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Liver



Multimodal Treatment of Hepatocellular
Carcinoma: an Eastern European experience
Simona Olimpia Dima1, Speranţa Iacob2, Florin Botea3, Emil Matei1, Bogdan Dorobanţu1, PhD,
Şerban Vasile1, Sorin Alexandrescu1, Adina Croitoru4, Traian Dumitraşcu1, Cezar Stroescu1,
Vlad Herlea4, Irinel Popescu1
1
Center of General Surgery and Liver Transplantation, Fundeni Clinical Institute of Digestive Disease
and Liver Transplantation, Bucharest, Romania
2
Center of Gastroenterology and Hepatology, Fundeni Clinical Institute of Digestive Disease and Liver
Transplantation Bucharest, Romania
3 nd
2 Clinic of Surgery, Ovidius University, Constanta, Romania.
Liver Surgery Unit, 3rd Department of Surgery, Humanitas Clinical Institute, Rozzano, Milan
4
Department of Pathology, Fundeni Clinical Institute of Digestive Disease and Liver Transplantation,
Bucharest, Romania, Str. Fundeni no. 258, 022328
Corresponding Author: Irinel Popescu, Professor, MD, PhD, FACS
Center of General Surgery and Liver Transplantation, Fundeni Clinical Institute,
Sos. Fundeni 258, sector 2, 022328, Bucharest, Romania
Tel: +40213180417, Fax: +40213180417, E-mail: irinel.popescu@icfundeni.ro

ABSTRACT
Background/Aims: The aim of the present study
was to evaluate the outcomes of a multimodal
treatment approach of hepatocellular carcinoma
(HCC) in a tertiary hepatobiliary specialty
center.
Methodology: A total of 294 consecutive patients
treated for HCC were retrospectively analyzed.
216 patients (73.4%) were male and 78 (26.6%)
were female. Liver resection (LR) was performed
in 201 patients (68.4%), liver transplantation (LT)
in 19 patients (6.5%), radiofrequency ablation
(RFA) in 74 patients (25.1%), and 56 (19%) patients received adjuvant systemic chemotherapy.
Results: The median follow-up was 15.7mo
(range 0.1-90.3). Five-year overall survival and
recurrence rates were 28% and 26.8%, respectiveINTRODUCTION
Hepatocellular carcinoma (HCC) is the sixth
most common neoplasm in the world (1) and the
main cause of death among cirrhotic patients (2).
Its incidence has increased dramatically worldwide
as a result of the current hepatitis C epidemic and
is expected to continue to do so over the next two
decades (3). Hepatitis B virus and hepatitis C virus
leading to cirrhosis remain the most powerful risk
factors for HCC, conferring an annual risk of developing HCC of approximately 5% (4). HCC develops
in 80% of patients with cirrhotic livers (5) and only
10-15% of these patients have potentially resectable tumors (6).
Since HCC usually arises in the setting of cirrhosis, several treatment modalities have been developed to better address both pathological processHepato-Gastroenterology 2009; 56:285-289
© H.G.E. Update Medical Publishing S.A., Athens-Stuttgart

ly. Serum AFP >43.8ng/ml (p=0.005), BCLC C/D
(p=0.006) and JIS 3/4/5 classifications (p=0.02)
were independent negative prognostic factors
for overall survival, while JIS 3/4/5 (p=0.01) and
BCLC C/D (p=0.01) classifications, tumors larger
than 6.5cm (p=0.001) and RFA (p=0.02) were independent predictors for recurrence.
Conclusions: The current treatment of HCC
should be multimodal, and therapeutic modalities
and their combinations should be tailored to each
patient. LT represents the best therapeutic option
for patients with HCC in the setting of cirrhosis.
Resection remains a good option in cirrhotic patients, while RFA is a safe and effective procedure
for small tumors.

es, i.e., malignancy and end-stage liver disease. The
choice of treatment depends primarily on the tumor
stage and the functional status of the liver (7).
Liver resection (LR), radiofrequency ablation
(RFA), transarterial chemoembolization (TACE),
systemic chemotherapy, and liver transplantation
(LT) are the main therapeutic options in the case
of HCC with or without associated liver cirrhosis.
Many studies (8-14) have compared outcomes of using various combinations as well as monotherapies,
but the results are controversial.
The purpose of this study was to evaluate the
outcomes after a multimodal treatment approach
involving LR, RFA, TACE, systemic chemotherapy,
and LT in patients with HCC treated in a tertiary
hepatobiliary specialty center, as well as to evaluate predictive factors for overall survival and HCC
recurrence after therapy.

