Hepatic Venous Invasion Research Articles

Intrahepatic Lymphatic Invasion Independently Predicts Poor Survival and recurrences after Hepatectomy in Patients with Colorectal Carcinoma Liver Metastases

Intrahepatic Lymphatic Invasion Independently Predicts Poor Survival and recurrences after Hepatectomy in Patients with Colorectal Carcinoma Liver Metastases

Role of Growth Factor Receptor–Bound Protein 7 in Hepatocellular Carcinoma

The human growth factor receptor-bound protein 7 (Grb7) is an adaptor molecule and is related to cell invasion. In this present study, we investigated the clinical and biological significance of Grb7 expression in human hepatocellular carcinoma (HCC). We reviewed 64 consecutive patients who had undergone liver resection for HCC, and we investigated the correlation between Grb7 expression and clinical outcome. To analyze the biological behavior of Grb7 in vitro and in vivo, we established Grb7 stable knockdown HCC cells using RNA interference technology. The positive staining of Grb7 protein was correlated with portal venous invasion (P < 0.01), hepatic venous invasion (P < 0.01), and intrahepatic metastasis (P < 0.05). Positive expression of Grb7 was significantly correlated with focal adhesion kinase (FAK) protein levels in HCC (P < 0.01). The Grb7- and FAK-positive group showed a significantly poorer prognosis as compared with the Grb7- and FAK-negative group (P < 0.05). Grb7 knockdown HCC cells exhibited significantly lower levels of invasion potential (P < 0.05) and motility (P < 0.05) than the control cells in vitro; moreover, Grb7 knockdown HCC cells showed delayed onset of the tumors compared with the control cells in vivo. Grb7 expression can modulate the invasive phenotype of HCC. Grb7 plays an important role in HCC progression and is strongly associated with expression of FAK. Grb7 could be a therapeutic target in HCC.

Predictors of hepatic venous trunk invasion and prognostic factors in patients with hepatocellular carcinomas that had come into contact with the trunk of major hepatic veins

In this study, we tried to identify the preoperative predictors of hepatic venous trunk invasion and the prognostic factors in patients with hepatocellular carcinoma (HCC) that had come into contact with the trunk of a major hepatic vein over a distance of 1.0 cm or more. Forty patients who had such HCCs resected were entered into this study and predictors of hepatic venous trunk invasion and prognostic factors were evaluated by univariate and multivariate analyses. A combined resection of the HCC and the venous trunk was performed in 29 patients. Hepatic venous trunk invasion was observed in 12 patients, including 2 with inferior vena cava tumor thrombus. A stepwise logistic regression analysis indicated that tumors larger than or equal to 7 cm in diameter and tumors showing a poorly differentiated histological grade were independent predictors of hepatic venous trunk invasion. The survival of patients without venous trunk invasion was significantly better than that for patients with venous trunk invasion (P = 0.048). A univariate analysis revealed that Child-Pugh classification B (P = 0.002), a high des-gamma-carboxy prothrombin concentration (> or =400 mAU/ml, P = 0.023), a large HCC (> or =5.0 cm in diameter, P = 0.002), the presence of portal vein invasion (P < 0.001), the presence of venous trunk invasion (P = 0.048), the presence of intrahepatic metastasis (P < 0.001), and poorly differentiated HCC (P = 0.006) correlated with a worse overall survival after hepatic resection. In a multivariate analysis, however, only the presence of intrahepatic metastasis (P = 0.037, relative risk 8.25) was an independent predictor of poor overall survival. Large tumors (> or =7 cm in diameter) and poorly differentiated HCCs were more likely to be associated with hepatic venous trunk invasion and intrahepatic metastasis was an independent prognostic factor in patients with HCC that had come into contact with the trunk of a major hepatic vein.

Clinical and biological significance of growth factor receptor bound protein 7 on progression in hepatocellular carcinoma

