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Angiosarcoma of the small intestine: a case report and literature review.

A case of primary intestinal angiosarcoma in a 59-yr-old man is reported. The patient had recurrent gastrointestinal bleeding with normal upper and lower gastrointestinal endoscopies, technetium-99m-labeled erythrocyte scan, and angiography. Barium small bowel series and abdominal computerized tomography showed an ileal mass. Pathological examination was consistent with hemangiosarcoma with both solid and vasoformative patterns. Metastatic disease was also identified in the small bowel mesentery, liver, spleen, lungs, and brain. No identifiable underlying or epidemiologic factors have previously been reported to be associated with this rare type of tumor of the gastrointestinal tract. The pertinent literature on gastrointestinal angiosarcoma also is reviewed.

Hemangiosarcoma↗

[Clinico-pathological studies on the lymph node metastases of the gastric cancer invading to proper muscle layer].

In 65 patients who underwent surgical resection of the gastric cancer invading to proper muscle layer (pm cancer), lymph node involvement at the time of resection and the site of recurrence were investigated. Patients who underwent gastrectomy for submucosal (sm cancer) or subserosal (ss alpha.beta cancer) gastric cancers during the same period served as controls. Lymph node involvement was positive at a higher rate in the pm cancer than in the sm cancer, but the rate for number of lymph node metastases was not dependent on the stage of lesions. Of the lesions in the pm cancer, those of the Borrmann type involved lymph nodes at a particularly high rate. Of the metastatic pattern in the lymph nodes, the rate of severe metastases in pm cancer was higher than in the sm cancer. In the pm cancer, the cancer recurred in the liver and peritoneum, but not in any lymph nodes, thus suggesting that the surgical resection and the dissection of regional lymph nodes had been successful.

Adult↗

Human ovarian carcinoma metastatic models constructed in nude mice by orthotopic transplantation of histologically-intact patient specimens.

We report here the first orthotopic transplant model for human ovarian cancer. Histologically-intact patient specimens of ovarian cancer were transplanted by microsurgical techniques under the capsule of the nude mouse ovary. The human tumors grew locally and gave rise to a patient-like metastatic pattern including the parietal peritoneum, colon, omentum, and ascites. The orthotopic model described here should be useful for evaluating new therapeutics and diagnostics for ovarian cancer.

Animals↗

Metastasis of chondrosarcoma.

This study was undertaken to analyse metastases of patients with intermediate- or high-grade chondrosarcomas. Out of 24 intermediate-grade tumours, 5 (21%) developed metastases, as did 6 of 10 high-grade tumours (60%) (P = 0.04). Four patients developed pulmonary metastasis only, 5 developed both pulmonary metastases and metastases of the other sites. Two patients showed a rare metastatic pattern: bone metastases only. The metastasis rate in the primary chondrosarcoma (42%) was higher than that in the secondary chondrosarcomas (0%) (P = 0.03). The metastasis rate was higher in patients with local recurrence (86%) than in those without local recurrence (19%) (P = 0.01). In 5 of 6 patients who had a local relapse and metastasis, the interval between the two relapses was a few months.

Adult↗

Metastasis of chondrosarcoma.

This study was undertaken to analyse metastases of patients with intermediate- or high-grade chondrosarcomas. Out of 24 intermediate-grade tumours, 5 (21%) developed metastases, as did 6 of 10 high-grade tumors (60%) (P = 0.04). Four patients developed pulmonary metastasis only, 5 developed both pulmonary metastasis and metastases of the other sites. Two patients showed a rare metastatic pattern: bone metastases only. The metastasis rate in the primary chondrosarcoma (42%) was higher than that in the secondary chondrosarcomas (0%) (P = 0.03). The metastasis rate was higher in patients with local recurrence (86%) than in those without local recurrence (19%) (P = 0.01). In 5 of 6 patients who had a local relapse and metastasis, the interval between the two relapses was a few months.

Cytomegalovirus↗

Current challenges of gene therapy for prostate cancer.