KEY WORDS:
Hepatocellular
carcinoma;
Multimodal
treatment;
Predictive factors
ABBREVIATIONS:
Alpha-Fetoprotein
(AFP);
Hepatocellular
Carcinoma (HCC);
Liver Transplantation (LT);
Liver Resection
(LR);
Radiofrequency
Ablation (RFA);
Transcatheter
Arterial
Chemoembolization (TACE)

et al. the diagnosis of HCC was confirmed by histological examination in all patients. we recorded age. Liver resection A hepatic resection was classified according to anatomic criteria. Procedure-related mortality was defined as death occurring within 30 days after the therapy. patients were categorized according to the primary treatment given. The time for disease recurrence was defined as the period from the first applied therapy until the detection of the initial HCC recurrence. and it was defined as major if at least three Couinaud segments were resected and minor if fewer segments were resected. Therapeutic approach 1. and the liver function. doxorubicin was injected into the arterial branch feeding the tumor. tumor variables (size. the extent of the tumor recurrence. ascites that required diuretics. Fl Botea. All tests were two-sided. Transarterial Chemoembolization (TACE). and recurrent disease status were also recorded. TACE. history of previous loco-regional therapy. Postoperative morbidity was defined as any postoperative complication that lengthened the hospital stay. Complications included liver failure. All statistical analyses were performed using SPSS version 15. BCLC (Barcelona Clinic Liver Cancer) (5). IL. Using the Seldinger technique. Patients were classified according to the following systems: TNM (Tumor node metastasis) (16). The tumor was considered resectable if there were no extrahepatic metastases. pulmonary complications. For statistical analysis. abdominal hemorrhage. Disease-free survival and overall survival were calculated according to the Kaplan-Meier method. JIS (Japan Integrated Staging) (18). After surgery. Okuda (19) and AJCC staging system (American Joint Commission on Cancer) (20). in addition to Milan criteria in the case of orthotopic LTs (21). Categorical data were expressed as the proportion of the subjects with a specific feature. Statistical analysis Continuous data were expressed as mean ± standard deviation. 4. Chicago. USA) were used. 2. gender. sepsis. Intrahepatic tumor recurrences were managed using a multimodal approach with repeat hepatectomy. and the liver remnant volume was adequate (at least 40% in a cirrhotic liver and at least 30% in a normal liver). Univariate and multivariable Cox proportional hazard regression analyses were used in order to identify predictors of mortality and recurrence. computed tomography or magnetic resonance imaging) of the tumors in order to characterize the tumor. and differences between groups were tested for significance using the log-rank test. to exclude extrahepatic liver disease and to assess for operability/operative risk. The extent of the resection was based on tumor location and parenchymal conditions. USA). number. Patients undergoing surgical resection were not given preoperative therapy. followed by embolization with lipiodol. Surgical protocols.. gastrointestinal bleeding.23). The study protocol was approved by the Institutional Ethics Review Board of Fundeni Clinical Institute and conformed to the ethical guidelines of the 1975 Declaration of Helsinki. All patients underwent preoperative imaging evaluation (abdominal ultrasound. Edmondson and Steiner grading (15) and type of therapy used. or 5-FU (425mg/m2 as a 4-day infusion) and leucovorin (2mg/m2 as a 4-day infusion) administered every 4 weeks for 6 months Follow-Up Serum AFP level monitoring and CT/MRI were performed at one and three months after surgery and then every six months. intraperitoneal abscess. 3. 480 KHz monopolar Cool Tip™ RF Ablation System and switching controller (Valleylab. Systemic chemotherapy The regimen consisted of either doxorubicin (60mg/m2/day given every three weeks). serum alpha-fetoprotein (AFP) level.0 for Windows (SPSS Inc. Hepato-Gastroenterology 56 (2009) METHODOLOGY Patients A total of 294 consecutive patients diagnosed with HCC in our center from January 2001 to December 2007 were retrospectively included in this study. and a pvalue of less than 0. bile leakage. CLIP (Cancer of the Liver Italian program) (17). Tyco Health Care.05 was considered to be statistically significant. ChildTurcotte-Pugh classification. etiology. . no thrombus in the main portal vein or inferior vena cava. All patients were followed until death or the end of the observation period (August 2008). location. A 200-W. S O Dima. Liver transplantation Surgical techniques included whole graft liver transplantation (cadaveric and domino) or living donor liver transplantation according to previously described protocols (22. S Iacob. ablative therapy and/or systemic chemotherapy according to the clinical status of the patient. Ablative Therapy The RFA protocol has been previously described (24). 5. For each patient. postoperative complications and operative mortality. Recurrence was defined clinically as a new lesion with features of HCC identified by two imaging studies (abdominal ultrasonography and contrast-enhanced computed tomography). RESULTS Patient characteristics The patient demographics for the entire cohort are outlined in Table 1.

