Aumento do espaço retro-retal; revisäo de patologias encontradas em 25 casos / Enlargement of the retrorectal space: a review of pathologies observed in 25 cases

Foi feito estudo retrospectivo de 25 pacientes com patologia retal e/ou pélvica que apresentaram aumento do espaço retro-retal (ERR), na incidência de perfil ao enema opaco pelo duplo contraste. As patologias foram classificadas em intestinais e extra-intestinais e subdivididas em inflamatórias e neoplásicas. As que mais aumentaram o ERR foram as intestinais, com 18 casos (72%), sendo 61% deles causados por processo inflamatório e os restantes 39% devido a processos neoplásicos. Nas patologias extra-intestinais, o aumento do ERR ocorreu em sete casos (28%), e 85% deles tiveram neoplasia como fator causal. Em todos os pacientes observaram-se alteraçöes da parede retal e/ou do sacro

[The characteristics of bile acid excretion in patients with cancer of the large intestine]. / Osobennosti ékskretsii zhelchnykh kislot u bol'nykh rakom tolstoi kishki.

Marked difference in bile acids excretion (on the same diet) was observed between patients with large bowel cancer and healthy controls. The peak level of the bile acids in feces was registered in female patients 46-59 years of age suffering right-sided cancer. It is suggested that bile acid excretion in man is determined both by nutritional factors and hormonal-metabolic peculiarities of the body. High excretion of the bile acids is associated with risk for colon cancer.

[Increase in the level of polypeptide growth factors and their receptors in induced carcinogenesis and regeneration of the intestinal mucosa in rats]. / Povyshenie urovnia nekotorykh polipeptidnyk faktorov rosta i ikh retseptorov pri indutsirovannom kantserogeneze i regeneratsii slizistoi obolochki kishechnika krys.

It has been established for the first time that in extracts of the regenerating and preneoplastic (4 months after the beginning of carcinogen introduction) intestine as well as in the peritumor tissue the content of EPR-similar polypeptides and insulin raises, whereas in tumours it remains not high. Proteins with molecular weight greater than 120 kD able to compete with 125I-EPR for the binding with the receptors of EPR and being, evidently, the precursors of EPP are found in case of carcinogenesis. Besides, the content of insulin receptors rises, this process being most typical of the large intestine.

[Immunohistochemical and clinicopathological studies of chromogranin immunoreactive cells in large bowel carcinoma].

We examined the clinicopathological relevance of chromogranin immunoreactive cells in a well documented series of 212 large bowel cancer patients. Chromogranin immunoreactive cells were detected in 33.5% of the carcinomas, occurring either as rare cases (19.3%) or as diffuse cases (14.2%). The tumors with chromogranin immunoreactivity were associated with a more aggressive clinical course than tumors without immunoreactivity (Generalized-Wilcoxon; p less than 0.08). Moreover, the survival of patients with diffusely immunoreactive tumors was significantly shorter than that of patients without such cells (Generalized-Wilcoxon; p less than 0.009). Therefore, the study of chromogranin immunoreactivity in large bowel carcinomas may enable the identification of a subpopulation of colorectal carcinomas associated with a relatively poor prognosis.

Primary malignant lymphoma of the large intestine complicating chronic inflammatory bowel disease.

Ten cases of malignant lymphoma of the colon and rectum complicating chronic inflammatory bowel disease are presented. Seven patients had chronic ulcerative colitis with a history varying from 6 to 20 years. There was extensive colitis in six of these patients and left-sided colitis in one. All seven lymphomas showed the pathological and immunohistological features of primary B-cell tumours of the gastrointestinal tract with a predominance of high-grade tumours. Three patients had Crohn's disease of the large intestine complicated by malignant lymphoma of the sigmoid colon or rectum. The history of Crohn's disease varied from 30 months to 20 years and in each case there was fissuring and fistulae. There was extensive anal involvement in two cases. Histologically the three lymphomas were heterogeneous: one was of 'granulomatous' T-cell type and the other two were markedly polymorphic and of equivocal phenotype. They were also characterized by numerous multinucleate tumour giant cells. Primary colorectal malignant lymphoma should be regarded as a rare, but significant, complication of ulcerative colitis. Immunosuppression may be an additional factor in the genesis of intestinal lymphoma in Crohn's disease. The prognosis appears to be dependent on factors already known to be of prognostic significance in primary gut lymphomas: a predominance of high-grade tumours suggests that the outlook is generally worse than that for idiopathic primary large intestinal lymphoma.

