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[Metastatic brain tumor in the elderly].

Authors have reviewed 322 consecutive patients with malignant tumors confirmed by pathological studies between October 1973 and August 1987 in order to determine the frequency, clinical presentation, and lesion localization of metastatic brain tumor in the elderly. Among 322 patients with malignant tumor, 7 patients with primary brain tumor and 21 patients with metastatic brain tumors were found. The over-all frequency of metastases to the brain was 5.8%. This frequency of brain metastasis in the elderly was lower than those of the previous literature which have varied from 9 to 35%. The patients' ages with metastatic brain tumor ranged from 65 to 88 years with a median age of 77.5 years. The primary tumor sites of metastatic brain tumors were limited to 5 kinds of organs. These metastases were found in 27.3% of 11 patients with breast cancer, 17.5% of 80 patients with lung cancer, 6.7% of 15 patients with bile duct system cancer, 5.0% of 20 patients with pancreatic cancer, and 2.0% of 91 patients with gastric cancer. There was no brain metastasis in the other kinds of carcinoma. Among 21 metastatic brain tumors, there were 14 patients with lung cancer, 3 patients with breast cancer, 2 patients with gastric cancer, 1 patient with cholangiocarcinoma, and 1 patient with pancreatic cancer. In this series, the frequency of single and multiple metastases were 13 and 8 cases, respectively. The multiple brain metastases ranged from 2 to 6 nodules. In 21 metastatic brain tumors, there were 42 metastatic nodules in total.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

The diversity expression of p62 in digestive system cancers.

The expression of p62 autoantigen and the frequency of p62 autoantibody have been reported in hepatocellular carcinoma (HCC) and many types of malignant tumors, respectively, but information regarding to the expression of p62 in other cancer tissues and the association of autoantibody to p62 with tumor behaviors is not available. In the current study, the expression of p62 in tissues and the appearance of p62 autoantibody in sera were detected by immunohistochemical staining and ELISA in four clinical types of digestive system cancers including gastric cancer, esophageal cancer, large intestine cancer and HCC, respectively. Interestingly, the immunohistochemistry staining of p62 has been shown in all of digestive canal tissues (stomach, esophagus, large intestine) including tissues with cancers, beside cancers and from non-malignant patients, whereas the frequencies were 62.5% and 0% in tissues with cancer and beside cancer in patients with HCC, respectively. Importantly, we found that the p62 expression and the frequency of autoantibody to p62 were associated to cell differentiation and tumor metastasis, respectively. These results suggest that the expression of p62 in tissues and the appearance of autoantibody to p62 in sera might be related to cell malignant manifestations. Moreover, p62 autoantibody is a significant marker for the prognosis of cancers and the evaluation of clinical treatments.

Adult↗

[Radiological aspects of malignant histiocytic pathology].

The histiocyte, macrophage of tissue monocyte is a cell of the mononuclear system. At the moment several different types of classification of the malignant histiocytic pathology are use. Seven cases of this pathology are documented: two cases of malignant histiocytosis, two cases of malignant histiocytic lymphoma, two cases of malignant histiocytoma of soft tissue and one malignant histiocytic tumor of bone. The purpose of this study is to analyse the usefulness the roentgenologic methods: conventional radiography, radionuclide scanning, computed tomography, sonography, xeroradiography, angiography. The evaluation of malignant histiocytic pathology has become more precise through the introduction of ultrasonography and computed tomography. This report adds to the understanding of the entities of this pathology in that the diagnosis of malignance was made using roentgenologic criteria and confirmed by histology.

Adult↗

Survival results depend on the staging system.

The results of expressing patient outcome are compared using two staging systems: localized, regional, and distant (LRD) and the TNM of the American Joint Committee on Cancer (AJCC). Expressing patient outcome depends on the staging system used. There is overlap between the stage definitions of the LRD and the TNM. A single stage in the LRD may include more than one stage grouping of the TNM and vice versa. For most sites, "localized" provides lower survival rates than stage I of the TNM. The TNM provides more precise information about prognosis because its definitions reflect the latest survival information and diagnostic technology. Time trends can be measured only with the LRD because of its stability over the years. The precision of the TNM has been achieved at the expense of time trend analysis. The LRD is usually not an acceptable end point for the assessment of early cancer detection.

Breast Neoplasms↗

Comparative genomic hybridization analysis of sporadic neuroendocrine tumors of the digestive system.

