Intravascular emboli relates to immunosuppressive tumor microenvironment and predicts prognosis in stage III colorectal cancer.

BACKGROUND: Stage III colorectal cancer (CRC) patients experience varying degrees of prognosis even if receiving standard therapeutic regimes. Intravascular emboli (IVE), a type of vascular invasion, impacts the clinical outcome in CRC. In this study, we confirmed the role of IVE in predicting the prognosis of stage III CRC patients and characterized the tumor microenvironment (TME) of CRC with IVE. METHODS: Data from 220 consecutive patients (cohort 1) with stage III CRC undergoing radical surgery was collected retrospectively between January 2009 to December 2014. According to the presence of IVE, which was confirmed by two independent pathologists, patients were classified into two groups. Univariate and multivariate Cox regression analyses were performed to evaluate the relation of IVE presence to patients' prognosis. The association between IVE and clinicopathological factors was also analyzed. Furthermore, differentially expressed genes (DEGs) and gene set enrichment analyses (GSEA) were performed to describe features of the TME based on microarray data consisting of 6 patients. Tumor tissues from a separate cohort of 73 patients with stage III CRC (cohort 2) collected between June 2014 and December 2015 were used to analyze tumor-infiltrating lymphocyte (TIL) by immunohistochemistry (IHC) staining. RESULTS: IVE was observed in 126 (57.3%) patients and could serve as an unfavorable independent prognostic predictor (P < 0.001) as well as lymph node metastasis (P < 0.05) and tumor location (P < 0.05). Additionally, patients with IVE had a higher neutrophil percentage (P = 0.002) and lower lymphocyte percentage (P = 0.002) relative to those without IVE. CRC with IVE had a significantly different profile of DEGs compared to CRC without IVE, and GSEA showed chronic inflammatory and immunosuppressive TME may promote IVE development. In cohort 2, tumors with IVE had fewer CD3+ TILs in the stromal region, as well as fewer CD8+ TILs in both stromal and tumoral regions relative to those without IVE. CONCLUSION: IVE, which was related closely to a chronic inflammatory and immunosuppressive TME, forecasted a worse prognosis of stage III CRC patients and may be taken into consideration when a therapeutic strategy is decided upon.

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.

Pulmonary vein mass with extension to the left atrium diagnosed by echocardiography.

We report a case of a man aged 65 years presenting with chronic cough, haemoptysis and intermittent atrial tachyarrhythmias on ECG. On 2D transthoracic echocardiography, an incidental left atrial mass was seen, initially thought to be a thrombus predisposed by intermittent atrial fibrillation. Transoesophageal echocardiography confirmed that this left atrial mass originated from a fixed, non-homogenous, right superior pulmonary vein mass with an extracardiac extension. Because of this finding, a thorough search for a primary focus lead to the discovery of a contiguous posterior mediastinal mass, which was a round cell neoplasm on histology. Management was deemed palliative. Although rare, left-sided cardiac masses should prompt the physician to search for a malignancy in the lung in high-risk patients, as haematogenous spread via the pulmonary vein is a potential mechanism for spread.

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.

Partial nephrectomy after selective embolization of tumor vessels in a hybrid operating room: A new approach of zero ischemia in renal surgery.

It is established that partial nephrectomy is the standard of care for tumors confined to the kidney. Achieving a partial nephrectomy without renal ischemia and limiting operative bleeding is the subject of numerous researches. Since 2010, hybrid operating rooms have been used to perform both interventional radiology and surgical procedures at the same place and time. We used this latest technology to treat 3 patients with localized kidney tumors. The tumors were of moderate complexity and all were treated after immediate hyperselective embolization by laparoscopic surgery without dissection and clamping of the renal pedicle. The embolization of tumor vessels could be performed using image-stitching software. After embolization, operative time was 50, 70 and 80 minutes and blood loss was less than 100 ml for each case. Postoperative control 3D arteriography confirmed the respect of the vascularization of the healthy renal parenchyma. No postoperative complications occurred. Combined approach including hyperselective embolization and partial nephrectomy in the same time in a dedicated operating room is a new approach of zero ischemia during partial nephrectomy which reduces the difficulty of the surgery, limits injury to the kidney and increases patient safety.

Grading system for blood vessel tumor emboli of invasive ductal carcinoma of the breast.

