Yoshimasa Otani

Indications of Endoscopic Polypectomy for Rectal Carcinoid Tumors and Clinical Usefulness of Endoscopic Ultrasonography

PURPOSEThis study was designed to define the indications of endoscopic polypectomy for rectal carcinoid tumors and evaluate the diagnostic value of endoscopic ultrasonography.METHODSA total of 66 rectal carcinoid tumors treated at our hospital were analyzed histopathologically to clarify risk factors for metastasis. The depth of invasion was determined for 52 lesions examined by endoscopic ultrasonography, and the value of endoscopic ultrasonography for deciding whether a lesion is indicated for endoscopic polypectomy was assessed.RESULTSNone of the 57 lesions measuring ≤ 10 mm in diameter invaded the muscularis propria or had metastasis. Of nine lesions with a diameter of ≥ 11 mm, five invaded the muscularis propria and four had metastasis. A central depression was found in three of the lesions with metastasis. The depth of invasion of 49 lesions examined by endoscopic ultrasonography was limited to the submucosa; 3 lesions invaded the muscularis propria. The depth of invasion of all lesions was correctly diagnosed by endoscopic ultrasonography. Ninety-six percent of the lesions that had submucosal invasion with narrowing of the upper two-thirds of the third layer (submucosa) as evaluated by endoscopic ultrasonography could be completely resected by endoscopic polypectomy.CONCLUSIONSRectal carcinoid tumors that satisfy the following three conditions are indicated for local resection, including endoscopic polypectomy: a maximum diameter of ≤ 10 mm, no invasion of the muscularis propria, and no depression or ulceration in the lesion. Endoscopic ultrasonography also is useful for estimating the depth of invasion of rectal carcinoid tumors and for determining whether endoscopic polypectomy is indicated.

Dye spraying and magnifying endoscopy for dysplasia and cancer surveillance in ulcerative colitis

PURPOSEThe aim of this study was to investigate detection of dysplasia or colitic cancer with ulcerative colitis by use of magnifying endoscopic observation.METHODSFrom 1986 through 2000, ulcerative colitis was diagnosed and treated in 886 patients at Kitasato University East Hospital. Of the total, we studied 25 patients in depth: 14 who had dysplasia alone, 5 in whom cancer was diagnosed during follow-up after the detection of dysplasia, and 6 who had colitic cancer.RESULTSDysplasia was detected in 11 (3.2 percent) of 345 patients with extensive colitis and in 8 (3.7 percent) of 217 with left-sided colitis. Colorectal cancer was diagnosed in nine patients (2.6 percent) with extensive colitis and in two (0.9 percent) with left-sided colitis. Neither dysplasia nor colitic cancer was found in patients with proctitis-type colitis. Endoscopically, dysplasia and early cancer were characterized by granular or nodular protruding mucosa or by lowly protruding or flat mucosa, often associated with redness. Dye-spraying endoscopy was useful for detection. Magnifying endoscopy of ten regions of dysplasia (7 patients) and five early cancers (4 patients) showed IIIS to IIIL type pits or IV type pits. Biopsy of sites showing tumorous pits on magnifying endoscopy revealed dysplasia and early cancer. Observation of the pit pattern was found to be diagnostically useful.CONCLUSIONSDye spraying and magnifying endoscopy are useful for the detection, targeted biopsy, and diagnosis of dysplasia and colitic cancer in patients with ulcerative colitis.

Feasibility of a novel weekday-on/weekend-off oral UFT schedule as postoperative adjuvant chemotherapy for colorectal cancer

Purpose: When oral anticancer agents are used for adjuvant chemotherapy of colorectal cancer, compliance and feasibility become issues because of the long treatment time. Appropriate studies of these issues are lacking. We investigated compliance and feasibility during a weekday-on/weekend-off schedule of oral UFT (uracil-tegafur) over a period of 1 year administered as adjuvant chemotherapy to patients with colorectal cancer. Patients and methods: A UFT dose of 600 mg/day was prescribed according to a weekday-on/weekend-off schedule to 87 patients after potentially curative resection. Compliance was investigated in three ways: physician interview, patient self-report, and chemical analysis of urine. The results were compared with the dose prescribed. Feasibility was evaluated on the basis of two indices: relative performance (RP), which was the ratio of the actual total dose taken to the total dose planned, and individual dose intensity (IDI), which was the ratio of the actual dose taken to the dose planned during a given period. Results: The compliance assessed by physician interview and by patient self-report conformed well with the prescribed dose, the rate of agreement among the three compliance measures being more than 94%. Chemical analysis of urine in 38 of the patients revealed that they were actually taking the drug. The RP was 0.72, and the IDI was 0.8. Conclusion: From these results, the feasibility of the weekday-on/weekend-off schedule was judged to be good. It is suggested that the feasibility would be even better if the dose of UFT was set according to body surface area.

