Koo Jeong Kang

A Prospective Randomized Controlled Study Comparing Outcomes of Standard Resection and Extended Resection, Including Dissection of the Nerve Plexus and Various Lymph Nodes, in Patients With Pancreatic Head Cancer

Objective:To prospectively evaluate the survival benefit of dissection of the nerve plexus and lymphadenectomy in patients with pancreatic head cancer. Background:Despite randomized controlled trials on the extent of surgery in pancreatic cancer, attempts have been made to perform more extended resections. Methods:A total of 244 patients were enrolled; of these, 200 were randomized to undergo standard resection or extended resection, with the latter including the dissection of additional lymph nodes and the right half of the nerve plexus around the superior mesenteric artery and celiac axis. We evaluated 167 patients from 7 centers who fulfilled all of the required criteria. Result:Operation time was longer and estimated blood loss was higher in the extended resection group than in the standard resection group, but the R0 resection rate was comparable. The mean number of lymph nodes retrieved per patient was higher in the extended resection group than in the standard resection group (33.7 vs 17.3; P < 0.001). The morbidity rate was slightly higher in the extended resection group than in the standard resection group. Two patients in the extended resection group died in hospital. Median survival after R0 resection was similar in the extended resection and standard resection groups (18.0 vs 19.0 months; P = 0.239) regardless of lymph node metastasis. Adjuvant chemoradiation had a positive impact on overall survival. Conclusions:This study suggests that extended lymphadenectomy with dissection of the nerve plexus does not provide a significant survival benefit compared with standard resection in pancreatic head cancer. Standard resection can be performed safely and efficiently, without negatively affecting oncologic efficacy or long-term survival, when compared with extended pancreaticoduodenal resection. (NCT00679913)?

Sulfatase 1 and sulfatase 2 in hepatocellular carcinoma: Associated signaling pathways, tumor phenotypes, and survival

The heparin‐degrading endosulfatases sulfatase 1 (SULF1) and sulfatase 2 (SULF2) have opposing effects in hepatocarcinogenesis despite structural similarity. Using mRNA expression arrays, we analyzed the correlations of SULF expression with signaling networks in human hepatocellular carcinomas (HCCs) and the associations of SULF expression with tumor phenotype and patient survival. Data from two mRNA microarray analyses of 139 and 36 HCCs and adjacent tissues were used as training and validation sets. Partek and Metacore software were used to identify SULF correlated genes and their associated signaling pathways. Associations between SULF expression, the hepatoblast subtype of HCC, and survival were examined. Both SULF1 and 2 had strong positive correlations with periostin, IQGAP1, TGFB1, and vimentin and inverse correlations with HNF4A and IQGAP2. Genes correlated with both SULFs were highly associated with the cell adhesion, cytoskeletal remodeling, blood coagulation, TGFB, and Wnt/β‐catenin and epithelial mesenchymal transition signaling pathways. Genes uniquely correlated with SULF2 were more associated with neoplastic processes than genes uniquely correlated with SULF1. High SULF expression was associated with the hepatoblast subtype of HCC. There was a bimodal effect of SULF1 expression on prognosis, with patients in the lowest or highest tertile having a worse prognosis than those in the middle tertile. SULFs have complex effects on HCC signaling and patient survival. There are functionally similar associations with cell adhesion, ECM remodeling, TGFB, and WNT pathways, but also unique associations of SULF1 and SULF2. The roles and targeting of the SULFs in cancer require further investigation.

The Autophagy-Related Marker LC3 Can Predict Prognosis in Human Hepatocellular Carcinoma

Background Defects of autophagy and endoplasmic reticulum (ER) stress are related to many diseases and tumors. However, only a few studies have examined hepatocellular carcinoma (HCC) as related to these processes. Therefore, in this study, we investigated the expression and extent of autophagy and ER stress-related markers in HCC and their influence on clinical characteristics and prognosis for each protein. Methodology The expression of autophagy-related markers (LC3 and Beclin-1) and ER stress-related markers (GRP78 and CHOP) was analyzed by immunohistochemistry on tissues from completely resected specimens of 190 HCC patients. Their influence on clinicopathologic features and prognosis were evaluated using the chi-square test and Kaplan-Meier analysis. Correlations of each protein were determined by Spearmans correlation analysis. Principal Findings LC3 expression was not correlated with TNM, BCLC stage, or Edmonson-Steiner grading, whereas it was correlated with longer overall survival (OS) (p = 0.039) and tended to be related with longer time to recurrence (TTR) (p=0.068) although it did not show statistical significance. Multivariate analysis indicated that LC3 expression was a significantly independent prognostic factor of OS (HR, 0.42; 95% CI, 0.22-0.80; p-value=0.009) and TTR (HR, 0.54; 95% CI, 0.33–0.90; p=0.017). Expression of LC3 in advanced stages of TNM (III) (p=0.045) and Edmonson-Steiner Grades (III and IV) (p=0.043) was correlated with longer survival, but not in the early stages. A positive correlation was not observed between the expression of autophagy-related markers and ER stress-related markers. Conclusion Our results suggest that the expression and extent of LC3 might be a strong prognostic factor of HCC, especially in patients with surgical resection.