8 8. a total of 121 (60.9% vs 8.9 29.3 15.9 4.10 47 88 92 45 22 16 29. There were 210 cases (71.2%) received therapy as a bridge-to-transplantation: TACE alone in .5 4. as shown in Tables 2 and 3.9 31.5 25.2 57.3% respectively. of which 12 (63.5±3.4 78.6 50 15.5 9 3.4%) and 78 were women (26.4yr (range 8-81).4%) with liver cirrhosis: 114 (38.4 5 103 132 50 4 1. 89 (30.6%).9 65 5. with the HCC diagnosis made by two imaging modalities.4 33 126 88 14 26 7 231 63 11.9cm (range 1-24cm).4 88 191 15 29.9%) were outside of Milan criteria.2%) resections were on cirrhotic livers.9 4.7 35 44.8±11. (51) (67.4 124 170 42.2 42. and seven (3%) were in class C of Child-Pugh classification before treatment.3 3.6 21.1 53 198 34 18 67.Treatment of Hepatocellular Carcinoma Hepato-Gastroenterology 56 (2009) TABLE 1 Patient Demographics and Tumor Characteristics Variables No Cirrhotic etiology Hepatitis virus HBV HCV HBV+HCV HBV+HDV HBV+HCV+HDV Alcohol Other Okuda classification Stage 1 Stage 2 Stage 3 CLIP score 0 1 2 3 4 JIS score 0 1 2 3 4 UICC I II IIIA IIIB IVA IVB Single lesion Multiple Milan criteria inside of Milan criteria outside of Milan criteria BCLC class A B C D Edmondson-Steiner grading Well Differentiated Moderately Differentiated Poorly Differentiated 210 N/A Percent 39 106 10 11 2 10 32 18. Liver transplantation was performed in 19 patients.8ng/ml. Based on Child-Pugh classification.8 93 147 45 9 31. Therapeutic modalities Different types of therapies were used in the treatment of our patients. ablation therapy in 20.8% Child-Pugh class A) than in the ablative group (68% Child-Pugh class B). The nine patients without histological data were patients that underwent percutaneous RFA without prior biopsy.2% vs 51% and LT in 7. Liver resection was performed in 71.4 6.3 11.8%) patients were in class A.6 50. liver function was better in the resection group  TABLE 2 Therapeutic Modalities for HCC Therapeutic modalities Patients % Cirrothic Non-cirrothic Liver resections Liver transplantation Ablative techniques 201 19 74 68. The surgical techniques included whole graft liver transplantation (cadaveric in 11 patients and domino in 1 patient) or living donor liver transplantation (n=7). Twelve patients (63. The median alpha-fetoprotein (AFP) level was 43.0001).3%) in class B.8 2.9% of patients with cirrhosis Child A versus 40. Mean age was 59.2 0.1%) were within Milan criteria and seven (36.2 Two-hundred-sixteen patients were men (73.4 7.6% of patients non-Child A cirrhosis. There was a statistically significant difference between patients with Child A class and patients with Child B/C class regarding type of therapy (p<0. Liver resection was performed via conventional open surgery in 190 patients and via laparoscopy in 11 patients.1 121 17 72 80 2 2 Total 294 100 210 84 TABLE 3 The Types of Liver Resection for HCC Type of hepatectomy* Cirrhotic All Nonpatients cirrhotic Child A Child B Child C Right hepatectomy Right trisectionectomy Left hepatectomy 27 4 7 21 3 5 6 1 2 0 0 0 0 0 0 Left lateral sectionectomy (II-III) 29 12 14 3 - Non anatomical resection 127 38 56 29 4 1 0 0 0 0 5 1 201 1 0 80 2 -0 82 2 1 35 0 0 4 Right posterior sectionectomy (VI-VII) Segmentectomy Bisegmentectomy Total *Nomenclature of segments and types of liver resection according to the Brisbane 2000 terminology.7 15.7 5. Mean tumor size was 6.9 17 1.