Different apoptotic activity and p21WAF1/CIP1, but not p27Kip1, expression in serrated adenomas as compared with traditional adenomas and hyperplastic polyps of the colorectum

PurposeSerrated adenomas (SAs), which include a wide spectrum of lesions, can be broadly divided into two subtypes: type I, closely mimicking hyperplastic polyps (HPs), and type II, unequivocal adenomatous tumor. Our preliminary findings showed clinicopathologic differences between them. The present study was conducted to investigate apoptotic activity and expression of the cell cycle regulator proteins p21WAF1/CIP1 and p27Kip1 in type I and II SAs, as compared with traditional adenomas (TAs) and HPs.MethodsApoptotic activity was estimated in hematoxylin-eosin stained specimens, and p21WAF1/CIP1 or p27Kip1 immunoreactivity was determined in 62 SAs (19 type I and 43 type II), 50 TAs and 19 HPs. The numbers (percentages) of apoptotic or immunoreactive cells were counted per 1,000 epithelial cells in equally separated crypt zones (upper, middle, and lower thirds).ResultsThe apoptotic activity in the middle, but not the upper or lower crypt zone was higher in type II SAs (median 0.2%, interquartile range 0.1–0.5%) than in HPs (0.1%, 0.1–0.2%, P<0.01), whereas it was lower in type I SAs (0.2%, 0.1–0.3%) than in TAs (0.5%, 0.2–0.6%, P<0.001). P21WAF1/CIP1 expression in the lower crypt zone was higher in both type I and type II SAs (19.8%, 7.0–33.2% and 20.4%, 3.9–47.8%, P<0.0001) than in TAs (1.2%, 0.6–5.2%), and a similar tendency was also observed for the middle crypt zone. p27Kip1 expression did not vary among the groups.ConclusionsThe differences in apoptotic activity and p21WAF1/CIP1 expression between SAs and TAs or HPs indicate that SA should be considered as a distinct subtype of colorectal neoplasm. The two subtypes of SA do not differ in these parameters despite specific clinicopathological features.

Unique characteristics of rectal carcinoma cell lines derived from invasive carcinomas in ulcerative colitis patients

To identify the characteristics of ulcerative colitis (UC)‐associated carcinomas, 8 lesions, high‐grade dysplasias and invasive carcinomas, were implanted into severely combined immunodeficient (SCID) mice and/or cultured in vitro. Intramucosal neoplasias consisting of high‐grade dysplasia showed extremely slow proliferation after implantation (2/3 cases) and in vitro culture failed (4 cases). However, invasive carcinomas demonstrated rapid growth both after SCID mouse implantation and in vitro (4/4 cases). From two cases of invasive carcinomas, 6 cell lines were established, and these are the first to be described in the literature. In addition to variation in immunohistochemically determined phenotypic expression regarding α‐fetoprotein, chromogranin A and estrogen receptors, the established cell lines showed varying differentiation (moderately or poorly differentiated adenocarcinoma, adenosquamous carcinoma and poorly differentiated adenocarcinoma with multinuclear giant cells and bone formation). The results are in contrast with findings for sporadic colorectal carcinomas. Although the prevalence of DNA alterations is not frequent, loss of heterozygosity (17p and 18q) and deletion of exons 8 to 11 in DPC‐4 were revealed in all of 6 cell lines, suggesting relatively high genetic instability. We found loss or translocation of many chromosomes (#3, 5, 6, 8, 10, 11, 13, 16, 17, 18 and 19) other than chromosomes 1, 5, 8, 11, 13, 17 and 18, which are frequently involved in sporadic colorectal carcinoma cell lines. Thus, the established cell lines may be good models of tumorigenesis and progression in the chronic inflammation‐carcinoma sequence.

Frequent Ki-ras mutations and transforming growth factor-alpha expression in adenocarcinomas of the small intestine: report of 7 cases.

Although the small intestine contains almost 90% of the mucosal surface area of the gastrointestinal tract, its incidence rate for cancer is only one fiftieth of that for the large intestine (1). Rapid turnover of small bowel mucosal cells is suggested as a possible reason for the low cancer rate, ie, partially transformed cells are shed before full carcinogenesis can occur (2, 3). However, this hypothesis has not been well investigated. Epidermal growth factor (EGF) and transforming growth factor-alpha (TGFα) are structurally related peptides that stimulate DNA synthesis and cell growth in various systems, including the gastrointestinal tract (4). Both EGF and TGFα recognize and compete for the same cell surface membrane receptor (EGF-R) through which they mediate their biological action (5). The vascular endothelial growth factor (VEGF) is a glycoprotein with specific actions on endothelial cells, mediating formation of new blood vessels from preexisting vasculature (6, 7). The role of these growth factors and related receptors regarding tumor growth and angiogenesis have been verified for colorectal carcinomas (8–11), but not fully investigated in small intestinal lesions.

Comparative Histologic Assessment of Proctocolectomy Specimens from Japanese and American Patients with Ulcerative Colitis with or Without Dysplasia

There have been no reports of histologic differences in ulcerative colitis (UC) between Japanese and American patients. We therefore compared histology in proctocolectomy resection specimens between Japanese patients with UC (19 cases with and 21 without dysplasia) at the Kitasato University East Hospital and American patients with UC (21 cases with and 24 without dysplasia) at the University of Washington Medical Center. In cases of UC with, but not without dysplasia, cryptitis (p = 0.010) and epithelial apoptosis (p < 0.001) in the nondysplastic mucosa were more frequently observed in Japanese than in American cases, whereas lamina propria fibrosis was more prominent in American counterparts (p = 0.008). In patients with UC with dysplasia, the duration of disease was significantly longer in American than in Japanese patients (median, 17 vs 14 years, respectively; p = 0.038). This might, in part, explain the histologic variation. Another possibility for the differences is that the preoperative medications may have differed in the populations.

SURVEILLANCE BY MAGNIFYING ENDOSCOPY IN PATIENTS WITH ULCERATIVE COLITIS

Background:  Patients with total or left‐sided ulcerative colitis (UC) for more than 10 years have an increased risk of colon cancer. We studied usefulness of magnifying chromoendoscopy for the surveillance of dysplasia and colitic cancer associated with UC.