Kazuyo Tsuchiya

Factors influencing outcome after surgery for stage IV colorectal cancer

PurposeAccording to the classification system of the Japanese Society for Cancer of the Colon and Rectum, Stage IV colorectal cancer is characterized by distant metastasis, which is defined by four factors: liver metastasis (H factor), metastasis to organs other than the liver (M factor), peritoneal dissemination (P factor), and distant lymph node metastasis (N factor). We conducted this study to investigate the postsurgical prognosis of patients with Stage IV colorectal cancer (CRC), in reference to each of these four factors.MethodsWe analyzed the medical records of 73 patients who underwent surgery for Stage IV CRC at our hospital between 1991 and 2001.ResultsUnivariate analysis revealed that P0 or P1 CRC (P < 0.001), absence of the M factor (P = 0.024), well or moderately differentiated adenocarcinoma (P < 0.001), resection of the primary tumor (P < 0.001), and curability B surgery (P < 0.0001) were associated with a better prognosis than other types of Stage IV CRC. Multivariate analysis revealed that tumor differentiation and surgical curability affected cancer-specific survival significantly.ConclusionSurgery with curative intent should be considered for patients with Stage IV CRC defined by the P1 factor or H factor.

Results of seton drainage and infliximab infusion for complex anal Crohn's disease.

BACKGROUND/AIMS To investigate the efficacy of infliximab for complicated perianal Crohns disease with special reference to maintenance therapy. METHODOLOGY Between June 2002 and April 2009, 20 patients (15 men and 5 women, aged 31.4±2.9 years old (mean ± standard error)) with complicated fistulizing anal Crohns disease underwent seton placement. For the induction therapy, intravenous infusion of infliximab was given 3 times after surgical treatment. Thereafter, infliximab was given every 8 weeks as maintenance therapy. Patients were followed-up for 31.8±4.2 months after the first infliximab infusion. The number of the infliximab treatments given was 13.6±2.5. RESULTS After induction therapy, complete response (CR) was observed in 8 patients (40%), partial response (PR) in 9 and progress disease (PD) in 3. With (n=17) or without (n=3) maintenance therapy following the induction therapy, CR was observed in 15 of 20 patients (75%). Of the 17 patients who received maintenance therapy, CR was of observed in 13 patients, of whom 7 patients showed PR or PD before maintenance therapy. CONCLUSIONS Seton drainage and infliximab therapy is effective in the patients with fistulizing perianal Crohns disease. Maintenance infliximab therapy might be effective in patients with perianal Crohns disease.

Adrenomedullin production is increased in colorectal adenocarcinomas; its relation to matrix metalloproteinase-9.

Adrenomedullin (AM) is highly expressed in various cancer cell lines, suggesting a possible association with cancer growth. In the present study, we examined the expression and/or concentration of AM, its related peptide, adrenomedullin2/intermedin (AM2/IMD) and their receptors in human colorectal cancer and the surrounding normal tissue. In addition, we assessed the correlation between the expression of AM and AM2/IMD with that of vascular endothelial growth factor (VEGF)-A and matrix metalloproteinase (MMP)-9. Using a specific immunoradiometric assay, we found that AM concentrations were 2-11-fold higher in colorectal cancer tissues than in the surrounding normal tissues. Moreover, real-time quantitative RT-PCR showed that the expression levels of preproAM (+548%), preproAM2/IMD (+2674%), calcitonin receptor-like receptor (CLR) (+518%), receptor activity modifying protein (RAMP)2 (+281%), RAMP3 (+178%), VEGF-A (+277%) and MMP-9 (+864%) mRNAs were significantly higher in cancer tissues than in the surrounding normal tissues, and there was a positive correlation between the gene expressions of MMP-9 and preproAM (r=0.352; p=0.005), but not with preproAM2/IMD (r=0.041, p=0.406). Both AM and AM2/IMD immunoreactivity were detected mainly within cancer cells, whereas MMP-9 immunoreactivity was mostly seen in the surrounding stroma. These findings suggest that AM produced in colorectal tumors acts in concert with MMP-9 in the stroma to contribute to the pathogenesis of colorectal cancer.

Side-to-side-to-end strictureplasty for Crohn's disease.

