Galectin-3 favours tumour metastasis via the activation of ß-catenin signalling in hepatocellular carcinoma.

BACKGROUND: High probability of metastasis limited the long-term survival of patients with hepatocellular carcinoma (HCC). Our previous study revealed that Galectin-3 was closely associated with poor prognosis in HCC patients. METHODS: The effects of Galectin-3 on tumour metastasis were investigated in vitro and in vivo, and the underlying biological and molecular mechanisms involved in this process were evaluated. RESULTS: Galectin-3 showed a close correlation with vascular invasion and poor survival in a large-scale study in HCC patients from multiple sets. Galectin-3 was significantly involved in diverse metastasis-related processes in HCC cells, such as angiogenesis and epithelial-to-mesenchymal transition (EMT). Mechanistically, Galectin-3 activated the PI3K-Akt-GSK-3ß-ß-catenin signalling cascade; the ß-catenin/TCF4 transcriptional complex directly targeted IGFBP3 and vimentin to regulate angiogenesis and EMT, respectively. In animal models, Galectin-3 enhanced the tumorigenesis and metastasis of HCC cells via ß-catenin signalling. Moreover, molecular deletion of Galectin-3-ß-catenin signalling synergistically improved the antitumour effect of sorafenib. CONCLUSIONS: The Galectin-3-ß-catenin-IGFBP3/vimentin signalling cascade was determined as a central mechanism controlling HCC metastasis, providing possible biomarkers for predicating vascular metastasis and sorafenib resistance, as well as potential therapeutic targets for the treatment of HCC patients.

Clinical characteristics of Japanese patients with epithelioid hemangioendothelioma: a multicenter retrospective study.

BACKGROUND: Epithelioid hemangioendothelioma is an exceedingly rare sarcoma often occurring as an indolent angiocentric vascular tumor at various anatomic sites. Few reports have evaluated large case series of epithelioid hemangioendothelioma. METHODS: We conducted a retrospective analysis of the clinical data of 42 consecutive patients with epithelioid hemangioendothelioma who were pathologically diagnosed between 1990 and 2014 at 13 Japanese tertiary hospitals. We analyzed their clinical characteristics, tumor features and prognostic factors. RESULTS: The study included 22 men and 20 women, with a median age of 54 (range, 18-78) years. Pain was the most common symptom, occurring in 15 (68%) of the 22 symptomatic patients. The median maximum tumor diameter was 4.0 (range, 1.0-12.8) cm. The most commonly involved organs were the liver (81%), lungs (57%), and bones (12%). The overall survival rates were 79.5% at 1 year and 72.0% at 5 years. Substantially better survival was observed in asymptomatic patients than in symptomatic patients (P = 0.03), and better survival was also ovserved in patients with Ki-67 index ≤10% than in those with Ki-67 index > 10% (P = 0.04). By multivariate analysis, tumor size > 3.0 cm was associated with decreased survival (P = 0.049, hazard ratio 13.33). CONCLUSIONS: This study showed the clinical characteristics of Japanese patients with epithelioid hemangioendothelioma. Tumor size > 3.0 cm is an independent indicator of a poor prognosis in epithelioid hemangioendothelioma. The presence of symptoms at the time of diagnosis and high Ki-67 index implied poor survival.

Clinical outcomes of perioptic tumors treated with hypofractionated stereotactic radiotherapy using CyberKnife® stereotactic radiosurgery.

