Patterns,treatments, and prognosis of tumor recurrence after resection for hepatocellular carcinoma with microvascular invasion: a multicenter study from China

BackgroundMicrovascular invasion (MVI) is a risk factor of post-hepatectomy tumor recurrence for hepatocellular carcinoma (HCC). The patterns, treatments, and prognosis have not been documented in HCC patients with MVI.MethodsA multicenter database of patients with HCC and MVI following resection was analyzed. The clinicopathological and initial operative data, timing and first sites of recurrence, recurrence management, and long-term survival outcomes were analyzed.ResultsOf 1517 patients included, the median follow-up was 39.7 months. Tumor recurrence occurred in 928 patients, with 49% within 6 months of hepatectomy and 60% only in the liver. The incidence of intrahepatic only recurrence gradually increased with time after 6 months. Patients who developed recurrence within 6 months of hepatectomy had worse survival outcomes than those who developed recurrence later. Patients who developed intrahepatic only recurrence had better prognosis than those with either extrahepatic only recurrence or those with intra- and extrahepatic recurrence. Repeat resection of recurrence with curative intent resulted in better outcomes than other treatment modalities.ConclusionPost-hepatectomy tumor recurrence in patients with HCC and MVI had unique characteristics and recurrence patterns. Early detection of tumor recurrence and repeat liver resection with curative intent resulted in improved long-term survival outcomes.     

Intraoperative thermal ablation therapy for small colorectal metastases to the liver

BACKGROUND/AIMS: Thermal ablation (TA) therapies such as microwave coagulation therapy (MCT) and radiofrequency interstitial thermal ablation (RFA) for colorectal metastasis to the liver cannot always achieve a complete tumor cell death, and the multiple insertions of the TA probe may lead to intrahepatic dissemination and/or distant metastasis. METHODOLOGY: The achieved local control rate, any recurrence in the residual liver, and any extrahepatic recurrence has been evaluated in 105 patients who underwent hepatectomy and/or intraoperative TA between 1994 and 2004. RESULTS: A total of 102 unresectable liver metastatic lesions (mean size 21mm) were selectively treated with TA either as initial treatment (32 patients) and/or as re-treatment (18 patients) for recurrence in the residual liver, in combination with hepatectomy. Overall, TA achieved a high local tumor control rate of 95%. Multivariate analysis revealed that initial-TA therapy was not a significant predictive factor of hepatic recurrence or any recurrence. CONCLUSION: TA therapies in combination with hepatectomy may offer increased resectability without increased risk of intrahepatic dissemination or extrahepatic recurrence for certain patients who would otherwise be deemed inoperable, when relatively small tumors are indicated for TA.     

Intrahepatic or systemic infusion of fluorodeoxyuridine in patients with liver metastases from colorectal carcinoma. A randomized trial

Objective: To compare the efficacy of direct hepatic arterial chemotherapy with systemic chemotherapy in patients with liver metastases from colorectal carcinoma. Design: Randomized trial with crossover allowed from systemic to intrahepatic therapy if tumor progression occurred on systemic therapy. Setting: Academic medical center, referral-based clinic. Patients: One hundred sixty-two patients with hepatic metastases from colorectal carcinoma agreed to be randomly assigned to treatment groups. At laparotomy, 63 were excluded from the study: 25 had hepatic resection; 33, extrahepatic disease; 1, infection; and 4, no tumor. Intervention: Fourteen-day continuous infusion of fluorodeoxyuridine each month using an infusaid pump (0.3 and 0.15 mg/kg body weight X d in the intrahepatic and systemic arms, respectively). Main Results: Intrahepatic therapy produced a significantly higher complete and partial response rate, 50%, compared with 20% for systemic therapy (p = 0.001). After tumor progression, 60% of the systemic patients crossed over to intrahepatic therapy; 25% then had a partial response, and 33% a minor response or stabilization of disease on intrahepatic therapy. Toxicity included ulcer disease (17%) and biliary sclerosis (8%) in patients receiving intrahepatic therapy and diarrhea (70%) in patients receiving systemic therapy. Extrahepatic disease occurred in 56% and 37% of the patients in the intrahepatic and systemic groups, respectively (p = 0.092). The median survivals were 17 and 12 months, for the intrahepatic and systemic groups, respectively. Conclusion: When compared with systemic therapy, hepatic arterial chemotherapy significantly increases response rate for hepatic metastases from colorectal carcinoma and appears to be a more effective treatment.     

