Health-related quality of life in patients with lower rectal cancer after sphincter-saving surgery: a prospective 6-month follow-up study.

This longitudinal descriptive study examined whether rectal cancer patients report changes in health-related quality of life (HRQOL) over a 6-month period after different types of sphincter-saving surgery (SSS): intersphincteric resection (ISR), ultra-low anterior resection (ULAR) and low anterior resection (LAR). It also compares HRQOL among the three groups of patients. Seventy-three patients from two hospitals in Japan completed questionnaires on HRQOL and defecation symptoms immediately before surgery and 1 and 6 months afterwards. Results showed that ISR patients had significantly worse HRQOL scores than ULAR and LAR patients and more defecation symptoms that persisted during the 6 months post-SSS. Thus, patients undergoing ISR require psychological and social support, including skills in competent self-management, during the early post-operative period. Furthermore, defecation problems substantially influence HRQOL. The first month post-SSS is particularly challenging. The assumption that HRQOL is better after SSS compared to living with a permanent stoma might not be valid.

Phase I/II study of irinotecan and UFT for advanced or metastatic colorectal cancer.

UNLABELLED: The aim of this study was to determine the recommended dose of irinotecan in combination with the fixed dose of oral UFT as first-line therapy in patients with advanced or recurrent colorectal cancer, and to evaluate the response rate and overall survival as a phase II study. PATIENTS AND METHODS: Thirteen patients were recruited into a phase I trial. Four doses of irinotecan ranging from 60 to 150 mg/m2/day were administered intravenously on day 1 and day 16 in combination with UFT given orally from day 2 to day 15. In a phase II study, 53 patients received at least one cycle of this therapy. RESULTS: The recommended dose of this combination was determined as irinotecan 120 mg/m2/day and UFT 400 mg/m2/day. Dose-limiting toxicities were neutropenia and prolonged leucopenia. On an intent-to-treat analysis, the response rate in the phase II study was 24.5% (95% confidence interval 13.8% to 38.2%). The median overall survival time was 20.3 months (95% confidence interval, 15.0-22.8 months). Out of 20 patients with stable disease, 17 who received more than 4 cycles of the regimen lived longer than the other 3 patients who received fewer than 3 cycles (p = 0.0353). Hematological adverse events were mainly grade 3/4 neutropenia observed in 6 out of 53 patients. Grade 3 non-hematological toxicities, such as diarrhea, anorexia, nausea/vomiting and alopecia were observed in 6 patients. CONCLUSION: Irinotecan combined with oral UFT was effective and well-tolerated. This regimen may be considered as a first-line therapy for advanced or metastatic colorectal cancer and may result in fairly long survival, even for patients with stable disease.

Close correlation between mutations of E2F4 and hMSH3 genes in colorectal cancers with microsatellite instability.

Defects in mismatch repair function can lead to the microsatellite instability (MI+; replication error) phenotype in certain human cancers. We previously reported that MI+ tumor-specific repeat number alteration at 13 consecutive trinucleotide (CAG) repeats within a coding exon of the E2F4 gene is a possible target of the defective repair pathway. Additional investigations revealed that E2F4 mutations are common (11 of 17 cases, 65%, mostly deletions) in a subset of human colorectal cancers with extensive MI+ phenotype, with respect to the proportion of loci affected and that most of these E2F4-mutated tumors (9 of 11, 82%) were accompanied by frameshift mutations in a polyadenine stretch within the seventh exon of the hMSH3 gene, a known mismatch repair gene that is responsible for repair of mismatch loops of two to four nucleotides. However, neither of these mutations was detected in 15 tumors with a lower incidence of MI+ loci. Similar repeat number alterations were less frequent in CAG repeats from other genes in all of the MI+ tumors we examined. These results indicate the presence of a novel cascade of mutational events that may be involved in acquisition of the malignant phenotype of human colorectal cancers with genetic instability.

Multiple microcarcinoids in a patient with long standing ulcerative colitis.

A male patient with a 17 year history of intractable ulcerative colitis of the entire type was treated by total proctocolectomy. Colonoscopy before surgery did not identify dysplasia. Histological examination of the resected colorectum revealed that, in addition to chronic inflammatory infiltrates, there were 21 areas of microcarcinoids located in the muscularis propria and in the superficial layer of the submucosa. Carcinoids may be more common than previously thought, and they may be a reactive phenomenon to a variety of factors in ulcerative colitis.

