Sotaro Sadahiro

Detection of tumor cells in the portal and peripheral blood of patients with colorectal carcinoma using competitive reverse transcriptase-polymerase chain reaction

In spite of many reports, it remains unclear whether the presence of tumor cells in circulating blood flow predicts a poor prognosis.

Comparison between oral antibiotics and probiotics as bowel preparation for elective colon cancer surgery to prevent infection: Prospective randomized trial

BACKGROUND We have already reported that, for patients undergoing elective colon cancer operations, perioperative infection can be prevented by a single intravenous dose of an antibiotic given immediately beforehand if mechanical bowel preparation and the administration of oral antibiotics are implemented. Synbiotics has been reported to reduce the rate of infection in patients after pancreatic cancer operations. The effectiveness of oral antibiotics and probiotics in preventing postoperative infection in elective colon cancer procedures was examined in a randomized controlled trial. METHODS Three hundred ten patients with colon cancer randomly were assigned to one of three groups. All patients underwent mechanical bowel preparation and received a single intravenous dose of flomoxef immediately before operation. Probiotics were administered in Group A; oral antibiotics were administered in Group B; and neither probiotics nor oral antibiotics were administered in Group C. Stool samples were collected 9 and 2 days before and 7 and 14 days after the procedure. Clostridium difficile toxin and the number of bacteria in the intestine were determined. RESULTS The rates of incisional surgical-site infection were 18.0%, 6.1%, and 17.9% in Groups A, B, and C, and the rates of leakage were 12.0%, 1.0%, and 7.4% in Groups A, B, and C, respectively, indicating that both rates were lesser in Group B than in Groups A and C (P = .014 and P = .004, respectively). The detection rates of C. difficile toxin were not changed among the three groups. CONCLUSION We recommend oral antibiotics, rather than probiotics, as bowel preparation for elective colon cancer procedures to prevent surgical-site infections.

Morphology of myenteric plexuses in the human large intestine: comparison between large intestines with and without colonic diverticula.

Background: Large intestines with diverticula exhibit functionally abnormal peristaltic activity and elevated luminal pressure that may indicate functional changes in the myenteric plexus; however, no studies have investigated the characteristics of either normal or diverticula myenteric plexuses. Methods: Tissue specimens obtained from 93 colorectal cancer patients without diverticula, 14 patients with perforated diverticulitis, and 12 colorectal cancer patients with asymptomatic diverticula were included in this study. Myenteric plexuses and ganglion cells were counted per centimeter, and the area and maximum diameter of the nuclei of ganglion cells were measured using an image analyzer. Results: The number of myenteric plexuses and ganglion cells per centimeter was significantly higher in the descending colon, sigmoid colon, and rectum than in the cecum, ascending colon, and transverse colon. The area of the nuclei of ganglion cells was significantly larger in the descending colon and sigmoid colon than in the cecum and ascending colon. Compared with large intestines without diverticula, the number of myenteric plexuses was significantly higher in large intestines with diverticula, whereas the number of ganglion cells decreased in both right-sided and left-sided large intestines with perforated diverticulitis or asymptomatic diverticula. The area of the nuclei of ganglion cells was significantly smaller in large intestines with diverticula. Conclusion: The morphology of myenteric plexuses and the ganglion cells differs significantly among segments of the human large intestine. Large intestines with diverticula had significantly more plexuses but significantly fewer ganglion cells than large intestines without diverticula. The area of the nuclei of ganglion cells was also significantly smaller in large intestines with diverticula. Further studies are required to clarify how these changes are related to intestinal function and how they are involved in the etiology of diverticulosis.

Risk of lymph node and distant metastases in patients with early invasive colorectal cancer classified as Haggitt's level 4 invasion: Image analysis of submucosal layer invasion

