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PubMed1995

Vascular pattern of a metastatic liver tumor in a dog:--a scanning electron microscopic study of resin casts.

Metastasis of a malignant mixed tumor occurring in the abdominal wall was found in the liver of a 15-year-old dog male. The vascular system of the metastatic lesion was examined by scanning electron microscopy using the resin cast technique. The existence of arterio-portal shunts was confirmed. The shunts arose from branches of the hepatic artery in retrograde or vertical direction and merged into the capillary plexus replacing the branches of the portal vein, forming the so-called thread and streaks vessel in the field of hepatic angiography. Vessels with the thread and streaks appearance histologically represented tumor emboli growing in the lumen of a large branch of the portal vein. There were capillaries running inside along the portal vein and forming a longitudinal dense network in the vein. Branches of the hepatic artery feeding the metastatic lesion were well developed and formed a coarse arterial network in their course. Tributaries of the hepatic vein from the lesion were also well developed.

Animals↗
PubMed1986

Myxoid malignant melanoma. A previously undescribed histologic pattern noted in metastatic lesions and a report of four cases.

Four patients are presented with malignant melanoma in which the stroma showed a prominent myxoid change. Since this peculiar feature had not been previously reported, metastatic lesions with this change caused considerable diagnostic confusion with other more commonly encountered myxoid tumors. On the basis of light microscopy, special stains, and electron microscopy, we demonstrated the melanomatous nature of the metastases and that the myxoid matrix is derived from reactive stromal cells rather than from the melanoma cells themselves. Three of the four patients had a history of primary melanoma; the longest interval between the primary lesion and the metastasis was 24 years.

Adult↗
PubMed1989

Two human melanoma xenografts with different metastatic capacity and glycosaminoglycan pattern.

Two human melanoma xenografts were compared with respect to their in vivo growth and metastatic potentials as well as glycosaminoglycan patterns. The less differentiated HT 168 tumor showed faster growth at primary sites and a more pronounced capacity for metastasis into the liver. Although chondroitin sulfate was the dominant glycosaminoglycan subtype in both tumors, the more invasive xenograft had a higher heparan sulfate/chondroitin sulfate (HS/CS) ratio. We suggest that tumor progression is influenced by this ratio in this human melanoma system.

Animals↗
PubMed1994

[Clinical significance of flow cytometric DNA analysis in metastatic lymph node of colorectal cancer].

Significance of flow cytometric DNA analysis in metastatic lymph nodes for assessing malignant potential of colorectal cancer was investigated using paraffin-embedded materials of primary lesions and metastatic lymph nodes from 65 patients who had been treated between 1975 and 1990. The DNA ploidy patterns of metastatic nodes were identical in 61.5% with those of primary lesions. Diploid cancers were significantly more frequent in metastatic nodes than in primary lesions. There were significantly more aneuploid cancers in proximal nodes than in distant nodes. There was no relation between ploidy patterns in primary lesions and survival. However, a significant relation was found between ploidy patterns in metastatic nodes and survival. Diploid cancer in metastatic nodes had a significantly better survival than aneuploid cancer, in all patients as well as those with curative resection. In patients with stage III and in those with the same depth of invasion, the survival rate of diploid cancer in metastatic nodes was significantly higher. There was no correlation between ploidy patterns in metastatic nodes and clinicopathological variables in primary lesions, such as histological type, depth of invasion, nodal involvement, peritoneal or hepatic involvement and stage. These results suggest that nuclear DNA content in metastatic lymph nodes may be a prognostic indicator in colorectal cancer with nodal involvement.

Colorectal Neoplasms↗
PubMed1997

Growth of newly diagnosed, untreated metastatic gastrinomas and predictors of growth patterns.

