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PubMed1985

Metastatic melanoma of the lacrimal sac.

The case history of a patient with metastatic melanoma obstructing the lacrimal sac is presented. To our knowledge, this case represents a unique metastatic pattern that has not been previously reported. The patient was first treated for a melanoma of the left arm, which was excised in continuity with the axillary lymph glands. She was free of disease for 3 years until she developed metastatic disease causing obstruction of the ipsilateral lacrimal sac. Anatomical details of the metastasis were provided by computed axial tomography. Treatment consisted of excision of the metastatic lesion with reconstruction using forehead and intranasal mucosal flaps, followed by irradiation, hyperthermia, and multiple-drug chemotherapy. Emphasis is placed here on the differential diagnosis of orbital adnexal tumors.

Aged↗

PubMed1995

Metastatic small cell carcinoma to the masseter muscle originating from the uterine cervix.

Metastatic tumors to the head from infraclavicular primaries are relatively uncommon. The vast majority of primary tumors that metastasize to the head originate from the lung and breast. Tumors metastatic to the masseter are exceedingly rare with only one other case being reported in the literature. The case of a 34-year-old woman with a history of surgically-treated small cell carcinoma of the uterine cervix is presented. This case and our review of the literature illustrates the unusual nature of metastatic patterns in the head and their diagnostic complexity. Masses localized to the buccomasseteric region are usually considered to be of parotid origin. The differential diagnosis for masses in this area is generally limited to cogenital, inflammatory, or neoplastic lesions. Though uncommon, metastatic tumors from non-head and neck primary malignancies should be considered in the diagnosis as they may herald the onset of a new disease or the recurrence of cancer.

Adult↗

PubMed1992

Breast carcinoma: periodicity in presentation of metastatic tumour growth in the axilla.

The clinical value of assessment of tumour load in the axilla in the treatment of breast cancer patients has stood the test of time. Much information is available on its extent and characteristic distribution but, in contrast, little is known of the biological factors that may control the timing of the metastatic phenomenon. There is recent circumstantial evidence that such factors may exist and this prompted the present detailed study of axillary metastases from a series of 437 consecutive cases of breast carcinoma. Evidence of such factors was found here also: the excess of micrometastases in cases coming to operation in the second half of the year was highly significant (P less than 0.001) and is consistent with a synchronized start to the metastatic process. The total metastatic pattern in the material further indicated that the process may show periods of inactivity, i.e. periods when new colonies are not recruited. Mechanisms controlling this periodicity could theoretically be light-mediated, opening up new possibilities in the development of anti-metastatic treatment regimes.

Axilla↗

PubMedDate not supplied

Development of lymphosarcoma lines with high metastatic ability to lymph nodes and visceral organs in BALB/c mice.

A metastatic tumor population was isolated in BALB/c mice during routine s.c. passage of the colon 26 adenocarcinoma. The tumor metastasized to lymph nodes, liver, spleen, ovary and kidney. A primary culture established from the s.c. growing tumor was composed of both adherent and nonadherent cells. These two cell types were successfully separated from the primary culture and designated CMS (suspension cells) and CMA (adherent cells). The CMS and CMA cell lines are morphologically distinct in culture; however both formed similar histopathologic tumors when inoculated s.c. Furthermore, both tumor lines showed identical metastatic patterns in BALB/c mice with involvement of lymph node, liver, spleen, ovary and kidney. CMS and CMA expressed T-antigen as revealed by FITC-labeled-anti-Thy 1.2 antibody. Chromosome analysis and morphologic studies by light and electron microscopy indicated that the present metastatic lines have no relationship with the colon 26 adenocarcinoma and seem to be non-thymic T-cell lymphosarcomas which developed spontaneously in BALB/c mice.

Animals↗

PubMed1978

The gray scale sonographic appearance of intra-abdominal mesenchymal sarcomas.

Twenty-eight patients with intra-abdominal mesenchymal sarcomas were examined with gray scale ultrasonography. Masses were present in the mesentery, abdominal hollow viscera, liver, and retroperitoneal areas. Four different ultrasonic patterns were observed in the extra hepatic abdominal masses: (a) hyperechoic masses intermixed with anechoic zones; (b) hyperechoic masses with central fluid-filled zones; (c) homogeneous hyperechoic masses; and (d) homogeneous hypoechoic masses. Three of 6 patients with hepatic masses were totally anechoic alongside other more typical metastatic patterns. The presence of a large mass with sonographic signs of necrosis should strongly suggest the possibility of sarcoma. The differential diagnosis is discussed.