PURPOSE Tumor invasion in patients with early invasive colorectal cancer has been classified into four levels proposed by Haggitt. Level 4 invasion into the submucosa has been defined as a risk factor for lymph node metastasis; however, the false-positive rate remains high. This study was designed to determine risk factors for lymph node and distant metastases in addition to Haggitt’s Level 4 invasion. METHODS Seventy-one of 142 patients with submucosa-invasive colorectal cancer underwent intestinal resection as an initial surgical treatment between 1975 and 2000. The subjects of this study were 65 of these 71 patients, all of whom were diagnosed as having Haggitt’s Level 4 invasion. The depth, width, and area of submucosal invasion were measured with an image analyzer. RESULTS Lymph node metastasis was noted in 11 (16.9 percent) of the 65 patients. There were no significant differences in the depth or area of submucosal invasion between node-positive and node-negative patients. However, the width of submucosal invasion was significantly greater in node-positive than in node-negative patients (P = 0.001). When 5-mm-wide submucosal invasion was used as an indicator for intestinal resection, 37 patients were found to have indications for bowel resection, and 11 (29.7 percent) of the 37 had lymph node metastases. Distant metastasis was noted in five patients (7.7 percent). The depth, width, and area of submucosal invasion in patients with distant metastasis did not differ significantly from those without distant metastasis. CONCLUSION Although further prospective investigation is required, the positive predictive value increases from 17 to 30 percent when the width of submucosal invasion is added to Haggitt’s Level 4 as an indicator for bowel resection.

A case of cecocolic intussusception with complete invagination and intussusception of the appendix with villous adenoma

Villous adenoma of the appendix is a rare neoplasm and intussusception of the appendix is a rare pathologic condition. A very rare case seen in a 35-year-old male with pain in the right lateral abdomen is reported. In this patient, the appendix along with the villous adenoma intussuscepted and invaginated into the cecal lumen, and presented as cecocolic intussusception. A polypoid lesion was diagnosed in the cecum by fiberoptic colonoscopy. Unlike polypoid lesions at other sites in the large intestine, polypoid lesions of the cecum may accompany intussusception and invagination of the appendix. Consequently, caution is required in performing endoscopic polypectomy in cases of polypoid lesions of the cecum.

An assessment of the mucous component in carcinoma of the colon and rectum.

It has been said that the prognosis of mucinous carcinoma of the colon and rectum is unfavorable. To determine the clinicopathologic significance of carcinomatous lesions with marked mucous production, the ratio of the area where there was significant mucous production (mucous component [MC]) to the area of the whole tumor on a tissue slice (area ratio) was determined by measurement with a digitizer in 281 patients with carcinoma of the colon and rectum. The MC was observed in the largest cross‐section of the tumor in 85 patients (30.2%). Of these 85 patients the MC area ratio was less than 10% in 42. In the 43 patients with an area ratio of 10% or more, no particular relationship was observed between the area ratio and the frequency of cases. If no MC was observed in the largest cross section of the tumor, the MC ratio in other regions of the tumor was almost 0. In the patients in whom the MC area ratio in the largest cross‐section was less than 10%, the MC area ratios in other sites of the tumor showed only a small variance, but in the patients with an MC area ratio of 10% or more, a large variance was observed according to the site. The prognosis for patients with an area ratio of 10% or more was less favorable than that for patients with no MC and with an MC area ratio of less than 10% (P < 0.05). These results suggest that it is reasonable to handle the patients with an MC area ratio of 10% or more as a group.

Risk of Lymph Node and Distant Metastases in Patients With Early Invasive Colorectal Cancer Classified as Haggitt’s Level 4 Invasion

AbstractPURPOSE: Tumor invasion in patients with early invasive colorectal cancer has been classified into four levels proposed by Haggitt. Level 4 invasion into the submucosa has been defined as a risk factor for lymph node metastasis; however, the false-positive rate remains high. This study was designed to determine risk factors for lymph node and distant metastases in addition to Haggitt’s Level 4 invasion. METHODS: Seventy-one of 142 patients with submucosa-invasive colorectal cancer underwent intestinal resection as an initial surgical treatment between 1975 and 2000. The subjects of this study were 65 of these 71 patients, all of whom were diagnosed as having Haggitt’s Level 4 invasion. The depth, width, and area of submucosal invasion were measured with an image analyzer. RESULTS: Lymph node metastasis was noted in 11 (16.9 percent) of the 65 patients. There were no significant differences in the depth or area of submucosal invasion between node-positive and node-negative patients. However, the width of submucosal invasion was significantly greater in node-positive than in node-negative patients (P = 0.001). When 5-mm-wide submucosal invasion was used as an indicator for intestinal resection, 37 patients were found to have indications for bowel resection, and 11 (29.7 percent) of the 37 had lymph node metastases. Distant metastasis was noted in five patients (7.7 percent). The depth, width, and area of submucosal invasion in patients with distant metastasis did not differ significantly from those without distant metastasis. CONCLUSION: Although further prospective investigation is required, the positive predictive value increases from 17 to 30 percent when the width of submucosal invasion is added to Haggitt’s Level 4 as an indicator for bowel resection.

