Kazuya Makiyama

Apoptosis of crypt epithelial cells in ulcerative colitis.

In the colon of ulcerative colitis (UC) patients, apoptotic bodies have been recognized in routine histopathological preparations. To investigate the extent of the apoptosis, colonic biopsies were examined from involved and uninvolved areas of untreated active UC and from normal areas in patients with colonic polyps, utilizing various markers of apoptosis. The markers included DNA breaks detected by TUNEL, Fas (CD95/APO‐1) and Fas ligand (Fas‐L) localized by immunohistochemistry, electron microscopic features of apoptosis, and laddering of extracted DNA. Apoptosis marker positive cells were found mainly on the luminal epithelium of the normal colon and were present in active UC in crypts of involved and uninvolved areas of the colon, in addition to the luminal epithelium. The DNA extracted from active UC colon electrophoresed as a ladder. These findings suggest that the loss of epithelial cells in active UC occurs mainly by apoptosis in crypts of involved and adjacent uninvolved areas and that the Fas/Fas‐L interaction is a mediator of the apoptosis.

Carcinoma in gastric hyperplastic polyps. A phenotypic study.

One-hundred twelve hyperplastic polyps were analyzed. The aim was to study their malignant transformation. Among them, four hyperplastic polyps harbored adenocarcinoma; two were from our own institution (1.8%). The majority were pedunculated and located in the antrum with an average of 14.5 mm in diameter. The four polyps bore well-differentiated adenocarcinoma. Dysplasia and intestinal metaplasia were detected in two and three polyps, respectively. The cancer and dysplastic foci shared the same type of neutral and acid mucosubstances. p53 oncoprotein was positive in three cancer foci and in the dysplastic areas, and nucleolar organizer region counts were higher in the cancer foci. In conclusion, hyperplastic polyps have malignant potential. Such possibility increases in polyps larger than 14.5 mm. In our cases, the carcinoma foci may have arisen from dysplastic areas. Once the neoplastic changes occur, the cancer cells proliferate and behave as other adenocarcinomas of the stomach.

Oral Spherical Adsorptive Carbon for the Treatment of Intractable Anal Fistulas in Crohn's Disease: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial

OBJECTIVES:Anal fistulas are common in individuals with Crohns disease (CD). We sought to evaluate the efficacy of oral spherical adsorptive carbon (AST-120) (Kremezin®; Kureha Corporation, Tokyo, Japan) for the treatment of intractable anal fistulas in patients with CD.METHODS:In this multicenter, randomized, double-blind, placebo-controlled trial, patients with CD and at least one active anal fistula under treatment were assigned to receive either AST-120 or placebo for 8 wk. Improvement was defined as a reduction of 50% or more from baseline in the number of draining fistulas observed at both 4 and 8 wk. Remission was defined by closure of all draining fistulas at both 4 and 8 wk. The Perianal Disease Activity Index (PDAI) and Crohns Disease Activity Index (CDAI) were also assessed.RESULTS:In total, 62 patients were randomized, of whom 57 received AST-120 (N = 27) or placebo (N = 30). The improvement rate in the AST-120 group (37.0%) was significantly greater than that in the placebo group (10.0%) (P= 0.025). The corresponding remission rates were 29.6% and 6.7%, respectively (P= 0.035). PDAI significantly improved at both 4 and 8 wk with AST-120, compared to placebo (P= 0.004 and P= 0.005, respectively). CDAI was also significantly improved at both 4 and 8 wk in the AST-120 group, compared to the placebo group (P= 0.007 and P= 0.001, respectively). AST-120 treatment was well tolerated and no life-threatening adverse events were observed.CONCLUSION:AST-120 is useful for the control of intractable anal fistulas in CD patients.

Differential mechanism of peptide YY and neuropeptide Y in inhibiting motility of guinea-pig colon

The effect of peptide YY on contractility, acetylcholine release and noradrenaline release was examined in the isolated guinea-pig colon, and findings were compared with those for neuropeptide Y. Peptide YY and neuropeptide Y inhibited the twitch contractions mediated by the stimulation of cholinergic neurons. Peptide YY, neuropeptide Y, [Leu31,Pro34]neuropeptide Y and neuropeptide Y-(13-36) inhibited the electrically stimulated release of acetylcholine. Neuropeptide Y, but not peptide YY, inhibited the high K(+)-stimulated tetrodotoxin-resistant release of acetylcholine, while the inhibitory effect of neuropeptide Y disappeared after treatment with yohimbine. Neuropeptide Y, but not peptide YY or neuropeptide Y analogues, evoked the release of noradrenaline. After desensitization to the effects of neuropeptide Y, peptide YY inhibited electrically stimulated acetylcholine release. Thus, peptide YY inhibits acetylcholine release through stimulation of a receptor, distinct from the site of action of neuropeptide Y, located on cholinergic neurons as well as the neuropeptide Y Y1 and Y2 receptors in the guinea-pig colon. Neuropeptide Y inhibits acetylcholine release due to the noradrenaline release mediated by stimulation of a receptor distinct from neuropeptide Y Y1 and Y2 receptors, located on adrenergic neurons.