Abdominal Neoplasms↗

PubMed1985

Metastatic potential of B16 melanoma cells after in vitro selection for organ-specific adherence.

Heterogeneous primary tumors contain subpopulations of cells that differ in ability to metastasize to specific host organs. We have used cryostat sections of host organs to select for metastatic variants of B16 melanoma cells with increased adhesion to specific syngeneic tissues. By repeating the selection procedure with lung tissue, a subpopulation of cells was isolated that demonstrated a specific increase in binding to cryostat sections of mouse lung. This altered binding was reflected by a sixfold increase in the frequency of lung metastasis 21 d after tail vein injection of the tumor cells. In contrast, B16 melanoma cells selected on cryostat sections of mouse brain showed no increase in adhesion to brain or lung tissue and the metastatic pattern in vivo was not significantly different compared with the parent cell line. When cells selected for increased adhesion to cryostat sections of lung were further examined in vitro, they showed altered morphology and increased motility but no change in growth rate. These results demonstrate that alterations in the adhesive interactions between metastatic tumor cells and a specific host tissue can directly affect the frequency of metastasis to that tissue in vivo.

Animals↗

PubMed2006

Gene expression profiling reveals reproducible human lung adenocarcinoma subtypes in multiple independent patient cohorts.

PURPOSE: Published reports suggest that DNA microarrays identify clinically meaningful subtypes of lung adenocarcinomas not recognizable by other routine tests. This report is an investigation of the reproducibility of the reported tumor subtypes. METHODS: Three independent cohorts of patients with lung cancer were evaluated using a variety of DNA microarray assays. Using the integrative correlations method, a subset of genes was selected, the reliability of which was acceptable across the different DNA microarray platforms. Tumor subtypes were selected using consensus clustering and genes distinguishing subtypes were identified using the weighted difference statistic. Gene lists were compared across cohorts using centroids and gene set enrichment analysis. RESULTS: Cohorts of 31, 72, and 128 adenocarcinomas were generated for a total of 231 microarrays, each with 2,553 reliable genes. Three adenocarcinoma subtypes were identified in each cohort. These were named bronchioid, squamoid, and magnoid according to their respective correlations with gene expression patterns from histologically defined bronchioalveolar carcinoma, squamous cell carcinoma, and large-cell carcinoma. Tumor subtypes were distinguishable by many hundreds of genes, and lists generated in one cohort were predictive of tumor subtypes in the two other cohorts. Tumor subtypes correlated with clinically relevant covariates, including stage-specific survival and metastatic pattern. Most notably, bronchioid tumors were correlated with improved survival in early-stage disease, whereas squamoid tumors were associated with better survival in advanced disease. CONCLUSION: DNA microarray analysis of lung adenocarcinomas identified reproducible tumor subtypes which differ significantly in clinically important behaviors such as stage-specific survival.

Adenocarcinoma↗

PubMed2006

Cystectomy for transitional cell carcinoma of the bladder: results of a surgery only series in the neobladder era.

PURPOSE: We studied the effect of radical cystectomy for transitional cell carcinoma of the bladder on survival and failure patterns when the 2 surgical standards cystectomy and neobladder were combined, when possible. MATERIALS AND METHODS: A consecutive series of patients undergoing radical cystectomy with pelvic lymph node dissection for transitional cell carcinoma of the bladder with curative intent was analyzed. Patients with neoadjuvant radiotherapy/chemotherapy were excluded. Pathological characteristics based on the 2002 TNM system, recurrence-free/overall survival and metastatic patterns were determined. RESULTS: A total of 788 patients with a mean age +/- SD of 65 +/- 10 years and a mean followup of 53.5 months who underwent surgery between 1986 and 2003 were analyzed. A neobladder was constructed in 75.4% of patients. Ten-year recurrence-free and overall survival rates were 59.1% and 44.9%, respectively. Positive lymph nodes were present in 143 patients (18%). The rate of recurrence-free survival at 5 years was 82.5% for pT2a pN0, 61.9% for pT2b and pT3a pN0, and 53.1% for pT3b pN0 disease. Local and distant failure rates were 4% and 9.5% for organ confined tumors, 15.9% and 19.2% for nonorgan confined tumors, and 20.4% and 45.1% in patients with positive lymph nodes, respectively. CONCLUSIONS: In patients with organ confined, lymph node negative transitional cell carcinoma excellent survival data can be achieved as long as the tumor is limited to the inner half of the detrusor. These data on a large group of patients support early aggressive surgical management for invasive bladder cancer. The results of this surgery only series may serve as a reference for other treatment modalities for bladder cancer.