Caution for Diagnosis and Surgical Treatment of Recurrent Cholangitis: Lessons From 5 Cases of Bile Duct Tumor Thrombus Without a Detectable Intrahepatic Tumor

The hepatocellular carcinoma (HCC) patients with bile duct tumor thrombus (BDTT) usually have no specific clinical symptoms at early stages. HCC with BDTT was usually misdiagnosed when the intrahepatic tumor was small, even undetectable.In this study, 5 cases of HCC with BDTT misdiagnosed as choledocholithiasis and cholangitis in the local hospital are described. We analyzed retrospectively and summarized our experiences of these 5 HCC patients with BDTT misdiagnosed in the local hospital during the past 5 years. The diagnosis, treatment, and outcome of the patients are discussed.Three patients underwent hepatectomy with thrombectomy and T-tube drainage. One patient underwent hepatectomy with the resection of the common bile duct and hepatojejunostomy, and palliative surgery was performed in 1 patient with portal vein tumor thrombus and intrahepatic metastasis. The patients were followed for 6–22 months; 4 patients died of tumor recurrence and metastasis or hepatic failure, despite 3 of these patients having received transhepatic arterial chemotherapy and embolization or radiofrequency ablation therapy.Early and accurate diagnosis of HCC with BDTT is very important. When patients have a history of abnormal recurrent cholangitis, HCC with BDTT should be highly suspected. Intraductal ultrasonography (US), intraoperative US, and histopathological examination are very valuable for the diagnosis. The prognosis of HCC patients with BDTT is dismal. Identification of this type of patient is clinically important, because surgical treatment may be beneficial.     

Prognostic factors of intrahepatic cholangiocarcinoma after hepatic resection: univariate and multivariate analysis

BACKGROUND/AIMS: Intrahepatic cholangiocarcinoma is clinicopathologically distinct from hepatocellular carcinoma and hilar cholangiocarcinoma, and the prognostic factors after hepatic resection of these rare tumors are not well documented. The aim of this study was to evaluate prognostic factors of intrahepatic cholangiocarcinoma after hepatic resection. METHODOLOGY: We retrospectively studied 20 consecutive patients with intrahepatic cholangiocarcinoma who underwent hepatectomy over a 15-year period from 1984 to 1998. Fifteen prognostic factors were evaluated for their association with overall and disease-free survivals in univariate and multivariate analysis (Cox's proportional hazards model). RESULTS: Eighty percent of the resected patients had major hepatectomy. Operative morbidity and mortality rates were 30% and 0%, respectively. Four patients (20%) survived more than 5 years without recurrence after hepatic resection. The 1-year, 3-year, and 5-year overall or disease-free survival rate after hepatic resection were 56.0% or 49.5%, 43.8% or 43.3%, and 43.8% or 37.3%, respectively. Univariate analysis showed young age and periductal invasion tumor or the presence of vascular invasion, lymphatic invasion, and lymph node metastasis as significant poor prognostic predictors contributing overall and disease-free survivals. Multivariate analysis revealed only lymph node metastasis as an independent prognostic factor affecting disease-free survival. During the same time, 17 unresectable patients were treated by intrahepatic arterial infusion chemotherapy (12), systemic chemotherapy (4), or radiation (1). Median overall survival time in resected patients (16 months) was significantly better than in unresectable patients (5 months) (P = 0.005). CONCLUSIONS: Hepatic resection remains to be the best current therapeutic option. The prognosis after hepatic resection for intrahepatic cholangiocarcinoma was determined by lymph node metastasis. New adjuvant chemotherapy after surgery is imperative for such patients.     

Complete response by a combination of 5-fluorouracil and interferon-alpha chemotherapy for lung metastasis of hepatocellular carcinoma after hepatic resection with portal and hepatic vein tumor thrombectomy.

