Biomedical subjects

Mitsuhiro Nakamura

Publications and source records attributed to Mitsuhiro Nakamura.

At least 19 recordsLinked to original sources

PubMed2006

Diffuse gastroduodenitis and pouchitis associated with ulcerative colitis.

We experienced a very rare case of ulcerative colitis (UC) accompanied with analogous lesions in the stomach, duodenum, and ileal J-pouch. Ileal J-pouch anal anastomosis was performed on a 29-year old woman in 1996. Six years later, she was admitted again to our hospital because of epigastralgia, nausea, watery diarrhea and low fever. Based on the results of endoscopic examination, we diagnosed it as pouchitis. Moreover, on hypotonic duodenography, expansion of the duodenal bulb and the descending portion were poor. Kerckring folds disappeared with typical lead-pipe appearance. The pathogenesis of the gastric and duodenal lesion in this patient was similar to that of the colonic lesions of UC. For the gastroduodenal lesions in this patient, symptomatic remission was obtained following administration of crushed mesalazine tablets (1500 mg/d) for 14 d with continuous administration of omeprazole. Firstly we used ciprofloxacin to treat pouchitis. On the fifth day, she got a fever because of catheter infection. In the catheter culture, methicillin-resistant Staphylococcus aureus (MRSA) was detected. Therefore we changed ciprofloxacin to vancomycin hydrochloride (Vancomycin). Vancomycin was very effective, and the stool frequency dramatically improved in three days. Now she continues to take mesalazine, but her condition is stable and there has been no recurrence of pouchitis.

Adult↗

PubMed2006

Stereoisomeric bio-inversion key to biosynthesis of firefly D-luciferin.

The chirality of the luciferin substrate is critical to the luciferin-luciferase reaction producing bioluminescence. In firefly, the biosynthetic pathway of D-luciferin is still unclear, although it can be synthesized in vitro from D-cysteine. Here, we show that the firefly produces both D- and L-luciferin, and that the amount of active D-luciferin increases gradually with maturation stage. Studies of firefly body extracts indicate the possible conversion of L-cysteine via L-luciferin into D-luciferin, suggesting that the biosynthesis is enzymatically regulated by stereoisomeric bio-inversion of L-luciferin. We conclude that the selection of chirality in living organisms is not as rigid as previously thought.

Animals↗

PubMed2006

Relationship between the shape of tibial spurs on X-ray and meniscal changes on MRI in early osteoarthritis of the knee.

OBJECTIVE: The purpose of this study was to evaluate the relationship between the shape of tibial spurs on plain X-rays and the meniscal changes on magnetic resonance imaging (MRI) in early osteoarthritis of the knee. MATERIALS AND METHODS: Sixty-three patients (age range, 40 to 59 years; average, 51.8) underwent X-ray and MRI examinations of their knees. Ligament injuries caused by trauma and Kellgren Radiographic Grades III and IV on X-ray were excluded. The shapes of the medial and lateral tibial spurs on X-ray were classified into four types: (a) normal type; (b) horizontal type, in which the spur protruded horizontally; (c) upward type, in which the spur protruded upward; and (d) downward type, in which the spur protruded downward. The femorotibial angle (FTA) on the X-rays was also measured. The medial and lateral meniscal displacement rates on MRI were measured by the proportion by which the meniscal lesion protruded from the edge of the tibial joint surface to the overall meniscal width. The medial and lateral meniscal signal changes on MRI were classified into three types: (a) normal type; (b) intrameniscal type, which showed a high signal within the meniscus; and (c) tear type, which showed a high signal extending to the tibial joint surface. The relationships between the shape of the medial and lateral tibial spur classification on X-ray, the medial and lateral meniscal displacement rates on MRI, the medial and lateral meniscal signal changes on MRI and the FTA were evaluated statistically. RESULTS: Statistically significant correlations were observed between the medial tibial spur classification on X-ray, the medial meniscal displacement rate on MRI and the medial meniscal signal change classification on MRI. In the downward type of medial tibial spur, the medial meniscal displacement rate (50.46+/-17.95%) and the percentage (8 out of 8 cases; 100%) involving the tear type of medial meniscus were greater than the other types. Statistical significance was not observed among the lateral tibial spur classification on X-ray, the lateral meniscal displacement rate on MRI and the lateral meniscal signal change classification on MRI. However, in the horizontal type of lateral tibial spur, the percentage (7 out of 10 cases; 70%) involving the tear type of lateral meniscus was greater than the other types. Correlations tended to be observed between the medial meniscal displacement rate on MRI and the FTA. CONCLUSIONS: In this study, there was a relationship between the shape of the tibial spur on X-ray and the meniscal changes on MRI in early osteoarthritis of the knee. The shape of the medial tibial spur on X-ray can be a useful indicator for predicting the progression of osteoarthritis of the knee. A downward type of medial tibial spur classification on X-ray may be a risk factor for developing severe osteoarthritis of the knee.