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.

Phase I/II Study of Preoperative Concurrent Chemoradiotherapy with S-1 for Locally Advanced, Resectable Rectal Adenocarcinoma

Purpose: To assess the maximum tolerability of a combination of S-1 and preoperative radiotherapy and to evaluate the feasibility and activity in patients with locally advanced rectal cancer. Methods: Patients (n = 30) with adenocarcinoma of the middle or lower rectum were enrolled in a phase I (n = 9) and/or phase II (n = 21) trial. A total dose of 45 Gy was delivered in 25 fractions over 5 weeks, and S-1 was orally administered twice a day on days 1–14 and 22–35. Surgical resection was scheduled 4–8 weeks after the completion of chemoradiation. Results: In phase I, the recommended dose (RD) of S-1 was 80 mg/m2/day, and the maximum-tolerated dose was never reached. A total of 27 cases, including the 6 RD cases in phase I, were enrolled in phase II. In phase II, a pathological complete response (pCR) was observed in 6/27 patients (22%), pathological downstaging was observed in 21/27 patients (78%), and a tumor volume reduction of 69 ± 22% was obtained. These results were similar to the previously reported pCR rates of 16–18%, pathological downstaging rates of 49–59%, and tumor volume reduction of 68% after chemoradiotherapy with capecitabine. Grade 3 adverse events consisted of one case of leukopenia (4%), 2 cases of anemia (7%) and 3 cases of diarrhea (11%). Overall, the adverse events were very mild. Hand-foot syndrome was not observed. Conclusion: The efficacy of chemoradiotherapy with S-1 seems to be equivalent to the efficacy reported for chemoradiotherapy with capecitabine, but the adverse events were much milder, although further study is warranted.

Biopsy Specimens Obtained 7 Days After Starting Chemoradiotherapy (CRT) Provide Reliable Predictors of Response to CRT for Rectal Cancer

PURPOSE Preoperative chemoradiation therapy (CRT) significantly decreases local recurrence in locally advanced rectal cancer. Various biomarkers in biopsy specimens obtained before CRT have been proposed as predictors of response. However, reliable biomarkers remain to be established. METHODS AND MATERIALS The study group comprised 101 consecutive patients with locally advanced rectal cancer who received preoperative CRT with oral uracil/tegafur (UFT) or S-1. We evaluated histologic findings on hematoxylin and eosin (H&E) staining and immunohistochemical expressions of Ki67, p53, p21, and apoptosis in biopsy specimens obtained before CRT and 7 days after starting CRT. These findings were contrasted with the histologic response and the degree of tumor shrinkage. RESULTS In biopsy specimens obtained before CRT, histologic marked regression according to the Japanese Classification of Colorectal Carcinoma (JCCC) criteria and the degree of tumor shrinkage on barium enema examination (BE) were significantly greater in patients with p21-positive tumors than in those with p21-negative tumors (P=.04 and P<.01, respectively). In biopsy specimens obtained 7 days after starting CRT, pathologic complete response, histologic marked regression according to both the tumor regression criteria and JCCC criteria, and T downstaging were significantly greater in patients with apoptosis-positive and p21-positive tumors than in those with apoptosis-negative (P<.01, P=.02, P=.01, and P<.01, respectively) or p21-negative tumors (P=.03, P<.01, P<.01, and P=.02, respectively). The degree of tumor shrinkage on both BE as well as MRI was significantly greater in patients with apoptosis-positive and with p21-positive tumors than in those with apoptosis-negative or p21-negative tumors, respectively. Histologic changes in H&E-stained biopsy specimens 7 days after starting CRT significantly correlated with pathologic complete response and marked regression on both JCCC and tumor regression criteria, as well as with tumor shrinkage on BE and MRI (P<.01, P<.01, P<.01, P<.01, and P=.03, respectively). CONCLUSIONS Immunohistochemical expressions of p21 and apoptosis together with histologic changes on H&E-stained biopsy specimens obtained 7 days after starting CRT are strong predictors of the response to CRT.