PURPOSE: The growth pattern of untreated metastatic neuroendocrine tumors is unknown. This uncertainty contributes to the disagreement regarding timing and could effect evaluation of the efficacy of antitumor treatment. The purpose of this study was to determine the growth rate of untreated hepatic metastatic gastrinoma and to identify its predictors. PATIENTS AND METHODS: Nineteen patients with histologically proven metastatic gastrinoma in the liver with Zollinger-Ellison syndrome were studied. Conventional imaging studies were performed initially and at 4- to 6-month intervals before any treatment. Metastases growth rates were calculated and correlated with laboratory and clinical parameters, as well as tumor extent on initial tumor assessment. RESULTS: Twenty-six percent of patients (five of 19) demonstrated no growth over a mean follow-up time of 29 months, 32% (six of 19) had slow growth (1% to 50% increase in volume per month) over a 19-month period, and 42% (eight of 19) had rapid growth (> 50% volume increase per month) over an 11-month period. In patients with rapid growth, 62% died; 0% of the no-growth or slow-growth group died. No clinical or laboratory parameter correlated with growth rate, except the rate increase in fasting serum gastrin and the presence of bilobar liver or bone metastases. The growth rate was highly predictive of death from tumor. CONCLUSION: The growth rate of metastatic gastrinoma varies markedly in different patients and 26% demonstrate no growth. The growth rate needs to considered in the determination of when and in whom antitumor therapy is initiated, as well as in the assessment of response to tumoricidal therapies.

Adult↗
PubMed1980

The chemotherapy of prostatic adenocarcinoma.

A number of chemotherapeutic agents show moderate promise for the palliative treatment of metastatic prostatic carcinoma. Although patterns of metastatic disease make classic response rates difficult to obtain and interpret, doxorubicin, cyclophosphamide, dacarbazine (DTIC), and cisplatin have activity in patients who have failed conventional hormonal treatment. In most studies, a survival advantage is seen for responders to these and other chemotherapeutic agents, but no survival advantage has been seen for the treatment cohorts when compared to groups not receiving chemotherapy. Therefore, estimates of the usefulness of these agents must be considered tentative. Multiple drug therapy has not yet shown definite superiority to single agent treatment. The uses and limitations of acid phosphatase as a tumor marker, as well as particular difficulties in measuring tumor response in the disease, are detailed herein.

Acid Phosphatase↗
PubMed2000

Metastatic neuroblastoma in infancy: what does the pattern of metastases contribute to prognosis?

BACKGROUND: The purpose was to investigate the influence of metastatic pattern and primary extension over midline on prognosis of infants with metastatic neuroblastoma. PROCEDURE: Data of 317 consecutive infants with metastatic neuroblastoma were analyzed. RESULTS: The amount of bone marrow infiltration (<10% vs. >10%) proved to be the most important factor and was more important than the presence of bone metastases. A disadvantage in outcome for patients with distant lymph node, intracranial, or atypical metastases or for patients with primary extension over midline could not be demonstrated. However, in the subgroup of patients treated with limited treatment, primary extension over midline proved a risk factor. CONCLUSION: A redefinition of Stage 4S on an international basis is suggested.

Follow-Up Studies↗
PubMed1995

Optimum combination of targeted 131I and total body irradiation for treatment of disseminated cancer.

PURPOSE: Radiobiological modeling was used to explore optimum combination strategies for treatment of disseminated malignancies of differing radiosensitivity and differing patterns of metastatic spread. The purpose of the study was to derive robust conclusions about the design of combination strategies that incorporate a targeting component. Preliminary clinical experience of a neuroblastoma treatment strategy, which is based upon general principles obtained from modelling, is briefly described. METHODS AND MATERIALS: The radiobiological analysis was based on an extended (dose-rate dependent) formulation of the linear quadratic model. Radiation dose and dose rate for targeted irradiation of tumors of differing size was in part based on microdosimetric considerations. The analysis was applied to several tumor types with postulated differences in the pattern of metastatic spread, represented by the steepness of the slope of the relationship between numbers of tumors present and tumor diameter. The clinical pilot study entailed the treatment of five children with advanced neuroblastoma using a combination of 131I metaiodobenzylguanidine (mIBG) and total body irradiation followed by bone marrow rescue. RESULTS: The theoretical analysis shows that both intrinsic radiosensitivity and pattern of metastatic spread can influence the composition of the ideal optimum combination strategy. High intrinsic radiosensitivity generally favors a high proportion of targeting component in the combination treatment, while a strong tendency to micrometastatic spread favors a major contribution by total body irradiation. The neuroblastoma patients were treated using a combination regimen with an initially low targeting component (2 Gy whole body dose from targeting component plus 12 Gy from total body irradiation). The treatment was tolerable and resulted in remissions in excess of 9 months in each of these advanced neuroblastoma patients. CONCLUSIONS: Radiobiological analysis, which incorporates simple models of metastatic spread, emphasizes the importance of the total body irradiation component in a targeting/total body irradiation combination strategy. However, the analysis favors a larger targeting component than is used in clinical practice at present. A cautious escalation of the 131I mIBG component in the combination treatment of advanced neuroblastoma appears justified.

