Vascular Metastasis Research Articles

The adhesion molecules NCAM, HCAM, PECAM-1 and ICAM-1 in normal salivary gland tissues and salivary gland malignancies.

Some malignant salivary gland tumors are known for their propensity to exhibit perineural invasion and vascular metastases. It was hypothesized that alterations in the expression of cell adhesion molecules are involved in these processes. The expression and distribution of neural cell adhesion molecule (NCAM), HCAM (CD44), platelet-endothelial cell adhesion molecule-1 (PECAM-1), and intercellular cell adhesion molecule-1 (ICAM-1) in normal salivary gland tissues and selected salivary gland malignancies, especially adenoid cystic carcinoma (AdCyCa) and polymorphous low-grade adenocarcinoma (PMLG), were determined immunohistochemically, and their influence on histologically demonstrated perineural invasion, vascular invasion, and tumor recurrence/patient death were investigated. NCAM, HCAM, and ICAM-1 were often found to be expressed by neoplastic cells, but no correlation to perineural invasion, tumor behavior, or patient prognosis was found. PECAM-1 was rarely and only focally expressed in three tumors, all of which were related to tumor metastases and patient death. Immunohistochemical demonstration of NCAM, HCAM, and ICAM-1 is not related to perineural invasion or tumor behavior. PECAM-1 expression was related to vascular invasion and poor patient prognosis in three cases.

Large cerebellar lesion as original manifestation of transitional cell carcinoma of the bladder

Patients with transitional cell carcinoma of the bladder classically present with irritative voiding symptoms or painless hematuria. Common sites of vascular metastases include the liver (38%), lung (36%), bone (27%), adrenal glands (21%), and intestine (13%). Vascular metastasis to the brain, without a prior history of chemotherapy, is extremely rare. To our knowledge, this is the first report of a patient with bladder transitional cell carcinoma whose original presentation was from a symptomatic, metastatic, cerebellar lesion.

Correlation of cyclooxygenase-2 pathway and VEGF expression in head and neck squamous cell carcinoma

The purpose of this study was to determine whether cyclooxygenase-2 (COX-2) was overexpressed in head and neck squamous cell carcinoma (HNSCC) in relation to vascular endothelial growth factor (VEGF) expression and lymph node metastasis. COX-2 has an important role in the promotion of carcinogenesis, tumor invasiveness and angiogenesis. VEGF is a proangiogenic factor that is up-regulated in various tumors. VEGF has been shown to interact with COX-derived prostaglandins in angiogenesis. To better understand the roles of these genes in HNSCC, we evaluated the immunohistochemical expression pattern of COX-2 and VEGF in relationship with histologic differentiation, clinical stage, and nodal status in 146 HNSCC. The COX-2/VEGF double immunofluorescein staining was evaluated with confocal scanning laser microscope. A positive expression was seen in 96% (140/146: 98 strong positive, 42 weakly positive) for COX-2 and in 98% (143/146: 63 strong positive, 80 weakly positive) for VEGF in HNSCC. A correlation was present in the positive expression of COX-2 with histologic differentiation, clinical stage, and nodal status. VEGF expression was also correlated with nodal status. A significant relation was observed between COX-2 and VEGF expressions. The simultaneous expression of COX-2 and VEGF was statistically significant (p<0.05). These results indicate that elevated COX-2 or VEGF expression is more common in HNSCC with poor prognostic characteristics. The present findings support the efforts to initiate clinical trials on the efficacy of COX-2 inhibitors in adjuvant treatment of HNSCC.

Upregulated expression of VEGF and Ca IX correlate with the vascular metastasis pattern of intestinal type carcinoma

Upregulated expression of VEGF and Ca IX correlate with the vascular metastasis pattern of intestinal type carcinoma

Hybrid thyroid carcinoma with a coarse chromatin pattern and nuclear features of papillary thyroid carcinoma.

