Câncer gástrico precoce: análise de 12 casos / Early gastric cancer: analysis of 12 cases

Em publicaçäo anterior foram analisados 266 pacientes operados na Disciplina de Cirurgia de Aparelho Digestivo do HC da UFPA, dos quais nenhum caso de câncer gástrico precoce foi registrado. Os dois primeiros autores reuniram, de suas clínicas privadas, 158 casos de adenocarcinoma gástrico dos quais 12 eram precoce. Os sintomas mais frequentes foram: epigastralgia, emagrecimento e síndrome ulcerosa de longa evoluçäo. A duraçäo dos sintomas, exceto os da síndrome ulcerosa, foi, em média, de sete meses. O exame físico era normal em todos os pacientes. Para o diagnóstico, realizaram-se endoscopias digestivas altas em todos os pacientes e sete seriografias. Todos os pacientes foram submetidos ao tratamento cirúrgico: nove gastrectomias subtotais tipo B-II, duas gastrectomias totais em Y de Roux e uma gastrectomia subtotal tipo B-I. Só um paciente apresentou complicaçöes pós-operatórias (deiscência de anastomose esofagojejunal), indo a óbito. Nenhum paciente submeteu-se a tratamento rádio ou quimioterápico. O seguimento desses pacientes foi em média de 7 anos (1 mês a 12 anos). Säo tecidas consideraçöes sobre o diagnóstico do câncer gástrico precoce e comparada a presente com a literatura médica

Distribution of beta-human chorionic gonadotropin-positive cells in noncancerous gastric mucosa and in malignant gastric tumors.

The authors examined the localization and behavior of beta-human chorionic gonadotropin (HCG)-positive cells in human gastric noncancerous mucosa and in gastric malignant tumors, using immunohistochemistry and the anti-beta-HCG antibody. The beta-HCG-positive cells were located mainly in the antral mucosa and were generally restricted to the neck portion of the pyloric glands, although a few were present in fundic glands of the gastric body. The beta-HCG-immunoreactive cells were found in gastric carcinomas in 53% of the 92 cases examined. These cells were observed more often in advanced carcinomas that were histologically poorly differentiated than in early carcinomas or in well-differentiated tumors, but this prevalence had no statistical significance. The presence of the beta-HCG-positive cells in the gastric carcinomas suggested no appreciable prognostic significance, even quantitatively. In the syncytiotrophoblast-like tumor cells seen in four gastric tumor samples with histologic features of a choriocarcinoma, immunoreactivity to the beta-HCG was striking. There was, however, no recognizable dominance in the number of beta-HCG-reactive cells in the noncancerous mucosa around the tumor.

[An autopsy case of extramural malignant leiomyoblastoma of the stomach with ovarian cancer: an immunohistochemical study].

The subject was an 85-year-old woman, who had been diagnosed as having an ovarian cancer and carcinomatous peritonitis and had been treated conservatively. She subsequently died from respiratory and renal insufficiency, and the autopsy that followed revealed that her pelvic cavity had been filled by a tumorous mass that size of a child's head. Histologically, the tumor was a serous cystadenocarcinoma of the ovary. Moreover another tumor, also the approximate size of a child's head, was found sited extramurally, beneath the posterior wall mucosa of the stomach body. Histological inspection of this tumor revealed a proliferation of round oval, and spindle-shaped tumor cells. A vacuolation of the cytoplasms and karyomitosis to the extent of 10/50 HPF also were observed. Based on the findings of being positive for Vimentin and a negative EMA, this tumor was diagnosed as being a malignant leiomyoblastoma of the stomach smooth muscle. The leioblastoma is a relatively uncommon neoplasm, and recent advances in immunohistochemical staining have indicated that some of these tumors are not only of smooth muscle derivation but also of nerve origin. Therefore, this tumor, given its morphological characteristics, had been generalized in this case as a gastric stromal tumor, and with negative findings for Desmin and S-100 protein, as well as positive for Vimentin.