Little information is available on the molecular mechanisms underlying neuroendocrine tumorigenesis. To obtain an overview of the genomic imbalances characterizing these tumors, we studied 20 benign or malignant sporadic endocrine gastroenteropancreatic tumors by comparative genomic hybridization. Chromosomal imbalances were found in all tumors. Gains of chromosomal material were more frequent than losses. The most frequent gains were of chromosomes and chromosome arms 5 (55%), 14 (55%), 17q (55%), and 7 (50%). Losses were most frequent from 11q (30%) and 16p (30%). Gains of chromosome 5 did not occur in nonmetastatic tumors, whereas losses of 9p were observed exclusively in intestinal tumors. In addition, we found two high-level amplifications, of 17q11-21 and 19q13. A complementary FISH analysis revealed that the gain in 17q11-21 included amplification of the protooncogene HER2/neu. As in multiple endocrine neoplasia type-1-associated tumors, deletions of chromosome band 11q13 appear to be involved in the development of sporadic digestive tract neuroendocrine tumors, but our results suggest that other chromosomal regions are also involved.

Adolescent↗

[Determination of serum DU-PAN-2 by enzyme immunoassay in patients with various digestive cancers].

In order to evaluate the usefulness of serum DU-PAN-2, we determined this antigen in 384 patients with various malignancies and in 215 patients with benign diseases using a sandwich enzyme immunoassay system (Kyowa Medex Co.). Elevated DU-PAN-2 levels (greater than 400 U/ml) were observed in 55% of hepatocellular cancers, 50% of pancreatic cancers, and 43% of biliary tract cancers. On the other hand, most false-positive cases with benign diseases were observed in patients with liver injury, especially in the acute phase of acute hepatitis, chronic active hepatitis, and liver cirrhosis. However, in only a few cases with other benign diseases including pancreatitis, increased levels were found. Moreover, among the pancreatic cancer or biliary tract cancer patients studied, DU-PAN-2 was positive in 7 of the 19 CA 19-9-negative (less than 37 U/ml) patients and 32 of the 68 CEA-negative (less than 5 ng/ml) patients. These results indicate that the assay of DU-PAN-2 by EIA may have diagnostic usefulness in digestive cancer, especially pancreatic cancer or biliary tract cancer.

Antigens, Neoplasm↗

Short- and long-term morbidity and mortality in the population exposed to dioxin after the "Seveso accident".

The early effects of 2,3,7,8-tetrachlorodibenzo-para-dioxin (TCDD) exposure in the population involved in the Seveso, Italy, incident in 1976, have been examined in numerous studies. Chloracne was the only effect linked with sufficient certainty to dioxin exposure. The possible long-term consequences were investigated with mortality and cancer incidence studies. Mortality and morbidity findings during the 20-year period following the accident showed increased risk from lymphoemopoietic neoplasm, digestive system cancer (rectum in males, and biliary tract among females, in particular) and respiratory system cancer (lung, among males). In the incidence analyses, also thyroid gland and pleura cancer appeared suggestively increased. Soft tissue sarcomas showed an increase in the largest, yet least exposed, exposure sub-cohort. Several hypotheses associating non-cancer effects with dioxin exposure were corroborated by findings in the Seveso population: this was the case with cardiovascular effects (possibly linked to both chemical exposure and stressful disaster experience), endocrine effects (diabetes among females) and reproductive effects: exposure of men to TCDD was linked to a lowered male/female sex ratio in their offspring. The results of many Seveso studies point to possible gender effects, in accordance with animal models. Notwithstanding the acknowledged study limitations (lack of individual exposure markers, short latency, and small population size for certain cancer types), results of previous experimental and epidemiological studies, along with mechanistic knowledge on dioxin toxicity, support the hypotheses that the observed excesses might be associated with dioxin exposure. The mortality and cancer incidence follow-up of the Seveso cohort are continuing.

Dioxins↗

BRAF gene mutations are rare events in gastroenteropancreatic neuroendocrine tumors.

The BRAF gene, one of the human isoforms of RAF, is activated by ras, leading to cooperative effects in cells responsive to growth factor signals. We studied the frequency of BRAF and k-ras-2 mutations in primary neuroendocrine gastroenteropancreatic (GEP) tumors. Mutation analysis of the BRAF and k-ras-2 genes was performed in 40 primary neuroendocrine tumors of the GEP system. The expression of extracellular signaling-related kinase (ERK) 1/2, an important downstream point of convergence in the ras-RAF-mitogen-activated protein-ERK pathway was analyzed immunohistochemically. We detected one 1796 T-->A BRAF mutation that led to a substitution of valine by glutamic acid at position 599 (V599E) in 40 primary neuroendocrine GEP tumors (3%). We failed to detect specific mutation of the k-ras-2 gene. We identified constitutively activated ERK in almost all neuroendocrine tumor tissues tested irrespective of BRAF mutation or localization or functional activity. These results suggest that BRAF mutations do not have a role in tumorigenesis of neuroendocrine tumors. Nevertheless, activation of the RAF/mitogen-activated protein kinase pathway might have a causative role in the development of neuroendocrine tumors, independent of BRAF or k-ras-2 mutation.

