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Background: Coloanal anastomosis and radiotherapy for the treatment of lower rectal carcinoma have been receiving increasing attention., Methods: Patients with rectal cancer were divided into two groups: anoabdominal rectal resection and colonic J pouch-anal anastomosis (CAA) plus preoperative intraluminal brachytherapy (IBT) (group 1; 68 patients) and CAA without IBT (group 2; 23 patients). Group 3, comprising 59 patients who underwent abdominoperineal excision (APE), was examined as a control group. Comparative results were reviewed., Results: Postoperative complications occurred more frequently in group 1 than in group 2. Actuarial 5-year survival rates were 73 per cent in group 1, 64 per cent in group 2 and 63 per cent in group 3. Cumulative local recurrence rates at 5 years were 11 per cent in group 1, 38 per cent in group 2 and 21 per cent in group 3. Intestinal continuity breakdown was seen in 14 per cent of all patients at 5 years after initial operation., Conclusion: The combination of CAA and preoperative IBT resulted in decreased local recurrence. IBT followed by CAA can be a good restorative option for combating lower rectal cancer.

Background: Radiation therapy in the treatment of rectal carcinoma has received attention. We attempted to learn whether preoperative intraluminal brachytherapy (IBT) gives an advantage in local control and/or prolongation of survival., Methods: One hundred and fifteen patients with middle and lower rectal carcinoma with penetration into or through the rectal wall were consecutively treated with preoperative IBT and radical operation. Patients were divided into the moderate-dose group (group A: 16-40 Gy; n = 96) and the high-dose group (group B: 40-80 Gy; n = 19). A control group of 115 rectal carcinoma patients who received no radiation prior to radical surgery was compared (group C)., Results: The rate of sphincter-saving resection was 72% in group A, 63% in group B, and 42% in group C (group A vs. group C; P < 0.0001). The local recurrence rate at 5 years was 11% in group A, 6% in group B, and 26% in group C (group A vs. group C; P = 0.005). The 5-year survival rate was similar among the three groups., Conclusions: These results suggested that IBT contributed to the improvement of local control but not survival after radical resection of rectal carcinomas. The application of IBT might be useful in preserving the intestinal continuity for rectal carcinomas.

To evaluate the factors that contribute towards the regrowth of rectal carcinoma after pre-operative radiotherapy. Of 120 patients, we pre-operatively treated with intraluminal brachytherapy or external beam radiotherapy since 1986, two showed regrowth of rectal carcinoma. For them, the case reports and findings for the resected specimen obtained using immunohistochemical staining for the P53 tumor suppressor gene (P53) and proliferating cell nuclear antigen (PCNA) were retrospectively evaluated. The regrowth of rectal carcinoma was observed 40 days after intraluminal brachytherapy in one patient, and 33 days after external radiotherapy in the other. Both P53 and PCNA staining was seen in the recurrent tumors or during the examination of the resected specimen. These results suggest that polypoid tumors with regrowth have a malignant potential. The interval between radiotherapy and operation reported in the literature varies widely. The potential for regrowth should be considered in the preoperative radiotherapy for rectal cancer.

The aim of this study was to determine the postoperative function of neorectoanal components using two different types of very low coloanal reconstruction. The two groups of patients assessed were 22 who underwent abdominal rectal resection and stapled "high" coloanal anastomosis without a pouch, being the HCAA-P group; and 34 who underwent anoabdominal rectal resection and "low" coloanal anastomosis with a colonic J-pouch, being the LCAA + P group. Manometric examination was performed 1, 3, 6, and 12 months postoperatively, and the patients were also assessed by a questionnaire. The LCAA + P group had remarkably less daily stool frequency and urgency, but there were no significant differences in the other functional parameters. Maximum resting pressure (MRP) was significantly less, while threshold volume (TV) and maximum tolerable volume (MTV) were greater in the LCAA + P group than in the HCAA-P group. The colonic J-pouch compensated for decreased MRP. Thus, when HCAA-P is performed, 3.0 cm of residual rectum with internal anal sphincter may be required, and construction of the pelvic pouch is desirable in low coloanal anastomosis.