[A case of pulmonary carcinoma presenting flow cytometrical heterogeneity of the nuclear DNA content between its primary focus and the metastatic foci].

We have experienced case involving a 63-year-old patient with a pulmonary carcinoma, who was given an enterectomy following a lobectomy, due to minimal intestinal metastasis. In this case, using flow cytometry, the cancer cell nuclear DNA content was analyzed for the primary tumor focus, the mediastinal lymph node metastatic focus, and the small intestinal metastatic focus. For the primary focus, a cancer cellular population of polyploidy with 2 ploidies of DNA content was observed, while for both the metastatic foci, only a single cancer cellular population was observed, indicating the heterogeneity of the nuclear DNA content between the primary focus and metastatic foci. These 2 metastatic foci had DNA contents completely corresponding to that for a ploidy with a high DNA content in the primary focus, suggesting a metastasis of only the above population from the primary focus. The present case apparently formed metastatic foci in other organs than the lungs but only by cancer cells more susceptible to metastasis among the cancer cells found in the primary focus.

The relationship of flow cytometric DNA analysis and clinicopathology in small-intestinal carcinoids.

Paraffin-embedded archival tissue samples were used for nuclear deoxyribonucleic acid (DNA) content study by flow cytometry on 56 surgically resected, primary, small-intestinal carcinoid tumors. Sample preparation was carried out using the methods of Hedley and Vindelov. To reduce nuclear aggregation, a procedure of sonication was also performed. Nineteen (34%) cases were DNA diploid, 34 (61%) cases showed significantly increased 4C peak (DNA tetraploid), and only three (5%) cases were DNA aneuploid. Cell cycle phase analysis revealed that carcinoid tumors had significantly higher G2% than those of nontumor control tumors. However, there was no significant correlation between clinical parameters and both DNA ploidy pattern and cell cycle phase analysis. Although the difference in survival between patients with DNA nondiploid tumors and DNA diploid tumors was not significant, all of the patients with DNA aneuploid tumor had poor prognosis followed by death from carcinoid tumor.

[The production of epidermal growth factor and polypeptides similar to it in the intestinal mucosa of rats in 1,2-dimethylhydrazine-induced carcinogenesis and compensatory regeneration]. / Produktsiia épidermal'nogo faktora rosta i podobnykh emu polipeptidov slizistoi obolochke kishechnika krys pri indutsirovannom 1,2-dimetilgidrazinom kantserogeneze i kompensatornoi regeneratsii.

The production of EGF and EGF-like polypeptides in the normal intestinal mucosa and during 1,2-dimethylhydrazine (DMH)-induced carcinogenesis and postresection regeneration was studied in albino rats using chromatographic separation of acid-ethanol extracts. Fractions after gel filtration on Biogel P-60 with subsequent reverse-phase high performance liquid chromatography in acetonitrile gradient were tested in radioreceptor assay for competition with EGF. It has been established that intestinal tumours induced by DMH and regenerating intestinal mucosa have amplified production of EGF--alpha-TGF and related proteins of high molecular weight (approx. 30; 45-55; 120 kD) with the EGF-competitive activity. It is supposed that the high molecular weight EGF-competitive material represents nonprocessed forms of EGF and/or alpha-TGF which are accumulated in rapidly proliferating low-differentiated cells due to the intensified expression of their genes.

[Long-term observation on transplanted tumors of human intestinal mucoid adenocarcinoma in nude mice].

Long-term observation on transplanted tumor of human intestinal mucoid adenocarcinoma in nude mice is reported. The transplanted tumor which has been passed 57 passages in 151 nude mice with transplant survival rate of 99.34% in more than 5 years is the tumor with the utmost number of passages domestically undertaken as yet. During the long-term observation, the transplanted tumor was not only identical to the primary tumor in histopathology, ultrastructure and chromosome pattern, but also constant in biological characteristics, such as secretion of mucin and production of carcinoembryonic antigen. These tumor cells were able to combine with CEA mcAb specifically by obviously showing the scanning image of transplanted tumor of human intestinal mucoid adenocarcinoma in nude mice with 131I-CEAmcAb. The roles of the transplanted tumor model in cancer research are discussed.

Glucagon and glucagon-like immunoreactive cells in mid- and hindgut carcinoids.