Hybrid follicular carcinoma (FC) and papillary thyroid carcinoma (PTC) have not been previously well described. Consecutive cases of 29 FC, 12 Hurthle cell carcinomas (HC), 247 PTC and 13 Hurthle cell PTC (HPTC) were reviewed with special attention to the coarse (CC) and fine chromatin patterns (FIC), as well as to the presence of nuclear grooves, pseudoinclusions or optically clear appearance. Limited nuclear features of PTC (LNF-PTC) are defined as areas of tumor with FIC in addition to some other nuclear features, but insufficient for the diagnosis of PTC. Tumors with nuclei showing an admixture of CC and PTC or LNFPTC were submitted for immunostaining for cytokeratin 19, HBME and Ret/PTC. FC and HC contained areas of LNFPTC in 25 tumors and focal PTC in 3 tumors. None of these cases was associated with lymph node metastasis. Areas with CC were found in 54 PTC and 3 HPTC. The rates of vascular invasion and distant metastasis tended to be higher for PTC with areas of coarse chromatin pattern than for PTC without such areas; however, the difference was not statistically significant. Immunoreactivity for cytokeratin 19 and HBME was moderate to strong for PTC and focal areas of PTC or LNFPTC in FC without Hurthle cell changes. Ret/PTC immunostaining was positive in areas of LNFPTC or focal PTC in three FC. Focal PTC or areas of LNFPTC are frequently seen in FC. Likewise, areas of CC are often present in PTC. The presence of these focal areas does not appear to change the clinical behavior of the tumor and therefore does not warrant a change of nomenclature.

Stromal sialyl Le(a) expression is correlated with vascular invasion of human gallbladder adenocarcinoma.

Sialyl Le(a) antigen (CA19-9), a member of a family of high molecular weight glycoproteins, was originally described as a gastrointestinal- and pancreatic-specific tumor marker. Recent studies have demonstrated that sialyl Lea is a ligand for E-selectin and may play an important role in tumor metastasis. However, expression patterns of sialyl Le(a) have not yet been established in human gallbladder carcinomas. In this study, we examined sialyl Le(a) expression in human gallbladder adenocarcinoma and its clinicopathological significance. Sialyl Le(a) immunoreactivity was detected not only in cancer cells (cytoplasmic type; 68.5%, 37/54) but also in cancer stroma (stromal type; 46.3%, 24/54). According to TNM classification, stromal sialyl Le(a) expression was detected in 60. 0% (24/40) and 7.1% (1/14) of the T2-4 and T1 cancers, respectively (p<0.01). Stromal sialyl Le(a)-positive gallbladder cancers frequently showed lymphatic invasion, venous invasion and lymph node metastasis (62.9%, 62.5% and 70.0%, respectively) (p<0.01). These observations suggested that sialyl Le(a) expression plays important roles in vascular invasion and metastasis of human gallbladder adenocarcinomas.

7018 Endoscopic ultrasonography in diagnosis and staging of ampullary carcinoma: a comparative study with surgical resection.

Aim: Prospective evaluation of endoscopic ultrasonography (EUS) for diagnosis and staging of ampullary tumors surgically resected. Patients and methods: Between may 95 and september 99, 16 consecutive patients (mean age: 62,2 years (44-74), sex-ratio: 0,5) admitted in our unit for diagnosis and pre-therapeutic staging of ampullary underwent bilio-pancreatic EUS (radial probe EUM3 et EUM20 7,5-12 MHz and miniprobe 20 MHz Olympus®) and following curative surgical resection. Diagnosis of ampulloma was suspected according to following criterias: jaundice (n=6), abdominal pain (n=1), acute pancreatitis (n=5), biological cholestastic syndrom (n=4). Results: EUS was performed in all patiens without complications. Dilatation of main pancreatic duct and/or main biliary duct were visualized at abdominal ultrasonography (US) and/or CT-scan (n=6). Ampullary lesion in CT-scan (n=4) showed an ampullary tumoral lesion in 4 cases (25%), all visualized in EUS. An ampullary tumor was revealed by EUS in 14 patients (87,5%), hypoechogenic (n=10), isoechogenic (n=2) or heterogenous (n=2). Two patients had a dilatation of main bile duct (n=1) and Wirsung duct (n=1). No vascular invasion or peritoneal metastasis were detected. A curative surgery was performed in all patients (Whipple resection (n=15), ampullectomy n=1) which showed ampullary carcinoma without vascular involvement in 14 cases (87,5%) including two tumors that had been not visualized by EUS. In the two remaining patients, a cholangiocarcinoma and an odditis was diagnosed. Correlation between EUS staging and surgical/pathological findings were: 6/10, 0/1 and 3/4 for ampullomas respectively classified T1, T2 and T3 - 12/13 and 3/1 for N staging. Conclusion: EUS is useful for the diagnosis of ampullary tumours not showed by classical morphologic exams (71.4%). EUS represents the most accurate imaging technique for detecting ampulloma potentially resectable.

A study on the correlation between P-selectin and lung cancer.

