Epithelial to mesenchymal transition is associated with shorter disease-free survival in hepatocellular carcinoma.

BACKGROUND: Epithelial to mesenchymal transition (EMT) is involved in cancer cell invasion and metastasis as well as chemoresistance. Elucidation of EMT in hepatocellular carcinoma (HCC) might contribute to deeper understanding of its biology. METHODS: Overall, 100 patients with HCC, who underwent resection, were analyzed. The messenger RNA (mRNA) expression of the epithelial marker E-cadherin and the mesenchymal marker Vimentin were measured, and the EMT status of each patient was determined as follows: Vimentin/E-cadherin <2 = Epithelial (E), Vimentin/E-cadherin ≥2 = Mesenchymal (M). The correlation between these values and clinicopathological factors and prognosis were analyzed statistically. Moreover, the expression of transcription factors involved in EMT (Twist-1, Snail, Slug, Zeb-1, and Zeb-2) were measured and the role of interleukin (IL)-6 in inducing EMT and chemoresistance was examined. RESULTS: Patients with a mesenchymal tumor were more prone to have an earlier recurrence than those with an epithelial tumor. EMT-inducing transcription factors were more highly expressed in mesenchymal tumors than in epithelial tumors, and Twist-1 and Zeb-2 were significantly overexpressed. α-Fetoprotein (AFP) values were significantly higher in patients with epithelial tumors, and AFP-expressing HCC cell lines were more responsive to sorafenib. IL-6 expression was significantly higher in mesenchymal tumors, and knockdown of IL-6 in mesenchymal HCC cell lines increased E-cadherin expression and sensitivity to sorafenib. CONCLUSIONS: Analysis of surgically resected tumors suggests that EMT is involved in early disease recurrence in HCC. Twist-1 and Zeb-2 might be important for inducing EMT, and IL-6 might be a potential therapeutic target for alleviating the chemoresistance of mesenchymal HCC tumors.

Pattern of first recurrent lesions in pancreatic cancer: hepatic relapse is associated with dismal prognosis and portal vein invasion.

BACKGROUND/AIMS: The aim of this study was to evaluate patterns of the initial recurrence after pancreatectomy for pancreatic cancer and risk factors in each pattern. METHODOLOGY: This study included 209 pancreatic cancer patients who underwent pancreatectomy and of whom the detailed information on the first recurrent lesions detected by imaging during postoperative followup were available. Relapse patterns were classified into 4 groups: liver, peritoneal, local and extra-abdominal recurrences. We evaluated their associations with prognosis and various clinicopathological factors to identify relevant risk factors. RESULTS: Cumulative numbers of patients with liver, peritoneal, local, and extra-abdominal recurrences were 81, 70, 98 and 22, respectively, for the first recurrences. Hepatic relapse was associated with significantly shorter overall survival than other sites (p<0.001) and was an independent prognostic factor in multivariate analysis (p<0.001). Pathological portal vein invasion was the only independent risk factor for hepatic relapse (p=0.045). There was no significant correlation between the depth of invasion and prevalence of hepatic relapse. CONCLUSIONS: Hepatic relapse was associated with a dismal prognosis and with pathological portal vein invasion. Novel therapeutic strategies are therefore required to reduce the incidence of hepatic relapse, especially in patients with portal vein invasion.

[Recurrent acute pancreatitis due to arteriovenous malformation of the pancreas].

A 46-year-old man presented with acute epigastric pain and was diagnosed with acute pancreatitis. Although successfully managed, it recurred shortly after; he was subsequently referred to our institute for further investigation. Dynamic computed tomography (CT) and endoscopic ultrasonography revealed an arteriovenous malformation (AVM) in the body and tail of the pancreas. A diagnosis of pancreatic AVM causing recurrent pancreatitis was made and distal pancreatectomy was performed. Follow-up CT after surgery confirmed no further recurrence of either the AVM or pancreatitis. AVM of the pancreas is rare, and surgical resection is necessary in symptomatic patients.

Surgical treatment for rectal cancer with abnormally expanded inferior mesenteric vein resulting from pancreatic arteriovenous malformations.

A 52-year-old Japanese man presented for evaluation and treatment of rectal cancer. Screening computed tomography revealed pancreatic arteriovenous malformations (P-AVMs) and abnormally expanded inferior mesenteric vein (IMV) that resulted from P-AVMs. One-stage surgery for rectal cancer was dangerous so we first performed distal pancreatectomy to cure P-AVM and thus normalize the abnormally expanded IMV. After the operation, the IMV was occluded by the thrombi, and then the IMV became normal. We could perform safely radical laparoscopic surgery for rectal cancer. This is the first case report of P-AVMs combined with rectal cancer.

A functional polymorphism in the epidermal growth factor gene predicts hepatocellular carcinoma risk in Japanese hepatitis C patients.

BACKGROUND: A single nucleotide polymorphism (SNP) in the epidermal growth factor (EGF) gene (rs4444903) has been associated with increased risk of cancer, including hepatocellular carcinoma (HCC). The aim of this study was to examine the relationship between the EGF SNP genotype and the development and prognosis of HCC, in a Japanese population. METHODS: Restriction fragment-length polymorphism was used to determine the presence of the EGF SNP genotype in 498 patients, including 208 patients with HCC. The level of EGF messenger ribonucleic acid (mRNA) expression in cancerous tissues was measured by quantitative reverse transcription polymerase chain reaction. The correlation between the EGF SNP genotype and prognosis was statistically analyzed in the patients with HCC. RESULTS: The proportion of the A/A, A/G, and G/G genotypes were 5.3%, 42.8%, and 51.9%, respectively, in the patients with HCC, whereas in those without HCC, they were 8.6%, 35.9%, and 55.5%, respectively, revealing that the odds ratio (OR) of developing HCC was higher in patients with a G allele (OR =1.94, P=0.080 for A/G patients and OR =1.52, P=0.261 for G/G patients, as compared with A/A patients). In particular, when the analysis was limited to the 363 patients with hepatitis C, the OR for developing HCC was 3.54 (P=0.014) for A/G patients and was 2.85 (P=0.042) for G/G patients, as compared with A/A patients. Tumoral EGF mRNA expression in G/G patients was significantly higher than that in A/A patients (P=0.033). No statistically significant differences were observed between the EGF SNP genotype and diseasefree or overall survival. CONCLUSION: The EGF SNP genotype might be associated with a risk for the development of HCC in Japanese patients but not with prognosis. Of note, the association is significantly stronger in patients with hepatitis C, which is the main risk factor for HCC in Japan.

The use of nanometer-sized hydrographene species for support material for fuel cell electrode catalysts: a theoretical proposal.

Density functional theory (DFT) calculations propose that nanometer-sized hydrographene species, graphene-based clusters terminated by H atoms are a promising candidate for a support material for Pt catalysts in fuel cell. The proposal is based on the following three criteria: a small HOMO-LUMO gap of a nanometer-sized hydrographene species with and without a Pt cluster being comparable to zero-gap in infinite-size graphene, strengthening interactions of a Pt cluster with hydrographene species by utilizing its edge, and spontaneous H(2) activation by a Pt cluster on a carbon surface.