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.

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.

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.

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.

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.

Association of enhanced cyclooxygenase-2 expression with possible local immunosuppression in human colorectal carcinomas.

BACKGROUND: Prostaglandin (PG) E2 has an influence on antitumor lymphocyte reactions and causes local immunosuppression at tumor sites. The contribution of cyclooxygenase (COX), a key enzyme in PGE2 synthesis, to this effect is still unclear. We examined if cyclooxygenase (COX)-2 is involved in local immunosuppression in human colon carcinoma cell lines and in clinical tumor specimens. METHODS: PGE2 concentrations were measured in culture media from a highly COX-2-expressing human colon carcinoma cell line (CE-1) and other cell lines. Lymphocyte proliferation in response to a mitogen was used to evaluate immunosuppression in tumor cell-lymphocyte cocultures with and without selective COX-2 inhibitor NS-398. We also evaluated expression of COX-2 mRNA in surgical specimens of colorectal carcinoma by reverse transcription polymerase chain reaction (RT-PCR) and COX-2 protein by immunohistochemistry, correlating COX-2 expression with clinicopathologic features. RESULTS: CE-1 cells produced large amounts of PGE2, which was significantly inhibited by NS-398. The proliferation index of lymphocytes cocultured with CE-1 cells was significantly less than that of control lymphocytes; again, this effect was inhibited by NS-398. While human colorectal carcinoma tissue expressed more COX-2 mRNA and protein than nonneoplastic tissue, no significant correlation was found between COX-2 levels and clinicopathologic features. CONCLUSIONS: Overexpression of COX-2 in colon cancer may cause local immunosuppression, and COX-2 inhibitors might be therapeutically useful against these tumors.

Quantitative analysis of hTERT mRNA expression in colorectal cancer.

OBJECTIVES: Telomerase is highly activated in a variety of malignant neoplasms including colon cancer. Among the major components of telomerase, human telomerase reverse transcriptase (hTERT) is thought to regulate telomerase activity. To assess the importance of telomerase for the diagnosis of colorectal cancer, we measured the expression of hTERT mRNA and telomerase activity in a large series of 140 colorectal cancers, 140 adjacent normal tissues, and 20 adenomas. METHODS: The expression level of hTERT was measured quantitatively by competitive reverse transcriptase-polymerase chain reaction (RT-PCR), and telomerase activity was examined by telomeric repeat amplification protocol (TRAP) assay in the same samples. RESULTS: The median expression level of hTERT mRNA in carcinomas was significantly higher than that in either adenomas or normal tissues. The median level of hTERT in adenomas was significantly higher than that in normal tissues. Telomerase activities in carcinomas were significantly higher than those in either adenomas or normal tissues. Telomerase activities in adenomas were also significantly higher than those in normal tissues. Furthermore, the relative expression levels of hTERT mRNA in adenomas and carcinomas were significantly correlated with the relative telomerase activities; the Spearman rank correlation was 0.53 (p = 0.021) and 0.18 (p = 0.031), respectively. CONCLUSIONS: Our data suggest that determination of hTERT mRNA by competitive RT-PCR is superior in quantitative accuracy and sensitivity and would support the importance of telomerase activity for the diagnosis of colorectal 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.

A simplified defaecographic procedure for the assessment of faecal incontinence or obstructed defaecation.

OBJECTIVE: Various types of defaecography have been reported for research purposes. A simplified method for clinical use has not been devised for the assessment of disordered defaecation. The aim of this study was to describe a simplified procedure of defaecography and evaluate its usefulness in the diagnosis of faecal incontinence or obstructed defaecation. PATIENTS AND METHODS: Anorectal manometry and simplified defaecography were performed in 82 consecutive patients. The procedure of defaecography consisted of instillation into the rectum with a 100% weight per volume of barium in the sitting position through a Foley catheter with an inflated balloon, and several series of static radiograph at rest, during squeezing and straining according to deflation of the balloon. RESULTS: Positive rate of barium leakage after barium insertion was significantly higher in incontinent patients than constipated or asymptomatic patients (P < 0.001, respectively). The degree of barium leakage was classified into mild in 18 patients with faecal incontinence, moderate in 4 and severe in 2. Constipated patients had more difficulty trying to expel a catheter than incontinent or asymptomatic patients (P=0.001, P=0.03). Twenty-four percent of patients with obstructed defaecation could not expel the balloon and 48% could not evacuate barium sulphate completely. The positive rate of morphological changes such as rectocele, internal intussusception and band formation was higher in constipated patients than incontinent or asymptomatic patients (P=0.01, P=0.04). CONCLUSION: The grade of barium leakage or balloon prolapse reflected the severity of faecal incontinence. The ability in rectal emptying of the balloon or barium sulphate also correlated with the degree of outlet obstruction. The authors concluded that the present defaecographic technique was useful for the assessment of faecal incontinence or functional outlet obstruction, and recommend it due to its simplicity.