INTRODUCTION: Stereotactic radiation technique is widely reported as an effective treatment for various types of benign intracranial tumors. However, single fraction radiosurgery (SRS) is not recommended for tumors located close to the optic apparatus due to the restricted radiation tolerance dose of the optic pathway. Recent advances in radiotherapy include advanced frameless radiosurgery using hypofractionated stereotactic radiotherapy (HSRT), and this has become an attractive treatment option for perioptic tumors within 2-3 mm of the optic pathway. Accordingly, the aim of this study was to investigate the clinical outcomes of perioptic tumors treated with HSRT using CyberKnife® (CK) robotic radiosurgery system relative to tumor control, vision preservation and toxicity. METHODS: This retrospective analysis of prospectively collected data included consecutive 100 patients that were diagnosed with and treated for perioptic tumor at the Radiosurgery center, Ramathibodi Hospital during the January 2009 to December 2012 study period. RESULTS: The median tumor volume was 6.81 cm3 (range 0.37-51.6), and the median prescribed dose was 25 Gy (range 20-35) in 5 fractions (range 3-5). After the median follow-up time of 37.5 months (range 21-103), two patients developed tumor progression at 6 and 34 months post-HSRT. The 5-year overall survival was 97%, and the 5-year local control was 97.5%. At the last follow-up, no vision deterioration or newly developed hypopituitarism was detected in our study. CONCLUSIONS: Although a longer follow-up is needed, HSRT yields a high level of local control and vision preservation, and should be considered a treatment of choice for perioptic tumor located close to the optic apparatus.

Prognostic value of Sox2 expression in digestive tract cancers: A meta-analysis.

The aim of the present study was to accurately evaluate the association of Sox2 expression with the survival of patients with digestive tract cancers. Relevant literatures were identified by comprehensively searching databases including the Pubmed, Embase, CBMdisc, and Wanfang (up to October 2014). A meta-analysis was performed to clarify the association between Sox2 expression and overall survival or clinicopathological parameters of patients with digestive tract cancers (esophageal, gastric, and colorectal cancers). The results showed a significant association between high Sox2 expression and poor overall survival in patients with digestive tract carcinomas (HR=1.55, 95% CI=1.04-2.31), especially for patients with esophageal cancer (HR=2.04, 95%CI=1.30-3.22), colorectal cancer (HR=1.40, 95% CI=1.04-1.89), and digestive tract adenocarcinoma (HR=1.80, 95% CI=1.12-2.89), for Europeans (HR=1.98, 95% CI=1.44-2.71) or patients who did not receive neoadjuvant treatment (HR=1.73, 95% CI=1.10-2.72). Furthermore, Sox2 over-expression was highly correlated with vascular invasion (OR=1.86, 95% CI=1.25-2.77) and poor differentiation (OR=1.88, 95% CI=1.14-3.08), especially in esophageal and colorectal cancers. In conclusion, Sox2 expression may serve as a novel prognostic factor for patients with digestive tract cancers. Over-expression of Sox2 that is correlated with vascular invasion and poor differentiation suggests poor outcomes of patients with digestive tract cancers.

Survival in Resected Stage II Colorectal Cancer Is Dependent on Tumor Depth, Vascular Invasion, Postoperative CEA Level, and The Number of Examined Lymph Nodes.

BACKGROUND: The aim of the present study was to determine which aspects of tumor histology influence postoperative early relapse and overall survival rates after radical resection of stage II colorectal cancer (CRC). METHODS: Data were collected for 425 patients with stage II CRC who began treatment at a single institution between January 2006 and October 2013. All the enrolled patients were followed up on until death or until December 2014. Clinically significant factors affecting postoperative early relapse and overall survival rates were analyzed. RESULTS: Using a multivariate analysis, tumor invasion depth (P = 0.008), vascular invasion (P = 0.029), postoperative carcinoembryonic antigen (CEA) level (P = 0.001), and retrieval of less than 12 lymph nodes (P = 0.002) were found to be independent predictors for postoperative early relapse. A combination of tumor invasion depth, vascular invasion, postoperative CEA level, and number of lymph nodes retrieved showed that the greater the number of predictors involved, the higher the likelihood of postoperative early relapse and the poorer the overall survival. CONCLUSIONS: This study revealed that T4 invasion, vascular invasion, postoperative CEA level, and the number of examined lymph nodes may significantly affect the prognosis of stage II CRC patients after radical resection. The risks of postoperative early relapse and worse clinical outcome increase in proportion to the values of these four parameters.