A 75-year-old female was admitted to our hospital and diagnosed with hepatocellular carcinoma (HCC). Computed tomography (CT) revealed a liver tumor with tumor thrombi in the portal trunk and main hepatic vein, as well as small lung metastases. The patient had good liver function with no sign of hepatitis B or C infection. She underwent right trisectionectomy of the liver with tumor thrombectomy. Intrahepatic recurrence and progression of lung metastases were observed 4 months later. Intrahepatic recurrent tumors were treated with transcatheter arterial chemoembolization (TACE), and lung metastases were treated with systemic combination chemotherapy of 5-fluorouracil (5FU) and interferon-alpha (IFN-alpha). Computed tomography showed no viable lesions in the liver and lung 6 months after these treatments. The patient has been disease free for 18 months. Prognosis is poor for patients with hepatocellular carcinoma with portal vein tumor thrombus (PVVT) or extrahepatic metastasis. This systemic combination chemotherapy with 5-fluorouracil and interferon-alpha might be effective for patients with good liver function when intrahepatic lesions are well controlled by multidisciplinary treatments, including hepatic resection with tumor thrombectomy.     

Successful hepatic resection for recurrent hepatocellular carcinoma after lenvatinib treatment: A case report

BACKGROUNDLenvatinib has been shown to be noninferior to sorafenib regarding prognosis and recurrence rate in patients with unresectable hepatocellular carcinoma (HCC) who have not received prior systemic chemotherapy. In patients treated with lenvatinib, 40% of cases achieved sufficient tumor reduction to make potential surgery possible. However, the outcomes of such surgery are unknown. We report a successful case of hepatic resection for recurrent HCC after lenvatinib treatment.CASE SUMMARYA 69-year-old man underwent right anterior sectionectomy for HCC in segment 8 of the liver. Ten months later, he was found to have an intrahepatic HCC recurrence that grew rapidly to 10 cm in diameter with sternal bone metastases. After confirming partial response to lenvatinib administration for 2 mo, a second hepatectomy was performed. Pathological examination showed that 80% of the tumor was necrotic. The patient did not develop any adverse effects under lenvatinib treatment. He was discharged at 25 d after surgery. Radiation therapy for bone metastases continued to be given under lenvatinib, and the patient has remained alive for 1 year after the second hepatectomy.CONCLUSIONThe prognosis of patients with recurrent HCC may be improved by liver resection combined with prior lenvatinib therapy.     

Clinicopathological characteristics of patients with extrahepatic recurrence following a hepatectomy for hepatocellular carcinoma

BACKGROUND/AIMS: None of the previous studies have compared the prognosis or clinicopathological factors between the patients with extrahepatic recurrence and those with intrahepatic recurrence of hepatocellular carcinoma after a hepatic resection. METHODOLOGY: The clinicopathological features and prognoses of patients with extrahepatic recurrence after a curative hepatectomy for hepatocellular carcinoma were investigated. RESULTS: Twenty-three patients with extrahepatic recurrence had more advanced-stage hepatocellular carcinoma at the primary operation compared to 186 patients with intrahepatic recurrence. After adjusting for tumor size, the prognosis of the 2 groups were comparable. However, among the patients with hepatocellular carcinoma exceeding 5 cm in diameter, the number of patients whose plasma levels of des-gamma-carboxy prothrombin was higher than 2.0 AU/mL in the patients with extrahepatic recurrence (62.5%) was significantly more (P < 0.05) than that in the patients with intrahepatic recurrence (20.0%). On the other hand, the prognosis of the 13 patients with extrahepatic recurrence alone was significantly better than in the 10 patients with both intrahepatic and extrahepatic recurrences. The prognoses of the 3 patients who underwent a surgical resection for isolated extrahepatic recurrence were markedly better than that of the remaining 10 patients only treated palliatively. CONCLUSIONS: If patients have tumors exceeding 5 cm in diameter and their plasma levels of des-gamma-carboxy prothrombin are higher than 2.0 AU/mL, more careful follow-up examinations than usual may thus be necessary in order to detect extrahepatic recurrence as early as possible. Furthermore, a surgical resection for the isolated extrahepatic recurrence of hepatocellular carcinoma is also recommended to produce long-term survivors.     