Adult↗

PubMed2006

Incidence of and risk factors for dysplasia in mucosectomy area in ulcerative colitis patients undergoing restorative proctocolectomy.

BACKGROUND AND AIMS: We evaluated the incidence of dysplasia in the mucosectomy area using resected specimens to determine preoperative risk factors for the occurrence of dysplasia in this area. PATIENTS AND METHODS: We prospectively studied a consecutive series of 137 patients, each of whom underwent a restorative proctocolectomy with a mucosectomy and hand-sewn ileal J-pouch anal anastomosis between January 2003 and December 2004. Sections from the anal transitional zone mucosa were taken from the dentate line to 2.5 cm above the resected line and stained with hematoxylin and eosin then characterized as indefinite for dysplasia, low-grade dysplasia, and high-grade dysplasia based on the criteria of an international working group for rectal mucosal atypia. RESULTS: Dysplasia of the mucosectomy area was present in six (4.4%) of the patients, including one with low-grade and five with high-grade dysplasia. A multivariate analysis showed relations between age at time of surgery (>or=40 years) and duration of disease (>or=10 years) with a risk for development of mucosectomy area dysplasia. CONCLUSION: The incidence of dysplasia of the mucosectomy area was 4.4%, and preoperative risk factors were shown to be duration of disease and age at time of surgery.

Adolescent↗

PubMed2006

Excipient hydrolysis and ester formation increase pH in a parenteral solution over aging.

Recently, the number of drug substances that are poorly water-soluble has increased dramatically. This makes improving solubility one of the most critical tasks in pharmaceutical development today. In this study, the physicochemical stability of an injectable solution of conivaptan hydrochloride salt was investigated. Because its free form is hydrophobic, the drug substance was solubilized in a co-solvent system, 40% of which was composed of different alcohols. Since the free form is also alkaline, lactic acid was added to the co-solvent system to further improve its solubility. Remarkably, the pH of the solution was found to increase gradually over time. Considering the physicochemical nature of the drug substance, uncontrolled increases in pH would pose a potential threat of reducing solubility and forming precipitates. For this reason, a risk evaluation was performed. The evaluation revealed that the pH increase was caused by the hydrolysis of lactic acid oligomers as well as by the ester formation occurring between lactic acid and the alcohols. High concentrations of lactic acid supplied as an excipient usually contain lactic acid oligomers, which are hydrolyzed into lactic acid monomers upon dilution with water. Commercial software was used to determine the pK(a) values of the lactic acid oligomers, which were found to be lower than that of lactic acid monomers. This indicates that hydrolysis causes the pH to increase. Ester formation consumes the acid, which also causes the pH to increase. However, both hydrolysis and ester formation equilibrated by the 16-month time point when stored at 25 degrees C. This information allowed the upper limit of the pH increase to be determined molecularly, thereby ensuring product quality through the prevention of precipitate formation due to reduced solubility. Increased awareness of the importance of risk evaluation in pharmaceutical development is critical as these kinds of chemical reactions between excipients constitute a potential risk factor, but tend to be overlooked.

Antidiuretic Hormone Receptor Antagonists↗

PubMed2006

Postoperative joint symptoms: a risk factor for pouchitis in ulcerative colitis patients.