Purpose: Usefulness of transrectal ultrasonography (TRUS) for detecting distal intramural spread of rectal carcinoma was investigated., Methods: Thirty-seven patients with advanced rectal carcinoma, who had not received preoperative adjuvant therapy, underwent TRUS before surgery. Distal intramural spread was evaluated by TRUS and by pathologic examination of resected specimens., Results: Distal intramural spread was found in 7 of 37 patients (19 percent) by pathologic examination. Presence or absence of distal intramural spread was correctly diagnosed by TRUS in 86 percent of the 37 patients. Misdiagnosis by TRUS mainly occurred when distal intramural spread was 5 mm. Tumor penetration of muscularis propria, lymph node involvement, and a higher histologic grade of malignancy showed a significant relationship with the presence of distal intramural spread., Conclusion: TRUS was useful for detecting distal intramural spread > 5 mm in patients with lower rectal carcinoma and may be helpful for selecting appropriate surgery.

A 44-year-old female with rectal cancer underwent anoabdominal rectal resection and colonic J pouch-anal anastomosis after preoperative intraluminal brachytherapy. Pelvic sepsis developed a rectovaginal fistula. We attempted to close the fistula and restore the anal function with coloanal re-anastomosis and bilateral gluteus maximus transposition. She regained good anal function without recurrence of the fistula.

In this study, we evaluated the postoperative functional results after resection of rectal carcinoma. A questionnaire and anal manometry were used to evaluate the severity of the symptoms. The patients were divided into the three groups of anterior resection (AR, 38 patients), low anterior resection (LAR, 34 patients) and stapled colo-anal anastomosis (SCA, 20 patients). Manometric examination and questionnaire evaluation were performed 1, 3, 6, and 12 months after the operation. The SCA group showed by far the poorest outcome in terms of soiling and urgency at 12 months. Anal sensation was recovered by 12 months in each group. Incomplete evacuation was frequently observed in the SCA and LAR groups. Each anal manometric parameter recovered in the AR group, but the maximum tolerable volume of the neorectum did not recover in either the SCA or LAR group. The threshold volume of the SCA group was lower than those in the other two groups. The reservoir function of the neorectum, which is composed of the colorectal muscle layer and nervous components, plays a role in maintenance of bowel function.

Background: We evaluated the ability of magnetic resonance imaging (MRI) to define local extension of rectal carcinoma., Study Design: Thirty-three patients with rectal carcinoma were preoperatively assessed by MRI., Results: When sagittal or coronal images, or both, were added to transverse images as needed, the sensitivity rate was 84.2 percent and the specificity rate was 92.9 percent. False-positive results when using only transverse images were mainly related to slight extramural spread, to an anterior location in the lower rectum (partial volume effect), and to massive extramural spread of the middle rectal tumors., Conclusion: Preoperative MRI was helpful to define tumor extension three-dimensionally.

The effects of preoperative intraluminal brachytherapy on bowel function after anoabdominal rectal resection and colonic J pouch-anal anastomosis were studied. The patients included eight not receiving irradiation (group 1), eight who received 30 Gy (group 2) and eight who received 80 Gy (group 3). Stool frequency and the incidence of soiling were significantly greater in group 3 than in the other groups. Anal resting pressure was lower in group 3 during the study period but J pouch distensibility was not reduced. The maximum tolerated volume, threshold volume and squeeze pressure were significantly lower in group 3 than in the other groups in the early postoperative period. These results suggest that high-dose brachytherapy affects the anal sphincters and colonic J pouch. A moderate dose of 30 Gy may be more suitable before restorative anorectal surgery.

Background: There has recently been increasing interest in coloanal reconstruction after proctectomy for low rectal carcinoma. We describe here our pilot experience with seven patients undergoing modified anoabdominal resection of the rectum and a colonic J-pouch anal anastomosis., Methods: The procedure varied according to the extent of internal anal sphincter (IAS) resection (type a, partial resection of the upper IAS; type b, circumferential resection of the upper IAS; type c, partial preservation of the lower IAS; and type d, total resection of the IAS)., Results: None of the patients had incontinence, but preservation of the lower half of the IAS (types a and b) showed functional superiority over more extensive IAS resection (types c and d). Only patients who underwent types c and d resection needed medications to reduce stool frequency., Conclusions: Our results suggest that the lower half of the IAS has a more important role than the upper half in the control of defecation. Total resection of the IAS did not sacrifice continence, but preservation of at least the lower IAS resulted in a better quality of life. Careful patient selection is needed when considering the use of these procedures for tumors in the lowest part of the rectum.