Biomarkers, Tumor↗

Aspirin use and risk of fatal cancer.

Aspirin and other nonsteroidal antiinflammatory drugs inhibit prostaglandin synthesis and tumor growth in many experimental systems, but it is unclear which of these tumor models are relevant to humans. We have reported reduced risk of fatal colon cancer among persons who used aspirin in a large prospective study. This analysis examines other fatal cancers in relation to aspirin among 635,031 adults in that study who provided information in 1982 on the frequency and duration of their aspirin use and did not report cancer. Death rates were measured through 1988. Death rates decreased with more frequent aspirin use for cancers of the esophagus, stomach, colon, and rectum but not generally for other cancers. For each digestive tract cancer, death rates were approximately 40% lower among persons who used aspirin 16 times/month or more for at least 1 year compared to those who used no aspirin. The trend of decreasing risk with more frequent aspirin use was strongest among persons who had used aspirin for 10 years or more; it remained statistically significant, except for esophageal cancer, in multivariate analyses that adjusted for other known risk factors. Biases such as early detection or aspirin avoidance among cases do not appear to explain the results. Our data suggest that regular, prolonged use of aspirin may reduce the risk of fatal cancer of the esophagus, stomach, colon, and rectum. Future epidemiological and basic research should examine all digestive tract cancers in considering the chemopreventive or therapeutic potential of nonsteroidal antiinflammatory drugs.

Acetaminophen↗

Lymph node metastases. Indicators, but not governors of survival.

Regional lymph node filter function has traditionally been assumed to be critical in the prevention of the systemic spread of malignant cells shed from the primary cancer. However, in a multitude of clinical studies involving a variety of cancers, prophylactic removal of such regional lymph nodes, with or without metastases, does not improve cure rates compared with the observation of these lymph nodes. Furthermore, laboratory studies indicate that lymph node filter function may not be either complete or effective, and that many lymphatic and lymphaticovenous shunts exists that bypass regional lymph nodes and allow both lymphatic and hematogenous dissemination of malignant cells. These facts emphasize that regional lymph node metastases are indicators, but not governors, of survival in cancer. The timing of the clinical appearance of regional lymph node metastases and their number are, with few exceptions, excellent indicators of the biologic behavior of the primary cancer and the cells that are shed from it. This shedding of cells into the vascular and lymphatic vessels undoubtedly occurs simultaneously in the vast majority of cancers, but the later progressive growth of cells and micrometastases distributed hematogenously to vital organs is the ultimate governor of survival.

Breast Neoplasms↗

[Influence of blood transfusion on development of infection in patients with malignant neoplasms of the digestive system].

BACKGROUND: Anemia affects up to 90% of cancer patients, with more than 60% requiring blood transfusion during or after treatment. AIM: To determine the influence of the allogeneic blood transfusion as a possible related factor to infection in patients with malignant neoplasms of the gastrointestinal system. PATIENTS AND METHOD: Charts of 400 oncological patients were randomly selected and divided into two groups: group 1 (n = 200)--patients submitted to allogeneic blood transfusion and group 2 (n = 200)--non transfused patients. Both groups were evaluated and compared according to the presence and type of infection and a possible association with age, sex, types of tumors and therapeutics approach. RESULTS: The relation between infection and blood transfusion, as well as age, sex, management and type of presented tumors were not significant. There was no difference in the incidence of infection between the non transfused patients (28) and those submitted to allogeneic blood transfusion (31). CONCLUSIONS: In the present investigation allogeneic blood transfusion was apparently not related to development of infection in patients with malignant gastrointestinal tumors.

Adolescent↗

Systemic Lipoplatin infusion results in preferential tumor uptake in human studies.