BACKGROUND: The prevalence and significance of joint symptoms appearing in patients with ulcerative colitis (UC) following a colectomy are unclear. AIM: We investigated the relationship between joint symptoms during steroid tapering following an ileal pouch-anal anastomosis (IPAA) and the cumulative risk for developing pouchitis. PATIENTS AND METHODS: The medical records of 571 patients who underwent an IPAA with a mucosectomy were retrospectively reviewed to evaluate their joint symptoms. A diagnosis of pouchitis was obtained using the Pouchitis Disease Activity Index (PDAI) and the cumulative risk of pouchitis was estimated using a Kaplan-Meier life table analysis. RESULTS: Joint symptoms during steroid tapering were reported by 126 (22.0%) of the UC patients and each of those had involvement of the small joints of the hand. The main symptoms were pain and stiffness, especially in the morning. The cumulative risk for developing pouchitis after 10 years was found to be 20% in patients who experienced joint symptoms during steroid tapering and 10% in those without those symptoms (p = 0.001). CONCLUSION: The presence of joint symptoms during steroid tapering is a significant risk factor for the development of pouchitis in patients who have undergone an IPAA for UC.

Adolescent↗

PubMed2006

Leukocyte removal therapy for ulcerative colitis does not affect postoperative complications.

BACKGROUND: We investigated the incidence of postoperative complications in patients treated with or without preoperative leukocyte removal therapy (LRT). METHODS: The case notes of 387 patients with ulcerative colitis (UC) who underwent surgical intervention were retrospectively reviewed. One hundred nine patients were treated with LRT within 8 weeks before surgery (LRT group), and 278 had not received LRT since at least 8 weeks before surgery (without LRT group). We reviewed the postoperative complications according to type of initial operation. RESULTS: Of the patients who underwent an ileal J-pouch anal anastomosis (IPAA) without an ileostomy, 3 (6.5%) in the LRT group developed pouch-related complications (PRC), while 11 (7.5%) in the without LRT group developed PRC. The overall postoperative complication rates were 28.3% in the LRT group and 21.8% in the without LRT group. For patients who underwent an IPAA with an ileostomy, the overall rates of postoperative complications were 39.1% in the LRT group and 31.8% in the without LRT group. Among those undergoing a total colectomy, 33.3% in the LRT group and 18.2% in the without LRT group had postoperative complications. No statistically significant differences were demonstrated between the two groups with respect to postoperative complications. CONCLUSIONS: Our results suggest that preoperative LRT does not influence the rate of postoperative complications in UC patients.

Adolescent↗

PubMed2006

High Twist expression is involved in infiltrative endometrial cancer and affects patient survival.

Epithelial-mesenchymal transition (EMT) is critical not only for morphogenesis during embryonic development but also the conversion of early-stage tumors into infiltrative phenotypes. The present study examines the expression of Twist, a highly conserved bHLH transcription factor that is known to promote EMT, and evaluated its prognostic significance in endometrial cancers. Tissue specimens from 70 patients with endometrial cancer who underwent primary surgery were immunohistochemically evaluated for Twist expression. A semiquantitative scoring system was developed based on the intensity and extent of cancer cells with Twist expression. Thirty-six patients (51%) exhibited high Twist expression and 34 (49%) had low expression. Most cases exhibited both cytoplasmic and nuclear staining mainly observed in cancer foci and, preferentially, at the margin but, in some cases, the stromal cells located adjacent to cancer foci as well. Among various clinical variables, high Twist expression was significantly associated with deep myometrial invasion (>1/2) (P = .012) and concurrent with decreased E-cadherin expression (P < .001), a hallmark of EMT. In univariate survival analyses, both myometrial invasion and Twist expression influenced overall survival, but Cox multivariate analyses revealed that only Twist was an independent predictor of patient survival (hazard ratio, 5.12; P = .023). Thus, our data implies that high Twist expression is a potential novel prognostic factor for disease survival of endometrial cancer. Furthermore, the present study implicates Twist as a potential therapeutic target for this tumor type.

Adenocarcinoma↗

PubMed2005

Firefly luciferase exhibits bimodal action depending on the luciferin chirality.

Firefly luciferase is able to convert L-luciferin into luciferyl-CoA even under ordinary aerobic luciferin-luciferase reaction conditions. The luciferase is able to recognize strictly the chirality of the luciferin structure, serving as the acyl-CoA synthetase for L-luciferin, whereas d-luciferin is used for the bioluminescence reaction. D-Luciferin inhibits the luciferyl-CoA synthetase activity of L-luciferin, whereas L-luciferin retards the bioluminescence reaction of D-luciferin, meaning that both enzyme activities are prevented by the enantiomer of its own substrate.

Acyl Coenzyme A↗

PubMed2005

Analysis of telomeric single-strand overhang length in human endometrial cancers.