To examine whether the dosage effect of germ-line mutations in patients with familial adenomatous polyposis (FAP) is sufficient to cause colorectal adenomas, or an additional somatic mutation of the normal allele is required as well, we have investigated somatic mutations of the APC gene in multiple adenomas developed in one FAP patient. In addition to a 5-bp deletion of one allele present constitutionally in this patient, the normal APC allele had been lost in five of seven DNA samples extracted from small adenomas (< 3 mm in diameter) with mild or moderate atypia. This result indicates that the inactivation of both alleles of the APC gene is probably essential for the development of an early-stage adenoma, in agreement with the two-hit mutational model underlying the concept of tumor suppressor genes.

We have found that in all patients who have undergone this procedure, normal defecation and complete continence are maintained. The surgical wound heals well and functional results have been uniformly good, even in instances in which only 1 centimeter of the rectum remains. This procedure may be useful for patients who are carefully diagnosed by preoperative transrectal ultrasonography in which the lower edge of the rectal tumor is within 8 centimeters of the anal verge, the tumors do not extend into the muscularis propria and there is no lymph node metastasis. Use of the CEEA stapling device can shorten the time of operation and is particularly beneficial for elderly patients and those who are at poor risk.

Since 1980, when the first description of hyperplastic polyposis of the colon appeared, 18 cases of hyperplastic polyposis have been reported in the literature. Only two of them bore colonic cancer. Here we add two cases of hyperplastic polyposis accompanying rectal carcinoma following cancer resection, in which residual hyperplastic polyps disappeared after resection.

Previous studies suggested that one or more genes on chromosome 5q21 are responsible for the inheritance of familial adenomatous polyposis (FAP) and Gardner's syndrome (GS), and contribute to tumor development in patients with noninherited forms of colorectal cancer. Two genes on 5q21 that are tightly linked to FAP (MCC and APC) were found to be somatically altered in tumors from sporadic colorectal cancer patients. One of the genes (APC) was also found to be altered by point mutation in the germ line of FAP and GS patients. These data suggest that more than one gene on chromosome 5q21 may contribute to colorectal neoplasia, and that mutations of the APC gene can cause both FAP and GS. The identification of these genes should aid in understanding the pathogenesis of colorectal neoplasia and in the diagnosis and counseling of patients with inherited predispositions to colorectal cancer.

Protein kinase C (PKC) activity was measured in normal-appearing colonic mucosa from patients undergoing colonic resection. Comparisons were made between cases with and without colorectal cancers. PKC activity in cytosolic and particulate fractions was significantly reduced in patients with colorectal cancer: 40 +/- 9 and 114 +/- 29 (pmol/min/mg) respectively, compared with patients without cancer; 129 +/- 11 and 250 +/- 38 (pmol/min/mg) (p less than 0.05). Normal-appearing colonic mucosa in patients with cancer showed significantly decreased total PKC activities in the cytosolic and particulate fractions compared with those in patients without cancer (10 +/- 1 and 20 +/- 3 vs. 30 +/- 2 and 33 +/- 6) (pmol/min/g tissue) (p less than 0.05). The cellular distribution (% particulate fraction) of PKC activity in normal-appearing mucosa in patients with cancer (64%) was higher than in patients without cancer (49%) (p less than 0.05). OUr data suggest that PKC activity may be used as a biological marker of risk of developing colorectal cancer or risk of bearing an asymptomatic tumor.

A 63-year-old man with recurrent rectal carcinoma was treated with high-dose-rate intraluminal brachytherapy (6 Gy x 4). After treatment, anal pain and bleeding were greatly improved. He died as a result of liver metastasis, but he was able to evacuate the bowels until death. bowels until death.

The authors report a case of the passage of a total colonic J-pouch "cast" per anus after anoabdominal rectal resection and colonic J-pouch-anal anastomosis. This occurred without development of cuff abscess and was not due to occlusion of the inferior mesenteric artery. This was successfully treated, with preservation of anal function, with resection of the colonic J-pouch by transanal approach.