Lipoplatin, a liposomal formulation of cisplatin, was developed with almost negligible nephrotoxicity, ototoxicity and neurotoxicity, as demonstrated in preclinical and Phase I human studies. A polyethylene-glycol coating of the liposome nanoparticles is supposed to result in tumor accumulation of the drug by extravasation through the altered tumor vasculature. We explored the hypothesis that intravenous infusion of Lipoplatin results in tumor targeting in four independent patient cases (one with hepatocellular adenocarcinoma, two with gastric cancer and one with colon cancer) who underwent Lipoplatin infusion followed by a prescheduled surgery approximately 20 h later. Direct measurement of the platinum levels in specimens from the excised tumors and normal tissues showed that the total platinum levels were on average 10-50 times higher in malignant tissue compared to the adjacent normal tissue specimens; most effective targeting was observed in colon cancer, with an accumulation up to 200-fold higher in colon tumors compared to normal colon tissue. Of the several surgical specimens, gastric tumors displayed the highest levels of total platinum suggesting Lipoplatin as a candidate anticancer agent for gastric tumors; gastric tumor specimens had up to 260 micrograms platinum /g tissue, that was higher than any tissue level in animals treated at much higher doses. Fat tissue displayed a high accumulation of total platinum in surgical specimens in three different patients, correlating to the lipid capsule of cisplatin in its Lipoplatin formulation. It was also inferred that normal tissue had more platinum trapped in the tissue but not reacted with macromolecules, whereas tumor tissue displayed platinum that reacted with cellular macromolecules; the data were consistent with a model where Lipoplatin damages more tumor compared to normal cells. In conclusion, Lipoplatin has the ability to preferentially concentrate in malignant tissue both of primary and metastatic origin following intravenous infusion to patients. In this respect, Lipoplatin emerges as a very promising drug in the arsenal of chemotherapeutics.

Adipose Tissue↗

Reduced expression of the CXC chemokine hIRH/SDF-1alpha mRNA in hepatoma and digestive tract cancer.

We isolated human intercrine reduced in hepatomas (hIRH) as a mRNA whose expression was reduced in differential displays from human hepatocellular carcinoma. hIRH is equivalent to the alpha-chemokine SDF-1alpha/PBSF. We have previously demonstrated on Northern blot analysis that although hIRH mRNA expression is common in human normal tissues, it is absent from pre-malignant colonic adenomas and from 27 human malignant cell lines. However, there are no reports on the mRNA status of hIRH in other human cancers. The present study was designed to investigate semi-quantitatively the expression of hIRH/SDF-1alpha mRNA in hepatocellular carcinoma and digestive tract cancers by reverse transcription-polymerase chain reaction (RT-PCR). The expression of hIRH/SDF-1alpha in the majority of cancer tissues analyzed was markedly reduced compared with that in adjacent non-cancer tissue. RT-PCR was more sensitive than Northern blots in the detection of hIRH mRNA. The average (mean +/- SE) tumor/normal (T/N) ratio determined by RT-PCR was 0.40 +/- 0.07 in 10 pairs of hepatoma, 0.38 +/- 0.09 in 14 pairs of colon cancers, 0.43 +/- 0.07 in 10 pairs of esophageal cancers and 0.70 +/- 0.09 in 26 pairs of gastric cancers. As a control, the mean G3PDH T/N ratio was 1.16 +/- 0.06. The distribution of T/N ratios was significantly different between gastric cancer and the other cancers, but there was no correlation between hIRH/SDF-1alpha expression and clinicopathological characteristics in gastric cancer. Our findings demonstrate that hIRH/SDF-1alpha expression is reduced in the majority of gastrointestinal tumors.

Adult↗

Cellular immune modulation after a single high dose of Levamisole in patients with carcinoma.

The effect of a single high dose of Levamisole (200 mg/M2) on delayed-type hypersensitivity (DTH) in vivo and on lymphocyte blastogenesis to mitogens and antigens in vitro was studied in 26 patients with carcinoma. Similar studies were conducted in 24 control patients. Levamisole had a moderate but significant enhancing effect on DTH to Dermatophytin detectable no earlier than eight hours and still present at 48 hours after the drug administration. A moderate but significant enhancing effect on lymphocyte blastogenesis to mitogens and antigens was also demonstrated during the same time sequence. Further clinical trials with Levamisole should be conducted with more attention paid to schedule of drug administration.

Breast Neoplasms↗

An application of immunocytology to the analysis of the cell kinetics of upper respiratory and digestive tract squamous carcinoma.

An antinucleoside immunofluorescence technique (ANIF) facilitated evaluation of labeling index (LI) from frozen sections of 36 upper respiratory and digestive tract squamous cancers (URDTS) from a group of 35 patients. There were 35 URDTS of the larynx, oral cavity, or pharynx and the LIs of this population ranged from 0-39.4%, (mean, 14.7%); 6% of URDTS (2 of 36) were not assessable by ANIF. The administration of nontherapeutic radioactive materials, the establishment of cell cultures, and perturbations in cell growth implicit in the removal of tumor from host prior to assessment are unnecessary in the application of this technique.