Risk factors for early extrahepatic metastasis in patients with liver metastasis from colorectal carcinoma

BACKGROUND/AIMS: Hepatic resection is one of the most effective therapies for colorectal liver metastasis. However, extrahepatic metastasis is frequently encountered within a short time postoperatively. We attempted to clarify the risk factors for extrahepatic metastasis in patients with colorectal liver metastasis. METHODOLOGY: We retrospectively analyzed data obtained from 116 consecutive patients with colorectal liver metastasis. To determine predictors of extrahepatic metastasis within 1 year of admission for treatment of colorectal liver, we examined 12 clinicopathologic factors by univariate and multivariate logistic regression analyses. RESULTS: Eighty-five underwent hepatectomy and/or thermal ablation (hepatectomy group) and 31 underwent only chemotherapy (non-hepatectomy group). Thirty-one in the hepatectomy group and 19 in the non-hepatectomy group developed extrahepatic metastasis at 1 year after admission. Univariate analysis showed that treatment without hepatectomy and lymphatic vessel permeation at the primary site were significant predictive factors for extrahepatic metastasis within 1 year. Multivariate analysis showed lymphatic permeation of the primary tumor, and treatment without hepatectomy to be significantly related to the occurrence of extrahepatic metastasis within 1 year. CONCLUSIONS: The two factors that we identified put patients with colorectal liver metastasis at high risk for extrahepatic metastasis. Systemic chemotherapy may be needed to prevent extrahepatic disease in such patients.     

Analysis of the prognostic factors for liver metastasis of gastric cancer after hepatic resection: a multi-institutional study of the indications for resection

BACKGROUND/AIMS: The number of reports of hepatic resection for metastatic gastric cancer is very small. The outcome and indications of hepatic resection for metastatic gastric cancer remains unknown. METHODOLOGY: A multi-institutional study was made. Thirty-six patients who underwent a hepatic resection for liver metastasis of gastric cancer with no residual tumor were included in this study. The clinicopathological factors were examined as prognostic factors by multivariate analyses. Thirty patients had recurrence and the recurrence pattern and risk factors for extrahepatic recurrence was examined. RESULTS: The overall survival rate was 64% at 1 year, 43% at 2 years, 26% at 3 years 26% at 5 years, and 26% at 10 years after hepatectomy. Multivariate analysis showed that lymphatic invasion, venous invasion of cancer cells of primary gastric cancer and the number of the liver metastasis (> 3) were independent poor prognostic factors after hepatic resection. The most common recurrence pattern was intrahepatic recurrence in 22 patients (73%). The risk factors for extrahepatic recurrence was serosal invasion, lymph node metastasis of primary gastric cancer, stage, and curability of operation. CONCLUSIONS: Hepatic resection for liver metastasis should be attempted in case primary gastric cancer has neither lymphatic invasion nor venous invasion. The most common recurrent site was the liver. In patients with advanced gastric cancer, having neither serosal invasion nor lymph node metastasis, who underwent a less curative operation, the intra-hepatic recurrence would be expected. Thus, aggressive adjuvant chemotherapy through the hepatic artery may improve the survival after hepatectomy in these patients.     

Recurrence hazard rate in patients with hepatocellular carcinoma and bile duct tumor thrombus: a multicenter observational study

BackgroundPatients with hepatocellular carcinoma (HCC) bile duct tumor thrombus (BDTT) have a high rate of postoperative recurrence. We aimed to describe the patterns and kinetics of recurrence in BDTT patients and provide management options accordingly.MethodsThis retrospective study included 311 HCC patients with BDTT who underwent surgery from 2009 to 2017 at five centers in China. The hazard rate of recurrence was calculated using the hazard function.ResultsThe hazard rate of intrahepatic recurrence was higher than that of extrahepatic recurrence (0.0588 vs. 0.0301), and both showed a decreasing trend, and the intrahepatic recurrence and extrahepatic recurrence risk decreased to a lower level after 40 and 20 months, respectively. Patients who underwent anatomic resection had a consistently lower hazard rate of recurrence than patients who underwent nonanatomic resection, whereas patients who received postoperative adjuvant transarterial chemoembolization (TACE) mainly had a lower hazard rate of recurrence in the first year than patients who did not.ConclusionThe follow-up of BDTT patients should be at least 40 months because of its high rate of recurrence, in parallel with the need for vigilance for extrahepatic recurrence within 20 months. Anatomic hepatectomy and adjuvant TACE are recommended to improve BDTT patient outcomes.     