Does histology predict outcome for malignant vascular tumors of the liver?

BACKGROUND AND OBJECTIVES: Malignant vascular tumors (MVT) of the liver are uncommon and poorly understood. We hypothesized that tumor histology is a predominant factor associated with survival in these tumors. METHODS: Patients with malignant histopathologic diagnoses of hepatic angiosarcoma (AS), hemangioendothelioma (HE) and its epithelioid variant (EHE), or hemangiopericytoma (HP) were identified using the SEER database (1973-2007). Overall survival (OS) was studied with Kaplan-Meier curves. RESULTS: We included 297 patients with MVT (207 AS, 28 HE, 56 EHE, 6 HP). All tumors demonstrated metastatic potential, although EHE and AS had the highest rate of regional or distant metastases (75% each). Patients with AS had the shortest median OS (1 month), however, those undergoing surgery had improved survival (6 months). Three patients with AS underwent liver transplant and lived for 11, 21, and 91 months each. Patients with EHE had the longest overall median survival of 75 months (30-183, P < 0.001). Surgical resection and transplant did not demonstrate an improvement in OS of patients with EHE in multivariable models. CONCLUSIONS: Histology is an important factor in determining survival for patients with hepatic MVT. Patients with EHE have the longest OS, whereas patients with AS have shorter survival but may benefit from surgery.

Clinicopathological features and management of hepatic vascular tumors. A 20-year experience in a Greek University Hospital.

PURPOSE: The aim of this study was to review the clinical features, diagnostic modalities, treatment options and pathological characteristics of various types of hepatic vascular tumors treated in our Institution over the last 20 years. METHODS: From 1991 to 2011, 761 cases of various hepatic lesions, benign and malignant, were surgically treated in our hospital. Among these, 56 (7.35%) hepatectomy specimens referred to vascular tumors. The records of these patients were retrieved and demographics , tumor characteristics, treatment, and actuarial survival were analyzed. The various therapeutic procedures, postoperative complications, follow-up data and the pre-and postoperative diagnostic difficulties were registered and analyzed. RESULTS: Pathological examination showed: hepatic hemangiomas in 35 (62.5%) patients (80% females), hepatic angiosarcomas in 7 patients (12.5%; males 71.4%), hepatic epithelioid hemangioendotheliomas in 9 (16%; females 50%) and hepatic angiomyolipomas in 5 patients (9%; females 60%). CONCLUSIONS: Vascular tumors of the liver comprise a heterogeneous group of neoplasms, benign, malignant and of intermediate degree of malignant behavior. These lesions can create great diagnostic difficulties, pre- and postoperative considerations, but the correct pathological diagnosis and classification of vascular hepatic tumors are most of the times mandatory in order to choose the proper therapeutic actions.

Modified primary tumour/vessel tumour/nodal tumour classification for patients with invasive ductal carcinoma of the breast.

BACKGROUND: We previously reported that the primary tumour/vessel tumour/nodal tumour (PVN) classification is significantly superior to the UICC pTNM classification and the Nottingham Prognostic Index for accurately predicting the outcome of patients with invasive ductal carcinoma of the breast in a manner that is independent of the nodal status and the hormone receptor status. METHODS: The purpose of the present study was to compare the outcome predictive power of a modified PVN classification to that of the newly devised pathological UICC pTNM classification and the reclassified Nottingham Prognostic Index in a different group of patients with invasive ductal carcinoma (n=1042) using multivariate analyses by the Cox proportional hazard regression model. RESULTS: The modified PVN classification clearly exhibited a superior significant power, compared with the other classifications, for the accurate prediction of tumour recurrence and tumour-related death among patients with invasive ductal carcinoma in a manner that was independent of the nodal status, the hormone receptor status, and adjuvant therapy status. CONCLUSION: The modified PVN classification is a useful classification system for predicting the outcome of invasive ductal carcinoma of the breast.