Adult↗

PubMed1999

[Clinical study of metastasis of thoracic lymph node in resectable lung cancer].

OBJECTIVE: To study the metastatic pattern of thoracic lymph node in resectable lung cancer. METHODS: From January 1992 to July 1998, the lymph nodes in hilar(N1) and mediastinal(N2) were resected based on their distribution in 160 patiens with resectable lung cancer and were examined by pathology. Number, size and colour of lymph nodes in each regions were recorded. Each lymph node was examined by routine pathology and immunohistochemistry. Quantity of metastatic lymph node was reported according to their regions. RESULTS: 99 cases(61.9%) had thoracic lymph nodes metastasis and 73 cases (45.6%) had mediastinal lymph nodes metastasis. Of those, only N1 metastasis was 16.3%, from N1 to N2 metastasis was 32.5%, only N2 metastasis was 13.1%. The metastatic frequencies in 11, 10, 7, 5 and 4 regions around the hilar or root of lung were 30.0%, 27.5%, 16.9%, 28.8% and 20.0%, respectively. Those were higher than 9, 6, 3, 2 and 1 regions far from the root of lung. The metastatic rate of lymph node in 2.0 cm or greater, 1.0 cm or greater and less than 1.0 cm was 60.7%, 15.5% and 4.3%, respectively (P < 0.001). The smallest metastatic lymph node was only 0.2 cm x 0.2 cm. Statistical analysis revealed that metastatic rate of thoracic lymph nodes was not relevant to different area, size and course of tumors. CONCLUSIONS: The lymph nodes metastases of most cases were spreading from the near to the distant, from lower to upper, through the hilar to the mediastinal. Lymph nodes metastases occurred easier in SCLC than in NSCLC (P < 0.05). It must be depended on pathologic examination to confirm whether or not the tumor has metastasis to lymph node.

Female↗

PubMed1992

Development and validation of prognostic models in metastatic breast cancer: a GOCS study.

The significance of several prognostic factors and the magnitude of their influence on response rate and survival were assessed by means of uni- and multivariate analyses in 362 patients with stage IV (UICC) breast carcinoma receiving combination chemotherapy as first systemic treatment over an 8-year period. Univariate analyses identified performance status and prior adjuvant radiotherapy as predictors of objective regression (OR), whereas the performance status, prior chemotherapy and radiotherapy (adjuvants), white blood cells count, SGOT and SGPT levels, and metastatic pattern were significantly correlated to survival. In multivariate analyses favorable characteristics associated to OR were prior adjuvant radiotherapy, no prior chemotherapy and postmenopausal status. Regarding survival, the performance status and visceral involvement were selected by the Cox model. The predictive accuracy of the logistic and the proportional hazards models was retrospectively tested in the training sample, and prospectively in a new population of 126 patients also receiving combined chemotherapy as first treatment for metastatic breast cancer. A certain overfitting to data in the training sample was observed with the regression model for response. However, the discriminative ability of the Cox model for survival was clearly confirmed.

Analysis of Variance↗

PubMed1991

B16 melanoma metastasis to an "artificial organ" implant.

The mouse B16 melanoma metastasizes in two stages, first to the lungs and then from lung metastases to systemic organs. Despite widespread dissemination, visible metastases generally occur only in the brain, adrenals, kidneys, ovaries, pancreas, and mesentery. As a novel approach to investigate the basis of metastatic patterning in this system, the possibility was explored that an implantable "artificial organ" could serve as a site for the occurrence and experimental modulation of secondary-stage metastasis. Each implant consisted of a cellulose disc 4 mm in diameter, with a central 1-mm polymer pellet to effect local sustained release of angiogenic or growth factors in a s.c. environment. During the secondary spread of tumors initiated with the B16 melanoma clone G3.12 and with the more metastatic variant G3.12/BM2, metastatic involvement of implants containing angiogenic factors was mainly as invisible micrometastases demonstrable by bioassay; visible metastases were rare and were located in implant blood vessels. Metastasis occurred in about 30% (G3.12) and 50% (G3.12/BM2) of implants with vasculature induced by ethylene-vinyl acetate copolymer alone. Endothelial cell growth factor and heparin promoted greater vascularization but did not significantly alter metastatic involvement of implants. Release of tumor cell mitogenic activity from pellets containing a crude extract of mouse lungs increased the incidence of G3.12/BM2 metastasis in implants to over 70% and stimulated growth of visible metastases within the cellulose matrix. In contrast, liver extract inhibited metastasis growth. Colonization of implants following intracardiac injection of G3.12/BM2 cells was generally similar to metastasis, but visible colonies formed more readily and were less dependent on the influence of lung extract. These results indicate that metastasis and colonization can occur regularly in implants and that the relative favorability of the implant environment for secondary tumor growth can be altered by incorporation of tumor cell growth modulators.