Gene therapy for prostate cancer faces hurdles similar to those being encountered for other cancers and nonmalignant processes. The greatest obstacle is the identification of efficient delivery systems, since numerous animal models and cell culture systems have shown potential efficacy when most cells express the introduced genetic material. Early prostate cancers are easily accessible to gene vector introduction, and the predictable metastatic patterns of this cancer may offer additional advantages for gene therapy. This article reviews gene vectors and gene products, as well as ongoing trials of gene therapy that have recently begun in prostate cancer.

Animals↗

Purification and characterization of human lung fibroblast motility-stimulating factor for human soft tissue sarcoma cells: identification as an NH2-terminal fragment of human fibronectin.

Paracrine motogenic factors, including motility cytokines and extracellular matrix molecules secreted by normal cells, can stimulate metastatic cell invasion. Both intact extracellular matrix molecules and their degradative products may exhibit these activities. We have found that human lung fibroblasts produce paracrine motility-stimulating factors for recently established human sarcoma cell strains. We purified the major fibroblast motility-stimulating factor (FMSF) from human lung fibroblast-conditioned medium by sequential heparin affinity chromatography and DEAE anion exchange chromatography. Lysylendopeptidase C digestion of FMSF and sequencing of peptides purified by reverse-phase high-pressure liquid chromatography identified FMSF as an NH2-terminal fragment of human fibronectin. Using SYN-1 sarcoma cells, FMSF predominantly stimulated chemotaxis and some chemokinesis, and it was chemotactic for a variety of human sarcoma cells, including fibrosarcoma, leiomyosarcoma, liposarcoma, synovial sarcoma, and neurofibrosarcoma cells. The FMSF activity present in human lung fibroblast-conditioned medium was completely eliminated by either neutralization or immunodepletion with a rabbit antihuman-fibronectin antibody, thus further confirming that the NH2-terminal fibronectin fragment was the FMSF responsible for the motility stimulation of human soft tissue sarcoma cells. Because human soft tissue sarcomas have a distinctive hematogenous metastatic pattern (predominantly lung), and lung-derived fibroblasts secrete large amounts of FMSF, FMSF and fibronectin may play a role in stimulating sarcoma invasion into lung tissue.

Amino Acid Sequence↗

[Scintigraphic follow-up of patients with liver and spleen metastases undergoing cytotoxic therapy (author's transl)].

The importance of scintigrpahy in the diagnosis of liver and spleen tumors is well known. There is, however, up to this time only poor information regarding the use of scintigraphy in follow up studies in patients with liver and spleen metastases undergoing cytostatic therapy. We had the opportunity to investigate 30 patients in whom Hodgkin's disease, Zollinger-Ellison syndrome, ovarian, breast or bronchial and GI malignancy was confirmed by histology. The scintigraphic examinations were performed by means of a scintillation camera using 99mTc sulfur colloid as radiotracer. In each case, three views of the organ were recorded firstly prior to therapy and (at least) once again during or after therapy respectively. The results of liver and spleen scintigraphy were compared with clinical findings, laboratory tests, laparoscopy and histopathology. In 13 of our patients, diminution of metastases was detected. In one patient an increase of the size of the tumors was seen after temporary improvement. In 8 patients, there was no change of the metastatic pattern after cytostatic therapy. 6 patients showed an increase of liver metastases under therapy. Two patients with normal liver scintigraphy in whom clinical and laboratory findings indicated liver involvement yielded no evidence of metastasis at autopsy. In 13 cases, the diagnosis of liver metastasis was detected earlier by scintigraphy than by laboratory tests.

Adult↗

Clinicopathologic differences between gastric remnant cancer and primary cancer in the upper third of the stomach.

