Tadahiko Masaki

Role of p53 and p21/WAF1 detection in patient selection for preoperative radiotherapy in rectal cancer patients

BACKGROUND: Recent studies showed that p53 and p21 may play major roles in determining tumor radiosensitivity through the apoptosis pathway. The aim of this study was to investigate the predicting value of radiosensitivity in human rectal carcinoma. METHODS: p53 and p21/WAF1 expressions in formalin fixed, paraffin-embedded, preradiation biopsy samples from 49 patients with primary rectal carcinoma were analyzed immunohistochemically. p53 and p21 expressions and their relationships with histopathologic changes after radiation and other clinical features were evaluated. RESULTS: Expressions of p53 and p21/WAF1 were 49 and 28.6 percent, respectively. In 36.7 percent of total tumors, significant histopathologic effect can be observed. There was a significant inverse expression of p53 and p21. Most of the p53(+) or p21(−) tumors were radioresistant, and the majority of p53(−) or p21(+) tumors were radiosensitive. Tumors size in the radiosensitive, p53(−), or p21(+) group decreased more significantly than in radioresistant, p53(+), or p21(−) group (P<0.01), and patients with radioresistant, p53(+), or p21(−) tumors had more local recurrence, more distant metastasis, and a shorter five-year survival rate than those with radiosensitive, p53(−), or p21(+) tumors, but without statistic significance. No statistically significant correlation can be observed between other tumor clinical features and radiosensitivity, p53, or p21 expressions. CONCLUSION: Immunohistochemistry detection of p53 and p21 expressions may be useful parameters for more radiosensitive patients selected for preoperative radiotherapy.

Malignant potential in flat elevations

Ninety-nine colonoscopically removed flat elevations were examined. They were divided into two groups: Group 1—flat elevations 1 to 5 mm in diameter (55 cases)- and Group 2—flat elevations 6 to 10 mm in diameter (44 cases). Group 2 had a higher percentage of adenomas (86.4 percent) than Group 1 (67.3 percent). In adenoma cases (flat adenomas), Group 2 tended to show a higher degree of dysplasia. The rates of mild and moderate dysplasia were 83.8 percent and 16.2 percent in Group 1vs.1.70 percent and 13.2 percent in Group 2, respectively. Group 2 contained six cases (15.8 percent) of intramucosal carcinoma (severe dysplasia), while there were no cancer cases in Group 1. Both malignancy rate and degree of dysplasia were size dependent; the larger the lesion the more severe the dysplasia. Our study also revealed that small flat elevations tend to contain higher numbers of nonneoplastic lesions than do larger lesions. Increased detection of nonneoplastic lesions seems to have contributed to an overall decline in the malignancy rate of flat elevations in recent reports.

Predictive value of histology at the invasive margin in the prognosis of early invasive colorectal carcinoma

Abstract: To accurately select patients with malignant colorectal polyps who are at high risk of adverse outcome, we examined the predictive value of clinicopathological factors, with special attention paid to the histology at the invasive margin. We examined 75 submucosal carcinomas from 75 patients, initially resected by polypectomy, including endoscopic, trans-anal, trans-sacral, and trans-sphincteric local excision. The associations between clinicopathological features such as sex and age; tumor size, location, shape, depth of submucosal invasion, vascular invasion, histology at the central part, and histology at the invasive margin; and the presence or absence of a residual adenomatous component and adverse outcome were examined by univariate and multivariate logistic regression analyses. Lymph node metastases were found in 2 patients, local recurrence in 4, and distant metastases in 2. Univariate logistic regression analysis showed that unfavorable histology at the invasive margin was significantly associated with lymph node metastasis or local recurrence (P = 0.0373), whereas the association of lymphatic invasion and vascular (lymphatic or venous) invasion with lymph node metastasis or local recurrence had marginal significance (P = 0.0785; P = 0.0990). Multivariate logistic regression analysis, with unfavorable histology at the invasive margin and lymphatic invasion as independent variables, showed that unfavorable histology alone had significance (P = 0.0373) in predicting adverse outcome. Widely accepted criteria such as massive submucosal invasion, positive vascular invasion, and poorly differentiated histology, were less useful in predicting adverse outcome. These results suggest that unfavorable histology at the invasive margin is a useful risk factor for predicting lymph node metastasis or local recurrence in patients with malignant colorectal polyps.