Anti-inflammatory effect of rebamipide enema on proctitis type ulcerative colitis: a novel therapeutic alternative

and established that a patient with vasculitis shall be said to have PAN if at least 3 of these 10 criteria are present (4). In our patient, the presence of four of these criteria (diastolic blood pressure.90 mm Hg, elevated creatinine, myalgias, and muscular weakness, and arteriographic abnormalities) allowed diagnosis of PAN with the contemporary involvement of multiple visceral organs including the rare manifestation of spleen infarction. Although PAN may occur with visceral infarction (1), the presence of same extraordinary aspects in our case, such as dramatic presentation of disease, contemporary multiple visceral involvement and unusual localization of infarctions.

Adenosquamous carcinoma of the pancreas

A 58-year-old Japanese man was admitted complaining of abdominal pain. An abdominal computed tomography examination demonstrated a tumor in the head of the pancreas and multiple calcifications. A laparotomy was performed and the tumor was removed by Whipples operation. Histologically, the neoplasm that invaded the duodenal wall and the papilla of Vater was composed of nests of malignant squamous cells with intercellular bridges and showed the formation of keratinized pearls with a small area of concurrently neoplastic glandular and squamous elements. On the basis of these features, the diagnosis of adenosquamous carcinoma of the pancreas was made. The patient died 18 months after the operation. The neoplastic behavior of this rare primary pancreatic carcinoma is similar to that of duct cell carcinoma as well as pure squamous cell carcinoma of the pancreas. As the pancreas can be the target of metastases of squamous carcinomas from other organs it is wise to be aware of this rare entity.

Efficacy of treatment with chimeric monoclonal antibody (Infliximab) to tumor necrosis factor-α for Crohn's disease in Japan: Evaluation by rapid turnover proteins, and radiologic and endoscopic findings

Background: Several studies have reported that the chimeric monoclonal antibody to tumor necrosis factor (TNF)‐α (Infliximab) is extremely valuable in the treatment of Crohns disease. The aim of this study was to clarify the efficacy of this treatment in Japanese patients with Crohns disease.

Efficacy of rebamipide enemas in active distal ulcerative colitis and proctitis: a prospective study report.

Rebamipide has a broad spectrum of pharmacological actions that include suppression of neutrophil functions and stimulation of mucosal epithelial cell regeneration by increasing the expression of epithelial growth factor (EGF) and the EGF receptor. Sixteen patients with active ulcerative colitis (UC; mild in 1 patient, moderate in 11, and severe in 4) were recruited. Enemas containing 150 mg rebamipide per dosing were administered during the daytime after passage of stool, twice a day for 4 weeks. UC disease activity index (UC-DAI), endoscopic activity index (EAI), and Florens grading (FG) of mucosal biopsy specimens were measured at entry and at 4 weeks. Five of 16 patients did not complete the study, and therefore, final efficacy assessment was done on 11 patients who completed the 4 weeks of treatment. Improvements were observed in UC-DAI (P= 0.0049), EAI (P= 0.0043), and FG (P= 0.0084). There was no serious rebamipide-related side effect in any of the 16 patients. In conclusion, rebamipide topical therapy appears to be effective for the treatment of mildly to moderately active distal UC. Further controlled studies are warranted for this promising drug.

Carcinoma of duodenal bulb arising from the Brunner's gland

A 75-year-old man was diagnosed as having a sessile tumor measuring 1.4 x 1.0 cm in size in the duodenal bulb after upper gastroduodenal series. The biopsy specimens revealed a proliferation of the adenomatous glands showing an acinar structure with papillary infolding; type III mucus, which is characteristic of Brunner’s glands. Antral glands and mucus neck cells of the fundic glands were also observed in the adenomatous glands by concanavalin A staining. Thus, it was clear that the tumor had originated from the Brunner’s glands. Three years and four months later, the sessile tumor had developed into a fungating ulcerated tumor via a polypoid form. The biopsy specimens revealed a papillary adenocarcinoma with foci of undifferentiated carcinoma. Retrospectively, the adenomatous glands in the biopsy taken from the sessile tumor should have been regarded as low grade carcinoma. Therefore, we propose that when a polyp or tumor shows an increase in size or change in macroscopic appearance, surgery should be considered.

A case of inflammatory malignant fibrous histiocytoma of the colon.

SummaryPrimary malignant fibrous histiocytoma seldom occurs in the alimentary tract. This report documents a case in which a 50-year-old man presented with abdominal fullness and anorexia, together with inflammatory reactions such as fever, leukocytosis, an elevated erythrocyte sedimentation rate and positive CRP. Radiologic and endoscopic studies revealed a large mass in the ascending colon. The histology of the resected tumor revealed inflammatory malignant fibrous histiocytoma, a histologie subtype which is rare among not only soft tissue fibrous but also as gastrointestinal histiocytomas. The inflammatory reactions disappeared following resection of the tumor. Although we suspected that the tumor produced granulocyte colony-stimulating factor because of the slightly elevated serum level and the characteristics of the tumor histology, an immunohistochemical study failed to show the G-CSF production by the tumor cells.