Immunoelectron microscopic localization of human type III collagen in human gastrointestinal carcinomas.

Ultrastructural immunolocalization of human type III collagen/procollagen was investigated in 28 cases of human gastrointestinal carcinoma by the pre-embedding method using a monoclonal antibody. In addition to immunoreactivity on collagen fibers, amorphous or finely fibrillar immunoreactive substances were observed in the extracellular matrix adjacent to the plasma membrane and in the cisternae of rough endoplasmic reticulum (rER). These substances were considered to represent type III procollagen and/or collagen before fiber formation. Cytoplasmic recesses containing immunoreactive fibers were also observed. These findings related to collagen production were detected in stromal fibroblasts in 16 of 28 cases and in carcinoma cells in six of 28 cases. The positivity rate of these findings was lower in diffuse-type gastric carcinoma. The present study thus clarified further details of collagen production and secretion, and revealed that carcinoma cells may also be involved in the production of stromal collagen in some cases as well as stromal fibroblasts.

[Studies on trace elements in cancerous stomach tissue of the patients with stomach cancer].

This study was performed to find out whether copper, zinc, manganese, selenium and iron concentrations in the cancerous and normal stomach tissues of the patients with stomach cancer vary within the malignant stages and Borrmann classification or not, and to investigate the interaction of copper, zinc, manganese, selenium and iron concentrations in blood of these patients. Copper concentration in cancerous tissues was not statistically significant as compared with normal tissues. Plasma and whole blood copper concentration of Stage IV showed a significant higher level than that of stage I. Zinc concentration in cancerous tissues was not statistically significant as compared with normal tissues. Selenium concentration in cancerous tissues showed a statistically significant high level as compared with that in normal tissues. Plasma selenium concentration of Stage III showed a significant lower level than that of stage I. Iron concentration in cancerous tissues showed a significantly lower level than that in normal tissues at stage IV. Whole blood iron concentration was low levels in proportion to the progress of stomach cancer. The correlation of selenium concentration between in cancerous tissues and in whole blood of these patients was significant with the correlation coefficient of 0.340. The correlation of iron concentration between in cancerous tissues and in whole blood of these patients was significant with the correlation coefficient of 0.423. The correlation between iron concentration in cancerous tissues and hemoglobin concentration in whole blood of these patients was significant with the correlation coefficient of 0.361.

Sialylpentaosylceramide detected with anti-GM2 monoclonal antibody. Structural characterization and complementary expression with GM2 in gastric cancer and normal gastric mucosa.

The ganglioside fraction of human gastric mucosa was analyzed with a newly established anti-GM2 monoclonal antibody KM531. Using this antibody, accumulation of GM2 was observed in all of four cases of gastric carcinoma. In all ganglioside fractions extracted from normal gastric mucosa obtained from eight cases of peptic ulcer GM2 itself was not detected, but three kinds of glycolipid showing slower mobility than GM2 on thin-layer plates were detected by immunostaining with KM531. These glycolipids were assigned as NGM-1, -2, and -3. They were completely lost in all carcinoma tissues and in non-cancerous gastric mucosa from two cases of gastric cancer, and they were also not detected in the ganglioside fraction of small or large intestine. Of these glycolipids, the major one, NGM-1, was isolated from the pooled ganglioside fraction of normal gastric mucosa obtained from cases of peptic ulcer. The structure was determined by proton nuclear magnetic resonance, negative ion fast atom bombardment-mass spectrometry, gas chromatography-mass spectrometry, and treatment with exoglycosidases and mild acid hydrolysis. The structure was GalNAc beta 1----4(NeuAc alpha 2----3) Gal beta 1----4GlcNAc beta 1----3 Gal beta 1----4Glc beta 1----1Cer, which has the same terminal sequence as GM2 but has internal neolacto series structure. This epitope was previously identified as Cad blood group antigen. The decrease of this glycolipid and the increase of GM2 was considered to be a cancer-associated change in gastric mucosa.