Child↗
PubMed2005

Elevated serum cytokines correlated with altered behavior, serum cortisol rhythm, and dampened 24-hour rest-activity patterns in patients with metastatic colorectal cancer.

PURPOSE: Incapacitating symptom burden in cancer patients contributes to poor quality of life (QOL) and can influence treatment outcomes because of poor tolerance to therapy. In this study, the role of circulating cytokines in the production symptoms in cancer patients is evaluated. EXPERIMENTAL DESIGN: Eighty patients with metastatic colorectal cancer with either normal (group I, n = 40) or dampened (group II, n = 40) 24-hour rest/activity patterns measured by actigraphy were identified. Actigraphy patterns were correlated with QOL indices, serum cortisol obtained at 8:00 a.m. and 4:00 p.m. and with serum levels of transforming growth factor-alpha, tumor necrosis factor-alpha, and interleukin 6 (IL-6) obtained at 8:00 a.m. and analyzed in duplicate by ELISA. Cytokine levels and survival were also correlated. RESULTS: Group II patients had significantly higher pre treatment levels of all three cytokines, displayed significantly poorer emotional and social functioning, had higher fatigue, more appetite loss, and poorer performance status compared with group I patients. Transforming growth factor-alpha (TGF-alpha) and IL-6 were significantly increased in the patients with WHO performance status >1 and in those with appetite loss. Fatigue was significantly associated with elevated TGF-alpha only. IL-6 was increased in those patients with extensive liver involvement and multiple organ replacement, and it was significantly correlated with dampened cortisol rhythm. In a multivariate analysis, IL-6 was correlated with poor treatment outcome. CONCLUSIONS: Significant correlations were found between serum levels of TGF-alpha and IL-6, circadian patterns in wrist activity and serum cortisol and tumor-related symptoms in patients with metastatic colorectal cancer. These data support the hypothesis that some cancer patient's symptoms of fatigue, poor QOL, and treatment outcome are related to tumor or host generated cytokines and could reflect cytokine effects on the circadian timing system. This interplay between cytokine signaling pathways, the hypothalamic-pituitary-adrenal axis, the autonomic nervous system, and efferent pathways of the suprachiasmatic nucleus that control circadian physiology, opens the way to new rational interventions for symptom management in cancer patients.

Activities of Daily Living↗
PubMed1994

Differences of E-cadherin expression levels and patterns in primary and metastatic human lung cancer.

Normal lung epithelium and 52 lung carcinomas obtained at surgical resection were examined by immunofluorescence for their expression levels and patterns of the calcium-dependent intercellular adhesion molecule E-cadherin. In dysplastic lung tissue and in well-differentiated squamous cell and adenocarcinomas, expression of E-cadherin was confined to the lateral cell border, similar to the expression level and pattern of normal lung tissue. The E-cadherin level was reduced and expression pattern was spotty or diffuse in moderately and poorly differentiated squamous cell and in small cell carcinomas of the lung. Most metastases resected also had a reduced level and an altered pattern of E-cadherin expression. In contrast, no such correlation was found in adenocarcinomas of the lung. This indicates that different cellular mechanisms are responsible in the progression of squamous cell carcinomas and adenocarcinomas of the lung.