BACKGROUND: The prognosis of gastric remnant cancer is considered to be poor compared with that of primary cancer. MATERIALS AND METHODS: This study was conducted to elucidate the differences of clinicopathologic findings and treatment results between 59 patients with gastric remnant cancer (GRC) and 579 patients with primary proximal gastric cancer (PGC). RESULTS: There was no significant difference in the incidence of lymph node metastasis between GRC and PGC. However, changes in the metastatic pattern to lymph nodes were observed in GRC. In GRC, the tumor easily invaded the neighboring organs due to the adhesions around the remnant stomach, resulting in a low resectability with curative intent. The 5-year survival rate after curative resection for advanced GRC was 50.9%. GRC patients without serosal invasion had a good prognosis. CONCLUSION: Although the survival rate after curative resection for GRC patients was similar to that of PGC, GRC patients without serosal invasion had a better prognosis. Therefore, early detection is an important way to improve overall survival in GRC.

Adult↗

Gray scale echographic patterns of hepatic metastatic disease.

Abnormal gray scale hepatic echograms in 76 patients with known or suspected metastatic disease were reviewed. A varied echographic pattern was found, with the gray scale appearances falling into three identifiable categories (dense, lucent, and bulls-eye) and a fourth group difficult to characterize. Prior chemotherapy seemed to have little consistent effect on echographic patterns. A pattern of dense lesions was associated in a large percentage of cases with adenocarcinoma. Carcinoma of the colon commonly produced this appearance. The remaining echographic patterns showed little correlation with specific primary sites or cell types.

Adenocarcinoma↗

Metastatic dissemination of B16 melanoma: pattern and sequence of metastasis.

The progressive metastatic spread from subcutaneous transplants of two subpopulations of the mouse B16 melanoma, slow-growing clone G3.5 and fast-growing clone G3.12, was examined during tumor growth in C57BL/6 mice and after surgical excision of tumors of various sizes. In addition to enumeration of visible and lethal or potentially lethal ("clinically relevant") metastases, the occurrence of visibly undetectable proliferating (occult) or nonproliferating (dormant) micrometastases was assessed by implanting lymph nodes and organs subcutaneously into normal mice and monitoring for resulting tumor growth. Occult or dormant metastases were disseminated initially to the lungs from G3.5 tumors of 3-4 mm in mean geometric diameter (MGD) and G3.12 tumors of 6-7 mm in MGD. The ipsilateral axillary lymph node (IALN), the regional draining lymph node for these tumors, received metastases after the lungs, initially from 10 to 12-mm tumors. Subsequently, occult or dormant and visible metastases first appeared in systemic organs and lymph nodes (kidneys, adrenal glands, ovaries, and contralateral axillary lymph node) at tumor sizes of about 26 mm in MGD. Systemic metastases occurred only in mice with large and numerous lung metastases and did not depend on the continuing presence of the subcutaneous tumor or on the presence of IALN metastases, which indicated that established lung metastases were a generalizing site from which systemic metastatic spread initiated. After tumor excision, death generally resulted from extensive lung metastasis. Occasional lethal or clinically relevant metastases were also observed in the IALN, kidneys, adrenal glands, ovaries, brain, eyes, and urinary bladder; liver involvement was evident exclusively as occult or dormant micrometastases. Terminal metastatic patterns of these B16 melanoma transplants were as widespread and indiscriminate as those of malignant melanoma in humans.

Animals↗

Hepatic resection for metastatic melanoma: distinct patterns of recurrence and prognosis for ocular versus cutaneous disease.