To investigate the role of P-selectin in metastasis of lung cancer. Expression of P-selectin were examined in 48 primary lung cancer specimens by the microware enhanced immunohistochemical staining method (SP) using a rat monoclonal antibody against human P-selectin , with 18 cases of adjacent non-cancerous tissue as control. The positive rate of P-selectin expression in adenocarcinoma was significantly higher than those of squamous cell carcinoma and adjacent non-cancerous tissues ( P < 0. 01) . In adenocarcinoma , the expression of P-selectin in stage III and IV was significantly higher than that of stage I and II ( P < 0. 01) .But there were no significant correlation between the expression of P-selectin and differentiation grade of tumor , lymph node metastasis , size of the primary tumor. P-selectin might be associated with vascular metastasis in adenocarcinoma.

The Indications for and Timing of Liver Transplantation

Since the 1970s, there has been dramatic growth in the annual number of liver transplants, with improving survival. We review indications for liver transplantation for fulminant hepatic failure (FHF), cholestatic liver disease, and hepatocellular liver disease. A decreased factor V level appears to be a sensitive indicator of FHF requiring transplantation, with a factor V level of less than 20% (less than 30% for age greater than 30 years) suggested as the main indication in encephalopathic patients. The King's criteria are also useful for identifying patients with FHF who require transplantation. FHF from Wilson's disease is universally fatal without transplantation. Any patient with FHF who is unlikely to recover spontaneously should be referred to a transplant center. In patients with primary biliary cirrhosis (PBC), the Mayo Clinic model is widely used to calculate a risk score (based on age, bilirubin, albumin, prothrombin time, and edema). PBC patients with a rapidly rising Mayo risk score and/or a rising bilirubin should be listed for transplantation. The Mayo Clinic survival model for primary sclerosing cholangitis is based on bilirubin, histological stage, age, and presence or absence of splenomegaly, but this model is limited by the emergence of recurrent bacterial cholangitis, dominant strictures, and cholangiocarcinoma. Patients with hepatitis C should be referred for transplantation upon onset of ascites, variceal bleeding, encephalopathy, and/or jaundice with decreasing synthetic function. In patients with autoimmune hepatitis, prognostic indicators that herald the need for transplantation include variceal bleeding, encephalopathy, ascites, hyperbilirubinemia, and worsening synthetic function. Patients with Budd–Chiari syndrome who have end-stage complications of cirrhosis are candidates for transplantation, but clotting disorders must be treated to minimize the risk of recurrent thrombosis. Although hepatocellular carcinoma was once a contraindication, the presence of a small tumor without vascular or distant metastasis is now an indication for liver transplantation. In summary, liver transplantation remains a lifesaving procedure for individuals with end-stage liver disease due to a variety of causes.

AN EARLY SMALL CELL CARCINOMA OF THE STOMACH-REPORT OF A CASE-

This paper describes a case of early small cell carcinoma of the stomach with a review of 98 cases including the case seen in the Japanese literature. A 66-year-old man had been complaining of gastric discomfort from January, 1996. Barium meal roentgenogram and endoscopic study were performed, and he was pointed out having a gastric cancer with slight ulceration, like a submucosal tumor at the posterior wall of the middle body of the stomach. In April, a distal partial gastrectomy and lymph nodes dissection were performed. There were no liver metastasis, distal metastasis and peritoneal dissemination, but the metastases of 7th lymph nodes existed. The histological findings showed small uniform anaplastic cells with large nucleocytoplasmic ratio proliferating to the submucosal layer. Grimelius staining for argyrophil granule was positive. It was diagnosed as small cell carcinoma of the stomach. In a review of the Japanese literature the death rate within 5 years was 32% or 43% in early cancers or advanced cancers of the stomach, respectively. As our case even early cancer often has lymph node metastasis. It is suggested that vascular invasion and lymph node metastasis which can occur in an early stage may lead the disease to have a poor prognosis.

Angiogenesis as a new target for cancer treatment.

Neovascularization is often required for rapid growth of solid tumors and also limits vascular metastasis of tumor cells. Neovascularization-targeting agents are a recent innovation that may be a novel means of anticancer therapy. These antiangiogenic drugs have been developed by targeting cell proliferation of vascular endothelial cells, basement-membrane-degrading enzymes, angiogenic factors/receptors, extracellular matrix, angiogenesis signaling, and cell-cell/cell-matrix interactions. In this report, we describe how tumor angiogenesis occurs and how antiangiogenic agents are developed.