Carcinoma, Squamous Cell↗

Encasement and other deformations of tumor-embedded host arteries due to loss of medial smooth muscles. Morphometric and three-dimensional reconstruction studies on some human carcinomas.

Surgical materials from 20 patients with gastric carcinoma and ten with colonic carcinoma, and autopsy materials from ten patients with pancreatic carcinoma were submitted to the morphometric study of host arteries remaining in and around the tumors, to analyze whether and to what degree the smooth muscles of their media were lost. An explanation would be made of the inertia of tumor-supplying vessels based on their retarded response to vasoactive drugs. It was noted that as arteries advance from a distance toward the inside of a tumor, their media loses smooth muscles gradually, and become amuscular tubes incapable of blood flow regulation. This appears responsible for the abnormal hemodynamics of tumor tissues. Host arteries embedded in cancer were often deformed to aneurysmal or crumpled shapes; this, which also results from relaxation of atonic vessels, was considered to be the pathologic background for the unusual vascular images characteristic of cancer angiograms.

Adenocarcinoma↗

Radioimmunoassay for plasma glutathione S-transferase-pi and its clinical application in gastrointestinal cancer.

BACKGROUND: Plasma acidic glutathione S-transferase (GST-pi) concentrations in 135 patients with gastrointestinal cancer were measured by an improved radioimmunoassay (RIA). METHODS: Blood was collected into a silicified glass tube containing a specific anticoagulant. The plasma, which was separated rapidly by centrifugation with adequate force, underwent RIA procedures (double antibody and polyethylene glycol separation method). RESULTS: The improved RIA for plasma GST-pi was specific and sensitive. Plasma GST-pi in 75% of patients with esophageal cancer, 64.44% of those with gastric cancer, 74.41% of those with colon cancer, 85.19% of those with hepatocellular carcinoma, and 60.00% of those with pancreatic cancer was elevated higher than 13.99 micrograms/l (mean + 1.96 standard deviation of normal controls). Plasma GST-pi levels in patients with gastric cancer with Stages I-II, III and IV disease increased in proper order. Plasma GST-pi concentrations in 57% of patients with colon cancer decreased to the normal range 14 days after surgery. Plasma GST-pi levels of patients with recurrent colon cancer were higher than of those with primary colon cancer. CONCLUSION: The procedure for specimen collection must be critical. Plasma GST-pi may be useful in diagnosing gastrointestinal cancer and in monitoring its clinical course.

Colonic Neoplasms↗

Syndecan-1 expression is up-regulated in pancreatic but not in other gastrointestinal cancers.

Syndecan-1 belongs to the syndecan family of cell surface transmembrane heparan-sulfate proteoglycans, which participate in cell proliferation, cell migration and cell-matrix interactions. Decreased expression of syndecan-1 has been observed in some gastrointestinal malignancies, and it is thought that high levels of syndecan-1 correlate with the maintenance of epithelial morphology and inhibition of invasiveness. In our study, we characterized the expression of syndecan-1 in normal, chronic pancreatitis and primary and metastatic human pancreatic cancer tissues, in cultured pancreatic cancer cell lines and in esophageal, gastric, colon, and liver cancers. Pancreatic cancer cell lines expressed syndecan-1 mRNA and protein at variable levels. In addition, these cells also released syndecan-1 into the culture medium. Pancreatic cancer tissues markedly over-expressed syndecan-1 mRNA in comparison with both chronic pancreatitis (2.4-fold increase, p < 0.01) and normal pancreatic samples (10.6-fold increase, p < 0.01). There was no difference in syndecan-1 mRNA expression between early and advanced tumors. By in situ hybridization and immunohistochemistry, syndecan-1 expression was evident at relatively low levels in the ductal cells and less frequently in acinar cells of the normal pancreas. In chronic pancreatitis, syndecan-1 was present at low to moderate levels in areas with atrophic acinar cells and ductular complexes. In contrast, in pancreatic cancer tissues, syndecan-1 was present at moderate to high levels in the majority of the cancer cells within the tumor mass and also in metastatic lesions of pancreatic tumors. Syndecan-1 mRNA levels in other gastrointestinal malignancies (esophageal, gastric, colon and liver cancers) were not significantly different from the levels observed in the corresponding normal samples. Together, our findings suggest that syndecan-1 expression by pancreatic cancer cells may be of importance in the pathobiology of this disorder and that its role in pancreatic cancer seems to be different from that in other gastrointestinal malignancies.

Adenocarcinoma↗