Sarcomatoid carcinoma of the stomach. A report of three cases with immunohistochemical and ultrastructural observations.

The authors report three cases of sarcomatoid carcinoma arising in the stomach. This uncommon tumor is characterized by a mixture of malignant epithelial and spindle cell elements. All three tumors were large (average diameter, 5 cm) and infiltrated deep into the stomach wall. Two of the tumors had a polypoid configuration; the third was ulcerated and endophytic. Intestinal metaplasia was present adjacent to the tumor in all cases, with dysplasia in two. Immunohistochemical studies showed positivity for cytokeratin, carcinoembryonic antigen, and epithelial membrane antigen in the epithelial component of all tumors, and Leu-M1 was positive in the epithelial component of one. The spindle cell components contained vimentin, and in tumor 2, the spindle cell component was also positive for desmin. Two tumors showed focal positivity for cytokeratin in the spindle cells immediately adjacent to the epithelial component. Ultrastructurally, the spindle cell component of two tumors was composed of undifferentiated cells without specific epithelial or mesenchymal features. The third tumor contained occasional cells with features of myofibroblasts.

[Gastrinoma and carcinoma-carcinoid tumor causing Zollinger-Ellison syndrome]. / Zollinger-Ellison-szindrómát okozó gastrinomák és carcinoma-carcinoid tumor.

7 gastrinomes and 1 gastrin-producer complex carcinoma-carcinoid tumor were examined by light and electron microscopical-method and by immunohistochemical method. In six cases, the tumor was in the pancreas or in the wall of duodenum; in two cases its localisation was of extra-gastroenteropancreatic (liver, lymph node). All patients developed Zollinger-Ellison syndrome, three patients bled and one had diarrhea. One patient had other tumors, besides gastrinome, which were characteristic of MEN-I syndrome. By immunohistochemical methods all tumors proved to be gastrin and neuron-specific-enolase positive. In four cases somatostatin positivity, in some cases glucagon, pancreatic polypeptide, S-100 protein, keratin and carcinoembryonal antigen positivity were detected. Relation could not be detected between other polypeptide hormones, produced besides gastrin, and biological behaviour of tumor and clinical symptoms.

[An analysis of the cellular DNA contents in lung-metastasized stomach cancers].

A study has been conducted of the cellular DNA contents in the primary and metastatic lesions of 30 cases of lung-metastasized stomach cancers, in which each DNA Index (DI) was calculated and analysed comparatively. As a consequence, the rate of the diploid type in the nodular lung metastases was found to be higher than the rate of the others. Further, the DI's of 22 out of 30 (73%) metastatic lymph nodes corresponded with those of the primary lesions. Four lung metastatic lesions out of five differed from their primary lesions, but all five lesions simulated their metastatic lymph nodes. Thus understanding of the properties of the metastatic lymph nodes, rather than their primary lesions, would seen to be helpful in planning the therapy to combat recurrent cancers.

Sex hormone receptors in gastric cancer.

Gastric adenocarcinoma that originates from mucosal tissue invades submucosa, muscle, and serosa in different stages. The level of progesterone receptors (PgR), estrogen receptors (ER), and androgen receptors (AdR) in the superficial part of gastric cancer tissues (CAs) from 16 patients was determined and compared with that of the corresponding normal gastric mucosal tissues (NLm). There were PgR in all CAs (100%) with values that ranged from 20.5 to 548.4 fmol/mg protein. Eight CAs (50%) had ER values that ranged from 6.8 to 325.1 fmol/mg protein. AdR was found in two CAs with values of 14.7 and 16.4 fmol/mg protein. In NLm, 15 (93.8%) had PgR values that ranged from 7.3 to 473.2 fmol/mg protein and ten (62.5%) had ER values that ranged from 0.9 to 87.9 fmol/mg protein. AdR were present in two NLm with values of 1.5 and 73.5 fmol/mg protein. There was no statistical difference in levels of PgR and ER between CAs and NLm. There were PgR in all gastric cancers and in 93.8% of NLm. The results suggest that gastric mucosa may be the target tissues for progesterone action. Furthermore, the lack of correlation between the levels of ER and PgR in gastric cancer tissue suggests that the PgR in gastric cancers are probably estrogen independent.