We previously reported that the number of mitotic and apoptotic figures in tumor cells in blood vessel tumor emboli had the greatest significant power for the accurate prediction of the outcome of patients with invasive ductal carcinoma of the breast. The purpose of the present study was to devise a grading system for blood vessel tumor emboli based on the mitotic and apoptotic figures of tumor cells in blood vessel tumor emboli, enabling accurate prediction of the outcome of patients with invasive ductal carcinoma of the breast. We classified 263 invasive ductal carcinomas into the following 3 grades according to the numbers of mitotic and apoptotic figures in tumor cells located in blood vessels within 1 high-power field: grade 0, no blood vessel invasion; grade 1, absence of mitotic figures and presence of any number of apoptotic figures, or 1 mitotic figure and 0 to 2 apoptotic figures; and grade 2, 1 mitotic figure and 3 or more apoptotic figures, or 2 or more mitotic figures and 1 or more apoptotic figures. Multivariate analyses with well-known prognostic factors demonstrated that grade 2 blood vessel tumor emboli significantly increased the hazard ratios for tumor recurrence independent of the nodal status, pathological TNM stage, hormone receptor status, or HER2 status. The presently reported grading system for blood vessel tumor emboli is the strongest histologic factor for accurate prediction of the outcome of patients with invasive ductal carcinoma of the breast.

Hemorrhagic collision metastasis in a cerebral arteriovenous malformation.

A 26-year-old patient with recurrent choriocarcinoma of the testis presented with headache and progressive left homonymous hemianopsia. On initial MRI a grade 4 arteriovenous malformation (AVM) was identified in the right occipital lobe, which was further characterized by catheter angiography. Continued worsening of the headache in the following days prompted a follow-up MRI, which revealed a new T2 hypointense nodule and adjacent vasogenic edema in the periphery of the AVM. A follow-up MRI showed a marked increase in the size of the nodule with intrinsic enhancement and worsening perilesional edema. Based on the imaging evolution, the nodule was diagnosed as a metastasis and the patient was started on chemotherapy and radiotherapy. One week after the MRI he developed a sudden hemorrhage within the mass requiring decompression craniectomy and resection of both AVM and tumor. The histopathology of the resected mass confirmed the diagnosis of choriocarcinoma metastasis to the AVM.

The critical role of CD133(+)CD44(+/high) tumor cells in hematogenous metastasis of liver cancers.

Metastatic hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide. However, the cell population responsible for its metastasis remains largely unknown. Here, we reported that CD133(+)CD44(+/high) defined a subgroup of tumor cells that was responsible for hematogenous metastasis of liver cancers. Immunohistochemical investigation of human HCC specimens revealed that the number of CD133(+) and CD44(+) HCC cells was increased and was associated with portal vein invasion. Purified CD133(+) or CD44(high) HCC cells were superior in clonogenic growth and vascular invasion, respectively. Thus, the combination of CD133 and CD44 was used to define a novel HCC sub-population. CD133(+)CD44(high), but not CD133(+)CD44(low/-), CD133(-)CD44(high) or CD133(-)CD44(low/-) xenografts, produced intrahepatic or lung metastasis in nude mice. Further analysis of human HCC samples by flow cytometry showed that the number of CD133(+)CD44(+) tumor cells was associated with portal vein metastasis. The cDNA microarray analysis of CD133(+)CD44(+) and CD133(+)CD44(-) tumor cells isolated from metastatic HCC patients revealed that these cells comprised of two different populations possessing distinct gene expression profiles. Our results suggest that CD133(+)CD44(+) tumor cells are a particular population responsible for hematogenous metastasis in liver cancers and that these cells might be targets for treatment of HCC metastasis.

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.

Abducens nerve palsy and Horner syndrome due to metastatic tumor in the cavernous sinus.

A 41-year-old man was diagnosed as having primary parotid carcinoma on the right side. After radical parotidectomy, radiation therapy and systemic chemotherapy, the primary parotid carcinoma was completely remitted. Two years later, right abducens nerve palsy and Horner syndrome appeared. Neuroimaging demonstrated a gadolinium-enhanced lesion in the posterior portion of the right cavernous sinus, and metastasis of parotid carcinoma was suspected. After radiosurgery and systemic chemotherapy, the intracavernous lesion disappeared. This is the first case of combination of abducens nerve palsy and ipsilateral Horner syndrome due to metastasis from parotid carcinoma to the cavernous sinus.

Expression of nm23-H1 gene product in esophageal squamous cell carcinoma and its association with vessel invasion and survival.

BACKGROUND: We assessed the nm23-H1 gene product expression and its relationship with lymphatic and blood vessel invasion in patients with esophageal squamous cell carcinoma. METHODS: Formalin-fixed and paraffin-embedded tissue sections from 45 patients who were treated surgically were used in this study. Pathologists graded lymphatic and blood vessel invasion in each of the tissue samples. Expression of nm23-Hl gene product was determined using a specific monoclonal antibody. RESULTS: Expression of nm23-H1 gene product was present in 17 (37.8%) cases. We found an inverse correlation between nm23-H1 gene product expression and lymphatic vessel invasion, whereas no correlation between nm23-H1 gene product expression and blood vessel invasion. Overall survival rate was not different between nm23-H1 gene product positive and negative patients (p = 0.21). However, reduced expression of nm23-H1 gene product was associated with shorter overall survival in patients with involved lymph nodes (p < 0.05), but not in patients without involved lymph nodes (p = 0.87). CONCLUSIONS: In patients with esophageal squamous cell carcinoma, there appears to be an inverse relationship between nm23-H1 gene product expression and lymphatic vessel invasion. Furthermore, nm23-H1 gene product expression might be a prognostic marker in patients with involved lymph nodes. Our data does not demonstrate any correlation between nm23-H1 gene product expression and blood vessel invasion.

