Extrahepatic Recurrence Of Hepatocellular Carcinoma Research Articles

Salvage Ablative Radiation Therapy for Isolated Intraabdominal Recurrences of Hepatocellular Carcinoma

<h3>Purpose/Objective(s)</h3> The standard of care for extrahepatic hepatocellular carcinoma (HCC) is a systemic therapy. However, some patients present with limited intra-abdominal disease that might benefit from local ablative radiation therapy (RT) with, or instead of, systemic therapy. This study explores outcomes of ablative RT for isolated intra-abdominal recurrences from HCC. <h3>Materials/Methods</h3> A single-institution retrospective chart review was conducted from 2013 to 2021. Inclusion criteria were any patient with HCC that had limited disease in an abdominal lymph node (LN) or adrenal gland (AG) treated with salvage ablative RT. The primary outcome was local control (LC) in the target lesion. Secondary outcomes were progression-free survival (PFS) and overall survival (OS) from the time of recurrence after completing RT. <h3>Results</h3> 31 patients met inclusion criteria, of which 21 (67.7%) had a recurrence in a LN while 10 (32.2%) had recurrences in an AG. 19 (90%) of LN recurrences were in the portal region. The median time from initial HCC diagnosis to extrahepatic recurrence was 18 months (range 0 to 152 months). Among all patients, 21 patients received immunotherapy (prior, concurrent, or after) in addition to salvage RT. 27 (87.1%) patients received salvage SBRT, and 4 (12.9%) patients received fractionated RT. The median dose was 4500 in 5 fractions. LC, as defined as no progression in target lesion, was 100%. The median PFS, defined by recurrence or death, was 18 months. The median OS was 29 months. There was a statistical difference in OS in patients that received IO and RT vs. RT alone (p=0.038) in favor of RT alone. There was no significant difference in OS for a LN recurrence versus salvage RT for an AG recurrence (p=0.389). <h3>Conclusion</h3> Salvage ablative RT, with or without immunotherapy, can produce meaningful PFS and OS in well-selected patients with limited intra-abdominal extrahepatic recurrence of HCC. This benefit appears the same for LN recurrences and AG metastases and might be independent of immunotherapy. Prospective data are needed to verify these results.

Multi-Institutional Development and External Validation of a Nomogram for Prediction of Extrahepatic Recurrence After Curative-Intent Resection for Hepatocellular Carcinoma.

Extrahepatic recurrence of hepatocellular carcinoma (HCC) after surgical resection is associated with unfavorable prognosis. The objectives of the current study were to identify the risk factors and develop a nomogram for the prediction of extrahepatic recurrence after initial curative surgery. A total of 635 patients who underwent curative-intent resection for HCC between 2000 and 2017 were identified from an international multi-institutional database. The clinicopathological characteristics, risk factors, and long-term survival of patients with extrahepatic recurrence were analyzed. A nomogram for the prediction of extrahepatic recurrence was established and validated in 144 patients from an external cohort. Among the 635 patients in the derivative cohort, 283 (44.6%) experienced recurrence. Among patients who recurred, 80 (28.3%) patients had extrahepatic ± intrahepatic recurrence, whereas 203 (71.7%) had intrahepatic recurrence only. Extrahepatic recurrence was associated with more advanced initial tumor characteristics, early recurrence, and worse prognosis versus non-extrahepatic recurrence. A nomogram for the prediction of extrahepatic recurrence was developed using the β-coefficients from the identified risk factors, including neutrophil-to-lymphocyte ratio, multiple lesions, tumor size, and microvascular invasion. The nomogram demonstrated good ability to predict extrahepatic recurrence (c-index: training cohort 0.786; validation cohort: 0.845). The calibration plots demonstrated good agreement between estimated and observed extrahepatic recurrence (p=0.658). An externally validated nomogram was developed with good accuracy to predict extrahepatic recurrencefollowing curative-intent resection of HCC. Thisnomogram may help identify patients at high risk of extrahepatic recurrence and guide surveillance protocols as well as adjuvant treatments.

Hepatocellular carcinoma with right atrial tumor thrombus.

