Cyclooxygenase 2- and prostaglandin E(2) receptor EP(2)-dependent angiogenesis in Apc(Delta716) mouse intestinal polyps.

To investigate angiogenesis during intestinal polyp development, we determined the microvessel density (MVD) in polyps of Apc knockout (Apc(Delta716)) mice, a model for human familial adenomatous polyposis. We scored MVD also in several compound mutants carrying Apc(Delta716), namely, mice with an additional mutation in Smad4, in which the polyps progress into invasive adenocarcinomas; mice with a cyclooxygenase (COX)-2 gene (Ptgs2) mutation, in which adenoma growth is suppressed; and mice with prostaglandin E(2) EP receptor gene mutations. In both simple Apc(Delta716) and compound Apc(Delta716) Smad4 mutants, MVD increased in a polyp size-dependent manner only in the polyps expanded beyond a threshold of about 1 mm in diameter. These results indicate that tumor angiogenesis is stimulated only after tumors grow to a certain size, and this angiogenic switch is common to both benign adenomas and malignant adenocarcinomas. In Apc(Delta716) polyposis attenuated by the COX-2 gene mutation, in contrast, MVD did not increase even in polyps larger than 1 mm. The same phenomenon was observed in the compound mutant mice with Apc(Delta716) and the EP(2) receptor gene mutations, but not in other EP compound mutants. We also immunohistochemically studied COX-2 and angiogenic factors, vascular endothelial growth factor and basic fibroblast growth factor. Interestingly, expression of these proteins was also increased in polyps larger than 1 mm. These results suggest that, in both benign and malignant mouse intestinal tumors, stromal expression of COX-2 results in elevated prostaglandin E(2) levels that stimulate cell surface receptor EP(2), followed by induction of vascular endothelial growth factor that causes tumor angiogenesis.

Sonographic and color Doppler findings of gastrointestinal myogenic tumors with a marked extraluminal growth.

We present five cases with gastro (four cases) and intestinal (one case) myogenic tumors with a marked extraluminal growth. In all cases, incidental discovery of an asymptomatic mass prompted further examination. One of three cases with a pedunculated growth mimicked a gallbladder cancer. The mass of a jejunal leiomyoma case changed markedly in location under probe compression. Color Doppler sonography confirmed not only the hypervascular nature of the mass but also feeding and draining vessels.

Fibroid polyps of intestinal tract are inflammatory-reactive proliferations of CD34-positive perivascular cells.

AIMS: Our aim was to determine the histogenesis of fibroid polyps (FP). These polyps are rare inflammatory-reactive, tumour-like lesions of unknown aetiology, arising in the submucosa or mucosa of the gastrointestinal tract. They are mainly due to a proliferation of characteristic spindle cells. METHODS AND RESULTS: Nine FP were investigated by light microscopy and immunohistochemistry with endothelial markers (Factor VIII, CD34, CD31), a neuronal marker (S100), muscular markers (desmin, alpha-smooth muscle actin) and histiocytic markers (PGMI, KP1, MAC387) using the highly sensitive avidin-biotin-peroxidase technique. We demonstrate, for the first time, a consistent positivity of the characteristic spindle cells of FP for CD34. The proposed endothelial, histiocytic or neuronal origin of FP could be completely ruled out. CONCLUSIONS: Because of the consistent positivity of the spindle cells of FP for CD34 we suggest an origin of these lesions from primitive perivascular or vascular cells. This origin and a probable relationship to gastrointestinal stromal tumours (GIST) is discussed.

[Angioarchitecture of the ileum and colon in Crohn disease]. / Angioarchitektur von Ileum und Colon bei Morbus Crohn.

Vascular changes in resected bowels of Crohn's disease were examined angiographically, microangiographically, micro-preparatorily and histologically. The proper angioarchitecture of the small and the large bowel is being destroyed in the course of the ongoing inflammatory process. Dilated capillaries, destruction of the primary angioarchitecture and its replacement by an irregular, partially bizarre pattern of scar vessels with bundling of the unchanged Vasa recta as varying vessel diameters caused by obliterating secondary fibroses can be seen in advanced Crohn's disease. The angioarchitecture of the pseudo-polyps in Crohn's disease is characterized by an increased number of vessels, bizarrely bended vessels and a radial pattern of veins. All these vascular changes in Crohn's disease are to be seen as secondary changes due to the inflammatory reaction.

Malignant colorectal polyps: venous invasion and successful treatment by endoscopic polypectomy.

We reviewed the pathology of 81 malignant colorectal polyps in 80 patients treated by endoscopic polypectomy and assessed the importance of carcinomatous invasion of veins in the stalk (submucosa). All the patients were followed up for at least five years. Venous invasion was present in 30 of the polyps (37%). The histological features of lymphatic invasion were considered too subjective to be of value. Most of the tumours were well or moderately differentiated adenocarcinomas, one was poorly differentiated, and one was a signet ring cell carcinoma. Seventy one patients were treated by polypectomy alone, and 58 of these were alive and well five years later, with no evidence of recurrence. Nine died of unrelated causes within five years, but four died of carcinomatosis: one with recurrent tumour, one with a possible metachronous caecal cancer, and in two patients there was late development of malignancy of uncertain nature. The remaining nine patients underwent surgical resection after initial endoscopic polypectomy because of incompleteness of excision, poor differentiation of the tumour, or a decision by the surgeon. Tumour was not present in the resection specimens apart from a single lymph node deposit in the patient with signet ring cell carcinoma. These nine patients were alive and well without evidence of recurrence five years later. The results reemphasize the necessity of good cooperation between endoscopist and pathologist, meticulous laboratory technique, strict histopathological criteria including examination of resection margins and degree of differentiation of the tumour, and regular endoscopic follow up. Endoscopic polypectomy of pedunculated and sessile malignant polyps is adequate treatment if the lesion can be removed in one piece, the tumour is well or moderately differentiated, and local excision is judged complete by endoscopic and histological criteria. Patients with histologically incompletely excised polyps, containing well or moderately differentiated carcinoma, can be safely managed by conservative treatment provided the endoscopist is certain there is no residual tumour. Venous invasion by tumour is a common finding in malignant colorectal polyps and seems to have no prognostic importance.

Histopathological assessment of bleeding from polyps of the colon and rectum.

One hundred and twenty seven colorectal polyps were examined to assess histopathological evidence of recent and old haemorrhage to test the usefulness of faecal occult blood tests in detecting colorectal neoplasia, in particular premalignant adenomas. Evidence of haemorrhage was consistently found in adenomas but was rare in non-neoplastic polyps. Haemorrhage within adenomas was predominantly stromal and associated with dilated, congested vessels. Factors associated with more severe haemorrhage were size, pedunculation, and villous growth; the degree of epithelial dysplasia and the age and sex of the patient were not associated factors. Proximal polyps showed more old haemorrhage than rectal polyps, but there was no such difference for recent haemorrhage.