[The significance of determination of urinary trypsin inhibitor related antigen in patients with cancer of the digestive organs].

A highly sensitive enzyme immunoassay was developed for the determination of urinary trypsin inhibitor related antigen (UTIRA) in plasma, urine and cancer tissues, and we investigated its significance as a tumor marker in patients with cancer of the digestive organs. Variations in UTIRA in plasma and urine were not associated with the age of the volunteers, but in urine, high average was observed in male volunteers. UTIRA levels in the urine of the patients with esophageal, stomach and colorectal cancer increased as the stage progressed, except in the patients with liver cancer. And those levels in the urine significantly decreased after a curative operation, but did not decrease after a non-curative operation. UTIRA levels in stomach cancer tissues were significantly higher than those in adjacent healthy mucosa, but UTIRA levels were not high in tissues of esophageal, colorectal and primary liver cancers. Therefore, we speculate that the high levels of UTIRA in urine and plasma in patients with cancer of the digestive organs may not be caused by UTIRA released from cancer tissues. The determination of UTIRA may be significant in a broad sense as an index of the cancer stage or recurrence of cancer, particularly of the stomach.

Cytophotometrically determined DNA content, mitotic activity, and lymph node metastasis in clinical gastric cancer.

Analyses of cytophotometrically determined DNA content and mitotic rate were carried out in 37 cases of gastric carcinoma to identify biologic significance of DNA abnormalities. Lymph node metastasis was also evaluated by DNA content and mitotic rate. According to the linear regression analysis, there were statistically significant correlations of mitotic rate with DNA variants such as the peak value, the mean value, and the frequency of cells with values exceeding tetraploid or hexaploid chromosome complement. There were significantly higher values for these DNA parameters in patients with lymph node metastasis compared with those without metastasis. Similarly, higher mitotic rates were observed in tumors with metastatic disease. Thus abnormal DNA fractions appear to be indicative of tumors with a high mitotic activity. The quantitative detection of the DNA abnormalities will provide pertinent biologic information required to predict the occurrence of metastasis in patients with gastric cancer.

Liver glutathione contents in patients with gastric adenocarcinomas.

Many antineoplastic agents alter the reduced glutathione (GSH) status of liver and tumor tissue by inhibiting cellular GSH-linked enzymes. Thus, intracellular GSH plays an important role in a wide variety of antineoplastic interventions regarding therapeutic efficacy and toxicity. Mean GSH values were 0.791 +/- 0.072 mg/m wet weight (ww) and 0.719 +/- 0.047 mg/g ww in gastric cancer tissue and nontumorous glandular mucosa, respectively. Whereas, the average GSH level of normal gastric mucosa was 1.709 +/- 0.135 mg/g, the mean GSH level of normal liver biopsies was 2.378 +/- 0.260 mg/g. The GSH values of normal liver tissue were higher than the hepatocellular GSH concentrations of patients with gastric adenocarcinoma and of another group of tumor-bearing patients who had received chemotherapy preoperatively. These results suggest that the GSH levels of tumor and liver may influence the efficacy and/or toxicity of chemotherapeutic agents.

Significance of gastric endocrine tumor and age-related gut peptide alterations in Mastomys.