Hepatocellular carcinoma with right atrial tumor thrombus is uncommon but with a dismal prognosis. By comprehensive retrieval of literature published between 2000 and 2019, 53 reports were obtained with 187patients recruited into this study. The extracted data included patient characteristics, tumor characteristics, treatment, follow-up and outcomes. Statistical analyses applied were student t, Fisher exact and I2 tests. Patients were devided into 6 groups according to treatment of choices: transarterial chemoembolization (TACE), surgery, radiotherapy, chemotherapy, interventional treatment and supportive care. The overall survival rate of this cohort was 40.8 %. The survival rate of patients receiving TACE was 33.3 % and that of surgical patients was 41.9 %. The survival time of patients with TACE was longer than surgical patients, but lack of a statistical significance. Patients had a follow-up of 15.7 ± 16.6 (median 10) months. The patients receiving radiotherapy had the longest follow-up among all groups. Intra- and/or extrahepatic recurrence of hepatocellular carcinoma was the major morbidity. The mortality rates in a decremental sequence for patients receiving different treatments were supportive care > radiotherapy > surgery > TACE > interventional treatment. No difference was found in mortality between patients reported from case reports and those from non-case reports. Advanced hepatocellular carcinoma with right atrial thrombus is an aggressive malignancy. Based on the results of median survival time, radiotherapy and TACE seemed to be associated with an improved prognosis and possible better survival.

Impact of eleven prognostic scores on intra- and extrahepatic recurrence of hepatocellular carcinoma after liver transplantation

Impact of eleven prognostic scores on intra- and extrahepatic recurrence of hepatocellular carcinoma after liver transplantation

Validity of eleven prognostic scores with respect to intra- and extrahepatic recurrence of hepatocellular carcinoma after liver transplantation.

Tumor recurrence is the most frequent cause of death after liver transplantation for hepatocellular carcinoma. We selected ten other prognostic classifications to evaluate their potential to predict the risk of recurrence after LT for HCC as compared to the Milan classification. All of the other scores have not been compared with one another in a single cohort. Data of 147 consecutive patients transplanted at our department between 1996 and 2014 were analyzed and staged for morphological and functional scores of underlying liver disease. For long-term follow-up, we analyzed intrahepatic (within the liver±distant metastases) and extrahepatic (distant metastases only) recurrence separately. The median survival time for all patients was 106months. The 5- and 10-year observed survival rates were 61 and 43%, respectively. The observed cumulative 5- and 10-year recurrence rates were 37 and 39%, respectively, 10-year intrahepatic and extrahepatic recurrence rates were 12 and 27%, respectively. Median survival time after diagnosis of first recurrence was 7.5 (0-120) months; 2 and 18months for all, intra- and extrahepatic recurrence, respectively. UCSF-, up to seven-, Shanghai Fudan- or Duvoux classifications can identify patients with a cumulative 10-year recurrence rate below 20%. The pre-therapeutic AFP level should be considered in addition to the geometry of the intrahepatic lesions.

Sorafenib and a novel immune therapy in lung metastasis from hepatocellular carcinoma following hepatectomy: A case report.

Sorafenib is the standard therapeutic strategy for recurrent hepatocellular carcinoma (HCC) following hepatectomy. However, only few patients truly benefit from this therapy. Thus, new strategies combined with sorafenib are urgently required. We herein present the case of a patient with hepatic and extrahepatic HCC recurrence following hepatectomy, who was treated by combined sorafenib, focused ultrasound knife and DRibbles-pulsed dendritic cell (DC) vaccine. Enzyme-Linked ImmunoSpot assay (ELISPOT) and intracellular staining (ICS) analysis were used to detect the secretion of interferon (IFN)-γ by T cells at different timepoints of the vaccine in order to evaluate the patient's specific T-cell response to SMMC-7721-derived DRibbles vaccine. The α-fetoprotein level decreased from 103,295 to 5 ng/ml and the patient displayed improved liver function, an Eastern Cooperative Oncology Group performance status score of 0, remission of liver metastases and disappearance of the lung metastases 8 months post-combination therapy. The computed tomography scan revealed the disappearance of liver metastases 2 years post-combination therapy. The ELISPOT data revealed a low antigen-specific T-cell response 4 weeks after the first vaccine cycle and the response decreased to nearly zero prior to the second cycle. However, high antigen-specific T-cell response was observed 2 weeks after the second vaccine cycle and did not decrease, even after 10 months, which was consistent with the result of the ICS analysis, which demonstrated that most of the secreted IFN-γ was produced by CD4+ T cells, whereas a low CD8+ T-cell response was observed (0.429 vs. 0.0665%, respectively). Our results demonstrated that antigen-specific T-cell response aimed to treat recurrent HCC may be induced through stimulation by the DC-DRibbles vaccine. The success of the treatment supports the combination of sorafenib, focused ultrasound knife and DC-DRibbles vaccine as a therapeutic strategy for patients with HCC recurrence following hepatectomy.

