Prognosis after intrahepatic recurrence in the patients who underwent curative resection for hepatocellular carcinoma.

BACKGROUNDS/AIMS: Intrahepatic recurrence is frequent result after hepatectomy for hepatocellular carcinoma (HCC). We analyzed the clinical results of patients who had the intrahepatic recurrences of HCC after curative surgical resections. METHODS: From January 2009 to December 2016, 320 patients underwent curative surgical resection for HCC in department of Surgery, Korea Cancer Center Hospital. After surgical resection, 155 patients had suffered HCC recurrence during follow-up period. Among them, 122 patients had only intrahepatic recurrence initially, who were included in this retrospective study. We analyzed about the period of the recurrence after surgery, treatment methods for the recurred tumors, and poor prognostic factors for survival after intrahepatic recurrences. RESULTS: Among the 122 patients, 83 patients had recurrence within 24 months after surgery. Thirty-eight patients underwent curative treatment for the recurred tumors (re-resection in 18, radiofrequency ablation in 20 patients). Non-curative treatments were performed in 77 patients (TACE in 68 patients, radiotherapy in 9 patients) and conservative management in 7 patients. Five-year survival rate of patients who underwent curative treatment is 86.4% (p≤0.001). Five-year survival rate of non-curative treatment is 55.7% (p≤0.001), conservative management is 0% (p=0.021). Among the clinical factors, non-curative treatment for recurred tumor, AFP level at the time of recurrence, size of recurred tumor were independent poor prognostic factors for survival after intrahepatic recurrences (p<0.001). CONCLUSIONS: For the patients who had intrahepatic recurrent HCC after surgery, aggressive local treatment can improve the prognosis in selective cases. Further study is necessary to validate this retrospective investigation.

Concurrent hepatocellular carcinoma metastasis to stomach, colon, and brain: A case report.

BACKGROUND: Extrahepatic metastasis (EHM) from hepatocellular carcinoma (HCC) occurs in 10%-15% of cases following initial treatment. The most frequent sites of EHM are the lung, lymph nodes, and bone. Gastrointestinal or brain metastasis from HCC is rarely reported. Here, we report a rare case of concurrent HCC metastases to the stomach, colon, and brain. CASE SUMMARY: A 72-year-old male with a history of alcohol induced HCC presented with multiple intrahepatic recurrences and tumorous lesions in the stomach and ascending colon. Three years earlier, he underwent right hemihepatectomy, and 1 year ago, he had a video-assisted thoracoscopic wedge resection for pulmonary metastasis of HCC. We decided on surgical resection of the new metastases because of massive gastric bleeding and concern for possible colonic obstruction. The patient underwent gastric wedge resection and right hemicolectomy. Two weeks later, the patient developed dysarthria and mild cognitive disorder. Magnetic resonance imaging of the brain revealed a left frontal lobe lesion, and he underwent resection of a metastatic brain tumor. Unfortunately, he died 6 weeks after the last surgery due to hepatorenal syndrome. CONCLUSION: Decision of surgery was carefully recommended in this case and may extend survival in other metastatic HCC patients with well-preserved hepatic function.

Clinical implication of tumor site in terms of node metastasis for intrahepatic cholangiocarcinoma.

BACKGROUND: The clinical implication of lymph node (LN) dissection of intrahepatic cholangiocarcinoma (ICCA) is still controversial, and LN metastasis (LNM) based on tumor site has not been confirmed yet. METHODS: Patients who underwent curative-intent surgery at 10 tertiary referral centers were identified and divided into peripheral (PP) and near second confluence level tumor (NC) groups on the basis of the distance from the second confluence and oncological outcomes were compared. RESULTS: Of 179 patients, 121 patients with LND were divided into the NC (n = 89) and PP groups (n = 32) on the basis of 4.5 cm from the second confluence. NC group showed higher LNM rate than PP group (46.1 vs 21.9%, p = 0.016) and NC was a risk factor for LNM (odds ratio: 4.367; 95% confidence interval: 1.234-15.453, p = 0.022). The 5-year overall survival (OS) rate (38.0% vs. 27.8%, p = 0.777) and recurrence-free survival (RFS) rates (22.8% vs. 25.8%, p = 0.742) showed no differences between the PP and NC groups. In the NC group, N1 patients showed worse 5-year OS (12.7% vs 39.0%, p = 0.004) and RFS (8.8% vs 28.6%, p = 0.004) than the N0 patients. In the PP group, discordant results in 5-year OS (48.9% vs. 50.0%, p = 0.462) and RFS (41.3% vs. 0%, p = 0.056) were found between the N0 and N1 patients. CONCLUSION: The NC group was an independent risk factor for LNM and LNM worsened prognosis in NC group for ICCA. In the PP group, LND should not be omitted because of high LNM rate and insufficient oncologic evidence.

Comparison of the clinical results of surgical resection for extrahepatic cholangiocarcinomas: Hilar cholangiocarcinoma and mid-to-distal cholangiocarcinoma.