Survival of patients with colorectal cancer liver metastases treated by regional chemotherapy

BACKGROUND/AIMS: Liver is the most common site of metastatic disease in colorectal cancer. Superior response rate was demonstrated in trials comparing hepatic arterial administration of cytotoxic agents with systemic chemotherapy. METHODOLOGY: Records of 109 consecutive patients with colorectal carcinoma metastatic to the liver treated by regional chemotherapy, who underwent implantation of a port system into hepatic artery or portal vein tributaries between 1991 and 1999, were reviewed and survival was evaluated using the log-rank test and multivariate analysis (Cox's proportional hazard regression). RESULTS: The median survival from diagnosis was 24 months. Survival was significantly longer for patients treated by radical resection, and patients treated in 1997-1999. On multivariate analysis, treatment by 6 or more chemotherapy cycles, stage 1 liver metastases, treatment with irinotecan and radical resection were associated with better survival, while the presence of extrahepatic disease had an adverse effect on the risk of death. Extrahepatic spread was subsequently detected in almost half of the patients who had originally isolated liver metastases. CONCLUSIONS: Patients treated by liver resection had the best outcome, while patients with extrahepatic diseases had poor prognosis. The prognosis of patients treated by regional chemotherapy improved significantly with the advent of irinotecan and better selection.     

Complete remission of hepatocellular carcinoma with portal vein tumor thrombus and lymph node metastases by arterial infusion of 5-fluorouracil and interferon-α combination therapy following hepatic resection

We report two cases of hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) and lymph node (LN) metastases successfully treated by hepatic arterial infusion of 5-fluorouracil (5-FU) combined with systemic injection of interferon (IFN)-α following hepatic resection for the liver tumor. Complete remission was obtained. Case 1 was a 51-year-old man who had HCC in the right lobe of the liver with PVTT and multiple intrahepatic metastases. He also had abdominal and mediastinal LN metastases. Case 2 was a 53-year-old man who had diffuse-type HCC in the right lobe of the liver with PVTT and intrahepatic metastases. A chest computed tomography scan revealed lymph nodes enlarged to 1.0 cm from the mediastinum to the left supraclavicular space. Both patients underwent the hepatectomy to reduce the tumor volumes and remove the PVTT to relieve portal vein obstruction. Following the surgery, the patients underwent IFN-α/5-FU combination therapy. Three months after this combined therapy, tumor markers (both α-fetoprotein and protein induced by vitamin K absence or antagonist II) returned to the normal range and residual tumors in the liver disappeared. The patients are alive without any recurrence more than 1 year after initial treatment. IFN-α/5-FU combined therapy following hepatic resection is a promising modality for the treatment of advanced HCC with LN metastasis.     

A novel intrahepatic arterial chemotherapy after radical resection for advanced hepatocellular carcinoma

BACKGROUND/AIMS: Advanced hepatocellular carcinoma (HCC) with portal vein invasion and/or intrahepatic metastasis has an unfavorable prognosis even after radical hepatic resection. The aim of this study was to evaluate the effectiveness of a novel postoperative adjuvant chemotherapy given through the hepatic artery and based on biochemical modulation using cisplatin (CDDP) and 5-fluorouracil (5-FU). METHODOLOGY: Fifteen patients with advanced HCC with portal vein invasion into the main trunk and/or intrahepatic metastases of more than 3 segments were included in this study. After radical hepatic resection, the patients were divided to two groups: the adjuvant chemotherapy group (n=7) given the novel arterial infusion regimen with CDDP and 5-FU, and the control group (n=8) given no adjuvant chemotherapy. RESULTS: Three-year survival rate of the adjuvant chemotherapy group tended to be significantly longer compared to that for the control group (p < 0.05). Most of the tumor recurrence was in the remnant liver, 5 cases in both of the groups. Significant difference of the recurrence patterns was recognized, rather than difference of the disease-free survival rate between the two groups. All of the intrahepatic recurrences are multiple in the control group, but in the adjuvant chemotherapy group, 2 cases of the recurrences showed a localized tumor surgically resected. It is noteworthy that the occurrence of multiple recurrence was significantly later in the adjuvant chemotherapy group compared to the control group (18.9 months vs. 6.5 months; p<0.05). CONCLUSIONS: Our data suggest that this novel adjuvant chemotherapy can improve the postoperative prognosis of patients with the advanced HCC.     