Predictive factors for extrahepatic recurrence of hepatocellular carcinoma following liver transplantation.

Recurrence of hepatocellular carcinoma (HCC) in patients treated with liver transplantation (LT) is associated with diminished survival. Particularly, extrahepatic localization of HCC recurrence contributes to poor prognosis. Clinicopathological data of patients who underwent LT for HCC between 1989 and 2010 in a high-volume transplant center were retrospectively evaluated, and predictors of extrahepatic recurrence were identified. Three hundred and sixty-four patients underwent LT for HCC. After a median follow-up time of 78 months, 93 patients (25%) were diagnosed with a recurrence. Median time to recurrence was 19 months. Recurrence was located exclusively in the liver in 19 cases (20%), and 74 patients (80%) had extrahepatic recurrence. Factors associated with extrahepatic recurrence in multivariate analysis included HCC beyond the Milan criteria (p < 0.0001) and the presence of macrovascular tumor invasion (p = 0.035). In patients with HCC beyond the Milan criteria who developed a recurrence (N = 73), macrovascular invasion was the only positive predictor of extrahepatic recurrence in multivariate analysis (p < 0.0001). In patients with HCC within the Milan criteria who recurred after LT (N = 20), DNA-index >1.5 (p = 0.013) was the only predictive factor for extrahepatic recurrence in multivariate analysis. Advanced HCC beyond the Milan criteria and the presence of macrovascular invasion are associated with an increased risk for extrahepatic recurrence and are currently considered as relative contraindications to LT. In patients with HCC within the Milan criteria, the DNA-index represents a valuable prognostic marker for the development of extrahepatic recurrence and may support the selection of patients for intensified postoperative tumor surveillance.

Late Extrahepatic Recurrence of Hepatocellular Carcinoma after Liver Transplantation: A Rare Case Report and Literature Review

Recurrence rate of hepatocellular carcinoma is reported below 15%, mainly within 2 years after liver transplantation. We report an original case of a 62-year-old man with HCV-related liver cirrhosis, complicated by small uninodular hepatocellular carcinoma (HCC) completely eradicated by intraoperative thermal ablation in April 2003, who underwent liver transplantation in April 2004. The histopathologic analysis of explanted liver described an occult well differentiated uninodular HCC of 7 mm in diameter, without vascular invasion. Despite a sustained virologic response to antiviral therapy for recurrence of HCV infection in the graft and alpha-fetoprotein always within the normal range, in 2014 (10 years after liver transplantation) the patient developed brain and renal lesions, resulted as undifferentiated hepatocellular carcinoma recurrences at the histopathologic analysis. After a complete surgical resection of both recurrences, we introduced therapy with Sorafenib and exchanged immunosuppressive therapy from Tacrolimus to Everolimus, but six months later alpha-fetoprotein abruptly increased and total body computer tomography shown a significant progression of disease with recurrences in liver, spleen, lung and lymph nodes. Nevertheless, to date the patient is still alive. This case illustrates the highly variable rate of HCC recurrence and progression after liver transplantation and raises interesting questions about its natural history and post-transplant surveillance.

Solitary Extra-hepatic Recurrence of Hepatocellular Carcinoma in Sternum After Liver Transplantation

Solitary Extra-hepatic Recurrence of Hepatocellular Carcinoma in Sternum After Liver Transplantation

Surgical treatment of extrahepatic recurrence of hepatocellular carcinoma.