9527 Background: Although hepatocellular carcinoma (HCC) is one of the most common cancers, the mechanisms that regulate its development and progression remain unclear. We reported that focal adhesion kinase (FAK) played an important role in HCC progression, especially vascular invasion (Clinical Cancer Research 2004). The objective of this study was to investigate whether growth factor receptor bound protein 7 (Grb7), which is one of downstream molecules of FAK, is involved in the progression of human HCC. Methods: Grb7 expressions in HCC cell lines were analyzed using Western blot analysis. Immunohistochemistry (IHC) analysis for Grb7 was performed on paraffin embedded tissues in 64 HCC samples, respectively. We also investigated the correlation between the Grb7 expression and the clinical outcome. Moreover, we established the Grb7 knock down HCC cell lines using RNA interference (RNAi) method. Using these cells, we evaluated its biological features in vitro and in vivo. Results: Western blot analysis showed Grb7 expression in HCC cell lines. Grb7 positive HCC was observed in 18 of 64 patients (28.1%), and also correlated with portal venous invasion (p<0.01), intra-hepatic matastasis (p<0.01), and hepatic venous invasion (p<0.05), and tendency for a poor prognosis. Grb7 positive expression correlated significantly with FAK positive expression (p<0.01). Grb7 knock down cells showed significantly lower level of invasion potential than the control cells using invasion assay (p<0.01) and wound healing assay (p<0.01). Grb7 knock down cells also showed lower level of tumor growth than the control cells in nude mice (p<0.01). Conclusions: The present study showed that Grb7 are strongly expressed in HCC cells and involved in the invasion potential of HCC. Grb7 could be a novel molecular target for HCC therapeutics. No significant financial relationships to disclose.

Prognostic factors for recurrence in stage II and III gastric cancer patients receiving a curative resection and postoperative adjuvant chemotherapy.

Prognostic value of clinicopathologic factors and biologic markers was analyzed in 185 patients who received a curative resection and adjuvant chemotherapy of pathologically confirmed stage II or III gastric cancer. No difference was found between the chemotherapeutic regimens according to the frequency of recurrence, but tumor type, histology, depth of invasion, nodal metastasis, and lymphatic and venous invasion were significantly different between recurrent (n=62) and non-recurrent (n=123) patients. However, the degree of lymphatic dissection and the patterns of biological markers (DNA ploidy, p53 staining and PCNA labeling) were not different. Hepatic metastasis and venous invasion were more frequent on patients recurring within one year, compared to those who recurred later. Multivariate analyses showed that depth of invasion, level 2 lymph node metastasis and tumor histology were risk factors for recurrence. Pathologic factors were more important for predicting recurrence than biological markers.

Gastric cancer in young patients

Background: Delayed diagnosis, a high rate of histologically undifferentiated types of tumors, and rapid disease progression are frequently cited as the main reasons for the poor prognosis of gastric cancer in young patients. An improved prognosis has been anticipated for young gastric cancer patients because of recent improvements in digestive tract diagnostic techniques. This retrospective study was designed to determine whether these trends have had an impact on young Japanese patients with gastric cancer, and to further elucidate differences in clinicopathologic features between elderly and young patients. Methods: From 1984 to 1995, 1654 patients with gastric cancer were admitted to our hospital. Of these, 86 patients (5.2%) were less than 40 years of age (young group). The clinicopathologic features of this young group were reviewed retrospectively, using hospital records, and compared with those of older patients (n = 499 [29.4%], 60 to 69 years of age). Results: The young group contained significantly higher percentages of female patients, epigastric pain symptoms, depressed superficial type lesions, mucosal invasion, and poorly differentiated histology; percentages of hepatic metastasis and venous invasion were lower. Survival rates for all patients and for the resected cases were significantly better in the young group (p = 0.035 and 0.017 respectively). The percentage of early stage stomach cancers for the group less than 40 years of age was 49.0% in 1984–89, but had risen to 60.9% by 1990–95. Conclusions: Early diagnosis has improved the prognosis of young gastric cancer patients. Furthermore, these data show a recent shift in stage distribution; additional prognostic improvement is anticipated for young patients with early gastric cancer.

Hepatocellular carcinoma: prospective assessments of the T-factor with CT, US, and MR imaging.

The capabilities of computed tomography (CT), ultrasonography (US), and magnetic resonance (MR) imaging were studied in order to determine the role of each of these noninvasive examinations for estimating the T-factor of hepatocellular carcinomas (HCCs). Fifty-one patients with surgically proven HCCs received CT (50 patients), US (46 patients), and MR (44 patients). The images of CT, US, and MR were prospectively evaluated for main tumor size, intrahepatic metastases, and vascular invasion, which compose the T-factor of HCC, and compared to pathological results. The sizes of the main tumor were estimated correctly by all examinations. For estimating intrahepatic metastases, US (74%) and MR (73%) were superior to CT (65%). For estimating portal invasion, CT (79%) was superior to US (70%) and MR (66%), because CT could demonstrate the segmental staining caused by portal invasion. The estimates of hepatic venous invasion were difficult during any of the examinations. We conclude that presurgical evaluations of the T-factor require the use of US and CT or MR and CT.