Therapeutic strategy for postoperative liver metastasis from esophageal squamous cell carcinoma; clinical efficacy of and problem with hepatic arterial infusion chemotherapy

BACKGROUND/AIMS: Despite recent advances in diagnosis and treatment, the prognosis for esophageal squamous cell carcinoma is unsatisfactory. Liver recurrence is frequent in postoperative esophageal squamous cell carcinoma patients, and the prognosis for patients with liver metastasis is poor. This report concerns the therapeutic strategy, especially the efficacy of and the problem with hepatic arterial infusion chemotherapy for liver metastasis from esophageal squamous cell carcinoma. METHODOLOGY: We performed a retrospective analysis of 8 patients who underwent hepatic arterial infusion between 1993 and 1998. All patients underwent esophagectomy and reconstruction with stomach roll without preoperative chemotherapy and/or radiotherapy. For 6 patients, preceding systemic chemotherapy was performed before hepatic arterial infusion. RESULTS: The overall response rate of hepatic arterial infusion was 50%, and for the responders, hepatic arterial infusion provided a good quality of life. Hepatic arterial infusion was effective for responders to preceding systemic chemotherapy, but ineffective for non-responders. A complete response was seen in 2 patients, and the liver tumors showed no re-growth after the completion of hepatic arterial infusion. Two patients developed stomach roll ulcers and one experienced the catheter thrombosis, but there were no instances of severe toxicity or complications. CONCLUSIONS: For postoperative liver recurrence of esophageal squamous cell carcinoma, hepatic arterial infusion is the favorable therapy in terms of efficacy and low-grade toxicity, but has a risk of causing severe complications. We consider it suitable that when preceding systemic chemotherapy is performed before hepatic arterial infusion, hepatic arterial infusion is performed in responders to preceding systemic chemotherapy, and that hepatic arterial infusion is continued as long as possible.     

Efficacy of surgical microwave ablation for recurrent hepatocellular carcinoma after curative hepatectomy

BackgroundLittle evidence exists regarding postrecurrence survival after microwave ablation for recurrent hepatocellular carcinoma (HCC) after curative hepatectomy; we aimed to evaluate the feasibility of surgical microwave ablation.MethodsIn this retrospective review, we enrolled patients who underwent curative hepatectomy for primary HCC in our department and had intrahepatic recurrence. We analyzed overall survival according to treatment modality to clarify the prognostic factors for survival.ResultsOf 257 patients, 119 had intrahepatic recurrence. Three patients underwent repeat hepatectomy; 75 patients underwent surgical microwave ablation, and 34 patients underwent transcatheter arterial chemoembolization or hepatic arterial infusion chemotherapy. The median postrecurrence survival time and 5-year postrecurrence survival after surgical microwave ablation were 37.4 months and 55.4%, respectively. The major complication rate (Clavien–Dindo classification IIIa or above) after surgical microwave ablation was 5.3% with no mortality. Multivariate analysis showed that microvascular invasion at primary tumors, and recurrent tumors within 3 cm and 3 nodules were independent prognostic factors for overall survival after surgical microwave ablation for recurrent HCC.ConclusionOur results suggested that surgical microwave ablation is safe and feasible for recurrent intrahepatic HCC after curative hepatectomy. Close follow-up and further curative treatment could be important for improving postrecurrence survival.     

Repeated hepatectomy for recurrent intrahepatic cholangiocarcinoma: report of two cases

Repeated hepatectomy for remnant liver recurrence of primary intrahepatic cholangiocarcinoma (ICC) is a seldom-encountered surgical technique because of its poor prognosis. Here, we present two long-term survivors of recurrent ICC by repeated hepatectomy. One patient underwent five hepatectomies in 6 years; first, extended left hepatectomy for a primary mass-forming-type ICC and then four partial hepatectomies for independent recurrent tumors all developing in segment V. The other patient underwent re-hepatectomy for a very large recurrent tumor 7 years after the first left hepatectomy for a primary periductal-infiltrating-type ICC; and has survived for approximately 2 years from the second operation under hepatic arterial infusion chemotherapy. The recurrent tumor in the latter case arose in the segment IV remnant corresponding to the cut margin of the liver after the first inappropriate left hepatectomy. The mode of hepatic recurrence seemed closely related to the portal segmentation: in the first case, intrahepatic metastases via portal tributaries; and in the second, the occult residual cancer spreading widely through bile ductules.     