4% and 28. respectively). respectively (p=0. In the cirrhosis group.1%).02) were independent negative prognostic factors for overall survival (Table 4).17).1%.006 JIS 3/4/5 classification 0.66 1. and one (1.2%. After excluding the 30-day mortality. sepsis (n=3).005 0. Child-Pugh classification.5 mo. 152 of the total 294 patients died (51. There was no difference regarding survival between transplanted patients inside or outside Milan criteria (p=0. 8. 37.3 mo).5%) and open or laparoscopic intraoperative RFA (n=58.6%. BCLC C/D classification (p<0. Major complications were liver failure (n=5). 72.0001). respectively.1% for patients with liver cirrhosis. S Iacob. Hepato-Gastroenterology 56 (2009) S O Dima. Treatment morbidity and mortality The overall postoperative morbidity rate was 21.01 0. The survival rate was 73.83 0.2%. after RFA (p=0.1).56 0. radiotherapy and RFA in 1 patient.007). 78. JIS 3/4/5 classification (p<0.6% for all post-transplantation patients. Patients with a tumor meeting Milan criteria had significantly higher survival rates compared to patients exceeding these criteria (p=0.57 1.57 0. The survival rate for patients with a single nodule was significantly higher than that for patients with multiple nodules (p=0.to poorly-differentiated HCC according to Edmondson-Steiner grading (p=0.05). TABLE 4 Overall survival .3mo (range 0. the one and three-year survival rates after LR.4%).6%.13). Patients treated by RFA with tumors ≤3cm had a higher overall survival rate in comparison to that for patients with tumors >3cm (p=0.04).001). During the follow-up. Variables found to be significant in the univariate analyses were included into a multivariate Cox analysis.77 0. respectively. and AFP level >43. systemic chemotherapy in 38 cases (27%).1%) patients were treated conservatively. Of the three liver transplantation patients developing extrahepatic recurrences.7mo (range 0.5%) after LR. and acute pancreatitis (n=1). hemoperitoneum (n=6).008).52 0. and 40%. acute pancreatitis (n=1).8% and 0%. Treatment was attempted in 69 cases (48.9% in cirrhotic patients and 3. Median survival after LR and RFA was 30. TACE combined with RFA in two cases (1. nine (16%) in the RFA group.8% (64/294). The LT group did not reach the median survival (range 1-82.005). CLIP 2/3/4 classification (p=0. The mortality rate in the LR group was 4.9%): TACE alone was used in ten cases (7.8%. 45. 72%. The survival curves for either treatment modality are shown in Figure 2. One patient (within Milan criteria) developed peritoneal carcinomatosis after eight months.Results of multivariate Cox Proportional Hazard Model Survival Analysis Variable Regression Hazards ratio coefficient p value Serum AFP >43. The second patient developed bone and brain . and 72. TACE combined with systemic chemotherapy in two cases (1. abdominal abscess (n=21).Results of Multivariate Cox Proportional Hazard Model Survival Analysis Variable Regression Hazards ratio coefficient p value Tumor size >6.0001).1-90.0001).4%). Factors influencing overall survival Multiple tumors (p=0. outside Milan criteria (p=0. Disease-free survival Recurrences were observed in 141 of 294 patients (47. respectively (p=0.7%). presence and etiology of cirrhosis.63 0.64 0. three and five years of 69.3%) after orthotopic LT. tumor size >6. The overall median survival for the entire group was 29.006) and JIS 3/4/5 classifications (p=0. with these 11 deaths due to liver failure (n=5).002).01 Ablative therapy 0. Fl Botea. and died at ten months postLT.and five-year overall survival rates were 81. et al. two were beyond Milan criteria. UICC stage III/IV (p=0.8% in non-cirrhotic patients.0001).02 TABLE 5 HCC Recurrence . repeated hepatectomy in six cases (4.51 0.3%) after RFA. gender. a serum AFP level >43.52 0. Procedure-related mortality occurred in nine cases (4. there was no significant difference between the three treatment groups (LT.4%.48 0.3%).001). chemotherapy. TACE associated with LR and chemotherapy in 1 patient. LT and RFA were 61.3%. after LR.9%).8 ng/ml (p=0.006).8%) in the LT group. 13. local ablative therapy in four cases (2. Five year overall survival rate for the entire series (n=294) was 28% (Figure 1). 43% and 25. LR and RFA).1-59). one case (5. and the remaining 72 (51. three.2%) were in the LR group. hemoperitoneum (n=2). of which 46 (82.8%).1 mo). The ablative group included all patients treated with ablative techniques only.71 0.5cm BCLC C/D classification JIS 3/4/5 classification 0.Analysis of 294 patients yielded an actuarial survival at one. and type of therapy were not found to influence the overall survival.2%.51) . 48% and 31% for patients without liver cirrhosis and 66.4) and 24mo (range 1.6 0. and TACE associated with LR. moderate.002) were found to be negative predictive factors for overall survival at univariate Cox analysis. 72. respectively. and one case (1. The overall in-hospital mortality was 3. BCLC C/D (p=0. such as percutaneous RFA (n=10. 38%. Other analyzed factors such as age.02 10 patients. Overall survival The median follow-up interval for all 294 patients was 15. Adjuvant systemic chemotherapy was carried out in 56 patients (19%).7%.3% and n=6.85 ng/ml BCLC C/D classification 0. Okuda III classification (p=0.1–90.8ng/ml (p=0. The one-.001 0.5cm (p=0.