It is said that the Paneth cells are found in the large intestine in a pathological state such as ulcerative colitis or adenoma. We examined the Paneth cells in the adenomas of familial polyposis coli. Nine cases including one case of Gardner's syndrome comprised the material for the examination of the Paneth cells because the caecum was available for the examination. The remaining one case had no Paneth cells. In two cases, the Paneth cells were found among the adenomas in the areas beyond the caecum and the proximal part of the colon ascendens. In one remarkable case, the Paneth cells were found in 43% of the adenomas in the caecum. Seven cases were carcinomas but no Paneth cells were found in or near the carcinoma. In the control cases, which were taken from the resected colon with a disease other than familial polyposis coli, the Paneth cells were found confined to the caecum. We concluded that the distribution of the Paneth cell-bearing adenomas reflects the distribution of the Paneth cells in the normal mucosa of the large intestine and that the Paneth cells in the adenoma may have differentiated in the adenoma.

A human colon carcinoma cell line was established from a metastatic lymph node of a patient with hereditary adenomatosis of the colon and rectum (ACR). Cells of this line, designated KMS-4, have been continuously propagated in culture during the past 24 months. The cells growing on the surface of culture dishes showed epithelial features, and, when inoculated into athymic nude mice, produced adenocarcinomas with a morphology similar to that of the original tumor. Electron micrographs showed that the cultured cells have desmosomes and numerous surface microvilli typical of colon epithelium. Chromosomal analysis revealed the cell line to be of human origin with a diploid mode of chromosome number, but the karyotypes examined were all abnormal. Most of the metaphases commonly had such abnormalities as 7p+, 12p+, +13, +16 and 17p+, accompanied by loss of chromosome No. 19 and/or 20, and, interestingly, all the metaphases contained 7p+ and +13. The cells had a log phase doubling time of 48 to 72 h. The cloning efficiency of the cells was 0.06% in the soft agar medium. Neither 12-O-tetradecanoylphorbol-13-acetate nor bile acids enhanced cell proliferation. The cells abundantly secreted CEA protein into the culture medium (700 ng/ml/106 cells during a 48 h period). The present colon carcinoma cell line derived from a genetically defined individual with ACR should prove useful for research in human oncology or genetics.

We have studied the chromosomal sensitivity to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) of human diploid skin fibroblasts derived from individuals with adenomatosis coli (AC), which is a dominantly inherited disorder associated with multiple adenomas of the colon and rectum. Spontaneous frequencies of chromosome aberrations in the cell strains from the AC patients were similar to those in the control cells from normal individuals. However, the AC cells exhibited elevated chromosome instabilities when cells were expected to MNNG, with aberration frequencies approximately twice as high as in similarly treated control cells. The present results, together with findings by others, suggest that the AC cells are defective in a function which regulates cellular condition and are in a state more susceptible to the action of agents that react with chromosomal DNA. These findings also raise the possibility of developing a diagnostic procedure for early detection of abnormal gene carriers of AC.

Lethal effects of mitomycin C (MMC), 4-nitroquinoline 1-oxide (4NQO) and ultraviolet light (UV) on fibroblast cell lines derived from a colon cancer-prone substrain of Wistar-Furth rats (WF/OSAKA rats) were measured in terms of the cellular colony-forming ability, and compared with the sensitivity to these agents of human fibroblasts from patients with adenomatosis coli and rectum (ACR). All 6 fibroblast strains from the cancer-prone WF/OSAKA rats were significantly more sensitive (though to various extents) to MMC as well as 4NQO than normal rat fibroblasts derived from the parental WF Hiroshima rats. These WF/OSAKA cell strains were slightly more sensitive to UV than normal rat cell strains. Similarly, 5 out of 6 fibroblast strains derived from ACR patients were hypersensitive to both MMC and 4NQO. Further, the WF/OSAKA cell strains were more susceptible to morphological transformation induced by Kirsten murine sarcoma virus than normal rat strains. The observed higher sensitivity to chemical agents and to viral transformation suggests a close similarity in cellular terms between the colon cancer-prone WF/OSAKA rats and human individuals affected with ACR.