Effect of high ligation on the long-term result of patients with operable colon cancer, particularly those with limited nodal involvement

OBJECTIVE To find out what effect the extent of nodal dissection has on patients with operable colonic cancer. DESIGN Retrospective study. SETTING Teaching hospital, Japan. PATIENTS 564 consecutive patients who had potentially curative operations for colon cancer. Patients treated by limited nodal dissection, in which only pericolonic nodes were dissected, were excluded. MAIN OUTCOME MEASURES Disease free survival classified by extent of nodal dissection. RESULTS High ligation gave no significant advantage when patients were subgrouped according to degree of nodal involvement. However, number of patients with aggressive involvement (including intermediate or central nodes) was small. 511 patients (91%) had limited nodal involvement (no nodal involvement or nodal involvement confined to pericolonic nodes). High ligation of the vessels gave no advantage even with meticulous subgrouping according to age, site, and depth of invasion. CONCLUSION Most patients with colonic cancer had limited nodal involvement. High ligation did not affect the long term results in these patients, so, less invasive low ligation should be considered. A larger study will be necessary to clarify the indications for low and high ligation for patients with aggressive nodal involvement.

Psoas abscess complicating Crohn's disease: Report of two cases

We describe herein the case of a psoas abscess complicating Crohn’s disease, and present a review of the literature on this unusual disease entity. A 22-yearold Japanese man with a 5-year history of Crohn’s ileocolitis presented with right lower abdominal and hip pain, and a diagnosis of right psoas abscess was subsequently made by abdominal computed tomography (CT). Following the administration of antibiotics and CT-guided percutaneous drainage of the abscess, the patient’s symptoms temporarily improved; however, 2 weeks later, the abscess cavity was found to have extended around the periarticular tissue of the right hip joint. To prevent the development of septic arthritis of the hip joint, surgical drainage of the abscess cavity and ileocecal resection were immediately performed, after which the patient’s condition greatly improved. The resected specimen showed Crohn’s ileocolitis with an external fistula in the terminal ileum which was considered to have caused the psoas abscess. Since psoas abscess in Crohn’s disease can result in serious complications such as septic arthritis of the hip joint if left untreated, aggressive treatment should be initiated without delay.

Results of the double stapling procedure in colorectal surgery.

In this report we review our results with the double stapling technique (DST) in 162 patients with colorectal diseases in an attempt to identify some of the potential pitfalls of this new technique. Among these 162 patients, there were 125 patients with colorectal cancer, 25 with chronic ulcerative colitis (UC), 9 with familial adenomatous polyposis (FAP), 2 with adult Hirschsprungs disease, and 1 with sigmoid colon fistula. A total of 46 anastomoses (28 for rectal cancer, 13 for UC, 3 for FAP, and 2 for adult Hirschsprungs disease) were performed at or near the dentate line. Of these, 10 had protective diverting colostomy or ileostomy. The results showed that 6 patients with rectal cancer had anastomotic leakage (3.7%); however, 4 of the 6 patients had also received preoperative irradiation. All the leaks healed after the patients had undergone diverting colostomy, but 7 patients with rectal cancer suffered from neurogenic bladder postoperatively (4.3%). Wound infection occurred in 4 patients (2.5%), anastomotic bleeding in 3 (1.9%), and anal pain in 1 (0.6%), respectively. One patient with rectal cancer and multiple liver metastases died of disseminated intravascular coagulation (DIC). These results thus suggest that the double stapling technique provides a safe anastomosis at or near the dentate line not only for rectal cancer but also for UC, FAP, and adult Hirschsprungs disease.