The purpose of this study was to clarify the clinicopathological features of extrahepatic hepatocellular carcinoma (HCC) recurrence after hepatectomy in order to schedule optimal treatment strategies for better long-term outcomes. A cohort of 206 patients who had undergone curative hepatectomy for HCC was analysed; 133 patients had developed relapse. Among them, 101 patients had intrahepatic recurrence only (IHR), and 32 patients had extrahepatic recurrence (EHR). Clinicopathological and survival data were compared between the two groups. The overall survival rate after hepatectomy was better in the IHR than in the EHR group (p<0.0001). The recurrence-free interval after hepatectomy was significantly shorter in the EHR than in the IHR group (258 vs. 487 days, p<0.0043). Patients in the EHR group were more likely to have a high PIVKA II, a large tumour, and microscopic portal vein invasion when compared with patients in the IHR group. Microscopic portal vein invasion was the most important independent risk factor for EHR after hepatectomy (p=0.0295). Patients with more than two risk factors for EHR showed poor prognosis in comparison with patients without any risk factors (p<0.001). In the EHR group, patients who underwent repeated resection had significantly better survival than patients receiving only the best supportive care (539 vs. 133 days, p=0.0098). Furthermore, among EHR patients with concomitant IHR, patients with controllable IHR had significantly better survival than those with uncontrollable IHR (524 vs. 147 days, p=0.0131). EHR of HCC was associated with early recurrence, and risk factors for the occurrence of EHR included the presence of high PIVKA II, large tumours, and microscopic portal vein invasion. Resection of recurrent tumour and local control of concomitant IHR may improve the prognosis of EHR patients.

High risk of lung metastasis after resection of hepatocellular carcinoma more than 7 cm in diameter

The relationship between the tumor size and organs of recurrence was analyzed to identify a high-risk group for the extrahepatic recurrence of hepatocellular carcinoma (HCC) after resection. A total of 544 patients with HCC underwent primary surgical resection for HCC between 2001 and 2010. Of these, 293 patients had a solitary tumor but no macroscopic vascular invasion. The prognostic factors for the overall survival and relapse-free survival were analyzed among these 293 patients. The recurrent organs and frequency of recurrence were also examined. The analysis of the 293 patients showed that both the overall and relapse-free survival rates of the patients with a large tumor (>7 cm in diameter) were significantly worse than those of the patients with a tumor <7 cm. The incidence of lung metastasis was remarkably high in the group of patients with tumors more than 7 cm (24.0 %), in comparison to those with tumors <7 cm. A multivariate analysis revealed that the tumor size was the only independent risk factor for lung metastasis. The patients with large HCC tumors more than 7 cm in diameter were at high-risk for a poor prognosis due to a high percentage of lung metastasis, even if there was no macroscopic vascular invasion.

Extrahepatic recurrence of hepatocellular carcinoma after curative hepatic resection.

Backgrounds/AimsThis study was designed to compare the recurrence patterns after curative hepatectomy, to compare the prognosis according to the initial site of metastasis, and to investigate the independent predictive factors associated with extrahepatic recurrence in hepatocellular carcinoma (HCC) patients after curative hepatectomy.MethodsFrom January 2000 to July 2009, 307 patients underwent curative hepatectomies for HCC at our institution; 152 patients showed recurrences. Patients were divided into 2 groups according to their initial recurrence site: the intrahepatic recurrence (IHR) group and extrahepatic recurrence (EHR) group. The IHR group was comprised of 111 patients and the EHR group was comprised of 41 patients. The study investigated the preoperative, intraoperative, and postoperative factors related to the recurrence pattern retrospectively and compared the prognoses of the patients.ResultsA five-year survival rate after an initial recurrence was lower in the EHR group (21.5%) than the IHR group (36.3%) (p<0.001). The preoperative alpha-fetoprotein (AFP) level was an independent risk factor for extrahepatic recurrence (p=0.014).ConclusionsPatients with a preoperative AFP level greater than 200 ng/ml have a higher incidence of extrahepatic metastases after a curative resection of HCC. Increased level of preoperative AFP is an indication for a short-term follow up hepatectomy.

Results of a surgical resection of pulmonary metastasis from hepatocellular carcinoma: prognostic impact of the preoperative serum alpha-fetoprotein level

Pulmonary metastasis is the most common type of extrahepatic recurrence of hepatocellular carcinoma (HCC). The outcome of pulmonary metastasectomy of HCC has not yet been thoroughly investigated. The outcomes of surgical treatment of pulmonary metastases from HCC were reviewed in order to analyze the postoperative survival and the relevant prognostic factors. This study retrospectively reviewed 20 patients who underwent pulmonary metastasectomy from an HCC between 1990 and 2007 at two institutions. The surgical outcome was evaluated by both the overall survival and cancer-specific survival after pulmonary resection. The association between various clinico-pathological factors and the survival outcome was analyzed. The overall survival rate after the initial pulmonary metastasectomy was 46.9% at 5years, and the cancer-specific 5-year survival rate was 63.2%. One patient died of surgery-related events 19days after the pulmonary resection. The preoperative AFP (alpha-fetoprotein) level was found to be a significant prognostic factor for both overall and cancer-specific survival for patients undergoing pulmonary metastasectomy. Both the overall and cancer-specific survival rates were significantly worse for the patients with AFP≥500ng/ml in comparison to those with AFP<500ng/ml (p<0.05). No other factors were associated with the survival after pulmonary metastasectomy. The serum level of AFP might be a valuable predictor for the outcome of pulmonary metastasectomy required for metastasis of HCC.

