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Enhancing effect of cholecystectomy on colon carcinogenesis induced by methylazoxymethanol acetate in hamsters.

The effect of cholecystectomy on colon carcinogenesis induced by methylazoxymethanol (MAM) acetate was examined in four groups of Syrian golden hamsters. For the sexes combined, the incidences of total large intestinal neoplasms and adenomas in Group 1, which received cholecystectomy and a single intravenous injection of MAM acetate (20 mg/kg body weight), were significantly higher than those of hamsters in Group 2, which were given MAM acetate alone. The combined multiplicities of total large intestinal neoplasms from male and female hamsters, and the multiplicities of those in females of Group 1 were also significantly higher than those in animals in Group 2, respectively. No intestinal tumors were observed in hamsters in Group 3 (cholecystectomy alone) or Group 4 (untreated control). These results indicate an enhancing effect of cholecystectomy on MAM acetate-induced large intestinal carcinogenesis in hamsters.

Adenocarcinoma↗

Combination of a poxvirus-based vaccine with a cyclooxygenase-2 inhibitor (celecoxib) elicits antitumor immunity and long-term survival in CEA.Tg/MIN mice.

The present study was designed to determine whether: (a) chronic administration of dietary celecoxib (Celebrex), a potent nonsteroidal anti-inflammatory drug, which targets the cyclooxygenase-2 (COX-2) enzyme, negatively impacts host immunity; and (b) celecoxib can be coupled with a poxvirus-based vaccine to impact tumor burden in a murine tumor model of spontaneous adenomatous polyposis coli. Naive mice fed the celecoxib-supplemented diets developed eosinophilia with lowered plasma prostaglandin E(2) levels and reduced COX-2 mRNA expression levels in their splenic T cells. Responses of splenic T, B, and natural killer cells to broad-based and antigen-specific stimuli were, for the most part, unchanged in those mice as well as COX-2 knockout mice; exceptions included: (a) reduced IFN-gamma production by concanavalin A- or antigen-stimulated T cells; and (b) heightened lipopolysaccharide response of naive B cells from mice fed a diet supplemented with 1000 ppm of celecoxib. When transgenic mice that express the human carcinoembryonic antigen (CEA) gene (CEA transgenic) were bred with mice bearing a mutation in the Apc(Delta850) gene (multiple intestinal neoplasia mice), the progeny (CEA transgenic/multiple intestinal neoplasia) spontaneously develop multiple intestinal neoplasms that overexpress CEA and COX-2. Beginning at 30 days of age, the administration of a diversified prime/boost recombinant CEA-poxvirus-based vaccine regimen or celecoxib (1000 ppm)-supplemented diet reduced the number of intestinal neoplasms by 54% and 65%, respectively. Combining the CEA-based vaccine with the celecoxib-supplemented diet reduced tumor burden by 95% and significantly improved overall long-term survival. Both tumor reduction and improved overall survival were achieved without any evidence of autoimmunity directed at CEA-expressing or other normal tissues. Celecoxib is prescribed for the treatment of familial adenomatous polyposis in humans, and the CEA-based vaccines have been well tolerated and capable of eliciting anti-CEA host immune responses in early clinical studies. The results suggest that the administration of a recombinant poxvirus-based vaccine is compatible with celecoxib, and this combined chemoimmuno-based approach might lead to an additive therapeutic antitumor benefit not only in patients diagnosed with familial adenomatous polyposis but, perhaps, in other preventive settings in which COX-2 overexpression is associated with progression from premalignancy to neoplasia.

Animals↗

[Malignant villous neoplasms of the large intestine].

An investigation of 532 villous tumors of the colon resected in 490 patients has shown that malignant tumors take place more often in patients with an increased volume of the villous component and the size of the tumor, in patients with more distal localization of adenoma in the colon and in adult people. In 38% of the patients the villous formation was removed through the endoscope, 12% of the patients were subjected to transanal dissection of the rectum tumor and 47.8%--to different operations with resection of the intestine.

Adenoma, Villous↗

A case of extragenital choriocarcinoma in the jejunum.

A case of extragenital choriocarcinoma which produces human chorionic gonadotropin (HCG) in the small intestine of a 48-yr-old Japanese women is reported. Only seven such cases have been reported. The patient complained of postprandial upper abdominal pain and vomiting of 5 months' duration. Nine years before, right upper lobectomy was performed because of lung undifferentiated carcinoma. Double-contrast examination of the small intestine showed irregular ulceration in the lower jejunum. Celiac angiography demonstrated a hypervascular tumor stain in the branch of the jejunal artery. The serum HCG level was elevated. Gynecological examination revealed nothing abnormal. A small intestinal neoplasm was diagnosed, and a partial resection of the jejunum was performed. Endoscopy on the operating table showed a large, irregularly shaped sessile ulcer. Histologically the tumor was diagnosed as choriocarcinoma, composed of syncytiotrophoblastic cells and cytotrophoblastic cells. Immunohistochemical staining for HCG was positive. No metastasis was present. Although extragenital choriocarcinoma in the small intestine is rare, it should be included in the differential diagnosis of small intestinal neoplasm.

Choriocarcinoma↗

Evaluation of the risk for metachronous colorectal neoplasms following intestinal polypectomy: a clinical, endoscopic and pathological study.