three.02). this study represents one of the largest published cohorts regarding the Eastern European experience in the multidisciplinary treatment of HCC. Median disease-free survival for LR and RFA were 29. FIGURE 2 Overall survival by treatment group. 34%.5%. There was a significant difference favoring LT patients and patients undergoing hepatectomy (Figure 4). three. tumors larger than 6. multifocal HCC (p=0.01) classifications. 71.5cm (p=0. DISCUSSION In the management of HCC patients.08). respectively.5%.01). tumor size >6. respectively) (p=0. The current study has confirmed several specific aspects of HCC. The serum AFP value was not a negative independent factor for HCC recurrence in our series. especially in the presence of cirrhosis. BCLC C/D (p=0. To the best of our knowledge. These findings are in agreement with the fact that the majority (>70%) of the cirrhotic patients listed Hepato-Gastroenterology 56 (2009)  FIGURE 1 Overall survival for the entire series (n=294). 24% and 0% among RFA treated patients.8ng/ ml (p=0.8–56.8mo (range 0.5cm (p=0.6%.02).02). Median disease-free survival for LT was not reached (range 1-82.5%) and HBV (18. Independent predictors of HCC recurrence were JIS 3/4/5 (p=0. and ablative therapy (p=0. FIGURE 3 Overall recurrence-free survival for the entire series (n=294). 78% and 78% among LT patients.2%. including the increased incidence of HCC in cirrhotic patients (n=210.001).02) (Table 5). The factors identified in the univariate analysis were serum AFP level >43.001) and ablative therapy (p=0.01) and BCLC C/D (p=0. The third patient developed lymph node metastases and tumoral portal vein thrombosis after six months. 22. classifications UICC III/IV (P=0. the question of the best therapeutic combinations still represents a matter of debate and concern. There were no statistically significant differences in the one-.003).6).5%.43%) and its main etiologies – HCV (50. JIS 3/4/5 (p=0. The high recurrence rate is still an unsolved problem.0003).9% vs. Patients with nodules <3cm who underwent RFA had a significantly better one and three-year recurrence-free survival rate compared to patients with larger tumors (76% and 60.1–90.and five-year disease-free survival rates were 67. The five-year recurrence-free survival rate for the entire cohort was 26. underwent chemo. underwent chemotherapy and was alive at 17mo post-LT. p=0.and five-year recurrence-free survival rates after LR in patients with cirrhotic liver in comparison with non-cirrhotic patients (61. 44% and 26% after LR.and radiotherapy and was alive at 25mo post-LT. 51% and 30% for patients with and without liver cirrhosis. The same prognostic variables analyzed as predictors of overall survival were entered in univariate and multivariate Cox Proportional Hazard Model Survival Analysis for predicting risk factors for HCC recurrence. FIGURE 4 Recurrencefree survival by treatment group. 52. .8% (Figure 3). respectively.4) and 14mo (range 0.0009). One-. and 86. respectively.6%).5% and 75%. 45% and 12.Treatment of Hepatocellular Carcinoma metastases after 12 mo.1 mo).

