Toshio Sawada

Small “flat adenoma” of the large bowel with special reference to its clinicopathologic features

Thirty-three small “flat adenomas,” not more than 1 cm in diameter, were collected from surgically and colonoscopically removed specimens, and their colonoscopic and histologic characteristics were described. There were 14 adenomas with mild atypia, five with moderate atypia, 14 with severe atypia (or focal carcinoma limited to the mucosa). The grade of atypia seems to increase with the size of lesions, and these lesions were assumed to play an important role in the adenoma-carcinoma sequence. The importance of recognizing the presence of these small “flat adenomas” in everyday practice is stressed.

Significance of lateral node dissection for advanced rectal carcinoma at or below the peritoneal reflection

Two hundred thirty two patients with rectal cancer at or below the peritoneal reflection, who underwent extended systematic lymphadenectomy, especially lateral node dissection, were reviewed with respect to survival rate, degree of surgical technique, and mode of recurrence. On the basis of the extent of lateral node spread, two types of lateral node dissection were performed, consisting of preservation of internal iliac vessels (conventional) anden bloc excision of these vessels (extended). The overall disease-free five-year survival rate was 69.4 percent in all patients—75.8 percent for those who underwent extended resection and 67.4 percent for those who underwent conventional resection an excellent survival rate of 49 percent of patients with lateral node metastasis was obtained. The analysis was carried out with regard to prognostic factors such as number of node metastases, obesity index, mode of recurrence, etc. We would recommend that systemic lymphadenectomy with lateral node dissection be performed for advanced rectal cancer at or below the peritoneal reflection.

Multicenter Randomized Controlled Trial for the Treatment of Ulcerative Colitis with a Leukocytapheresis Column

The administration of steroids is not always effective for the treatment of ulcerative colitis (UC). Their long-term use often causes adverse effects which sometimes result in their stoppage and acute exacerbation. Therefore, an alternative treatment is necessary in order to decrease steroid dosage and avoid the clinical problems associated with steroids. Methods The effectiveness and adverse effects of a leukocytapheresis (LCAP) were investigated in a controlled multicenter trial with randomized assignment of 76 active-stage UC patients in two groups. In the LCAP group (39 patients), LCAP weekly for 5 weeks as an intensive therapy was added to the on-going drug therapy, while steroids were maintained but not increased, and then LCAP was gradually reduced to once every 4 weeks as a maintenance therapy. In the high dose prednisolone (h-PSL) group (37 patients), PSL was added or increased 30 approximately 40 mg/day for moderately severe and 60 approximately 80 mg/day for severe patients and then gradually tapered. Findings The LCAP group showed a significantly higher effectiveness (74% vs. 38%; p=0.005) and lower incidence of adverse effects (24% vs. 68%; p<0.001). The patients were able to continue the trial for a longer period in the LCAP group than the h-PSL group (p=0.012). Clinical activity and endoscopic indexes showed the LCAP group had better improvements than the h-PSL group. Interpretation The results of the trial show that LCAP permits a reduction in total PSL dosage and is more effective and safer than high-dose PSL administration for intensive therapy, and LCAP may maintain remission longer than PSL.

Randomized, controlled trial of lateral node dissection vs. nerve-preserving resection in patients with rectal cancer after preoperative radiotherapy.

PURPOSE: The effectiveness of preoperative radiation therapy for advanced lower rectal carcinoma to preserve the function of pelvic organs and reduce local recurrences was examined in a prospective, randomized, controlled study. METHODS: Fifty-one patients with a diagnosis of localized and resectable adenocarcinoma of the lower rectum undergoing 50 Gy of preoperative radiotherapy were recruited into the trial between April 1993 and March 1995. The patients were randomly allocated to complete autonomic nerve-preserving surgery without lateral node dissection (D1), or surgery with dissection of the lateral lymph nodes including autonomic nerves (D2) followed by oral administration of carmofur for one year. RESULTS: No difference was observed in either survival or disease-free survival between D1 and D2 groups. There was no difference between the two groups in terms of recurrence rate. A significant difference was observed in urinary and sexual function (P= 0.02 and 0.02, respectively) one year after surgery between D1 and D2 groups. CONCLUSION: This study suggests that lateral node dissection is not necessary in terms of curability for patients with advanced carcinoma of the lower rectum who undergo preoperative radiotherapy.