The 3' single-strand telomeric overhang (3'-OH) is a key component of telomere structure. Although telomere length has been well analyzed in a variety of human cancers, no information is available on the 3'-OH length in cancers. In the present study, we examined the 3'-OH length in normal and malignant endometria using telomere-oligonucleotide ligation assay. Although 3'-OH lengths varied among patients, 3'-OH length observed in endometrial cancers was significantly shorter than that found in samples derived from normal endometria (P < 0.001: Student's t-test), suggesting that erosion of 3'-OH length induces impaired telomeric integrity and genomic instability, leading to carcinogenesis. Interestingly, we found that the most aggressive subtypes of endometrial cancers harbored significantly longer 3'-OH length than those with non-aggressive subtypes (P < 0.001: Sheffe's test), suggesting that cancer cells with long 3'-OH length have growth advantage due to their stabilized telomere ends. In contrast, we failed to observe an association between overall telomere length and any clinicopathological characteristics of endometrial cancers. These findings suggest that erosion of 3'-OH length, rather than overall telomere length, play roles in endometrial carcinogenesis. Furthermore, long 3'-OH may serve as a molecular marker for aggressive phenotype of tumors.

Blotting, Southern↗

PubMed2005

Adenylyl cyclase-cAMP system inhibits thrombin-induced HSP27 in vascular smooth muscle cells.

We previously reported that thrombin stimulates the induction of heat shock protein (HSP) 27 via p38 mitogen-activated protein (MAP) kinase activation in aortic smooth muscle A10 cells. In the present study, we investigated the effect of the adenylyl cyclase-cAMP system on the thrombin-stimulated induction of HSP27 in A10 cells. Forskolin, a direct activator of adenylyl cyclase, reduced the thrombin-induced p38 MAP kinase phosphorylation, and significantly suppressed the thrombin-stimulated accumulation of HSP27. However, dideoxyforskolin, a forskolin derivative that does not activate cAMP, failed to suppress the HSP27 accumulation. Furthermore, dibutyryl-cAMP (DBcAMP), a permeable analog of cAMP, significantly suppressed the accumulation of HSP27. On the other hand, calphostin C, an inhibitor of protein kinase C (PKC), reduced the thrombin-induced p38 MAP kinase phosphorylation, and significantly suppressed the thrombin-stimulated accumulation of HSP27. Moreover, forskolin reduced the p38 MAP kinase phosphorylation induced by the 12-O-tetradecanoylphorbol-13-acetate (TPA), a PKC-activating phorbol ester, and significantly suppressed the TPA-stimulated accumulation of HSP27. These results indicate that adenylyl cyclase-cAMP system has an inhibitory role in thrombin-stimulated HSP27 induction in aortic smooth muscle cells, and the effect seems to be exerted on the thrombin-induced PKC- p38 MAP kinase signaling pathway.

Adenine↗

PubMed2005

Safety of one-stage restorative proctocolectomy for ulcerative colitis.

PURPOSE: The aim of this study was to compare clinical outcomes in patients with ulcerative colitis who underwent restorative proctocolectomy with and without diverting ileostomy. METHODS: A series of 245 consecutive patients who underwent ileal pouch anal anastomosis with mucosectomy with an ultrasonically activated scalpel (harmonic scalpel) was studied. Of these patients, 92 patients had a diverting ileostomy and 150 selected patients did not. The decision for or against an ileostomy was made at the end of the operation. RESULTS: Twelve patients (8 percent) in the group without ileostomy had pouch-related complications, which necessitated secondary ileostomy in five patients (3.3 percent). Intestinal obstruction developed in 17 patients (11.3 percent) who had no ileostomy and in 12 patients (13.0 percent) who underwent ileostomy. Two of 17 patients who had no ileostomy and 1 of 12 patients with ileostomy required laparotomy with division of adhesions, whereas the remaining patients responded to conservative measures. There were no significant differences in the incidence of postoperative complications after the initial operation between the two groups. In the group with ileostomy, the morbidity rate for ileostomy was 12.1 percent, and that for ileostomy closure was 18.7 percent. The total postoperative complication rate for the group with ileostomy was significant higher than that for the group without ileostomy. CONCLUSION: We conclude that restorative proctocolectomy with mucosectomy by use of an ultrasonically activated scalpel and without diversion is a superior therapeutic choice for selected patients.