Expression of drug resistance related proteins in sarcomas of the pulmonary artery and poorly differentiated leiomyosarcomas of other origin.

Sarcomas are known to develop resistance to current chemotherapeutic strategies, displaying a multidrug-resistant phenotype. Mechanisms involved in drug resistance include reduced cellular drug accumulation, drug detoxification as well as alterations in drug target specificity. In seven sarcomas of the pulmonary artery (SPA) and ten leiomyosarcomas of other origin, we studied the immunohistochemical expression of P-glycoprotein (P-gp), multidrug-resistance protein (MRP), lung resistance protein (LRP), metallothionein (MT) and topoisomerase IIalpha. Upregulation was found in tumour cells for P-gp but not for MRP in SPA and other leiomyosarcomas. Topoisomerase IIalpha was expressed at high levels in tissue of primary tumours as well as recurrent tumours. Both P-gp and topoisomerase IIalpha were present in numerous tumour-associated vessels. LRP was expressed at high levels in SPA but to a lesser extent in the other leiomyosarcomas. MT was expressed at low levels but was markedly present at the border of necrosis. The overall survival and the relapse-free survival did not correlate with the expression of these factors. There was no significant relationship between treated and non-treated patients with respect to the expression of the examined molecules. P-gp, but not MRP, may play a role in the development of drug resistance. P-gp, LRP and topoisomerase IIalpha contribute to drug resistance through expression in tumour-associated vessels. Unique high levels of topisomerase IIalpha reflect the high proliferation rate of these tumours. MT seems to serve as a detoxifying agent of metabolites at the border of necrosis. Our findings underline the fact that multiple factors contribute to chemoresistance and that examination of a spectrum of relevant molecules is probably necessary to plan the best therapy.

Vascular tumors of the orbit.

Eighty-five vascular lesions of the orbit examined and treated between 1963-1993 were reviewed retrospectively to reveal the types of vascular tumors, age and sex distribution, clinical characteristics, treatment options and prognosis. Capillary hemangioma was the most frequent orbital vascular tumor accounting for 37 of 85 cases making up 43.5% of the entire orbital masses. Cavernous hemangioma accounted for 35 cases (41.2%), varices for 3 cases (3.5%), anteriovenous malformations for 3 cases (3.5%), angiosarcomas for 3 cases (3.5%), lymphangiomas for 3 cases (3.5%) and hemangiopericytoma for one case (1.2%). Of the 85 vascular tumor cases 43 were encountered in children aged 18 years or less. Capillary hemangioma was the most frequent pediatric orbital vascular lesion, making up 86% of the vascular tumors in this age group. Capillary hemangiomas have been treated with observation and intralesional corticosteroid injections. Cavernous hemangiomas, vascular malformations, lymphangiomas and two cases of angiosarcomas received orbitotomy. One case each of angiosarcoma and hemangiopericytoma underwent exenteration because of the advanced stage of the lesion. There was one tumor-related death who was a 9-year-old boy diagnosed with angiosarcoma. Vascular tumors with the exception of angiosarcomas and hemangiopericytoma behaved as benign lesions.

Symptoms, diagnosis, and therapy of primary sarcomas of the pulmonary artery.

Primary sarcoma of the pulmonary artery is a rare tumor which must be considered in differential diagnosis of pulmonary embolism. The data of the 93 cases published up to now is evaluated synoptically after a report on a primary sarcoma of the pulmonary artery. Modern diagnostic imaging methods (pulmonary DSA, perfusion scintigraphy, echocardiography, computer tomography, nuclear magnetic resonance tomography) may corroborate the suspicion of a sarcoma of the pulmonary artery. With a median survival time of 1.5 months, the prognosis of patients with primary sarcomas of the pulmonary artery must be regarded extremely poor. After tumor excision, the median survival time of the patients could be prolonged (statistically significant; p less than 0.01) to ten months. The significance of adjuvant chemotherapy and/or radiotherapy cannot be appraised at present.