The occurrence of glucagon/glucagon-like immunoreactivity in 31 small intestinal, 34 rectal and 18 appendiceal carcinoids were investigated immunocytochemically using, sequence specific antisera. Glucagon/GLI immunoreactive cells were found in five small-intestinal and five rectal carcinoids, but none were observed in any of the appendiceal carcinoids examined. Glucagon/GLI immunoreactive cells constituted a minor cell population, except in one rectal carcinoid, where most of the tumour cells were of this type. Glucagon/GLI immunoreactive cells were detected with only some sequence-specific antisera, and not with antisera directed against the rest of the glucagon/glicentin molecule. This might indicate that these cells contain a molecule which shares some antigenic binding sites with glucagon/glicentin rather than genuine glucagon/glicentin. It is concluded that this finding contributes to explain why hindgut carcinoids rarely give rise to symptoms related to neuro-endocrine product(s).

[Ornithine decarboxylase activity and polyamine content in human adenocarcinomas of the stomach and large intestine]. / Aktivnost' ornitindekarboksilazy i soderzhanie poliaminov v adenokartsinomakh zheludka i tolstogo kishechnika cheloveka.

Ornithine decarboxylase (ODC) activity and polyamine content were studied in the intact mucosa and tumours of human stomach and large intestine adenocarcinomas. ODC activity has been found to be much higher in the neoplastic tissue than in the corresponding intact mucosa. Concentrations of polyamines in neoplasms were also higher than in mucosa. Interrelation was found between ODC activity polyamine content and degree of differentiation of the tumour cells in rectal adenocarcinomas.

Morphometry and cytophotometric assessment of DNA in smooth-muscle tumors (leiomyomas and leiomyosarcomas) of the gastrointestinal tract.

The difficulties in predicting the biologic behavior of gastrointestinal (GI) smooth-muscle tumors (leiomyomas and leiomyosarcomas) based on the usual criteria of malignancy are discussed. In order to evaluate the prognostic importance of the nuclear DNA content and nuclear dimensions, measurements were performed on Feulgen-stained sections of GI smooth-muscle tumors from 66 patients. The best discrimination between benign and malignant tumors was obtained by using DNA index and tumor size as descriptors in a linear discriminate analysis. This method separated 79% of the benign and 97% of the malignant smooth-muscle tumors. However, as with conventional criteria for malignancy, there remained a group of tumors close to the discriminating line with an indeterminate malignant potential. In an attempt to reduce the number of such indeterminate tumors, future studies will include the use of several descriptors in a multivariate analysis system and the application of flow cytometric studies to all tumors.

Immunohistochemical demonstration of desmin in canine smooth muscle tumors.

Sections of formalin-fixed, paraffin-embedded canine leiomyomas, leiomyosarcomas, or fibrosarcomas were examined by immunohistochemical methods for the presence of desmin. Twenty-two leiomyomas and leiomyosarcomas were stained using the avidin-biotin complex technique, and 14 samples demonstrated positive staining for desmin. The eight negative results obtained may reflect differences in fixation or the affinity of the primary antibody for the tissues examined. Desmin was specific for myogenic tissues. Five canine fibrosarcomas examined immunohistochemically were all negative for desmin staining. The results indicate that desmin is a useful marker for immunohistochemical identification of canine leiomyomas and leiomyosarcomas.

Histological demonstration of immunoreactive metallothionein in rat and human tissues.

Antibody to rat liver metallothionein prepared by the method of Brady and Kafka (1979) was used to localise immunoreactive metallothionein using a sensitive DNP hapten sandwich technique applied to formalin fixed wax embedded tissues. Rat tissues examined were liver, kidney and small intestine, taken from normal animals, from animals fasted after receiving either an oral dose of water, or 1 ml zinc acetate solution either orally or by intraperitoneal injection, (3-4 mg Zn++/Kg body weight). Human tissues examined were 6 histologically normal liver biopsies and small intestine including histologically normal jejunal biopsies and samples of ileum obtained at operation. Pathological tissue including liver from cases of Indian childhood cirrhosis with copper retention and ileum from cases of inflammatory bowel disease were also examined. Immunoreactive metallothionein (IMT) was found in both rat and human liver localised in the hepatocyte cytoplasm, nucleus, sinusoids and canaliculi. In some livers IMT was found in the portal and hepatic veins. In the small intestine the IMT was localised consistently in the enterocyte cytoplasm and nucleus, and in the basement membrane region. The rat kidney IMT was localised in the cytoplasm of the distal convoluted tubules the collecting tubules and the ducts of Bellini. The distribution of IMT in rat tissues showed changes associated with fasting, stress and zinc administration. In man, inflammatory bowel disease appeared to decrease the intestinal IMT and no significant difference was seen when patients had received steroid therapy. The greatest amounts of IMT were seen in the control group of patients. The distribution of IMT in human liver in Indian childhood cirrhosis did not correspond with that of copper associated protein.