Nitric oxide synthase expression and nitric oxide production in human colon carcinoma tissue.

BACKGROUND AND OBJECTIVES: Nitric oxide (NO), the production of which is dependent on NO synthase (NOS), has been shown to contribute to various pathogeneses in cancer. The aim of this study was to determine whether inducible NO synthase (iNOS) is overexpressed in human colon carcinoma tissue, and whether NO is produced in tumor tissue. METHODS: We investigated iNOS mRNA expression in 24 human colon carcinoma tissue specimens by reverse transcription-polymerase chain reaction (RT-PCR). We then examined the expression of iNOS protein and nitrotyrosine, which indicates NO production in tissue, by immunohistochemistry. The possible immunosuppressive role of NO produced by colon carcinoma cells was analyzed in vitro. RESULTS: Semiquantitative RT-PCR analysis showed that iNOS mRNA expression in carcinoma tissues is elevated significantly compared to that in noncarcinoma tissue. Immunohistochemistry revealed that iNOS and nitrotyrosine are expressed strongly in carcinoma tissues. In vitro experiments showed that the supernatant from a culture of cytokine-treated colon carcinoma cells, which contained high levels of NO, significantly reduced the phytohemagglutinin (PHA)-stimulated, human lymphocyte proliferative response (60% of the control value). CONCLUSIONS: In human colon carcinoma tissue, iNOS mRNA, protein, and NO products are overexpressed and may contribute to tumor-related immunosuppression.

Mediastinal lymph node metastasis of colon cancer: report of a case.

We herein describe a patient with mediastinal lymph node metastases which occurred after both a primary sigmoid colon cancer and metachronous ovarian metastasis had been resected. The most likely route of metastases to the mediastinum in this case is the paravertebral venous plexus probably connected to the ovarian metastasis, or so-called remetastasis. This case illustrates that the mediastinum is thus a possible metastatic site in patients with colon cancer. Surgeons should therefore pay attention to the mediastinum as well as the lung fields when checking chest X-ray films during a follow-up of patients after a resection of colon cancer.

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.

Terminal ileal transposition procedure in ileoanal anastomosis following proctocolectomy.

We introduced a terminal ileal transposition procedure (TITP) in ileal pouch-anal anastomosis, in which a 50 to 70 cm isolated ileal segment 20 to 40 cm from the ileocecal valve was interposed between the terminal ileum and the anus. Twelve patients underwent this procedure in two or three-staged operations. Mean stool frequency per 24 hours was 4.4 +/- 1.7, and stool consistency was formed and soft in all patients at the mean of 13 months after TITP. We observed neither surgical technique-related complications nor metabolic disorders, except for iron deficiency anemia, during and after the operations. The serum level of vitamin B12 significantly increased after the operation in eight patients (P < 0.05). TITP has advantages such as preventing the terminal ileum from metabolic dysfunction due to pouchitis, avoiding sacrifice of the terminal ileum in the two-staged operation, and obviating the need for reconstruction of ileostomy in the three-staged operation. It may also promote intestinal absorption and reduce late metabolic complications.

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.

Change in colonic motility after extrinsic autonomic denervation in dogs.

Changes in colonic motility were compared in dogs undergoing autonomic denervation of the paraaortic and presacral (group A), paraaortic (group B), or mesocolonic region (group C), and sham operation (group D). Five bipolar recording electrodes were placed into the seromuscular layer of the colon and rectum. The numbers of continuous electrical response activity and contractile electrical complex after an intragastric olive oil injection were smaller in group A than in the other groups (P < 0.05) from three weeks through six months after denervation. This difference was significant even in the proximal colon. These data suggest that the pelvic plexus may play an important role in colonic motility including the proximal colon. The damage to the plexus did not recover for at least six months after denevation. Pelvic plexus injury may thus be one of possible explanations for the prolonged change in bowel habit after anterior resection of the rectum.