Genomic Predictors for Recurrence Patterns of Hepatocellular Carcinoma: Model Derivation and Validation

In this study, Lee and colleagues develop a genomic predictor that can identify patients at high risk for late recurrence of hepatocellular carcinoma (HCC) and provided new biomarkers for risk stratification.

Carcinosarcoma of the Liver: A Case Report

Primary hepatic carcinosarcoma is a rare tumor comprised of a mixture of carcinomatous and sarcomatous elements. Less than 20 adequately documented cases have been reported, however the imaging features of two cases were briefly described. We present here a case of carcinosarcoma of the liver in a 46-year-old woman, which was confirmed based on pathology. Imaging showed a large mass with large necrotic portions, small cystic portions, calcifications and bone formations.

Genes Associated with Recurrence of Hepatocellular Carcinoma: Integrated Analysis by Gene Expression and Methylation Profiling

Gene expression is suppressed by DNA methylation. The goal of this study was to identify genes whose CpG site methylation and mRNA expression are associated with recurrence after surgical resection for hepatocellular carcinoma (HCC). Sixty-two HCCs were examined by both whole genome DNA methylation and transcriptome analysis. The Cox model was used to select genes associated with recurrence. A validation was performed in an independent cohort of 66 HCC patients. Among fifty-nine common genes, increased CpG site methylation and decreased mRNA expression were associated with recurrence for 12 genes (Group A), whereas decreased CpG site methylation and increased mRNA expression were associated with recurrence for 25 genes (Group B). The remaining 22 genes were defined as Group C. Complement factor H (CFH) and myosin VIIA and Rab interacting protein (MYRIP) in Group A; proline/serine-rich coiled-coil 1 (PSRC1), meiotic recombination 11 homolog A (MRE11A), and myosin IE (MYO1E) in Group B; and autophagy-related protein LC3 A (MAP1LC3A), and NADH dehydrogenase 1 alpha subcomplex assembly factor 1 (NDUFAF1) in Group C were validated. In conclusion, potential tumor suppressor (CFH, MYRIP) and oncogenes (PSRC1, MRE11A, MYO1E) in HCC are reported. The regulation of individual genes by methylation in hepatocarcinogenesis needs to be validated.

Benefit of systematic segmentectomy of the hepatocellular carcinoma: revisiting the dye injection method for various portal vein branches.

Background: Systematic segmentectomy is useful in treating small hepatocellular carcinoma in the cirrhotic liver. However, accomplishment of an exact systematic segmentectomy still remains a challenging procedure because of the variable anatomy of portal branches. We evaluated the usefulness of the dye injection method for systematic segmentectomy, which focuses on the various patterns of portal vein (PV) branches feeding the tumor. Methods: From January 2001 to May 2011, systematic segmentectomy by the dye injection method was performed in 70 patients. We evaluated the efficiency of systematic segmentectomy by ultrasonogram-guided dye injection into the portal branches that feed the tumor-bearing segments. The type of tumor-feeding PV branch, perioperative outcome, and survival rates were analyzed retrospectively. Results: There were variations in the PV branches that fed the masses in 70 patients in whom the dye injection method for anatomical segmentectomy was tried. Forty masses (54.8%) were fed by a single main PV branch (type 1), 17 masses (23.3%) by a couple of PV branches (type 2), and 11 masses (15.1%) were supplied partially by single PV branch (type 3). In 5 patients (7.1%), masses were supplied by several small distributed PVs (type 4). For types 1 and 2, the tumor-bearing segments were resected anatomically with the help of staining; type 3 was partially stained and as the opposite side was not discrete, it was demarcated through counterstaining; and in type 4, dye injection could not be performed. Anatomical systematic segmentectomy was obtained in types 1 to 3; however, nonanatomical resection was inevitable for type 4. The 3- and 5-year overall survival rates were 80.5% and 67.2%, respectively, and the 3- and 5-year disease-free survival rates were 61.5% and 42.5%, respectively. The anatomical segmentectomy group showed better overall and disease-free survival than the nonanatomical group, even though it is not significant statistically. Conclusion: Systematic segmentectomy by the dye injection method overcomes the variation in PV tributaries in the segments and can be done according to the natural branching pattern of PVs.