Resection of Hepatocellular Carcinoma Recurring in the Diaphragm after Right Hepatic Lobectomy

We describe a 35-year-old man with hepatocellular carcinoma (HCC) that recurred in the diaphragm after right hepatic lobectomy. The patient had undergone right hepatic lobectomy for HCC with chronic hepatitis B virus infection 1 year previously. On pathological examination, the tumor measured 15 × 14.4 × 11 cm and was moderately well differentiated. The surgical margins were negative. After 1 year, computed tomography of the abdomen revealed a mass extending from the right side of the diaphragm to the retroperitoneal space. The mass was enhanced in the early phase and washed out in the late phase. Extrahepatic recurrence of HCC in the diaphragm was diagnosed. We performed tumor resection with partial resection of the right side of the diaphragm and wedge resection of the right lower lobe of the lung. The diaphragm was reconstructed with a sheet of artificial pericardium. The histopathological diagnosis was recurrence of HCC in the diaphragm with invasion of the right lung. The postoperative course was uneventful, and the patient was discharged on postoperative day 8. He underwent chemotherapy with cisplatin and 5-fluorouracil. After 9 months, the patient died of unresectable recurrence of HCC in the brain. No recurrence was detected in the right subphrenic area.

Predictors of Extrahepatic Recurrence After Curative Hepatectomy for Hepatocellular Carcinoma

The aim of this study was to elucidate the predictors of extrahepatic hepatocellular carcinoma (HCC) recurrence after hepatectomy. A cohort of 252 patients with HCC who underwent hepatectomy following a recurrence were reviewed. The patients were categorized into 2 groups according to the pattern of their initial recurrence. Clinicopathological and survival data were compared between the groups. Of the 252 patients, 218 had intrahepatic recurrence (IHR) (86.5%) and 34 had extrahepatic recurrence (EHR) (13.5%) as their initial recurrence. The mean duration of time until the initial recurrence after hepatectomy of the EHR and IHR groups was 1.8 and 2.2years, respectively. The rate of recurrence within 6months after hepatectomy of EHR and IHR groups was 35.3 and 14.2%, respectively (P=.002). The 3-, 5-, and 10-year cumulative survival rates of EHR group were 60.3, 24.0, and 6.0%, respectively, which were significantly lower than that of IHR group (74.5, 57.7, and 23.1%, P=.004). A multivariate analysis showed that blood loss during surgery and microscopic hepatic vein invasion remained as independent risk factors for increased EHR after hepatectomy for HCC. Furthermore, the combination of these 2 independent factors showed a significant association with the EHR. EHR of HCC was associated with early recurrence and a poor survival after a hepatectomy. The combination of 2 independent factors for EHR, the presence of microscopic hepatic vein invasion and the blood loss during surgery, may be useful for predicting the risk for occurrence of EHR during the follow-up period.

Long-term survival after resection of extrahepatic recurrence of hepatocellular carcinoma at the right colon

Long-term survival after resection of extrahepatic recurrence of hepatocellular carcinoma at the right colon

Patterns and clinicopathologic features of extrahepatic recurrence of hepatocellular carcinoma after curative resection

