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PubMedDate not supplied

Endogenous E. coli endophthalmitis.

A case of Escherichia coli septicemia with associated metastatic en dophthalmitis and endocarditis is presented. The ocular signs and symptoms were the initial manifestations of sepsis. Irreversible damage to the eye occurred in less than 24 hours. The pattern of metastatic bacterial endophthalmitis has changed since the introduction of potent antimicrobial agents, with an increased incidence of Gram-negative bacillemia. E. coli endophthalmitis carries a poor prognosis. Early diagnosis and systemic treatment will prevent the life-threatening complications of sepsis.

Aged↗

PubMed1997

Ganglioside expression in melanomas from Japanese individuals: unusual pattern in two patients with metastatic lesions of acral lentiginous melanomas.

Melanoma among Japanese is rare, and differs in its clinical and histological characteristics from that found in Caucasians. In this study, the ganglioside expression of melanoma specimens obtained from Japanese was determined and compared with previously published data on Caucasians. The ganglioside composition of 25 biopsy melanoma specimens, including 13 primary and 12 metastatic lesions, was studied using thin layer chromatography. Four gangliosides (GM3, GD3, GM2, GD2) were most commonly expressed in melanomas in Japanese. The expression of gangliosides was quite variable in both primary and metastatic melanomas as seen in previous reports. No significant differences were observed between gangliosides from primary and metastatic sites. A new type of ganglioside expression, in which GM3 was nearly the only ganglioside (> 95%), was found in metastatic tumors from two Japanese patients with acral lentiginous melanoma (ALM), which is the most common clinical and histopathological type of melanoma among Japanese but is very unusual among Caucasians. The patterns of expression were similar to those in Caucasians except for the detection of a "new" pattern.

Adult↗

PubMed1989

Metastatic bone marrow involvement from supraglottic squamous cell carcinoma.

A case of an aggressive supraglottic squamous cell carcinoma, which was managed with neo-adjuvant chemotherapy and radical surgery, is described. The post-operative course was of rapid deterioration and death due to progressive metastatic disease involving bone marrow and liver. This is the first reported case of bone marrow infiltration by squamous cell carcinoma of the head and neck diagnosed ante-mortem. The incidence and pattern of metastatic disease from head and neck tumours is reviewed, and the importance of initial staging in determining the risk of distant metastatic disease is emphasised.

Bone Marrow↗

PubMed2005

Early prediction of response to chemotherapy in metastatic breast cancer using sequential 18F-FDG PET.

UNLABELLED: Chemotherapy is currently the treatment of choice for patients with high-risk metastatic breast cancer. Clinical response is determined after several cycles of chemotherapy by changes in tumor size as assessed by conventional imaging procedures including CT, MRI, plain film radiography, or ultrasound. The aim of this study was to evaluate the use of sequential 18F-FDG PET to predict response after the first and second cycles of standardized chemotherapy for metastatic breast cancer. METHODS: Eleven patients with 26 metastatic lesions underwent 31 (18)F-FDG PET examinations (240-400 MBq of 18F-FDG; 10-min 2-dimensional emission and transmission scans). Clinical response, as assessed by conventional imaging after completion of chemotherapy, served as the reference. 18F-FDG PET images after the first and second cycles of chemotherapy were analyzed semiquantitatively for each metastatic lesion using standardized uptake values (SUVs) normalized to patients' blood glucose levels. In addition, whole-body 18F-FDG PET images were viewed for overall changes in the 18F-FDG uptake pattern of metastatic lesions within individual patients and compared with conventional imaging results after the third and sixth cycles of chemotherapy. RESULTS: After completion of chemotherapy, 17 metastatic lesions responded, as assessed by conventional imaging procedures. In those lesions, SUV decreased to 72% +/- 21% after the first cycle and 54% +/- 16% after the second cycle, when compared with the baseline PET scan. In contrast, 18F-FDG uptake in lesions not responding to chemotherapy (n = 9) declined only to 94% +/- 19% after the first cycle and 79% +/- 9% after the second cycle. The differences between responding and nonresponding lesions were statistically significant after the first (P = 0.02) and second (P = 0.003) cycles. Visual analysis of 18F-FDG PET images correctly predicted the response in all patients as early as after the first cycle of chemotherapy. As assessed by 18F-FDG PET, the overall survival in nonresponders (n = 5) was 8.8 mo, compared with 19.2 mo in responders (n = 6). CONCLUSION: In patients with metastatic breast cancer, sequential 18F-FDG PET allowed prediction of response to treatment after the first cycle of chemotherapy. The use of 18F-FDG PET as a surrogate endpoint for monitoring therapy response offers improved patient care by individualizing treatment and avoiding ineffective chemotherapy.