BACKGROUND: Resection of melanoma metastatic to the liver remains controversial. We evaluated the efficacy of hepatic resection in patients with metastatic ocular and cutaneous melanoma and assessed factors that could affect survival after resection. METHODS: Forty patients with hepatic melanoma metastasis underwent resection at four major hepatobiliary centers. Clinicopathologic factors were evaluated with regard to recurrence and survival by using chi(2) and log-rank tests. RESULTS: The primary tumor was ocular in 16 patients and cutaneous in 24. The median disease-free interval from the time of primary tumor treatment to hepatic metastasis was the same for both groups (ocular, 62.9 months; cutaneous, 63.1 months; P = .94). Most patients underwent either an extended hepatic resection (37.5%) or hemihepatectomy (22.5%). Twenty-six patients (65%) received perioperative systemic therapy. Thirty (75.0%) of 40 patients developed tumor recurrence. The median time to recurrence after hepatic resection was 8.3 months (ocular, 8.8 months; cutaneous, 4.7 months; P = .3). Patients with primary ocular melanoma were more likely to experience recurrence within the liver (53.3% vs. 17.4%; P = .015), whereas patients with a cutaneous primary tumor more often developed extrahepatic involvement. The 5-year survival rate for patients with a primary ocular melanoma was 20.5%, whereas there were no 5-year survivors for patients with cutaneous melanoma (P = .03). CONCLUSIONS: Patterns of recurrence and prognosis after resection of hepatic melanoma metastasis differ depending on whether the primary melanoma is ocular or cutaneous. Resection should be performed as part of a multidisciplinary approach, because recurrence is common.

Adult↗

Metastatic proclivities and patterns among APUD cell neoplasms.

Neoplasms of APUD cell origin are quite variable in their metastatic behavior. Whereas pituitary and parathyroid tumors almost never metastasize, all oat cell lung cancers, malignant melanomas, trabecular carcinomas of the skin and medullary thyroid cancers are capable of dissemination. The metastatic proclivity of individual carcinoids, pancreatic and extrapancreatic islet cell tumors, and paragangliomas is much less predictable. In particular, there are no reliable histological markers of risk for lymphatic or hematogenous dissemination. The behavior of many carcinoids, islet cell carcinomas and paragangliomas is relatively indolent, even when metastatic disease is already present. However, unresectable distant metastases, especially liver involvement, connote a poor prognosis. Mortality is more often related to uncontrolled tumor growth and metastasis than to associated endocrinopathies. Curative or debulking surgical resection should be aggressively pursued as recent data show that worthwhile clinical disease-free survival can be realized in at least some patients.

APUD Cells↗

Intertrabecular pattern of tumors metastatic to bone.

BACKGROUND: The prevalence of radiologically invisible metastatic tumors to bone is not known. To clarify this, the authors examined histologic sections, radiographs, bone scans, and magnetic resonance (MR) images of autopsied patients with bone metastases. METHODS: Complete slices of the vertebral column, including C3-S1, were obtained from 52 cadavers with metastatic tumors to the spine. Macroscopic and histologic features were compared with postmortem roentgenographs (52 patients), bone scans with 99mTc-labelled methylene diphosphonate (17 patients), and MR images (4 patients). Morphologic patterns were classified into intertrabecular, osteoblastic, osteolytic, mixed, small lesion, and compression fracture. RESULTS: Metastatic lesions were found in 734 of the 1194 vertebral bodies. The lesions were intertrabecular in 255 vertebrae, osteoblastic in 185, osteolytic in 114, mixed in 70, small lesion in 83, and compression fracture in 27. Postmortem radiographs demonstrated lesions in 367 (50%) of the 734 vertebrae, bone scans in 103 (34.7%) of the 297 vertebrae examined, and MR images in all 42 (100%) vertebral bodies imaged. Lesions showing an intertrabecular pattern were detected in only 7.1% of the radiographs and 4.5% of the bone scans. CONCLUSIONS: Radiographs and bone scans often fail to show metastatic lesions, especially those with an intertrabecular pattern. The intertrabecular pattern is a unique histologic form that is difficult to detect on radiographs and bone scans.

Adult↗

Serum peptidome patterns that distinguish metastatic thyroid carcinoma from cancer-free controls are unbiased by gender and age.