Little is known about the metastatic pattern in patients with extrahepatic metastasis after the removal of primary hepatocellular carcinoma (HCC). The aim of the present study was to determine the clinicopathologic characteristics and prognosis of patients with extrahepatic metastasis from HCC according to the recurrence pattern. Among the patients who underwent hepatic resection for HCC between 1981 and 2001, 80 patients had no recurrence; 221 patients had intrahepatic recurrence, and 47 patients experienced extrahepatic metastasis within a mean follow-up period of 4.8 +/- 3.7 years (+/-SD; range, 2-15 years). The pattern of extrahepatic metastasis after hepatic resection was divided into pattern I (first recurrence in the liver and then spread outside the liver after repetitive intrahepatic recurrences and repetitive locoregional treatments), pattern II (simultaneous recognition of intrahepatic and extrahepatic recurrences), and pattern III (extrahepatic, but no intrahepatic, lesions at first recurrence). There were significant differences in proportions of patients with invasion of the portal vein, hepatic vein, or inferior vena cava, intrahepatic metastases, and tumor stage between patients with intra- and extrahepatic metastases. The disease-free survival and extrahepatic metastasis-free survival in pattern I were better than pattern II. Survival after extrahepatic metastasis did not correlate with the 3 patterns. Although long-term overall survival was better in patients with pattern I of extrahepatic recurrences, prognosis was poor in all patterns once extrahepatic metastasis developed.

Positron emission tomography/computer tomography in guidance of extrahepatic hepatocellular carcinoma metastasis management

Hepatocellular carcinoma (HCC) is one of the most common primary cancers in the world. Surgery is the gold standard for treatment of patients with HCC. Recurrence and metastasis are the major obstacles to further improve the prognosis of HCC. Most recurrences are intrahepatic. However, 30% of the recurrences are extrahepatic. The role of resection in intrahepatic recurrences is widely accepted. The role of resection in extrahepatic HCC recurrence and metastasis is not well established. 18F fluorodeoxyglucose (18F-FDG) positron emission tomography/computer tomography (PET/CT) is useful in detecting distant metastasis from a variety of malignancies and shows superior accuracy to conventional imaging modalities in identification of intrahepatic and extrahepatic metastasis. We present one patient with one new isolated omental lymph node metastasis, who had a history of huge HCC resected six years ago. The metastatic focus was identified with 18 F-FDG PET/CT and resected. The follow-up revealed good prognosis with a long-term survival potential after resection of the omental lymphatic metastasis.

The significance of surgical resection for pulmonary metastasis from hepatocellular carcinoma

Background Pulmonary metastasis, which is the most common type of extrahepatic recurrence of hepatocellular carcinoma (HCC), has been considered unsuitable for surgical resection because most pulmonary metastases are multiple. Until now there have been few reports about surgical resection for pulmonary metastasis from HCC. The aim of the present study was to evaluate the significance of surgical resection for pulmonary metastasis from HCC. Methods Among 615 patients who underwent radical hepatic resection for HCC in our hospital over the past 15 years, 8 patients who had developed 1 or 2 pulmonary metastases underwent pulmonary resection for the pulmonary metastases (resection group), the other 6 patients who had developed 1 or 2 pulmonary metastases did not undergo pulmonary resection (nonresection group). The clinicopathologic features and long-term prognosis of the resection group were examined and compared with those of the nonresection group. Results In the resection group, although intrahepatic recurrences were present before the diagnosis of pulmonary metastasis in 4 patients, they were well controlled by repeated transarterial chemoembolization and/or further hepatic resections. The average survival periods after the pulmonary resection and after the initial hepatic resection were 29 months (range, 5–80 mo) and 61 months (range, 24–133 mo), respectively. No patients in the resection group showed pulmonary recurrence after the pulmonary resection, and the cause of death of the patients in the resection group was not pulmonary metastasis. The survival rate of patients in the resection group was significantly better than that in the nonresection group. Conclusions It may be concluded that surgical resection for pulmonary metastasis from HCC might be beneficial in selected patients.

Resection for extrahepatic recurrence of hepatocellular carcinoma.

A total of 277 patients with hepatocellular carcinoma (HCC) underwent hepatic resection over a 20-year period. Twelve of 36 patients with recurrence confined to extrahepatic organs underwent surgical resection. There were no complications but one patient died in hospital from secondary intrahepatic recurrence. The 1-, 2- and 5-year survival rates for these 12 patients after hepatic resection were 92, 52 and 26 per cent respectively and were better than those of 24 patients who did not undergo resection for recurrence. The mean survival following resection for recurrent disease was 19.7 months and the longest survival time was nearly 8 years. Secondary recurrence after resection of metastases developed more commonly in the liver than in extrahepatic organs. Among the eight patients who survived for more than 4 months after the second operation, secondary recurrence developed in the liver and extrahepatic organs in eight and four patients respectively. In selected patients with isolated extrahepatic recurrence of HCC, surgery is effective in controlling extrahepatic disease and offers the only chance of long-term survival.