Adult↗

PubMed1986

Actin filament organization of the Dunning R3327 rat prostatic adenocarcinoma system: correlation with metastatic potential.

Recently, Volk, Geiger, and Raz (Cancer Res., 44: 811-824, 1984) addressed the question of whether variations in actin organization in clones of the murine K-1735 melanoma tumor correlated with their metastatic capability. Using immunofluorescence techniques, they found that clones which had a more ordered actin network were less metastatic, whereas clones having a diffuse actin staining pattern were more metastatic. Similarly, we have found that in the Dunning rat R3327 prostatic adenocarcinoma tumor system, the non-metastatic (less than 0.1%) H-prostatic tumor cell line has a prominent network of actin filament bundles, whereas the highly metastatic (greater than 90%) MatLyLu cell line has a diffuse actin staining pattern. In the low-metastatic (less than 10%) AT1 cell line an intermediate actin organization between H and MatLyLu was observed. Analysis of cell extracts from H- and MatLyLu-cells revealed differences in the level of activity of cellular proteins which affect actin filament assembly and structure in a manner similar to that of the cytochalasins, fungal metabolites which bind with high affinity to the fast-growing end of actin filaments. Extracts of MatLyLu were significantly more effective than those of H-cells in decreasing the extent of actin filament network formation and in inhibiting the rate of filament assembly by blocking monomer addition onto the fast-growing end. Measurements of spin-lattice nuclear magnetic resonance water proton relaxation times (T1) were made in surgically removed tumor tissue from four sublines (H, AT1, MatLyLu, and MatLu) of the Dunning R3327 tumor system. The highly metastatic cell lines had significantly longer water proton T1 relaxation times than did the lines with low metastatic potential. These differences in T1 may reflect the observed alterations in organization of actin filaments within these various sublines of the Dunning R3327 prostatic adenocarcinoma tumor system.

Actin Cytoskeleton↗

PubMed1987

Renal pelvic carcinoma: morphological correlates of metastatic behavior.

We report a clinicopathological analysis of morphological parameters in relation to subsequent biological behavior in 48 patients with renal pelvic carcinoma. The relationships of subsequent metastasis to tumor stage and grade, as well as the presence of vascular, renal parenchymal or renal hilar invasion were evaluated by parametric and nonparametric statistical tests. Corrected 5-year survival rates for grades 1 to 3 tumors were 100, 67 and 5 per cent, respectively. Grade 3 tumors demonstrated more invasion of the blood vessels, hilus and renal parenchyma compared to grades 1 and 2 tumors (p less than 0.005, 46 patients). Moreover, invasion of renal hilar tissues had greater predictive value for subsequent distant metastatic spread (95 per cent, nonparametric) than either vascular (83 per cent) or renal parenchymal (77 per cent) invasion. Metastases developed in 27 of 48 patients during followup periods of 2 to 39 years. The pattern of metastatic lesions revealed that local spread to hilar soft tissues occurred in 92 per cent of the patients who subsequently had distant metastases. Spread to retroperitoneal lymph nodes and ipsilateral ureteral mucosa occurred in 84 and 44 per cent of the patients, respectively. Our study illustrates the potential value of analysis of individual histological parameters to evaluate the likelihood of subsequent metastasis.

Aged↗

PubMed1993

Correlation of VLA-4 integrin expression with metastatic potential in various human tumour cell lines.