Suppression of gelatinase production with decreased invasiveness of choriocarcinoma cells by human recombinant interferon beta

OBJECTIVE: Choriocarcinoma is a highly invasive gynecologic tumor, and hematogenous metastases frequently develop. To establish a molecular basis for antiinvasion therapy of choriocarcinoma, we examined the effects of human recombinant interferons on gelatinase production and invasion by choriocarcinoma cells. STUDY DESIGN: Using the five choriocarcinoma cell lines, we measured gelatinase activity by gelatin zymography. The effects of recombinant interferons (rIFN-α, riFN-β, and rIFN-γ) were then analyzed by Western blot analysis and chemoinvasion assay. RESULTS: High levels of 72 kd gelatinase activity were detected in the highly invasive choriocarcinoma cell lines, two of which also contained an active form of 72 kd gelatinase with an apoparent molecular mass of 88 kd. Gelatinase production was decreased by incubation with rIFN-β. In the chemoinvasion assay, only rIFN-β had an inhibitory effect on the invasiveness of tumor cells without a cytotoxic effect. CONCLUSION: Choriocarcinoma cells showed high 72 kd gelatinase activity, which suggested a role for the enzyme in vascular metastasis. Studies on the use of rIFN-β to inhibit metastasis of choriocarcinoma via suppressio of gelatinase production are warranted.

STUDY OF CLINICAL CASES OF SUPERFICIAL CARCINOMA OF THE ESOPHAGUS

The malignancy of superficial carcinomas of the esophagus was investigated for clinicopathological features by comparing such patients with those died of recurrence. Subjects were 31 cases of the disease, including 2 cases of ep, 6 cases of mm, and 23 cases of sm. There were 9 death cases which were comprised of 5 cases of n (-)/sm and 4 cases of n (+)/sm carcinomas, or 2 cases with invasion depth of sm2 and 7 cases with sm3. Histologically all cases had squamous cell carcinoma. No significant correlation between differentiation and longer diameter of the tumor, and prognosis. The positive rate in No 1 and 2 lymph nodes was as high as 17.9%, but the death due to recurrence in this patient group was only one. On the contrary, the positive rate was low in mediastinal lymph nodes or those of the 3rd group, but the patients of this group died of recurrence early after metastasis once occurred. Recurrence patterns included vasculsar type in 6 cases, lymphatic type in one, and both in 2. The 5-year survival rate was as poor as 50.0% in n (-)/sm carcinomas or 42.9% in n (+)/sm carcinomas. Submucosal carcinomas necessitate sufficient lymph node dissection for the high lymph node positive rate, and some postoperative adjuvant therapies for the predominance in vascular metastasis.

Patterns of CEA-related antigen expression in invasive squamous carcinoma of the cervix.

The recognition of an adhesive role for the CEA-related antigens emphasizes the need for clear demonstration of the changes in CEA expression and subcellular localization between normal and neoplastic tissues. Using a panel of monoclonal and polyclonal antibodies, membranous and cytoplasmic CEA expression was seen in 50 invasive cervical squamous carcinomas in four distinct patterns dependent on tumour type and differentiation. Membranous CEA expression is a marker of differentiation in squamous carcinomas and may influence tumour behaviour and hence patient survival. Strong CEA positivity was seen on the endothelium of vessels containing tumour in ten cases where vascular metastases were prominent. Staining of these ten cases revealed concomitant sialated Lewis X positivity in tumour cells with weak endothelial positivity in three cases; cervical squamous tumour cells may localize to vascular endothelium, and hence disseminate, through specific binding of CEA and/or sialated Lewis X.

Malignant seminoma in a horse

Summary An antemortem diagnosis of malignant seminoma was made on a 14-year-old Quarter Horse stallion. Castration was performed and histopathology showed evidence of vascular and lyumphatic metastasis. Ten months later the horse was off feed with diffuse swelling in the rear leg. Necropsy confirmed the diagnosis of malignant seminoma.

Squamous-Cell Carcinoma of the Pharyngeal Cavity in a Jersey Black Giant Rooster

Squamous-cell carcinoma of the pharyngeal cavity was diagnosed in a 3-year-old Jersey black giant male chicken. Grossly, the carcinoma was round with irregular edges, yellow-tan, cauliflower-like with a crusty surface, and attached to the roof and sides of the pharyngeal cavity. Histologically, the surface of the mass was covered by a dense mat of necrotic mucosa and inflammatory cells. A broad front of neoplastic cords consisting of squamous epithelial cells extended into the lamina propria. There was no evidence of vascular invasion or metastasis.