Association between thyroid cancer of cribriform variant and familial adenomatous polyposis.

A case of a 20 year old Japanese woman who developed thyroid cancer exhibiting unusual cribriform structures while being followed up for familial adenomatous polyposis/Gardner's syndrome is reported. The patient presented with osteomas, pigmented retinal lesions, and adenomas of the duodenum and the papilla of Vater, in addition to numerous adenomatous polyps in the colorectum. On ultrasonography, the thyroid cancer was localised to the right lobe and was identified as an irregular, internal echo tumour with a peripheral hypoechoic zone, measuring 1.8 cm in diameter. Histological examination of the resected tumour showed a concomitance of papillary proliferation and cribriform structures with follicles of varying sizes. These features can be distinguished from sporadic thyroid cancer.

Gallstones and their composition in patients with ileoanal anastomosis.

Cholelithiasis is known to occur in 15%-24.5% of proctocolectomized patients. However, the clinical features and chemical analysis of gallstones in these patients have not been reported. We describe two cases of cholelithiasis that developed in patients after proctocolectomy with ileoanal anastomosis. These patients had a high output of watery stools and more frequent bowel movements than the average for Japanese patients with ileoanal anastomosis. The chemical composition of the resected gallstones was 93.0% cholesterol and 80.9%, respectively, in the two patients, indicating that cholesterol gallstones are formed in patients with ileoanal anastomosis after proctocolectomy.

Comparison of blood flow assessment between laser Doppler velocimetry and the hydrogen gas clearance method in ischemic intestine in dogs.

Blood flow of the colon and the ileum was measured before and after intestinal devascularization by laser Doppler velocimetry and the hydrogen gas clearance technique in 10 dogs in order to evaluate the clinical usefulness of laser Doppler velocimetry. The submucosal blood flow of the colon and the ileum measured by the hydrogen gas clearance method was significantly decreased, as was the subserosal blood flow of both sites measured by laser Doppler velocimetry. There was a linear relationship between the flow values using the two methods both in the colon (r = 0.7192, p less than 0.001) and in the ileum (r = 0.7646, p less than 0.001). These data suggested laser Doppler velocimetry may be a useful method to assess the degree of intestinal ischemia because of its noninvasiveness and good correlation with submucosal blood flow by the hydrogen gas clearance technique.

Complete ten-year postgastrectomy follow-up of early gastric cancer.

The postoperative courses of 109 patients with early gastric carcinoma treated from 1970 through 1976 were followed for 10 years. The cumulative 5-year survival rate was 96 percent and the 10-year survival rate was 92 percent. In this series, there was no significant difference in the survival rates between the mucosal cancer and submucosal invasion groups or between patients with and without lymph node metastasis. Five patients died from the recurrent cancer. The other causes of death were metachronous primary cancer in eight patients, synchronous primary cancer of sigmoid colon or rectum in two, cerebrovascular accident in six, heart disease in six, other causes in four, and unknown causes in four. Although the prognosis of early gastric cancer is remarkably good, patients should be carefully followed over a long period for late recurrence of the primary cancer and possible metachronous cancer of the other organs.

p53 and PTEN/MMAC1 mutational analysis of the small-intestinal cancer.

A 66-year-old female, suffering from small-intestinal cancer underwent resection of the small intestine. Genome DNAs were extracted from the patient's blood and small-intestinal cancer and were subjected to a polymerase chain reaction-single strand conformation polymorphism and nucleotide sequence analysis for exons of the p53 and PTEN/MMAC1 genes to search for any mutations. The sequence analysis revealed a point mutation of the p53 codon 93 in the cancer DNA; however, no mutation of the PTEN/MMAC1 gene was observed in either the blood or cancer DNA. The p53 mutation, therefore, seems to be related to tumour progression of small-intestinal cancer; however, no relationship was found between the PTEN/MMAC1 gene and the small-intestinal cancer.

Intraoperative enteroscopy detects more lesions but is not predictive of postoperative recurrence in Crohn's disease.