This investigation has focused on whether a number of molecular species, which have recently been recognised as components of cell attachment receptors utilised in recirculatory leukocyte traffic, are expressed on metastatic tumour cell populations. This has been studied on live cultured metastatic and non-metastatic tumour cell lines as well as on histological sections of frozen tissue from primary tumours and metastases which they formed after inoculation into nude mice. Here we report data we have obtained using immunofluorescence microscopy, fluorescence activated cell analysis, immunocytochemistry and pathological investigation of tumour behaviour in vivo, which converge to indicate that expression of the integrin molecule VLA-4 is positively associated with the execution of the metastatic process. This molecule is known to be a receptor for at least two ligands, namely the inducible endothelial adhesion molecule VCAM-1 and the extracellular matrix component fibronectin, and is thought to be mechanistically important in the attachment and diapodesis of lymphocytes. The present findings, indicating differential expression of this molecule on metastatic cell populations relative to non-metastatic cell populations, support and extend recent reports from other laboratories, of the presence of various leukocyte adhesion receptors on metastatic tumour cells. This accumulating evidence suggests that inappropriate expression of one or more of these surface adhesion molecules in tumour cell lineages may endow the progeny of the affected clones with some of the properties needed for metastatic behaviour. The total information so far assembled by various groups also provides some early clues suggesting that the types of molecules expressed may be related to the histogenetic origin of the tumour and its pattern of metastatic spread.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed2005

Gastrointestinal stromal tumors: CT and MRI findings.

The objective of this study was to report the CT and MRI appearances of primary and metastatic gastrointestinal stromal tumor (GIST). The clinical and imaging findings of 31 patients with histological and immunohistochemical diagnosis of GIST were reviewed. The CT and MRI findings were assessed independently for size, location, enhancement characteristics, and pattern of metastatic disease. The tumors were of enteric (n=13), gastric (n=12), duodenal (n=2), and rectal (n=3) origin. In one case the primary site was the mesentery, without involvement of bowel. Primary tumors were typically exophytic (79%), larger than 5 cm (84%), and inhomogeneously enhancing (84%). Central necrosis of all tumors (37%) and aneurysmal dilation of enteric tumors (33%) were less common. Metastases were most commonly to mesentery (26%) or liver (32%). Less common findings were ascites (7%) and omental caking (3%). Liver metastases were hypervascular in 92% of patients and rapidly became cystic following therapy with imatinib mesylate (Gleevec; Novartis, East Hanover, NJ, USA). Lung metastases, bowel obstruction, vascular invasion, and significant lymphadenopathy were not seen in any patient. GISTs have some specific CT findings which could help differentiate them from other gastrointestinal tumors. Liver metastases became cystic following therapy, mimicking simple cysts. MRI was better than single-phase CT for assessing liver metastases, while CT was more sensitive for mesenteric metastases.

Adult↗

PubMed1980

Malignant melanoma. Analysis of an autopsy population.

This report analyzes 92 malignant melanoma cases from a series of 12,383 consecutive autopsies. There were 12 cases of primary ocular malignant melanoma, 76 cases of primary nonocular malignant melanoma, and 4 cases of unknown primary site. Subjects with malignant melanoma were characterized by age, sex, and race; metastatic disease patterns as well as survival periods were analyzed. In the 12 ocular malignant melanoma cases, tumor size, cell type, and survival were considered. Discussion is concerned with the distribution of primary tumor site, the location of metastatic lesions secondary to malignant melanoma, and survival in cases with primary ocular malignant melanoma.

Adolescent↗

PubMed2006

Maintenance of head and neck tumor gene expression profiles upon lymph node metastasis.

Spread of cancer and development of solid metastases at distant sites is the main cause of cancer-related deaths. To understand and treat metastases, it is important to determine at which stages the most pivotal steps for development of metastases occur. In head and neck squamous cell carcinoma (HNSCC), metastasis nearly always occurs first in local lymph nodes before development of distant metastasis. Here, we have investigated gene expression patterns in HNSCC lymph node metastases using DNA microarrays. Several types of analyses show that the gene expression patterns in lymph node metastases are most similar to the corresponding primary tumors from which they arose, as long as samples contain sufficient proportions of tumor cells. Strikingly, gene expression patterns of metastatic primary HNSCC are largely maintained upon spread to the lymph node. Only a single gene, metastasis-associated gene 1 (MTA1), was found to show consistently changed expression between a large number of matched primary tumor-lymph node metastasis pairs. The maintained expression pattern includes the predictive signature for HNSCC lymph node metastasis. These results underscore the importance of the primary tumor gene expression profile for development and treatment of metastasis. The findings also agree with the concept that disseminated cancer cells alter the surrounding tissue into a metastatic environment that resembles the primary tumor microenvironment.

Adult↗

PubMed1985

Malignant thoracopulmonary small-cell ("Askin") tumor.