BACKGROUND/AIMS: Surveillance programs are recommended for patients with previous intestinal polypectomy because of the high rate of adenomatous recurrences and risk of subsequent colorectal cancer. The parameters to identify patients at higher risk and the length and schedules of follow-up have not yet been established. We considered some clinical, endoscopic and pathological parameters in order to assess the probability of developing new colorectal neoplasms and eventually to schedule proper surveillance programs. METHODOLOGY: Patients with removed adenomas were enrolled into a clinico-endoscopic follow-up, comprehensive of two colonoscopies the first at 1 year and the second at 3 years. We evaluated the risk of new neoplasms dividing the patients into four groups according to the number and size of the adenomas removed and the parameters considered. RESULTS: Of 164 patients enrolled 156 completed the study. We had an overall 21.3% of adenomatous recurrences at 1 year and 12.8% at 3 years. Most of the adenomas removed were tubular and small in size (< 1 cm). The percentage of patients who had adenomas with advanced pathological features was 1.82% at 1 year and 0.64% at 3 years. The increase in number and size of the adenomas removed on the initial colonoscopic examination was the only one parameter statistically significant, X(2)1 (trend) 5.11; p<0.05 at the first follow-up and X(2)1 (trend) 4.87; p<0.05 at the second follow-up. CONCLUSIONS: Patients with previous single adenoma showed few recurrences of extremely benign histological features. Since they do not require short-term endoscopic examination, it would be reasonable to defer the next colonoscopy for at least another 5 years. During follow-up, patients with multiple polyps had adenomas with advanced pathological features so it was useful to follow-up at 1 year. The tendency for advanced pathological features of removed polyps was not seen at 3 years, suggesting the importance of long-term follow-up, but with longer intervals.

Adenoma↗

Morphological evaluation of canine platelets on Giemsa- and PAS-stained blood smears.

The morphology of canine platelets (changes in size, shape, staining characteristics, degree of activation and clump formation, distribution of granules, appearance of vacuoles on Giemsa-stained smears) was investigated in 20 healthy control and 181 diseased dogs. In the group of the sick dogs 84 animals suffered from disorders affecting directly the haematological parameters or the haematopoietic organs such as bleeding, thymic haemorrhage, haemolytic disorders, lymphoma, immune-mediated thrombocytopenia, and other 97 dogs were affected by other diseases (hepatopathy, nephropathy, hepatic, splenic or intestinal neoplasm, skin diseases, diabetes mellitus, Cushing's syndrome, sepsis). The alterations found in platelet morphology were not specific for any disorder. The most common platelet abnormalities were polychromasia and the presence of giant platelets. These changes occurred in a high number in disorders accompanied by bleeding or haemolysis. Anisocytosis was the most frequent finding in hepatic, splenic or intestinal neoplasms and in certain endocrinopathies. Microcytosis was observed in immune-mediated thrombocytopenia, hepatic neoplasms and endocrine disorders. Extreme platelet activation was common in haemolysis, hepatopathies, neoplastic diseases and sepsis. Vacuolisation was present in thymic haemorrhage, pancreatitis, diabetes mellitus and Cushing's syndrome. A new morphologic phenomenon, i.e. a ring-like formation of granules, was described in the cytoplasm of the platelets both in healthy and diseased animals. In addition, two forms of pathologic granulation were also described for the first time in Giemsa-stained blood smears: the pseudonuclear and the spot-like formation of granules, which were observed especially in disorders affecting the blood cells. The granulation and morphological characteristics of platelets on smears stained by periodic acid-Schiff reaction (PAS) were also studied. Three localisations of granulation were observed, such as peripheral, eccentric and diffuse. The ratio of PAS-positive and -negative platelets was evaluated in several diseases. Our findings support the diagnostic value of platelet evaluation by light microscopy and help clinicians/clinical pathologists to understand why morphologic changes of thrombocytes might be expected in several diseases.

Animals↗

Tumors of the small intestine.

Tumors of the small intestine offer a unique challenge. As a result of their infrequent occurrence, they invariably present difficult problems in diagnosis and management. Although the prognosis for benign lesions is excellent, malignant small bowel tumors are perhaps the most devastating GI malignancies; at the time of diagnosis, only approximately 50% of these lesions are completely resectable for cure. Symptoms are often absent until the tumor has progressed to produce a complication. Even then, the presentation is often vague and nonspecific, intermittent pain, obstruction, and chronic anemia. The cornerstone of diagnosis is the contrast radiograph. However, in practice only about 50% of these lesions are diagnosed radiographically before surgery. This situation is further complicated by the variety of small bowel tumors, each with different symptoms and manifestations. Surgical excision is the treatment of choice for almost every small intestinal neoplasm. For most benign lesions simple excision is adequate. In contrast, for malignancies, segmental resection including as much adjacent mesentery as is reasonable, is required. In the duodenum, these tumors may necessitate pancreaticoduodenectomy; in the ileum, right colectomy may be required. In the case of advanced disease, palliative resection to relieve bleeding or obstruction may be indicated. The challenge of the future will be to reduce the morbidity and mortality of small bowel neoplasms not only by earlier recognition, diagnosis, and therapy but also through the development of alternative or adjunctive therapy for patients in whom surgical cure is not possible. This will require not only a high index of suspicion when confronted with patients with vague abdominal complaints but also an aggressive approach to diagnosis in the face of normal initial studies. In addition, multi-institutional trails of chemotherapy and radiation therapy of these tumors are needed.

Adenoma↗