Survival outcomes of hepatic resection compared with transarterial chemoembolization or sorafenib for hepatocellular carcinoma with portal vein tumor thrombosis

Background/Aims: Treating hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) remains controversial. We compared the outcomes of hepatic resection (HR), transarterial chemoembolization (TACE), and sorafenib therapy as treatments for HCC with PVTT. Methods: Patients diagnosed as HCC with PVTT between January 2000 and December 2011 who received treatment with sorafenib, HR, or TACE were included. Patients with main PVTT, superior mesenteric vein tumor thrombosis, or Child-Turcotte-Pugh (CTP) class C were excluded. The records of 172 patients were analyzed retrospectively. HR, TACE, and sorafenib treatment were performed is 40, 80, and 52 patients respectively. PVTT was classified as either involving the segmental branch (type I) or extending to involve the right or left portal vein (type II). Results: The median survival time was significantly longer in the HR group (19.9 months) than in the TACE and sorafenib groups (6.6 and 6.2 months, respectively; both p<0.001), and did not differ significantly between the latter two groups (p=0.698). Among patients with CTP class A, type I PVTT or unilobar-involved HCC, the median survival time was longer in the HR group than in the TACE and sorafenib groups (p=0.006). In univariate analyses, the initial treatment method, tumor size, PVTT type, involved lobe, CTP class, and presence of cirrhosis or ascites were correlated with overall survival. The significant prognostic factors for overall survival in Cox proportional-hazards regression analysis were initial treatment method (HR vs. TACE: hazard ratio=1.750, p=0.036; HR vs. sorafenib: hazard ratio=2.262, p=0.006), involved lobe (hazard ratio=1.705, p=0.008), PVTT type (hazard ratio=1.617, p=0.013), and CTP class (hazard ratio=1.712, p=0.012). Conclusions: Compared with TACE or sorafenib, HR may prolong the survival of patients with HCC in cases of CTP class A, type I PVTT or unilobar-involved HCC.

Risk factors for early recurrence after surgical resection for hepatocellular carcinoma

BACKGROUND/AIMS Early recurrence (ER) after liver resection is one of the most important factors impacting the prognosis and survival of patients with hepatocellular carcinoma (HCC). This study aimed to identify the factors associated with ER after curative hepatic resection for HCC. METHODS From the July 2000 to July 2006, 144 patients underwent hepatic resection for HCC at a single institution. After excluding those with ruptured HCC, combined or mixed HCC, and who died during admission, 116 patients were analyzed. Patients with ER (defined as within 1 year) were compared with those who remained free of disease for more than 1 year. Various clinical characteristics including tumor and operative factors were evaluated to determine the factors predicting postoperative ER using univariate and multivariate analyses. RESULTS ER occurred in 51 patients (44%). In the univariate analysis, tumor size (P=0.001), microvascular invasion (P=0.003), portal vein invasion (P=0.001), TNM stage (P=0.010), serum levels of alpha-fetoprotein (AFP) (P=0.002) and aspartate aminotransferase (AST) (P=0.011), and operative time (P=0.033) were significantly associated with ER. AFP and AST were the independent predictors of ER in the multivariate analysis (P<0.05). CONCLUSIONS Preoperative serum AFP and AST levels were the independent risk factors for ER after surgical resection for HCC. Close postoperative surveillance is recommended for early detection of recurrence and additional treatments in patients with these factors.

Anatomical resection of hepatocellular carcinoma: A critical review of the procedure and its benefits on survival

Hepatocellular carcinoma (HCC) is the sixth most common type of cancer and the third most frequent cause of cancer-related death. Advances in preoperative assessment of HCC (e.g., imaging studies and liver function tests), surgical techniques, and postoperative care have improved the surgical outcomes and survival of patients who undergo hepatic resection for HCC. However, in the last 20 years, the long-term survival after hepatectomy has remained unsatisfactory owing to the high rates of local recurrence and multicentric occurrence. Anatomical liver resection (AR) was introduced in the 1980s. Although several studies have revealed tangible benefits of AR for HCC, these benefits are still debated. Because most HCCs occur in patients with liver cirrhosis and poor hepatic function, there are many factors that affect survival, including the surgical method. Nevertheless, many studies have documented the perioperative and long-term benefits of AR in various conditions. In this article, we review the results of several recently published, well-designed comparative studies of AR, to investigate whether AR provides real benefits on survival outcomes. We also discuss the potential pitfalls associated with this approach.