The clinical, radiographic, and pathologic features of 10 patients with documented malignant small-cell tumor of the thoracopulmonary region (Askin tumor) were reviewed. The tumor represents a distinct pathologic entity of neuroectodermal origin. Clinically, it presents as a chest-wall mass with or without pain. Its radiographic appearance is that of a soft-tissue mass with or without pleural or rib involvement, often with metastatic disease--to the skeletal system, bone marrow, thorax, and sympathetic chain. Two patients developed metastases to the adrenal gland and liver, one after autologous bone marrow transplantation. The radiologist should be aware of this entity and its pattern of metastatic spread since metastases are treated aggressively.

Adolescent↗

PubMed2005

VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche.

The cellular and molecular mechanisms by which a tumour cell undergoes metastasis to a predetermined location are largely unknown. Here we demonstrate that bone marrow-derived haematopoietic progenitor cells that express vascular endothelial growth factor receptor 1 (VEGFR1; also known as Flt1) home to tumour-specific pre-metastatic sites and form cellular clusters before the arrival of tumour cells. Preventing VEGFR1 function using antibodies or by the removal of VEGFR1(+) cells from the bone marrow of wild-type mice abrogates the formation of these pre-metastatic clusters and prevents tumour metastasis, whereas reconstitution with selected Id3 (inhibitor of differentiation 3)-competent VEGFR1+ cells establishes cluster formation and tumour metastasis in Id3 knockout mice. We also show that VEGFR1+ cells express VLA-4 (also known as integrin alpha4beta1), and that tumour-specific growth factors upregulate fibronectin--a VLA-4 ligand--in resident fibroblasts, providing a permissive niche for incoming tumour cells. Conditioned media obtained from distinct tumour types with unique patterns of metastatic spread redirected fibronectin expression and cluster formation, thereby transforming the metastatic profile. These findings demonstrate a requirement for VEGFR1+ haematopoietic progenitors in the regulation of metastasis, and suggest that expression patterns of fibronectin and VEGFR1+VLA-4+ clusters dictate organ-specific tumour spread.

Animals↗

PubMed1980

Metastasis in head and neck cancer, 1979.

Metastatic spread of head and neck cancer signifies a grave change in prognosis for the patient. The presence or absence of detectable metastasis is valuable knowledge both in planning treatment and in predicting prognosis. Knowledge of the metastatic behavior patterns of such tumors, and of the diagnostic means of detecting metastasis, is essential. The available knowledge on this problem is comprehensively reviewed to present, in a single source, the requisite knowledge for any physician treating head and neck cancer. Metastatic spread is reviewed according to incidence, detection methods, anatomical sites, and correlation with characteristics of the primary tumor. Finally, methods of detecting metastasis are reviewed and a practical approach to patient evaluation recommended.

Bone Neoplasms↗

PubMed1982

Surface properties of the metastatic cell.

The possible importance of the cell surface in determining the particular properties of the metastatic cell has been the basis for a number of different types of surface investigation in recent years. The results from these studies are currently reviewed in order to assess whether characteristic changes have been found that can be related to the behaviour pattern of metastatic cells. It is concluded that no evidence yet exists to suggest that metastatic transformation is accompanied by the appearance of any common specific surface feature. Certain reported specific changes are probably system related rather than metastasis related. Nevertheless, the metastatic cell surface does appear to show some non-specific changes that may subsequently prove to be important in aiding the metastatic cell to fulfil its biological role.

Animals↗

PubMed2003

Phenotypic heterogeneity of end-stage prostate carcinoma metastatic to bone.

To better understand the clinical and pathologic features of end-stage, androgen-independent carcinoma of the prostate (CaP), we performed rapid autopsies on 14 men who died of progressive CaP and recorded relevant clinical data. The timing of tumor progression varied widely. The median time to androgen independence was 2 years (range, 4 months to 13.6 years). The median survival after androgen independence was 1 year (range, 1 month to 3.6 years). Because osseous metastases are prevalent in progressive CaP, up to 20 bone sites were systematically sampled in each patient. Bone metastases were widespread; tumor filled the marrow in an average of 14 bone sites. Tumor histology and expression of prostate-specific antigen (PSA) and chromogranin A (CGA) were examined in all metastases and were compared with the primary tumor. Five histological patterns of metastatic tumor were observed: solid (10 patients), macroacinar (1 patient), microacinar (1 patient), clear cell (1 patient), and comedocarcinoma (1 patient). Gleason grade of the primary tumor did not predict the histological pattern of the metastases. Although >70% of tumor cells expressed PSA, the fraction of PSA-positive cells varied widely in separate metastases in some patients (standard deviation >25). Likewise, the fraction of neuroendocrine (NE) (CGA-positive) tumor cells in different metastases varied widely. For example, between 0 and 95% of tumor cells in different metastases in 1 patient had a NE phenotype. The present study highlights the heterogeneity--histologically and immunophenotypically--of metastatic CaP. Consequently, therapy directed to the phenotype of 1 metastasis may have no effect on other metastases in the same patient because of phenotypic heterogeneity.