The Mastomys (Praomys natalensis) species are a unique natural model in which the bioactivity of gastric carcinoids may be studied. Several investigators have previously demonstrated that these tumors contain large amounts of histamine. In this study we investigated the presence of peptides associated with the neoplasm. The levels and location of gastrin, gastric inhibitory peptide (GIP), neurotensin, peptide YY (PYY), pancreatic polypeptide (PP), glucagon, bombesin, vasoactive intestinal peptide (VIP) and somatostatin (SRIF) were investigated by radioimmunoassay and immunocytochemistry. In addition the distribution of these peptides were evaluated in the gastrointestinal tract of young and old animals to investigate possible age-related changes. PYY and enteroglucagon (EG) were significantly (P less than 0.001) elevated in both tumor tissue (676 +/- 152, 551 +/- 164 pmol/g) and plasma (620 +/- 160, 500 +/- 147 pmol/l) of tumor-bearing animals. Immunocytochemistry revealed PYY- and EG-like immunoreactivity in 20-30% of tumor cells. A significant decrease (P less than 0.05) in bombesin was noted in older animals, but no changes in gastric tissue content of PYY or EG could be detected between young and old animals. Gastrin was not detected in tumors and there were no significant changes in tissue or plasma levels with age. Small bowel concentrations of VIP and PYY were higher in the older mastomys (P less than 0.05). In contrast, colonic levels of bombesin, VIP, somatostatin and PYY were significantly lower (P less than 0.05) in older mastomys compared with young. The age-related changes in several peptides may reflect an adaptive response to acid hypersecretion. The multi-hormonal character of these neoplasms suggests that these tumors develop from a pluripotential stem cell.

Advanced gastric carcinoma simulating early gastric carcinoma.

Eighty-six cases of advanced gastric carcinoma simulating early gastric carcinoma were studied clinicopathologically. Cytophotometric DNA analysis was also performed in 33 cases. Most of these particular carcinomas were of the depressed type on gross inspection. Histologically, the tumors were of diffuse type in 60%. The rate of the carcinomas restricted to within the muscularis propria was 48% and high in comparison with those in conventional advanced gastric carcinomas. There were four main growth patterns: small invasion type (Type A, 43 cases), ulcer-connected type (Type B, 19 cases), vessel permeation type (Type C, six cases), and diffusely infiltrative type (Type D, 13 cases). There was a relationship between growth patterns, lymph node metastasis, and prognosis: Types A and B had a small percentage of lymph node metastasis and a good prognosis, whereas Types C and D a high percentage and a poor prognosis. DNA analysis revealed that two thirds of the examined cases showed a low ploidy pattern. The DNA ploidy patterns were concerned with the tumor growth pattern: high-ploidy cases were rarely seen in Types A and B yet were frequent in Types C and D. The 5-year survival rate was 73%, but results were poor in cases of tumors with blood vessel permeation, in those with lymph node metastasis, in those with the Type D or C growth patterns, and in those with high DNA ploidy pattern. Since these carcinomas can be understaged endoscopically and by gross examination, a precise study of the surgically excised tissues will aid in making an accurate prognosis.

Immunohistochemical demonstration of epidermal growth factor in human gastric cancer xenografts of nude mice.

Thirty-two surgical specimens and three cell lines of human gastric cancers were used for subcutaneous transplantation into nude mice, resulting in the establishment of eight (25%) xenografts from the surgical specimens and two (67%) from the cell lines. The localization of epidermal growth factor (EGF) in the surgical specimens and cell lines of the gastric cancers and their xenografts in nude mice was then investigated immunohistochemically. Epidermal growth factor was stained in the cytoplasm of the cancer cells, being detected in 16 (50%) of the 32 surgical specimens and in all of the cell lines. Seven (44%) of the sixteen EGF-positive surgical specimens and one (6%) of the 16 EGF-negative ones were tumorigenic in nude mice. All of the xenografts in nude mice were positive for EGF. The tumorigenicity of human gastric cancer xenografts in nude mice may, therefore, be correlated with the presence of EGF in cancer cells.

Procoagulant activity of human stomach and colon cancers.

Procoagulant activity in extracts from human stomach and colon cancers was examined, using chromogenic substrate S-2222. The activity of direct activator of factor X varied between 6 and 96% of total procoagulant activity of the tested extracts. The direct activator of factor X from stomach cancer was sensitive to heating and was inhibited by phenylmethylsulphonylfluoride and also by iodoacetic acid and HgCl2. Such results lead to the assumption that investigated activator is of enzymatic nature.