BACKGROUND: The aim of this investigation was to elucidate the clinical value of intraoperative enteroscopy (IOE) for Crohn's disease, and to determine the value of IOE in predicting recurrent disease. METHODS: In this study 27 patients requiring surgery were examined by both preoperative radiography and IOE. The findings obtained by these procedures in the remnant small intestine were compared. In 19 patients, the clinical course and colonoscopic or radiographic findings after surgery were analyzed. RESULTS: Intestinal lesions were identified in 23 patients by IOE, and in 19 patients by radiography. Longitudinal ulcers were equivalently detected by IOE (63%) and radiography (56%), whereas small ulcers and inflammatory polyps were less frequently detected by radiography than by IOE (37% vs 74% and 19% vs 33%, respectively). Neither the presence nor the distribution of IOE findings was related to postoperative recurrence. CONCLUSIONS: Whereas IOE demonstrates small intestinal lesions in detail, the procedure alone cannot predict postoperative recurrence in Crohn's disease.

Risk of cancer development in the rectal remnant of patients with familial adenomatous polyposis/Gardner's syndrome.

BACKGROUND/AIMS: Current treatment for familial adenomatous polyposis usually entails total colectomy. However, the question of whether or not to remove the rectum has yet answered decisively. This paper represents an attempt to clarify the position on whether the surgeon should remove the rectum. PATIENTS AND METHODS: Twenty patients from 16 families with the established diagnosis of FAP, or Gardner's syndrome, who had been treated by total colectomy with ileorectal anastomosis, were followed up by proctoscopy for at least 5 years. The clinical features were compared between the patients with histologically verified rectal cancer and those who had been free from cancer development. RESULTS: During the observation periods ranging from 5 to 27 years (mean, 11.4 years), five rectal cancers were identified in 4 patients. These cancers included two cancers in adenomas, two nonpolypoid cancers, and one invasively ulcerating tumor. While the clinical and pathologic features at surgery and the incidence of colonic cancer in the resected specimen had not differed between the patients with rectal cancer and those without cancer, the former group of patients had more colonic polyps and they tended to have been observed over longer periods than the latter group of patients. CONCLUSION: These findings suggest that clinical features at surgery of patients with FAP are not relevant for predicting the development of rectal cancer during follow-up.

Rapidly and infiltratively growing Crohn's carcinoma of the small bowel: serial radiologic findings and a review of the literature.

We carried out a retrospective evaluation of serial changes in the small bowel radiographs of a patient with small bowel cancer accompanied by long-standing Crohn's disease. During the 8 months before diagnosis, marked morphological changes were noted. A solitary and irregular protrusion, and rapidly growing stricture under careful medical management of the underlying disease may indicate the development of cancer.

Comparison of accuracy of physical examination and endoanal ultrasonography for preoperative assessment in patients with acute and chronic anal fistula.

BACKGROUND: This study was undertaken to evaluate the accuracy of endoanal ultrasonography for preoperative assessment of anal fistula, with special reference to the difference between acute and chronic fistula. METHODS: The subjects comprised 401 patients treated for acute or chronic anorectal sepsis of cryptoglandular origin during the period January through December 2005. All patients underwent physical examination and endoanal ultrasonography. Agreement between the physical and endosonographic findings and the definitive surgical findings were evaluated with special reference to classification of the primary tract and horseshoe extension and localization of the internal opening. The difference in accuracy of endosonographic assessment between acute and chronic fistula was also evaluated. RESULTS: The accuracy of endoanal ultrasonography was significantly higher than that of physical examination in detecting the primary tract (88.8% vs. 85.0%, p=0.0287) and horseshoe extension (85.7% vs. 58.7%, p<0.0001) and in localizing the internal opening (85.5% vs. 69.1%, p<0.0001). Furthermore, localization of the internal opening by endosonography was significantly more accurate in chronic fistula than in acute fistula (89.5 % vs. 76.8%, p<0.0001), although the accuracy in detecting the primary tract and horseshoe extension was not significantly different. CONCLUSIONS: Endoanal ultrasonography is reliable and useful for preoperative assessment of anal fistula, particularly for detecting horseshoe extension and localizing the internal opening. Endosonographic assessment provides clearer depiction of the internal opening during periods of quiescence than during the period of abscess formation. For patients with acute anorectal sepsis, initial surgical drainage and subsequent fistula surgery, rather than one-stage fistula surgery, may be advisable to avoid misidentification of the internal opening.