Adenocarcinoma↗
PubMed1986

Pathophysiology of experimental leishmaniasis: pattern of development of metastatic disease in the susceptible host.

A clear understanding of the etiology of the various forms of leishmaniasis will require knowledge of how physiological properties of the parasite and host immunity influence the pattern of development of the disease. Of particular importance are how these factors affect the growth rate of Leishmania spp. at the site of inoculation in the skin, their capacity to disseminate to visceral and distant cutaneous sites, and their capacity to multiply once there. This paper details the pattern of development of disseminated Leishmania major infection in susceptible BALB/c nu/+ and BALB/c nu/nu mice. It was found that the parasite disseminates from the hind footpad to distant cutaneous sites soon after metastatic foci are established in the liver and spleen. Both mononuclear phagocytes and neutrophils may be the vehicles for the transport of the parasite in the blood. Once visceral and cutaneous metastases are established, the parasites in those foci increase in number progressively. L. major has the capacity to multiply at visceral and cutaneous sites at the same rate. Despite the presence of viable parasites in a number of skin sites, cutaneous metastatic lesions developed almost exclusively on the feet and the tail. Furthermore, these lesions appeared to develop preferentially at sites near joints, suggesting that factors other than temperature may influence the development of cutaneous metastatic lesions.

Animals↗
PubMed1997

Intrabiliary growth of metastatic colonic adenocarcinoma: a pattern of intrahepatic spread easily confused with primary neoplasia of the biliary tract.

Because of its propensity to spread along epithelial surfaces, colonic adenocarcinoma can mimic other neoplasms. For example, colonic adenocarcinoma can grow along the surface of the urinary bladder and can simulate primary bladder neoplasia, and metastatic colonic adenocarcinoma can grow along alveolar walls and can mimic primary lung neoplasia. Intraepithelial spread along bile ducts, however, is not a well-recognized behavior of hepatic metastases. Indeed, dysplastic change in the epithelium lining the biliary tract is sometimes used to discriminate primary biliary neoplasms from metastatic adenocarcinoma. We report on eight cases of colonic adenocarcinoma metastatic to the liver that demonstrated prominent spread throughout the biliary tree along intact basement membranes. Morphologically, this pattern closely resembled high-grade dysplasia (i.e., carcinoma in situ) of the extrahepatic and intrahepatic bile ducts. Clinically, two of the tumors were mistaken for primary biliary neoplasia because of the common radiologic finding of intrabiliary masses with distended bile ducts. A definite diagnosis of metastatic carcinoma was established by careful attention to the medical history, thorough evaluation of the morphologic features, and histologic comparison with the primary colon cancer. For patients with a history of colonic adenocarcinoma, consideration of a liver metastasis is appropriate even when certain histologic and radiographic features point to a neoplasm of biliary origin.

Adenocarcinoma↗
PubMed2004

Initially metastatic breast carcinoma has a distinct disease pattern but an equivalent outcome compared with recurrent metastatic breast carcinoma.