Animals↗

PubMed1989

Patterns of metastasis in uterine sarcoma. An autopsy study.

The autopsy findings of 73 patients with uterine sarcoma were studied to determine the sites and possible modes of metastasis. Homologous mixed mesodermal tumors were the most frequent (41%) followed by leiomyosarcoma (26%), heterologous mixed mesodermal tumor (18.3%), stromal sarcoma (12%), and endolymphatic stromal myosis (3%). The peritoneal cavity and omentum were the most frequently involved sites (59%), followed by the lung (52%), pelvic lymph nodes (41%), paraaortic lymph nodes (38%), and liver parenchyma (34%). The presence of lung metastasis was not associated with pelvic or paraaortic node metastasis or intraperitoneal disease. Metastasis to other distant sites including the brain, heart, kidney, and bone were independent of pelvic and paraaortic nodal metastasis or intraperitoneal disease. Metastatic sites were not different among various histologic types. Distant metastatic sites were statistically associated with lung metastasis. Hematogenous metastasis best explains this metastatic pattern and adjuvant systemic therapy seems indicated.

Adult↗

PubMed2005

Developments in diagnosis and treatment of metastatic midgut carcinoid tumors. A review.

Carcinoids are neuroendocrine tumours derived from enterochromaffin cells which are widely distributed in the body and may, therefore, arise from any site. They are traditionally described as originating from the foregut, midgut and hindgut. Localisation in the gastrointestinal tract is the most frequent, among which the appendiceal involvement is often found at laparoscopy for appendicitis and the small bowel is known for the liver metastases with the production of serotonin causing the characteristic carcinoid syndrome with diarrhoea and flushes. The overall incidence of carcinoid disease has increased in the past decades, but whether this is a true increase or due to early detection or better recognition at pathology is not known. The prognosis of metastatic carcinoid tumours has improved during the last decade resulting in a 5 year survival of approximately 50% in the Netherlands. Due to a longer survival, complications such as carcinoid heart disease and new metastatic patterns like skin and bone metastases may become a more important feature in carcinoid disease. New developments are in the field of diagnostics (fine-tuning of the pathology, videocapsule endoscopy to find the primary tumour, positron emission tomography [PET] scanning) and treatment options (radiofrequency ablation, radioactive octreotide, meta-iodobenzylguanidine combinations). The new serum marker of carcinoid, chromogranin A, may play an important role in the follow-up and NT-proBNP for the detection of heart problems. Combining new diagnostic and treatment modalities in metastatic carcinoid patients may result in a better quality of life and a longer survival. The increasing number of therapeutic options and diagnostic procedures requires a multidisciplinary approach focused on tailor-made therapy based on patients' specific conditions preferably in specialised centres and in clinical studies.

Carcinoid Tumor↗

PubMedDate not supplied

Abdominal metastases of infiltrating lobular breast carcinoma: CT and fluoroscopic imaging findings.

Infiltrating lobular carcinoma accounts for only a small fraction of breast carcinomas, with most patients having infiltrating ductal carcinoma. The metastatic patterns of ductal and lobular carcinoma have been shown to be markedly different. Infiltrating lobular carcinoma metastasizes significantly more often to the gastrointestinal tract, pelvic organs, peritoneum/retroperitoneum, and urinary tract than does infiltrating ductal carcinoma. This point has significance for follow-up, the diagnosis of abdominal symptoms, and the therapeutic options for these patients. This article illustrates the broad spectrum of abdominal metastases from lobular breast carcinoma that may be detected with computed tomographic and fluoroscopic examinations, and it describes the role of imaging in the diagnosis of metastatic disease in these patients.

Abdominal Neoplasms↗

PubMed1977

Ths significance of metastases to the adrenal glands in adenocarcinoma of the colon and rectum.