Adenocarcinoma↗

PubMed1985

Metastatic adenocarcinoma of unknown primary site: abnormalities of cellular DNA content and survival.

Using a new flow cytometric technique we measured the cellular DNA content of tumour biopsies taken from 152 patients presenting with metastatic adenocarcinoma or undifferentiated carcinoma of unknown primary site. One hundred and six (70%) contained populations of cells with an abnormal cellular DNA content and the remainder were diploid. The incidence of aneuploidy was similar for the two sexes and bore no obvious relationship to the various patterns of metastatic involvement. Median survival of patients with diploid tumours was 4.2 months and for patients with aneuploid tumours, 4.8 months. Nine of the 46 patients with diploid tumours (i.e. 18%) survived for more than 2 yr compared to 10 of 106 (9%) of those with aneuploid tumours. These results indicate that the incidence of aneuploidy in this heterogeneous group of patients is similar to that reported for adenocarcinomas of known histogenesis, such as breast or colorectal cancer. In contrast to many of these tumour types, however, patients with metastatic adenocarcinomas of unknown primary which are diploid do not on the whole have a more favourable prognosis.

Adenocarcinoma↗

PubMed1995

Expression of leukocyte cell adhesion molecules on gastric carcinomas: possible involvement of LFA-3 expression in the development of distant metastases.

Expression of the cell adhesion molecules ICAM-1 (CD54) and LFA-3 (CD58) was examined on primary gastric carcinomas, autologous benign mucosa and metastatic lesions. Although ICAM-1 was never observed on benign gastric epithelium, even in the presence of chronic inflammation and a strong leukocyte infiltrate, 38% (26/69) of the primary tumors expressed this molecule. ICAM-1 was restricted to differentiated tumors and correlated with the presence of leukocytes and the absence of vessel invasion. The ICAM-1 expression pattern of metastatic lesions reflected that of the primary tumor, suggesting that most tumors retain the non-inducible phenotype seen in normal mucosa while some become cytokine-sensitive. ICAM-1 expression showed no correlation with tumor relapse or survival. LFA-3 was absent from 8% (4/49) of the primary tumors and reduced (e.g., < or = 50% positive cells) in 33% (16/49). Expression of LFA-3 by more than 50% of the tumor cells correlated with cellular dedifferentiation (G3, G4), histologically detectable vessel invasion, tumor recurrence and decreased survival time. Primary tumors and metastases in draining lymph nodes demonstrated a broad range of LFA-3 expression. In contrast, distant metastases (liver and peritoneum) had uniformly high frequencies of LFA-3-positive cells, suggesting a selective advantage for these cells in the establishment of distant metastases.

Biomarkers, Tumor↗

PubMedDate not supplied

Predictive value of some clinical and pathological parameters on upper level axillary lymph node involvement in breast cancer.

The role of radical axillary dissection in breast cancer management is presently under discussion. In this study we have evaluated the relationship between the pattern of metastatic axillary lymph node involvement by level and some of the main prognostic factors (age of the patient, size, grading, estrogen receptor and progesterone receptor status of the primary tumor) in 185 patients with operable breast cancer. The III level appeared to be involved in 31 (16.8%) out the 108 patients with axillary lymph nodes positive for metastases. A discontinuous pattern of axillary involvement (skip metastases) was observed in about 10% of cases. Logistic regression analysis of the data shows that only G3 is significantly correlated with the risk of III level invasion (p less than 0.05). We conclude that, at present, a selection of possible candidates for a less than radical axillary dissection is not as yet feasible. Since the risk for III level invasion cannot be sufficiently defined.

Breast Neoplasms↗