Serum peptidomics is a special form of functional proteomics. The small number of blood proteins that are the source of most prominent peptides in human serum serve as a substrate pool for commonly occurring and/or cancer-derived proteases. Exoprotease activities in particular, when superimposed on the ex vivo coagulation and complement degradation pathways, contribute to generation of not only cancer-specific but also "cancer type"-specific serum peptides. Following development of a unique, semiautomated serum peptide profiling platform and after completing investigations to eliminate common experimental bias, we have now studied possible effects of gender and age on serum peptidomes of 200 healthy men and women, ages 20-80, and of 60 patients (30 men and 30 women) with metastatic thyroid carcinomas. Extensive MALDI-TOF MS and data analysis suggested negligible contributions of both age and gender to the serum peptidome patterns except that healthy men and women under 35 years, but not older individuals, could be distinguished with approximately 70% accuracy. Considering the more advanced age of most patients, this finding is unlikely to interfere with peptidomics analysis of most cancers. By examining patient samples and age/gender-matched controls followed by variability analysis of either demographic or disease (versus control) groups, we could conclusively rule out demographic bias. An optimized, 12-peptide ion thyroid cancer signature was then developed, enabling classification of an independent validation set with 95% sensitivity and 95% specificity (binomial confidence intervals, 75.1-99.9%). Ten of these peptides had previously been assigned to signature patterns of other solid tumor cancers. One of the two newly discovered peptides was dehydro-Ala(3)-fibrinopeptide A. As we expand this study to include hundreds of thyroid cancer patients, the peptide signature will be adjusted, further validated, and then evaluated in a clinical setting used either independently or in combination with existing markers.

Adult↗

Characteristics of transplantable tumors induced in the rat by N-2-fluorenylacetamide: elevations in tissue and serum sialic acid.

The correlation between levels of sialic acid and sialic acid-containing glycolipids (gangliosides) in tumors and serum with the growth characteristics of the tumors was investigated in transplantable hepatomas and squamous cell carcinomas initiated with the carcinogen N-2-fluorenylacetamide and propagated in vivo and in tissue culture. Tumor lines varied in histologic classification, growth rate, and ability to form pulmonary metastases. There was neither a correlation between growth rate and histologic classification nor between either of these two parameters and the ability to metastasize. Total and ganglioside sialic acid levels were elevated in carcinogen-treated liver and in transplantable hepatomas when contrasted with normal liver. Levels of sialic acid showed a weak correlation with the growth rate of hepatomas. Gangliosides from nonmetastatic hepatoma lines exhibited less N-acetylneuraminic acid--galactose--glucose-N--acylsphingosine (GM3) and an increased ratio of total monosialogangliosides to disialogangliosides than did metastatic lines. Ganglioside patterns of metastatic hepatoma lines more closely resembled the ganglioside patterns of normal liver than did those of the nonmetastatic lines. Concomitant elevations of total and ganglioside sialic acid levels were observed in sera of animals bearing subcutaneous implants. Serum levels of total sialic acid did correlate with total sialic acid levels found in the tumor tissues. The levels of serum sialic acid were not correlated directly with levels of serum sialyltransferase activity. Elevations of both tissue and serum ganglioside sialic acid were consistent features of liver tumorigenesis in the rat after N-2-fluorenylacetamide administration. They appeared, furthermore, to be early events not directly related to tumor cell differentiation or metastasis.

2-Acetylaminofluorene↗

Interactions among clonal subpopulations affect stability of the metastatic phenotype in polyclonal populations of B16 melanoma cells.

Analysis of the metastatic properties of clones isolated from mouse B16 melanoma cell lines (B16-F1 and F10) shows extensive cellular heterogeneity and the presence of subpopulations that have widely differing metastatic abilities. This pattern of metastatic heterogeneity is maintained during serial passage in vitro and in vivo. In contrast, even a short serial passage of individual clones isolated from these heterogeneous parent lines results in rapid emergence of variant subclones that have different metastatic properties. If several clones are mixed and cocultivated, this instability is not expressed. These data suggest that, in polyclonal populations, the various clonal subpopulations somehow interact with one another to "stabilize" their relative proportions within the population. Restriction of clonal diversity by selective killing of the majority of clones in a polyclonal population eliminates the stabilizing restraints and stimulates rapid emergence of new subpopulations to create heterogeneous populations containing a new panel of phenotypically diverse subpopulations that then reach stable proportions until the next selection pressure(s) is encountered.

Animals↗