2%) (36). A major argument for liver transplantation over resection is the lower recurrence rate (40). or 4–5 nodules less than 3cm. (23.9% after RFA vs. similar to that in Western European countries (26). but none are currently considered standard. Many patients with an HCC beyond the Milan criteria from the beginning only have transplantation as a potential cure. optimal treatment should depend on the severity of the underlying liver disease (28).0001) (44). Wakai et al found that hepatectomy provides better long-term S O Dima.8%) being outside Milan criteria. survival (37). and patients with HCC were favored in the MELD era. Liver transplantation offers the best chance for long-term survival in cirrhotics. there was no pathological evidence of clear margins or complete tumor necrosis after RFA and some can argue that our result may be related to . reported a significantly improved recurrence–free survival rate in cases undergoing systematic resection as compared to those undergoing partial resection (31). none of which may exceed 5cm (23. in contrast to other studies (27). major resection was performed less frequently in the cirrhotic patients.42) In this study. Inamura et al. Fl Botea. et al. S Iacob. However. Mazzaferro V et al. In the present study. who account for just 5% of cases in Western countries and about 40% in Asia (29). Our results concerning the recurrence rate are similar to those from the literature. In the cases of liver resections in cirrhotic patients (n=121).007). A recent prospective randomized trial demonstrated similar cancer-related survival rates in patients with small. with the sum of the diameters not exceeding 8cm. Hepato-Gastroenterology 56 (2009) for LT have viral-induced cirrhosis (25). According to a study by Scatton O et al. and are consistent with the changing prevalence of HCV infection in Romania. Heckman et al. but the proportion of cirrhotic patients was rather low (48. Few studies have aimed to evaluate histologically the precise results after RFA. especially vascular infiltration. We believe that aggressive treatment of local recurrences is important in prolonging survival. (46) has proven a complete destruction of HCC at histology in 55% of targeted nodules. The results of a recent study analyzing the survival outcomes in the US population showed that the five-year survival rates were 67% after transplantation. This finding was also the case in our study. which are consistent with our results.6%. In our study. 20% after RFA and 3% for no or incomplete local therapy (p<0.. Other examples of extended criteria are those established by the Barcelona Clinic Liver Cancer which require a single nodule less than 7cm. Various nonsurgical treatments are now available for HCC.33). the multidisciplinary approach of HCC constitutes the standard of care in our center in accordance with other centers around the world. The effectiveness of RFA in small tumors less than 3cm is well known and led to the assignment of RFA in the role of “curative” treatment for HCC in these cases (45). Nowadays. reported that the indication for hepatectomy should be expanded in order to not exclude from radical therapy patients that could benefit from it (35). whereas late recurrence (more than two years) is reported to be primarily associated with the presence of cirrhosis (32. Ablative therapy proved to be a predictive factor for HCC recurrence in our study. Previous studies have shown that the treatment of local recurrences with TACE is effective in prolonging patients’ survival (34) Capussotti et al. Due to this situation. as only 6. the liver function and the patient’s general condition. Makuuchi (Tokyo rule) which requires no more than five tumors. and the 5–5 rule of M. Treatment was adapted to each case. irrespective of tumor size.5cm or 2–3 nodules up to 4. these non-surgical approaches are used in HCC for palliation or as an adjunct to a surgical attempt to cure. There was no significant difference in five–year survival rates between cases with and without cirrhosis. however. in part due to their inefficacy. Surgery represents the treatment of choice for HCC in non-cirrhotic patients. 35% after LR. We explored the expansion of the transplant eligibility beyond Milan criteria. with lower morbidity rates after RFA when compared with LR (38.46% of HCC patients were transplanted. according to the tumor status.39). p=NS). p=0. even though a living donor transplant program is available. proved that there was no statistical difference in overall survival between patients with and without bridging treatments prior to transplant (43). Over the past ten years. the three-year recurrence-free survival rate was significantly higher after LT than after LR or RFA (LT versus RFA. recurrence-free survival was significantly better in the LR group in comparison to the RFA group. 64% after LR at four years. It has already been reported that HCC has a higher resectability rate in the non-cirrhotic liver than in the cirrhotic liver (30). Early recurrence (two years after LR) is associated mainly with adverse tumor factors. organ shortage is a limiting factor.0003 and LT versus LR. In a retrospective study on 149 patients with tumors ≤4cm comparing the results after surgical resection or percutaneous ablation. early tumors (67. only nine patients underwent major resections. A study analyzing patients who underwent LR for tumors >10cm reported an overall survival rate of 28. 2–3 nodules less than 5cm. with 7 out the 19 transplanted patients (36. In general. p=0. treatment for HCC has changed in our center with the introduction of novel surgical and non-surgical techniques. Both univariate and multivariate analyses did not show any significant difference in overall and recurrence-free survival between patients with HCV or HBV infection and patients with non-viral-induced HCC.5cm. an extension of the Milan criteria has been proposed. This reality is reflected in our experience.41) The most well known extended criteria are the so-called San Francisco criteria: single nodules up to 6. and this percentage increased to 63% for tumors <3cm.

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