A study to determine the frequency of metastases to the adrenal glands following carcinoma of the colon and rectum was undertaken. Patients with, or without, adrenal spread were compared regarding age, sex, race and survival time. The over-all metastatic pattern was analyzed to determine its usefulness for predicting the presence of metastases to the adrenal glands. Autopsy reports and clinical records of patients with adrenal spread were reviewed regarding the extent of tumor involvement in the glands and possible adrenal insufficiency. Of 457 patients with adenocarcinoma of the colon and rectum who underwent autopsy, 63 or 14% had metastasis to the adrenal glands. Of these, 29 had bilateral involvement. Patients with bilateral metastases had a lower median age than did those without adrenal spread. No correlation was found between adrenal metastatic status and sex or race. Although survival time was found to be shorter for patients with bilateral metastases of the adrenal glands, adrenal insufficiency did not seem to be the reason for this shorter survival time. In retrospect, however, the presence of adrenal insufficiency could not be ruled out in several of these patients. Eight sites were studied with regard to whether or not metastatic involvement in a specific site might indicate a higher risk for simultaneous metastases to the adrenal glands. It was found for all sites that, when involved, there was a higher frequency of metastases to the adrenals than if free of tumor. Metastases especially above the diaphragm indicated a considerable risk for adrenal involvement. Different sites were combined in groups and studied in the same way. It was found that the more sites involved, the higher the relative chance of metastases to the adrenals. It was suggested that the results presented may be useful in predicting the relative chance of adrenal metastases in patients with advanced carcinoma of the colon and rectum.

Adenocarcinoma↗

PubMed1988

Role of concomitant resistance in the development of murine lung metastases.

An attempt was made to explain the distinct lung metastatic patterns of 2 mammary adenocarcinomas with a common BALB/c origin: M3, which does not induce spontaneous metastases, and MM3 with an almost 100% incidence. No difference between the 2 tumors was detected with respect to host mononuclear cell content, degree of immunogenicity or lung-colony-forming ability. Conversely, there was a marked difference in the capacity to induce concomitant resistance: M3-bearing mice induced stronger and earlier resistance against i.v. challenge of both M3 and MM3 tumor cells than MM3-bearing mice; this resistance was expressed as lower number of lung metastases and lower tumor-cell proliferation in metastatic nodules. M3 was also able to control the development of spontaneous metastases: metastases developed in all M3-excised mice, compared with none in M3-bearing mice, while MM3-bearing mice also bearing a secondary M3 tumor developed fewer metastases than mice bearing MM3 only. This anti-metastatic effect does not appear to depend on classical immunological mechanisms since no difference could be detected between the 2 tumors in response to T cells, NK, macrophages or antibodies.

Adenocarcinoma↗

PubMed1991

Patterns of recurrence in Western and Japanese women with breast cancer.

The patterns of relapse in Western women with breast cancer were compared with women from Japan. The results reported are based on a review of the literature. A significant difference between Japanese and Western women was seen with regard to relapse in bone, lung, and liver as assessed clinically. More Western women had bone metastases, but the incidence of pulmonary and liver metastases was higher in Japanese women. A significant difference between the races was also seen with regard to locoregional recurrence of disease, with Japanese women showing a higher incidence of relapse in the supraclavicular lymph nodes compared to Western women. Postmortem studies showed that although the initial metastatic pattern may differ between Japanese and Western women, at time of death the disease is as widely disseminated in the former as it is in the latter.

Autopsy↗

PubMed2002

Quantification of human Alu sequences by real-time PCR--an improved method to measure therapeutic efficacy of anti-metastatic drugs in human xenotransplants.

For measuring the efficacy of new anti-metastatic drugs in preclinical models, macroscopical analysis or classical histology of secondary organs are established methods. However, macroscopical evaluation does not take into consideration intra-organ metastasis. Histological analysis is often performed in few sections of the relevant organs, and this may be misleading, since equal distribution of tumor cells within an organ is unlikely. In addition, recent studies have demonstrated that anti-tumorigenic drugs are able to promote metastasis and to change the metastatic pattern. Therefore, extensive analysis of metastasis is mandatory for the evaluation of new compounds. A feasibility study was conducted to find out if the quantification of human Alu sequences could be applied as a surrogate marker for metastasis in xenografts. Alu PCR was performed by using the LightCycler system, which allows PCR reaction and subsequent quantification of the PCR products in less than 30 min. We found that i) the equivalent of one human tumor cell in 1 x 10(6) murine cells could be detected; ii) in tumor-carrying mice, Alu signal increased over time in secondary organs; iii) this increase was more prominent using highly metastatic tumor cells; iv) Alu signal intensity in DNA extracted from tissue slides correlated with the expression of histological tumor markers; v) in three different tumor models (colon, breast and lung), treatment with Taxol or 5-fluorouracil reduced the amount of Alu in different organs. In contrast, reduction of Alu by the matrix metalloproteinase inhibitor RO 28-2653 was not significant. Taken together, quantification of Alu sequences is a fast and accurate method to evaluate the therapeutic efficacy of anti-metastatic drugs in xenografts.

Alu Elements↗