Adolescent↗

PubMed2005

Aberrant expression and mutations of TGF-beta receptor type II gene in endometrial cancer.

OBJECTIVE: Transforming growth factor beta (TGF-beta) is a multifunctional cytokine that strongly inhibits epithelial cell growth. Disabling of TGF-beta signaling is thought to be involved in development of a variety of tumors in which abnormal expression or function of TGF-beta receptor plays critical roles. In the present study, we examined aberrant expression and mutation of the gene TGF-beta receptor type II (TbetaRII) in endometrial cancers of endometrioid subtype. METHODS AND RESULTS: Real-time PCR analysis using surgical tissue specimens of 27 endometrial cancers and 24 normal endometria revealed that endometrial cancers had significantly decreased levels of TbetaRII mRNA expression (mean level 2.44 +/- 2.65), compared to normal endometria (mean level 7.23 +/- 6.07) (P < 0.001). Methylation status of TbetaRII promoter containing 30 CpGs was examined by bisulfite sequencing analysis, and 98% (51/52) of the patients were found to have unmethylated TbetaRII promoter, indicating that promoter hypermethylation is not the major cause of decreased expression of TbetaRII in endometrial cancers. Mutational analysis revealed that 15.1% (8/53) of endometrial cancers had frameshift mutations at polyadenine repeats in exon 3 of the TbetaRII gene. Notably, these mutations were preferentially accumulated in patients with MSI-H phenotype (7/19:37%) (P < 0.001) or with those with methylated MLH1 promoters (6/16:38%) (P < 0.01). Thus, it appears that the TbetaRII gene is a target of mismatch repair deficiency. CONCLUSION: Taken together, we found that the decreased expression of TbetaRII as well as frameshift mutation of TbetaRII via mismatch repair deficiency frequently occurs in this tumor type, possibly causing loss of receptor function and unresponsiveness of TGF-beta signaling that may lead to endometrial carcinogenesis.

Acetylation↗

PubMed2005

Efficient inhibition of human telomerase reverse transcriptase expression by RNA interference sensitizes cancer cells to ionizing radiation and chemotherapy.

Telomerase activation plays critical roles in tumor growth and progression in part through the maintenance of telomere structure. Indeed, the ubiquitous expression of telomerase in human cancers makes telomerase a promising target for cancer therapy. Genetic, pharmacologic, and antisense methods to inhibit telomerase have been described; however, in most cases, cancer cell death was observed only after many cell divisions. Here, using retroviral delivery of small interfering RNAs (siRNAs) specific for the human telomerase reverse transcriptase (hTERT), we successfully inhibited telomerase activity in cervical cancer cell lines. Cells lacking hTERT expression exhibited significantly decreased telomerase activity and showed shortened telomeres and telomeric 3' overhangs with passage. These cells entered replicative senescence after a considerable number of cell divisions. Notably, the proliferative rate of these cells was significantly impaired, compared with control cells with telomerase activity, even in low-passage cells (population doubling 5). Likewise, colony-forming ability and tumorigenicity in mice were attenuated in low-passage cells lacking hTERT. We further examined the effects of chemotherapy and ionizing radiation on cells in which hTERT expression was suppressed. Cells lacking hTERT showed a significantly increased sensitivity, compared with control cells, to ionizing radiation or chemotherapeutic agents that induce DNA double- strand breaks, such as topoisomerase inhibitors or bleomycin. These findings suggest that an siRNA-based strategy can be applied to the development of novel telomerase inhibitors, the antitumor effects of which may be enhanced in combination with ionizing radiation and chemotherapy.

Animals↗

PubMed2005

Pharmacokinetics of paclitaxel in ovarian cancer patients and genetic polymorphisms of CYP2C8, CYP3A4, and MDR1.