DNA ploidy pattern of flat adenomas of the large bowel

In an attempt to clarify the nature of “flat adenomas,” DNA content was measured by means of microspectrophotometry. Thirty-nine flat adenomas (FA), 13 with mild, 22 with moderate, and 4 with severe atypia, were collected for this study. In FA, diploidy (D), polyploidy (P), and aneuploidy (A) were found 100, 0, and 0 percent in mild atypia, 41.9, 4.5, and 54.5 percent in moderate atypia, and 0, 0, and 100 percent in severe atypia, respectively. It is assumed that FA have a much higher malignancy potential than previously expected since, histologically, benign-appearing FA with moderate atypia have already contained malignant DNA patterns. In particular, those more than 5 mm in diameter show aneuploidy in 80 percent. These data suggest that FA with moderate atypia play an important role in the pathogenesis of small colonic carcinomas.

A schwannoma of the cecum: Case report and review of Japanese schwannomas in the large intestine

Abstract: A 66-year-old Japanese man had a positive fecal occult blood test at a regular check-up, and a large polypoid mass was detected in the cecum by barium enema study. Colonoscopy showed a submucosal tumor with ulcer protruding into the cecal lumen. A large-forceps biopsy specimen was taken from the bottom of the ulcer. With the tentative diagnosis of neurogenic tumor, ileocecal resection was performed. The tumor showed spindle-cell proliferation in a concentric or fascicular pattern. Immunohistochemically, the tumor cells were diffusely positive for S-100 protein, and they had intracytoplasmic periodic acid Schiff (PAS)-positive crystalloids. The mitosis count was low (about 1 per 20 high-power fields). The pathological diagnosis of this tumor was benign gastrointestinal schwannoma. A large number of schwannoma cases have been reported since 1910 when Verocay reported it as a true tumor that stemmed from Schwann cells and did not contain neuroganglion cells. However, gastrointestinal schwannomas are rare, and schwannomas of the large intestine are extremely rare. We reviewed 40 cases already reported in Japan and this present case in order to clarify the clinicopathological features of this tumor.

DNA ploidy pattern in rectal carcinoid tumors.

The nuclear DNA pattern of 22 rectal carcinoids was determined by cytophotometry of paraffin embedded tissues. The results were compared with clinical as well as histopathologic features of the tumor. Three of the carcinoids with synchronous or metachronous metastasis had aneuploid DNA pattern, whereas 19 tumors with no metastasis showed diploid DNA pattern. No other single clinical or pathologic feature of the tumor could predict more accurately the malignant potential and the subsequent course of the rectal carcinoid. It is concluded that DNA aneuploidy in rectal carcinoid tumors is not so rare as indicated by earlier studies and that it is a factor of significant prognostic value.

Rapid growth of residual colonic tumor after incomplete mucosal resection

Abstract: We report an 89-year-old man with colon cancer that developed rapidly after an incomplete endoscopic mucosal resection (EMR), and discuss the adverse effect of this maneuver on the tumor biology. A sessile polyp, 15 mm in size, was detected at the hepatic flexure. EMR was performed immediately. Histologi-cal examination showed well differentiated adenocarcinoma with an adenomatous component invading the submucosal layer. There was vascular invasion (positive on elastica van Gieson staining) and the surgical margin was positive for cancer. A right hemicolectomy was performed. The surgical specimen showed the residual tumor, 22 mm in diameter. The relevant histopathological findings of the surgical specimen were: well differentiated adenocarcinoma, with partly mucinous carcinoma and a tubular adenomatous component, depth muscularis propria (mp), lymph node (LN) (0/9). Most of the submucosally invasive cancer was resected by the initial EMR, but the small residual tumor showed rapid growth within only 3 months after the EMR. It was assumed that the residual tumor cells had acquired more malignant characteristics after EMR. In regard to EMR we propose that: (1) except for patients who are at high risk for a major operation, EMR should be avoided for carcinoma with massive submucosal invasion, (2) colonic resection should be performed immediately when histology shows a positive surgical margin for carcinoma, and (3) patients operated after an incomplete EMR should be watched very carefully for the detection of recurrence.