[Cytometry of premalignant states]. / Zytometrie prämaligner Zustände.

The development of cancer in humans is considered as a multistep process ultimately leading to clinically detectable disease and further progression of the tumour. By use of cytometric techniques it has been possible to perform quantitative measurements and detect qualitative alterations in malignant tumours. This mainly applies to DNA aberrations and deviations in nuclear size and morphology. Such alterations may also be present for a long period prior to malignant, invasive growth, i.e. at a preneoplastic stage. A survey of available data on such preneoplastic changes is given. Since the type of aberrations is both dependent on the tissue of origin and the tumour type, this must always be taken into consideration. A particularly rapid expansion has taken place in the field of flow cytometry, where high resolution measurements of cellular DNA content as well as cell cycle distribution and other parameters can be performed shortly after sampling of the tissue. It is expected that cytometric methods will be used in future diagnostics of early cancerous growth in several organ systems, including the skin, the gastrointestinal tract, the urinary bladder, the breast and female genital organs.

Interferon-induced nuclear DNA alterations in malignant carcinoid tumors in vivo.

Tumor cell specimens were obtained by ultrasonically guided percutaneous needle liver biopsy from 23 patients with metastatic small intestinal carcinoid tumors. The patients were admitted to the hospital for antitumor therapy (streptozocin, 5-fluorouracil, and leukocyte interferon). The tumor cell samples were used for DNA cytofluorometry. All tumors (12 cases) from untreated patients exhibited diploid DNA stem lines with low proliferative activity. The mean number of tetraploid cells was 8%. Altered nuclear DNA records were obtained in tumors of 8 patients, all of which were treated with leukocyte interferon at 3-6 X 10(6) IU/day for 4-32 months. The DNA records in these tumors varied, but they were mainly in the range between diploid and tetraploid values. In some cases several nuclear DNA peaks were observed within the limits for the cell cycle. It is assumed that the interferon treatment was responsible for the development of altered DNA cell lines because: 1) all untreated tumors yielded regular diploid DNA histograms, 2) interferon was the only drug administered to all patients with tumors displaying altered DNA records, and 3) modal diploid DNA values were observed prior to the interferon treatment in some patients. It is suggested that interferon in vivo blocked carcinoid tumor cell populations in different phases of the cell cycle. This result might explain the nuclear DNA profiles registered in the treated patients as well as the therapeutic effect obtained by interferon.

[Characteristics of the epidermal growth factor receptors in the epithelium of the gastrointestinal tract of rats and in intestinal tumors induced by 1,2-dimethylhydrazine]. / Kharakteristika retseptorov épidermal'nogo faktora rosta v épitelii zheludochno-kishechnogo trakta krys i v opukholiakh kishechnika, indutsirovannykh 1,2-dimetilgidrazinom.

Using the Scatchard analysis of 125J-EGF binding it was shown that plasma membranes of gastric and small intestinal epithelial cells contain approximately 20 times less EGF-receptors (EGF-R) than liver cells. Investigation of the phosphorylation activity of EGF-R-kinase was performed in vitro on plasma membranes from intestine, intestinal tumours and liver cells. The main protein phosphorylated at tyrosine in the tumours was p34 but the intensity of EGF-R autophosphorylation and its total protein-tyrosine kinase activity were reduced (as compared with small-intestinal and liver cell membranes). In the tumours of the colon induced by DMH an increased binding of 125J-EGF has been observed as compared with normal colonic enterocytes and increased number of EGF-R was clearly demonstrated. Phosphorylation of p34 in the intestinal membranes proceeds much more intensively than that of EGF-R.

S-100 protein in carcinoid tumours of appendix.

A series of 12 carcinoid tumours of the appendix were examined with regard to S-100 protein immunoreactivity. All tumours were both argentaffin and argyrophil, and displayed immunoreactivity after application of a monoclonal antibody against serotonin. The S-100 protein immunoreactivity appeared in 11 of the 12 tumours, preferably in cells presumably of Schwann cell origin with long slender processes localized at the periphery of the carcinoid tumour buds. Immunoreactive cells with cytoplasmic processes were also seen extending between individual tumour cell in the tumour aggregates. In a few tumours S-100 immunoreactivity occurred in the cytoplasm of tumour cells with or without cytoplasmic extensions. The presence of S-100 protein immunoreactive cells, apparently as an integral component, and its shape and distribution indicate that the peripheral nervous system (PNS) is histogenetically involved in the development of carcinoid tumours of the appendix.