ANALYSIS OF HEMATOGENOUS METASTASIS FROM COLORECTAL CANCER

Among 337 patiens undergone curative resections for primary colorectal cancers, 65 had the recurrences and 43 (15 with colon and 28 with rectal cancer) out of the 65 hematogenous recurrences. In these patients liver metastasis was observed in 30 (69.8%), pulmonary metastasis in 12 (27.9%), and bone or brain metastasis in 8 (18.6%). Hematogenous recurrences were most commonly observed within 3 years, in which an elevated serum CEA was the most useful indicator in detecting the recurrence. Histopathologically, there was no difference by tissue types, however, the recurrence was more frequently noted in patients group having vascular invasion and lymphnode patients group having vascular invasion and lymphnode metastasis. The recurrence rate was elevated with an advance of the stage of the disease. The hematogenous recurrent rate for cases in aneuploid was higher than that in diploid pattern. For 14 patients with recurrent liver metastasis, curative resection of liver metastatic lesions was carried out and the resulting 5-year survival rate was as favorable as 42.5%.

Two Cases of Lipid-Secreting Carcinoma of the Breast: Case Reports with an Electron Microscopic Study

Two very rare cases of lipid-secreting carcinoma of the breast are reported, together with a review of the literature. Both patients were Japanese women aged 70 and 81 years, respectively. In each, a mass had been found in the breast, and radical mastectomies were performed based on a diagnosis of breast cancer at an early clinical stage. Both resected tumors were found to be solid and localized. In them, both estrogen and progesterone receptors were negative. Microscopically, hematoxylin-eosin staining showed the tumor cells to have foamy and vacuolated eosinophilic cytoplasm. Lipid staining showed the vesicles in the cytoplasm of the tumor cells to be colored a flaming red and consequently recognized as lipid droplets. An electron-microscopic study showed that the tumor cells contained various sizes of lipid droplets in the cytoplasm with no degenerative changes, and suggested that these lipid droplets were produced and stored in the tumor cells. It would appear, from the literature that lipid-secreting carcinomas have aggressive clinical courses, but neither vascular invasion nor lymph node metastasis was seen in either of our two cases.

Analysis of morphological factors of hepatocellular carcinoma in 98 autopsy cases with respect to pulmonary metastasis.

The morphological features of ninety-eight autopsy cases of hepatocellular carcinoma (HCC) were analyzed in relation to pulmonary metastasis. Extrahepatic hematogenous metastasis was observed in 64% and lung was most frequently involved (62%). A close relationship was observed between intrahepatic vascular invasion and extrahepatic hematogenous metastasis to lungs. Portal vein-invasion was found in 80% of cases and significant correlations were recognized between the rates of portal vein-invasion and hepatic vein-invasion, and between the rates of portal vein-invasion and pulmonary metastasis. There was a close correlation among the macroscopic growth-pattern, incidence of vascular invasion, and pulmonary metastasis, and their degrees. Namely, the expansive type HCC showed significantly lower rates of vascular invasion and pulmonary metastasis than the infiltrative or mixed type HCC. These rates were particularly low in the expansive type, single nodular subtype HCC with size of a primary tumor less than 10 cm. Significantly low rates of pulmonary metastasis and portal vein-invasion were also noted in well-differentiated carcinoma (Grade I or II). The existence of cirrhosis or fibrosis of liver in cases with HCC was not definitely related to the occurrence of pulmonary metastasis. It was originally clarified that invasion to the portal vein and the size of HCC played a main role in pulmonary metastasis.

Histologic infiltrating pattern of gastric microcarcinoma by means of serial sections.

Two hundred eighty serial histologic sections, 5 micron thick, were made of a very small gastric carcinoma with submucosal invasion in order to assess the initial infiltrating pattern into the submucosa, as well as the growth therefrom. The small carcinoma infiltrated into the submucosa through four independent small channels, 0.02 to 0.05 mm2 in size, despite its small spread (3 mm in diameter) on the mucosal layer. Each small channel always was accompanied by the small blood vessels penetrating the lamina muscularis. The size of carcinoma in submucosa grew further to reach 3 to 10 times small infiltrating sites of lamina muscularis mucosa. The growth pattern of the carcinoma in the submucosa, therefore, seemed to be an "expanded balloon." Moreover, a small but distinct vascular invasion could be demonstrated within the balloon, suggesting a possible vascular metastasis.