Results of surgical treatment for recurrent hepatocellular carcinoma; comparison of outcome among patients with multicentric carcinogenesis, intrahepatic metastasis, and extrahepatic recurrence

No consensus has been reached on the indications for and effectiveness of surgery for secondary intrahepatic hepatocellular carcinoma (HCC) and extrahepatic metastasis after macroscopically complete removal of primary HCC. Secondary intrahepatic HCCs, usually regarded as recurrence are classified into those arising as a result of multicentric carcinogenesis or intrahepatic metastases derived from the primary HCC. The present study was designed to evaluate the utility of surgical treatment in relation to the pathogenesis of the secondary HCC: classified as multicentric carcinogenesis (MC), intrahepatic metastasis (IM), and extrahepatic metastasis. Thirty patients underwent extirpation of secondary HCC: 22 patients had secondary HCCs in the remnant liver (MC group;n = 8; IM group,n = 14), 6 patients had extrahepatic metastases, and 2 patients had both intrahepatic and extrahepatic metastases. Survival rates after the re-resection in the 22 patients with the secondary intrahepatic HCCs were 94.7% at 1 year, and 50.2% at 3 years postoperatively, and the 8 patients with extrahepatic metastasis had survival rates of 62.5% at 1 year, 37.5% at 3 years, and at 5 years. The survival rates after re-resection in the MC group were 100% at 1 year and 80.0% at 3 years, whereas those in the IM group were 91.7% at 1 year, and 38.1% at 3 years. Surgery can be indicated not only in patients with localized intrahepatic secondary HCCs but also in those with extrahepatic metastasis. In particular, patients with secondary HCCs arising as a result of multicentric carcinogenesis are expected to have a good prognosis.     

Role of intrahepatic tumor control in the prognosis of patients with hepatocellular carcinoma and extrahepatic metastases

Background and Aim: There has been little information about the long‐term outcome and prognostic factors in patients with hepatocellular carcinoma (HCC) and extrahepatic metastases. The purpose of this study was to investigate the clinical factors affecting survival after extrahepatic metastasis and to determine the survival benefit of controlling intrahepatic HCC. Methods: Between 2004 and 2009, a total of 240 consecutive patients with HCC and extrahepatic metastasis were recruited. Based on tumor extent, performance, and hepatic function, the patients underwent locoregional and/or systemic treatments. The treatment response of the intrahepatic tumor after extrahepatic metastasis and other prognostic parameters were analyzed retrospectively. Results: During the mean follow up of 276 days, 222 patients died; the median survival time was 146 days. Multivariate analysis revealed that Child–Pugh class A, smaller hepatic tumor size, absence of portal venous invasion, single metastatic organ involvement, and objective treatment response of the intrahepatic tumor were the favorable prognostic factors for survival. Of the 183 evaluable patients, 24 achieved complete or partial response for intrahepatic tumors after treatment. The overall survival for the 24 responders was significantly improved, with a median of 521 days, as compared to 170 days for the remaining 159 patients without objective tumor response. The leading cause of death was progressive intrahepatic tumor. Conclusions: Intrahepatic tumor status and hepatic reserve are among the significant predictors of survival in patients with HCC and extrahepatic metastases. This study indicates that even in patients with metastases from advanced HCC, therapeutic approaches to control intrahepatic tumors are important in improving patient survival.     

Surgical treatment for extrahepatic recurrence after hepatectomy for colorectal metastases

BACKGROUND/AIMS: Recurrence of the remnant liver or extrahepatic sites after hepatic resection for colorectal metastases is concerned as a significant prognostic factor. While regional chemotherapy may reduce recurrence of the liver, appropriate therapy for extrahepatic metastases needs to be elucidated. METHODOLOGY: We identified 207 patients undergoing hepatectomy for colorectal metastases. Patient characteristics, clinicopathological features, sites of extrahepatic recurrence, and outcome are examined. RESULTS: Recurrence of the lung, brain, bone, and other site after hepatic resection was seen in 49, 8, 8, and 12 cases, respectively. Fourteen patients underwent pulmonary resection, and three patients are alive and disease-free survival was 35, 79, and 128 months after the second resection. Overall 2- and 5-year survival was 64 and 18%. Univariate and multivariate analysis indicated that time and number of pulmonary metastases, and serum CEA levels are independent prognostic factors. Surgical resection for brain metastasis was only in one case who survived for 31 months. Other treatment such as gamma-knife may not improve outcome. CONCLUSIONS: Both hepatic and pulmonary resection for colorectal metastases could prolong survival in selected patients. Surgical indication for other extrahepatic metastases must be strictly selected, although resection of brain metastasis might lead to better outcome.