BACKGROUNDS/AIMS: Hilar cholangiocarcinomas (HLC) are known to have worse prognoses than mid-to-distal cholangiocarcinomas (CBDC). We analyzed the clinical results of surgical resections for extrahepatic cholangiocarcinomas to validate the differences in the prognoses of HLC and CBDC. METHODS: Two hundred and eighty-one patients underwent curative surgical resections for extrahepatic cholangiocarcinomas at the Department of Surgery in the Korea Cancer Center Hospital. Among them, we analyzed the T2 and T3 patients and compared the clinical results between those with HLC (n=74) and those with CBDC (n=65). RESULTS: The rate of R1 resections was significantly higher in the HLC patients compared to the CBDC patients (31.1% vs 12.3%, p=0.006). The overall survival rate of the T2/T3 patients was lower in the HLC group than in the CBDC group (24.5% vs 51.7, p=0.039). The recurrence-free survival rate was 23.3% in the HCL patients and 50.9% in the CBDC patients (p=0.06). In the subgroup analysis, the survival rates were not different in patients who had lymph node metastases or in patients who underwent R1 resections between the HLC and CBDC patients. Poor independent prognostic factors for the overall and recurrence-free survival rates in the T2/T3 extrahepatic cholangiocarcinoma patients were the presence of lymph node metastases and the hilar locations of tumor. CONCLUSIONS: HLC patients had poorer prognoses than CBDC patients. However, in patients with lymph node metastases, the prognosis was poor and was not different between the HLC and CBDC patients. Other adjuvant treatment methods are needed for extrahepatic cholangiocarcinoma patients with lymph node metastases to improve their prognoses.

Promoter methylation of cysteine dioxygenase type 1: gene silencing and tumorigenesis in hepatocellular carcinoma.

BACKGROUNDS/AIMS: Cysteine dioxygenase type 1 (CDO1) acts as a tumor suppressor and is silenced by promoter methylation in various malignancies. The relationship between the CDO1 methylation status and hepatocellular carcinoma (HCC) tumorigenesis was evaluated. METHODS: Using a HCC cell line (SNU423), an in vitro demethylation study was performed to confirm whether promoter methylation causes CDO1 down-regulation. The SNU423 cells transfected with the CDO1 cell function was compared to that of naïve cells. An in vivo study using immunohistochemical staining of HCC specimens that were collected from patients who underwent curative liver resection was also performed. RESULTS: CDO1 was activated after demethylation treatment in the HCC specimens. Moreover, tumor cell proliferation, colony-forming, migration, and invasion activities significantly decreased after CDO1 transfection (p<0.05). The percentage of tumors that were larger than 5 cm was higher in patients who had a lower expression of CDO1 (p=0.030). Vascular invasion and histological grade were independent prognostic factors for poor overall and recurrence-free survival. The degree of CDO1 expression was not an independent prognostic factor in this study's population. CONCLUSIONS: These results suggested that methylation down-regulated CDO1 expression in the HCC cells. CDO1 methylation may be a potentially valuable diagnostic biomarker for HCC.

Hepatectomy, combined with intraoperative radiofrequency ablation in patients with multiple hepatocellular carcinomas.

BACKGROUNDS/AIMS: We compared the efficacy and safety of a hepatectomy, combined with intraoperative radiofrequency ablation to those of wider extent hepatectomy, alone, in patients with multiple hepatocellular carcinomas (HCCs). METHODS: Between January 2004 and December 2013, 78 patients with multiple HCCs underwent surgery. 25 patients were treated by hepatectomy, combined with intraoperative radiofrequency ablation (RFA) (group A), and 53 underwent hepatectomy only (group B). We retrospectively analyzed medical records to compare the clinical features of these two groups. RESULTS: Patients in group A had more limited resections (less than 2 segments) than those in group B (p<0.001). Patients in group A also tended to have fewer red blood cell transfusions than those in group B (p=0.060). Liver function- and surgery-related complications occurred only in group B. There were no in-hospital mortalities in both groups. The overall survival and disease-free survival outcomes were not significantly different between groups A and B (p=0.177 and p=0.305, respectively). CONCLUSIONS: Hepatectomy combined with intraoperative RFA could be a safe and effective treatment option for patients with multiple HCCs, comparable to extended hepatectomy alone.

CD44 expression in patients with combined hepatocellular cholangiocarcinoma.

PURPOSE: Combined hepatocellular cholangiocarcinoma (ChC) is a rare type of primary liver cancer, which is thought to have a poorer prognosis than hepatocellular carcinoma (HCC). Cancer stem cells are associated with tumorigenesis, tumor progression, recurrence, metastasis, and poor prognosis in several malignancies including HCC. The aim of this study was to investigate the expression pattern of cancer stem cell markers in ChC and HCC, and to evaluate whether this pattern correlated to patient prognosis. METHODS: Thirteen patients who underwent curative hepatic resection for ChC and 13 patients who underwent curative hepatic resection for HCC (matched control cases) were included. Immunohistochemical staining for cancer stem cell markers (cytokeratin [CK]7, CK19, C-kit, cluster of differentiation [CD] 44, CD133, and epithelial cell adhesion molecule) was performed and clinical outcomes were analyzed retrospectively. RESULTS: There was no significant difference in cancer stem cell marker expression between ChC and HCC. In ChC, the group that expressed CD44 showed earlier recurrence than the group that did not express CD44 (P = 0.040). CONCLUSION: The expression of cancer stem cell markers in ChC did not show a different pattern compared to that found in HCC. The expression of cancer stem cell marker CD44 was associated with poor prognosis in patients with ChC.