Intravascular bronchioloalveolar tumor with skin metastases.

Intravascular bronchioloalveolar tumor (IVBAT) is a rare pulmonary tumor that occurs in the younger age groups. In the present article, we describe a patient who manifested systemic growth after the resection of the primary tumor. Skin metastasis, which has never been reported, is histologically examined.

Intravital videomicroscopy of the chorioallantoic microcirculation: a model system for studying metastasis.

The chick embryo is a useful model for studying hematogenous metastasis. Cancer cells injected into veins of the chorioallantoic membrane (CAM) circulate briefly through all tissues but form metastases predominantly in the CAM. This respiratory organ is particularly suitable for intravital microscope because of its accessibility without the need for surgery and the density and planar configuration of its vessels (which we confirmed by microcorrosion casting). Using an inverted microscope with oblique transillumination for high-resolution images and epifluorescence to identify labeled B16F1 melanoma cells, we studied successive stages of metastasis formation in the CAM in vivo. By 2 min postinjection (pi) all cancer cells had become arrested within the microvasculature. This initial arrest appeared to be due to size restriction, based on measurements of cell and vessel diameters. At 15-60 min pi, trapped cells were seen in tapering arterioles (27%), orifices from arterioles to the capillary plexus (61%), or in the plexus itself (12%). Some cells had extravasated into the underlying mesenchyme by 3 hr (pi), and at 24 hr all cancer cells had completed this process. The mean rate of migration out of capillary lumens was approximately 1 micron/hr. Micrometastases grew in a planar configuration just beneath the capillary plexus, with a cell doubling time of approximately 24 hr. Our technique is also applicable to other tumor types and host animals and provides a powerful tool to complement studies on the molecular basis of metastasis.

Cavernous sinus syndrome as the presentation of malignant lymphoma: case report and review of the literature.

Cavernous sinus syndrome (CSS) is an unusual presentation of malignant lymphoma. We report a patient with lymphoma that presented with CSS, and we review the literature on nine other reported cases. Sharp retroorbital pain, paraesthesia around the orbit, and complete 6th nerve palsy were dominant presenting symptoms. In all cases, the tumor developed on the right side. The computed tomographic scan was abnormal in only two of the nine patients during the early stages of the disease. The dominant histological type was large cell lymphoma. The mean age of the patients was 45 years. The mean survival time after the first presenting symptom was 8.7 months. Two of the reported patients as well as our patient had disseminated disease, which became evident at autopsy.

An immunohistochemical study on "neoplastic angioendotheliosis": demonstration of B lymphocyte markers in the neoplastic cells.

Frozen cerebral and renal tissue sections of an autopsied "neoplastic angioendotheliosis (NAE)" case were investigated immunohistochemically using monoclonal and heterologous antibodies to lymphocyte, monocyte, endothelial, epithelial and histiocytic antigens. In both tissues, positive stainings for surface immunoglobulin (sIg) mu and chi, but not lambda, were observed in most of the neoplastic cells. These cells were also positive for other B cell markers (BA-1, Leu-12 and HLA-DR). No distinct staining was observed in the neoplastic cells with antibodies to T lymphocyte (OKT-11 and Leu-1) or monocyte (OKM-1) markers. Positive stainings were observed only in some small round lymphoid cells which were distributed sporadically in and around blood vessels and were considered to be reactive. No positive staining was observed in the neoplastic cells with antibodies to endothelial (factor VIII), epithelial (cytokeratin) or histiocytic (lysozyme) antigens. Thus, our NAE case was shown to be of monoclonal B cell lymphoma in nature.

[A case of vascular leiomyosarcoma of the superficial soft tissues]. / Su di un caso di leiomiosarcoma vascolare dei tessuti molli superficiali.

The authors report a case of vascular leiomyosarcoma of the superficial soft tissues, and point out its epidemiologic (rareness of the report), biologic (high degree of malignancy, trend to local relapse and remote conversion into metastases), histopathologic aspects. They consider significant as to prognostic value the appraisal of the "mitotic index" and the opportunity of a radical intervention, followed by radiotherapy. They, moreover, think it useful, in consideration of the frequency of the relapses, to perform a periodic checking of the patient.