BACKGROUND: To date, the clinical features and outcomes of patients with initially metastatic breast carcinoma (IMBC) have not been compared with the corresponding characteristics in patients with recurrent metastatic breast carcinoma (RBC). This issue may be particularly relevant to clinical research, as it may shed light on a potential bias with respect to the selection of patients for clinical trials. METHODS: A retrospective analysis of the medical records of 1350 patients with breast carcinoma was performed. Outcome variables included overall survival, response rate, and progression-free survival. RESULTS: One hundred nineteen of 370 patients with metastatic breast carcinoma had IMBC, whereas the remaining 251 had RBC. The median follow-up duration was 39.4 months, and the median overall survival duration was 24 months. With regard to clinical characteristics, patients with IMBC were older than patients with RBC (61.7 years vs. 58.1 years; P < 0.001) and had a higher incidence of lobular carcinoma (15.9% vs. 7.7%; P = 0.018), a greater proportion of T3-4 tumors (58.8% vs. 27.9%; P < 0.001), a higher incidence of bone as the dominant metastatic site (41.2% vs. 21.5%; P < 0.001), a lower incidence of soft tissue as the dominant metastatic site (10.1% vs. 26.7%; P < 0.001), and a similar incidence of the viscera as the dominant metastatic site (48.7% vs. 51.8%; P = 0.78). Median overall survival duration was similar for patients with IMBC (25.1 months) and patients with RBC (23.3 months; P = 0.81). Statistical analyses also revealed nonsignificant differences between patients with IMBC and patients with RBC in terms of response rate (40.7% vs. 35.2%, respectively; P = 0.35) and median progression-free survival duration (10.2 months vs. 9.0 months, respectively; P = 0.58). CONCLUSIONS: Although patients with IMBC and patients with RBC exhibit distinct histologic and clinical characteristics, similar treatment efficacy results and survival outcomes are observed in these two groups.

Adult↗
PubMed1990

Hepatocellular carcinoma presenting well differentiated, normotrabecular patterns in peripheral or metastatic loci. Analysis of 103 resected cases.

In a series of 103 surgically resected hepatocellular carcinomas (HCCs), the tumor boundaries were rather clearly defined in 85 cases (82.5%). Twelve tumors had an ill-defined margin because adjacent pseudolobules were replaced by HCC with a well differentiated growth pattern (group A1). This peripheral pattern was unrelated to the predominant histologic type of the major tumor nodules. Despite its close resemblance to normal hepatic parenchyma, we were able to determine the area of the normotrabecular HCC on the basis of, differences in stain-ability, variable nuclear crowding and frequent microacinar formation. Moreover, scattered occurrence of nuclear atypia and midtrabecular conversion were also observed within the normotrabecular HCC. In an additional 6 cases, a band-like zone of normotrabecular HCC was evident peripherally around the primary lesion (group A2). Fourteen other cases (13.6%) had intrahepatic metastatic lesions formed either within the portal vein or in pseudolobules. Of these, 5 cases showed intrapseudolobular metastases with a normotrabecular pattern (group B). For precise evaluation of surgical HCC specimens, it seems to be particularly important to realize that HCCs sometimes have a highly differentiated appearance in a locus of peripheral invasion as well as intrahepatic metastasis.

Carcinoma, Hepatocellular↗
PubMed2005

The radiology of gastrointestinal stromal tumours (GIST).

Gastrointestinal stromal tumours (GISTs) comprise a group of smooth muscle mesenchymal alimentary tract tumours of variable malignancy. Recently, the pathophysiology and radiology of these tumours has generated enormous interest following the discovery of a specific, highly effective, chemotherapeutic agent in the form of ST-571 (Imatinib; Glivec, Novartis, Frimley UK). At the time of this review, 106 patients with malignant gastrointestinal stromal tumours seen at the Royal Marsden Hospital have been entered into trials examining the efficacy of varying doses of Imatinib. Burkill et al., also from the Royal Marsden Hospital, have previously reported the distribution, imaging features and pattern of metastatic spread of these tumours (Burkill GJ, Badran M, Al-Muderis O et al. Malignant gastrointestinal stromal tumor: distribution, imaging features, and pattern of metastatic spread. Radiology 2003; 226: 527-32). This new review re-examines the radiological features of GISTs at presentation and well as their changed imaging features following treatment with Imatinib.

Antineoplastic Agents↗
PubMed1986

The distribution of metastases of different primary tumors in the liver.

The distribution of the number and volume of liver metastases in both lobes of the liver was investigated. The density of the metastases and their volume were analyzed. The study of 71 human metastatic livers revealed an almost homogeneous pattern of metastatic distribution. There was no difference whether the spread of the tumor cells had occurred via the portal vein or the hepatic artery. Both sides of the liver were affected similarly.

Hepatic Artery↗