Interleukin-6 and stress hormone responses after uncomplicated gasless laparoscopic-assisted and open sigmoid colectomy

PURPOSE: Laparoscopic colectomy has increasingly been advocated as an option for treatment of colonic disease. The purpose of this study was to compare effects of laparoscopicassisted sigmoid colectomy (LAS) and conventional open colectomy (OPEN) on postoperative cytokine and stress hormone responses. METHODS: Fourteen patients with sigmoid colon cancer, apparently free of preoperative complications, were analyzed. Patients in both groups underwent sigmoid colectomy with lymphadenectomy. LAS was performed by the gasless abdominal wall-lifting method. A 5 cm incision was placed at the beginning of the operation. Blood samples were taken preoperatively and postoperatively for measurement of interleukin-6, glucagon and C-reactive protein. Urinary catecholamine excretions were also determined postoperatively. RESULTS: The two groups of patients were similar with respect to age (61±7 for LASvs.64±9 for OPEN) and sex. Intraoperative blood loss did not differ significantly between groups (112±97 ml for LASvs.366±380 ml for OPEN). Operative times for LAS tended to be longer than those for OPEN (231±67vs.169±45 minutes;P=0.08). Similar time courses of postoperative interleukin-6, C-reactive protein, and stress hormone responses were observed in both groups. No significant differences were observed in the magnitude of changes except that the serum interleukin-6 level on day of surgery (postoperative day 0) was significantly higher in LAS patients than in those receiving OPEN. In addition, interleukin-6 levels showed a significant positive correlation with operative duration (r=0.582;P<0.05). CONCLUSIONS: Data suggest that stress responses after sigmoid colectomy, in patients undergoing LAS, are comparable with those of patients receiving OPEN and that the early interleukin-6 response after surgery appears to be associated with operative time.

Peutz-Jeghers polyposis associated with carcinoma of the digestive organs. Report of three cases and review of the literature.

Three cases of Peutz-Jeghers polyposis with carcinoma of the digestive organs are studied. Although mucocutaneous pigmentation was not present in two of the three patients, the features of intestinal polyposis are consistent with those of Peutz-Jeghers syndrome. One patient had a carcinoma of the pancreas and the other two had carcinomas with colonic Peutz-Jeghers polyps. Previous reports on carcinomas associated with Peutz-Jeghers syndrome are reviewed. An unusual location in the gastrointestinal tract, together with occurrence at an early age, characterize the carcinoma in Peutz-Jeghers syndrome. In Japanese patients, the large bowel is the site of the greatest number of carcinomas. On the other hand, Western patients showed a relatively even distribution. A possible surveillance protocol for early detection of gastrointestinal carcinoma in patients with Peutz-Jeghers syndrome is discussed.

Colonoscopic polypectomy in diagnosis and treatment of early carcinoma of the large intestine

Histologic investigation and analysis of 370 polyps, removed via colonoscope, demonstrated a malignancy rate of adenomas of about 20 per cent. Even small adenomas under 1 cm in diameter were found to have a higher malignant potential than previously appreciated. The malignancy rate was higher with increasing size, and adenomas in females had a much higher malignant potential than in males. It is obvious that colonoscopic polypectomy is valuable in detecting and treating early carcinomas of the colon.

Distribution and quantification of somatostatin in inflammatory disease.

To study the possible alteration of mucosal-submucosal somatostatin-containing cells in inflammatory bowel diseases (IBD), the total numbers of somatostatin-containing endocrine cells (SCEC) and submucosal ganglion cells (SGC) were counted in Crohns disease (CD) and ulcerative colitis (UC). Tissue specimens from 25 CD and 25 UC patients were fixed in Hollandes fixative immediately after resection and were investigated by immunohistochemical staining. A single specimen was collected from 25 colorectal cancer patients, the control group. There was a significant difference in the number of SCEC between the tissues taken from the proximal colon (ascending and transverse colon) and the distal colon (descending and sigmoid colon). The distal colon tended to contain more somatostatin-immunoreactive cells than did the proximal colon. In IBD, SCEC were decreased in number compared with the controls. This decrease was related to the degree of inflammation in CD; the higher the grade of inflammation, the lower the number of SCEC. The number of SGC was decreased in IBD: however, a significant decrease was noticed only in CD. The anatomic origin and the degree of inflammation did not affect the number of SGC. In the present study, the decrease of somatostatin-containing cells was noticed in both CD and UC, but there was no significant difference between CD and UC. Therefore, it was assumed that this decrease was secondary to inflammation. However, the decrease of somatostatin, which works as an inhibitory peptide for inflammation, might have some role in the pathogenesis of IBD.

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.

Prevention of local recurrence by extended lymphadenectomy for rectal cancer

This study was undertaken to determine if the degree of lymphadenectomy correlates with the prevention of local recurrence. The authors retrospectively reviewed the clinical data of 269 patients who underwent curative surgery for rectal cancer. The study was divided into three periods based on the method of lymphadenectomy as follows: period I (1963–1979) when extended lymphadenectomy was not performed; period II (1980–1985) when this was partially done with no attempt to dissect the obturator and proximal middle rectal lymph nodes; and period III (1986–1990) when this was completely performed for patients with appropriate indications. The local recurrence rates were 21%, 10%, and 8% for Periods I, II, and III, respectively (P<0.05). The incidence of local recurrence tended to be greater in period I versus periods II and III according to type of operation, location, and stage of the primary tumors. The local recurrence rates arising from lateral node metastases were 11%, 4%, and 2% for periods I, II, and III, respectively (P<0.05), while the incidence related to an insufficient surgical margin was approximately 5% throughout the three periods. We thus conclude that the degree of lymphadenectomy is a major determinant of local recurrence following a curative operation for rectal cancer.