PURPOSE: Side-to-side strictureplasty is a useful procedure for preserving the bowel in patients with Crohn’s disease. However, bowel resection is required in some patients, and diseased proximal bowel and disease-free distal bowel exist after resection. We performed a modified new technique called side-to-side-to-end strictureplasty. METHODS: Four patients with Crohn’s disease underwent this procedure. After resection of the diseased bowel that was not suitable for strictureplasty, side-to-side strictureplasty was performed with use of the proximal diseased loop. Thereafter, the distal end of the side-to-side stricture was anastomosed to the distal disease-free bowel in a side-to-side-to-end manner. RESULTS: The length of the small intestine requiring surgical intervention was 69.8 ± 26.4 (mean ± standard deviation) cm, and the length of the small intestine necessitating resection was 31.8 ± 12.6 cm. Side-to-side stricture was performed by use of 48.8 ± 20.2 cm of the diseased proximal bowel, which was anastomosed to the disease-free distal bowel. Intra-abdominal abscess, which was not associated with this procedure, was observed in one patient, but was treated by drainage. The recoveries of all four patients were uneventful, without recurrence, after a follow-up of 21.5 ± 16.2 months. CONCLUSIONS: Side-to-side-to-end strictureplasty may be a useful procedure when diseased proximal bowel and disease-free distal bowel are present after bowel resection in patients with Crohn’s disease.

Frequency of CD4+CD161+ T Cell and Interleukin-10 Expression in Inflammatory Bowel Diseases

Mucosal immune dysregulation associated with T cells plays a critical role in the development of inflammatory bowel diseases (IBD). However, the definite significances of these cells in IBD still remain unclear. Therefore, we investigated the population and expression of CD4+CD161+ T cells in the colonic lamina propria mononuclear cells (LPMCs) in patients with IBD by analyses using flow cytometry and immunohistochemistry. Interleukin-10 (IL-10) mRNA levels in both LPMCs and CD4+ T cells in lamina propria (LP-CD4+ T cells) were measured using a real-time quantitative reverse transcription-polymerase chain reaction. IL-10 production was investigated with immunohistochemistry. The results revealed that the population of CD4+CD161+ T cells was significantly decreased in active ulcerative colitis (UC) compared with inactive UC (P < 0.05). The CD4+CD161+ T cell population was inversely correlated with disease activity in patients with UC (r = −0.6326, P = 0.0055), but there was no significant correlation in those with Crohn’s disease. Over-expression of IL-10 mRNA in both LPMCs and LP-CD4+ T cells were detected in active UC. Immunohistochemistry revealed decreased frequency of CD161+ cells and increased IL-10 positive cells in active UC. The frequency of CD4+CD161+ T cells and IL-10 expression was supposed to be associated with the pathological status of mucosal immunoregulation in IBD.

Fluorodeoxyglucose Positron Emission Tomography Can Provide Useful Information for Differentiating Thymic Epithelial Tumors

Abstract Background We examined the usefulness of fluorodeoxyglucose (FDG) positron emission tomography (PET) in predicting the World Health Organization (WHO) histologic type and Masaoka stage of thymic epithelial tumors. Methods A total of 73 patients with thymic epithelial tumors who underwent preoperative FDG‐PET were included. Relationships between the maximum standardized uptake value (SUVmax) and WHO histologic type and the Masaoka stage of the tumor were examined. Differences in SUVmax between the various groups were calculated. To avoid the effect of the tumor size on SUVmax, the ratio of SUVmax to tumor size (SUVmax/T) was also examined. Results There was a significant relationship between SUVmax and WHO histologic type. SUVmax of high‐risk thymomas (types B2 and B3) was significantly higher than that of low‐risk thymomas (types A, AB, and B1). SUVmax of thymic carcinomas was also significantly higher than those of the low‐risk and high‐risk groups. The relationship between the SUVmax/T and WHO histologic type showed more significant results. SUVmax and SUVmax/T showed higher values in patients with advanced Masaoka stage disease than in those with early‐stage disease. Conclusions FDG‐PET can provide useful information for differentiating thymic epithelial tumors. The SUVmax/T is more useful than the SUVmax for differentiating between low‐risk and high‐risk thymomas.

Rectal localized giant inflammatory polyposis with indeterminate colitis.

Only two cases of rectal giant inflammatory polyposis with ulcerative colitis have been reported in the English literature and both concern children. This is the first report of a case of localized giant inflammatory polyposis of the rectum in an adult with indeterminate colitis. A 71-year-old man underwent sigmoidectomy due to stenosis of the sigmoid colon. Final histological diagnosis was indeterminate colitis. Three years following the first operation, a rectal tumor with giant polyposis was observed, and abdominoperineal resection was performed. Macroscopic and microscopic examination indicated a localized giant inflammatory polyposis of the rectum.