Effect of total colectomy and mucosal proctectomy on intestinal absorptive capacity in dogs.

Changes in intestinal absorptive capacity for water and electrolytes were investigated in dogs after total colectomy and mucosal proctectomy reconstructed with interposing jejunum into the anorectal area. Rate of absorption of water and sodium from the ileum increased significantly at 29 weeks postoperatively. The absorption of water, sodium, and chloride in the jejunum was significantly higher than in the neorectum. The net secretion rate of potassium increased significantly in the ileum and neorectum. The authors suggest that intestinal adaptation achieved after proctocolectomy is enhanced in the jejunum and ileum rather than in the neorectum.

Morphology following proctocolectomy in dogs: effect of introduction of a 'neocolon' using an interposed jejunal segment.

Intestinal mucosal morphology was studied in dogs given a new reconstruction procedure following proctocolectomy in which a jejunal segment was interposed between the terminal ileum and the anus to function as a 'neocolon'. Chronic inflammatory cell infiltration, villous atrophy, and fibrosis of the lamina propria were sought in three different intestinal sites and assigned a severity score. Twenty-four weeks after proctocolectomy, villous atrophy and fibrosis of the lamina propria were noted both in the interposed jejunum (neocolon) (p < 0.05, p < 0.01, respectively) and the terminal ileum (p < 0.05, p < 0.05, respectively). Similar changes were also observed in the proximal jejunum, but a significant difference compared to the preoperative time was not seen. Fibrosis of the lamina propria in the interposed jejunum tended to be more advanced than that in the other two sites. A statistical difference in severity was obtained between the interposed jejunum and the proximal jejunum (p < 0.05). Chronic inflammatory cell infiltration was similar in all sites examined. No obvious evidence of acute inflammation was found at any site examined. These data suggest that chronic morphologic changes inevitably occur at any site in the remaining intestine after proctocolectomy and that an interposed jejunal segment is most severely affected. The new interposition procedure may be effective in reducing the morphologic changes in the terminal ileum because of its proximal displacement.

Clinical and manometric evaluation of anorectal function following low anterior resection with low anastomotic line using an EEA stapler for rectal cancer.

Anorectal function was evaluated in eight patients who had low anterior resection of the rectum with a low anastomotic line, using an EEA stapler, with determination of function based on periodic manometric studies and clinical symptoms. Immediately following surgery all patients suffered from frequent bowel actions and soiling. These symptoms improved with time and most patients could enjoy almost normal daily life by the sixth postoperative month. One month after surgery, anal canal resting pressure and maximum squeeze pressure were significantly reduced and rectoanal inhibitory reflex was absent; neither showed a distinct tendency to improve thereafter. Rectal sensation and reservoir capacity, which also were seriously impaired, recovered satisfactorily by the time of the six-month examination. This suggests that an improvement of clinical symptoms following this operation is dependent upon the recovery of reservoir capacity and sensation of the neorectum, and that this operative procedure is a functionally acceptable option for low rectal cancer.

Regional difference in intestinal adaptation after total colectomy as judged by the changes of mucosal Na-K ATPase, cyclic AMP, and transmural potential difference.

Intestinal adaptation and its regional difference after total colectomy were investigated in dogs by measuring mucosal Na-K ATPase, cyclic AMP, and transmural electric potential difference (PD). Twenty-four weeks after the total proctocolectomy, Na-K ATPase activity and PD increased significantly in all intestinal sites, whereas cyclic AMP showed no significant changes. The regional difference in the remaining intestine was examined in the jejunum, ileum, and interposed jejunum (neorectum). Na-K ATPase activity showed no significant regional difference, but the largest increase was found to occur in the ileum. PD also increased markedly in the ileum and there was significant difference between the ileum and other intestinal sites. These facts suggest that the increased active ion transport mediated by mucosal Na-K ATPase and transmural PD in the ileum is closely related to the intestinal adaptation occurring after total colectomy and indicates a greater potential of the ileum for adaptive compensation than either jejunum or neorectum.