Interindividual differences in the pharmacokinetics of paclitaxel and its metabolites in Japanese ovarian cancer patients were investigated in relation to genetic polymorphisms of the CYP2C8, CYP3A4, and MDR1 genes. The area under the concentration-time curve (AUC) ratios of paclitaxel/6alpha-hydroxypaclitaxel and paclitaxel/3 -p-hydroxypaclitaxel calculated as the metabolic index of CYP2C8 and CYP3A4 showed 13- and 12-fold interindividual variations, respectively. No patient had any CYP2C8 variants, while 2 patients were heterozygotes of CYP3A4*16. For the MDR1 gene, the frequencies of -129C, 1236C, 2677T, 2677A, and 3435T alleles were 2.2%, 8.7%, 56.5%, 4.4%, and 52.2%, respectively. Subjects possessing the 3435T allele had a significantly (P < .05) higher AUC of 3'- p-hydroxypaclitaxel compared to those possessing the 3435C allele. Leukocytopenia was significantly (P < .05) related to the AUC of paclitaxel. Genotyping of the CYP2C8, CYP3A4, and MDR1 genes might not be essential to predict adverse effects of paclitaxel in Japanese patients, although an allelic variant of MDR1 may functionally affect the pharmacokinetics of its metabolite.

Area Under Curve↗

PubMed2005

Novel relationship between the antifungal activity and cytotoxicity of marine-derived metabolite xestoquinone and its family.

Xestoquinone and related metabolites (the xestoquinone family) occur in marine sponges and are known to show a variety of biological activities. In this study, the first comprehensive evaluation of antifungal activity was performed for xestoquinone and nine natural and unnatural analogues in comparison with their cytotoxicity. The cytotoxicity against two human squamous cell carcinoma cell lines, A431 and Nakata, indicated that the terminal quinone structure of the polycyclic molecules was important (xestoquinone, etc.) and that the presence of a ketone group at C-3 of the opposite terminus dramatically diminished the activity (halenaquinone, etc.). In contrast, a ketone group at C-3 enhanced the antifungal activity against the plant pathogen, Phytophthora capsici, regardless of the presence of a quinone moiety. The cytotoxicity and antifungal activity of the xestoquinone family were negatively correlated with each other.

Animals↗

PubMed2005

Association of mismatch repair deficiency with PTEN frameshift mutations in endometrial cancers and the precursors in a Japanese population.

We studied mismatch repair deficiency and PTEN (phosphatase and tensin homologue deleted on chromosome 10) mutations in endometrial cancers and hyperplasias in a Japanese population. Methylation-sensitive restriction enzyme polymerase chain reaction revealed MLH1 hypermethylation in 21 (38%) of 56 endometrial cancers. Sequencing analysis revealed PTEN mutations in 22 patients with cancer (39%) in exons 5 and 8. A PTEN frameshift mutation was associated significantly with MLH1 hypermethylation (P = .01) and a highly positive phenotype with microsatellite instability (P < .001) but not with a PTEN missense mutation. In hyperplasia, MLH1 hypermethylation was similarly observed (11/27 [41%]), but the PTEN mutation was less frequent (5/27 [19%]), observed only in atypical hyperplasias; among the 5 patients with a PTEN mutation, the 2 patients with frameshift mutations had MLH1 hypermethylation, but the 3 patients with missense mutations had unmethylated MLH1. These findings indicate that MLH1 hypermethylation is an early event frequently occurring in hyperplasia without atypia, whereas the PTEN mutation occurs later, mostly in atypical hyperplasia, possibly caused by MLH1 hypermethylation.

Adaptor Proteins, Signal Transducing↗

PubMed2004

Incidence and therapeutic outcome of pouchitis for ulcerative colitis in Japanese patients.

AIM: The aim of this study was to examine the cumulative risk of pouchitis following restorative proctocolectomy for UC and FAP in Japanese patients, and to assess the response to medical treatment and its outcome. PATIENTS AND METHODS: 521 patients with UC and 117 FAP patients underwent proctocolectomy and received a J-shaped IPAA at our department of surgery. We investigated these patients using PDAI for the diagnostic criteria of pouchitis. RESULTS: Pouchitis occurred in only 32 UC patients (6.1%). The cumulative risk of developing pouchitis for a UC patient was 7% at 5 years after and 12% at 10 years after surgery. The medical treatment of acute pouchitis was usually oral metronidazole (250 mg twice daily) for 2 weeks or oral ciprofloxacin (200 mg thrice daily) in patients who could not tolerate metronidazole. Single episodes of pouchitis occurred in 21 patients (65.6%) and chronic or frequent relapses of pouchitis in 11 patients (34.4%). Three patients (9.4%) required re-ileostomy. Two patients (6.3%) required pouch excision. There were no patients with complicated dysplasia. CONCLUSION: The cumulative risk of pouchitis in Japanese UC patients is lower than that of western countries.

Adenomatous Polyposis Coli↗