasion,tumor rupture,and distant metastasis.HCC with stage B is mostly multinodular tumor.The BCLC staging system doesn't recommend hepatectomy for these patients with stage B.Due to the high mortality and recurrence rate after hepatectomy,the BCLC even listed HCC with stage B as a relative contraindication for hepatectomy,and only palliative care is recommended,such as transarterial chemoembolization(TACE).For patients with stage C in the BCLC,sorafenib or other targeted drugs are recommended.But in clinical practices,surgeons in many countries,especially in Asia,don't follow the BCLC guides completely.In many countries,studies have shown that the hepatectomy for HCC with stage B in the BCLC is safe and effective,and they call for the extension of the indications for hepatectomy.Therefore,in the treatment guidelines for the hepatopathy,the indications for hepatectomy is relatively wide,such as hepatic functional Child-Pugh level A or B,multiple nodules tumor,multiple invasion of portal vein.Those may be considered for hepatectomy.However,these are mostly small sample studies,and lack of highlevel evidence.It is necessary to use systematic evaluation methods to demonstrate the efficacy and safety of hepatectomy through big data.The initial series of literature of BCLC group show that HCC with stage B in the BCLC includes HCC patients,whose the diameter of a single tumor ?5cm.Many centers both at home and abroad are also used this definition.However,the recent series reviews of the BCLC team highlights that HCC with stage B in the BCLC refers to “ ?2 tumors” and “the maximum diameter of tumor > 3cm”;and “ ?4 tumors”.“the diameter of a single tumor <5cm” belongs to phase A inthe BCLC.The reasons for the persistence of the dispute for hepatectomy in HCC patients with stage B in the BCLC are:(a)to resect the tumor maximally in order to reduce postoperative recurrence rate,and to be able to retain sufficient residual liver in order to reduce the incidence of complications and maintain the postoperative quality of life;how to find the best balance between the two is a difficult problem;(b)the heterogeneity of HCC tumor with stage B in the BCLC is large,and there are many factors affecting the prognosis of patients.Therefore,it is necessary to perform subgroup analysis to compare the differences in safety and long-term efficacy between groups.At the same time,to observe the curative effect of hepatectomy as time goes on in order to demonstrate the rationality of the hepatectomy.In addition,the recent series reviews of the BCLC team emphasizes that single HCC tumors regardless of size,are BCLC A,as long as there are no major vascular invasion and lymphatic metastasis.In the staging system of many other solid tumors(such as breast cancer),tumor size is an important factor in determining tumor staging.In HCC,multivariate analyses of many clinical studies show that tumor size is an independent risk factor for long-term prognosis after hepatectomy.Therefore,it is necessary to further explore the HCC tumor staging of individual nodules and compare the prognosis of single nodular patients with different diameters.It basically is to optimize the BCLC staging of these patients and provide more evidence of evidence-based medicine in treatment options for HCC patients with single nodules.Part ?Hepatic resection for hepatocellular carcinoma involving a single large tumor or multiple tumors: a systematic reviewObjective This systematic review examined whether the available evidence justifies using hepatic resection(HR)during later stages of hepatocellular carcinoma(HCC),which contravenes treatment guidelines but is current practice at many medical centers.Methods Several databases were systematically searched for studies examining the safety and efficacy of HR for treating HCC involving a single large tumor(>5 cm)or multiple tumors.Results We identified 50 studies involving 14,808 patients that investigated the use of HR to treat large/multinodular HCC.Median in-hospital mortality for patients with either type of HCC was significantly lower in Asian studies(2.7%)than in non-Asian studies(7.3%,P < 0.001).Median overall survival was significantly higher for all Asian patients with large/multinodular HCC than for all non-Asian patients at both 1 year(81% vs 65%,P < 0.001)and 5 years(42%vs 32%,P < 0.001).Similar results were obtained for median disease-free survival at 1 year(61% vs 50%,P < 0.001)and 5 years(26% vs 24%,P <0.001).There was an upward trend in 5-year overall survival in patients with either type of HCC.Conclusions HR is reasonably safe and effective at treating large/multinodular HCC.The available evidence argues for expanding the indications for HR in official treatment guidelines.Part ?Historical comparison of overall survival after hepatectomy for patients with large and/or multinodular hepatocellular carcinomaAims The present study compared the efficacy of hepatic resection(HR)in patients with large hepatocellular carcinoma(HCC)and those with multinodular tumor and examined how that efficacy has changed over time in a large medical center.Methods A consecutive sample of 927 patients with preserved liver function and large and/or multinodular HCC who were treated by initial HR were divided into three groups: those with a single tumor ?5 cm in diameter(n =588),2-3 tumors with a maximum diameter >3 cm(n = 225),or >3 tumors of any diameter(n = 114).Hospital mortality and overall survival(OS)in each group were compared for the years 2000-2007 and 2008-2013.Results Patients with >3 tumors showed the highest incidence of hospital mortality of all groups(P < 0.05).Kaplan-Meier survival analysis showed that OS varied across the three groups as follows: single tumor > 2-3 tumors > 3+tumors(all P < 0.05).OS at 5 years ranged from 24% to 41% in all three groups for the period 2000-2007,and from 35% to 46% for the period 2008-2013.OS was significantly higher during the more recent 6-year period in the entire patient population,those with single tumor,and those with 3+ tumors(all P <0.05).However,in patients with 2-3 tumors,OS was only slightly higher during the more recent 6-year period(P = 0.084).Conclusions Prognosis can vary substantially for these three types of HCC.Patients with >3 tumors show the highest hospital mortality and lowest OS after HR.OS has been improving for all three types of HCC at our medical center asa consequence of improvements in surgical technique and perioperative management.Part ?Optimizing stage of single large hepatocellular carcinoma: subgroup analysis by tumor diameterObjective This study aims to refine the designation for single hepatocellular carcinoma(HCC)>5 cm by comparing the post-resection prognosis of these patients with those who have a single-tumor ?5?cm and those with stage B.Methods Patients with a single-tumor were classified into subgroups based on diameter.Of the 1132 patients analyzed,426 had a single-tumor >2 and ?5?cm;229,a single-tumor >5?cm and ?8 cm;52,a single-tumor >8?cm and <10cm;150,a single-tumor ?10 cm;and 275,stage B.Results Hospital mortality and complications increased with tumor size among the single-tumor subgroups and median survival decreased with increasing of tumor size.Overall survival(OS)among patients with a singletumor >5?cm was significantly lower than among patients with a singletumor >2 and ?5?cm(P ? 0.001),but significantly higher than among patients with clearly stage B(P ? 0.001).Patients with a single-tumor >5?cm and ?8 cm showed lower OS than patients with a single-tumor >2 and ?5?cm(P < 0.001).Patients with a single-tumor >8?cm and <10 cm or a single-tumor ?10 cm showed lower OS than patients with a single-tumor >5?cm and ?8 cm(P =0.033 and 0.006),and similar OS to patients with stage B(P = 0.323).Conclusion Patients with a single-tumor >5 cm and ?8 cm may be assigned to a new stage between early and intermediate.Patients with a single-tumor >8cm may be assigned to intermediate stage. |
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