Histologically confirmed case of cerebral vasculitis associated with Crohn's disease--a case report.

BACKGROUND: Extraintestinal manifestations in Crohn's disease (CD) are frequent and well recognized. However, neurological involvement secondary to CD is rare, and there have been few histologically confirmed cases of cerebral vasculitis secondary to CD. CASE PRESENTATION: A 58-year-old left-handed man with a history of refractory CD who had fever of over 38 °C, progression of CD symptoms, and Gerstmann's syndrome consulted our hospital. Laboratory data showed elevation of C-reactive protein (CRP) and hypoproteinemia. T2-weighted magnetic resonance imaging (MRI) revealed a right parietal high-intensity lesion. Catheter angiography showed segmental multiple narrowing and occlusion in the distal part of the middle cerebral artery and anterior cerebral artery. Angiography also revealed multiple venous occlusions in the affected parietal area. To confirm the diagnosis, the patient underwent open biopsy, and histological examination revealed cerebral vasculitis. The patient was then started on high-dose prednisolone (60 mg/day) in addition to his previous therapy, which included mesalazine, adalimumab, and azathioprine. CRP elevation, hypoproteinemia, and gastrointestinal symptoms immediately improved after starting this treatment. Neurological status improved simultaneously with CD symptom improvement, and follow-up brain MRI revealed a reduction in the size of the right parietal lobe lesion. He returned to normal status and was discharged from our hospital 5 weeks after admission. CONCLUSION: This is an important case of histologically confirmed cerebral vasculitis associated with CD. The clinical course of our case clearly illustrates the relevance of the occurrence of cerebral vasculitis and the exacerbation of CD.

MicroRNA-31 expression in colorectal serrated pathway progression.

MicroRNAs have been increasingly recognized as useful biomarkers for colorectal cancers (CRC). We have recently observed that microRNA-31 (miR-31) expression is associated with BRAF mutation and prognosis in CRC. Moreover, high miR-31 expression is frequently detected in sessile serrated adenomas compared with hyperplastic polyps (HPs). These results suggest that miR-31 may contribute to the progression of serrated lesions. At a follow-up colonoscopy, we observed the case of a 75-year-old man with a 7-mm flat-elevated lesion in the cecum and diagnosed the lesion as an early invasive carcinoma with serrated features. Tissue specimens were obtained from the representative areas to compare the molecular alterations in the carcinoma component with those in the HP component. Higher miR-31 expression was observed in the carcinoma component (57-fold increase) and the HP component (8-fold increase) compared with the paired normal mucosa, suggesting that miR-31 may be one of the key molecules in serrated pathway progression.

IGF2 differentially methylated region hypomethylation in relation to pathological and molecular features of serrated lesions.

AIM: To investigate insulin-like growth factor 2 (IGF2) differentially methylated region (DMR)0 hypomethylation in relation to clinicopathological and molecular features in colorectal serrated lesions. METHODS: To accurately analyze the association between the histological types and molecular features of each type of serrated lesion, we consecutively collected 1386 formalin-fixed paraffin-embedded tissue specimens that comprised all histological types [hyperplastic polyps (HPs, n = 121), sessile serrated adenomas (SSAs, n = 132), traditional serrated adenomas (TSAs, n = 111), non-serrated adenomas (n = 195), and colorectal cancers (CRCs, n = 827)]. We evaluated the methylation levels of IGF2 DMR0 and long interspersed nucleotide element-1 (LINE-1) in HPs (n = 115), SSAs (n = 120), SSAs with cytological dysplasia (n = 10), TSAs (n = 91), TSAs with high-grade dysplasia (HGD) (n = 15), non-serrated adenomas (n = 80), non-serrated adenomas with HGD (n = 105), and CRCs (n = 794). For the accurate quantification of the relative methylation levels (scale 0%-100%) of IGF2 DMR0 and LINE-1, we used bisulfite pyrosequencing method. Tumor specimens were analyzed for microsatellite instability, KRAS (codons 12 and 13), BRAF (V600E), and PIK3CA (exons 9 and 20) mutations; MLH1 and MGMT methylation; and IGF2 expression by immunohistochemistry. RESULTS: The distribution of the IGF2 DMR0 methylation level in 351 serrated lesions and 185 non-serrated adenomas (with or without HGD) was as follows: mean 61.7, median 62.5, SD 18.0, range 5.0-99.0, interquartile range 49.5-74.4. The IGF2 DMR0 methylation level was divided into quartiles (Q1 ≥ 74.5, Q2 62.6-74.4, Q3 49.6-62.5, Q4 ≤ 49.5) for further analysis. With regard to the histological type, the IGF2 DMR0 methylation levels of SSAs (mean ± SD, 73.1 ± 12.3) were significantly higher than those of HPs (61.9 ± 20.5), TSAs (61.6 ± 19.6), and non-serrated adenomas (59.0 ± 15.8) (P < 0.0001). The IGF2 DMR0 methylation level was inversely correlated with the IGF2 expression level (r = -0.21, P = 0.0051). IGF2 DMR0 hypomethylation was less frequently detected in SSAs compared with HPs, TSAs, and non-serrated adenomas (P < 0.0001). Multivariate logistic regression analysis also showed that IGF2 DMR0 hypomethylation was inversely associated with SSAs (P < 0.0001). The methylation levels of IGF2 DMR0 and LINE-1 in TSAs with HGD (50.2 ± 18.7 and 55.7 ± 5.4, respectively) were significantly lower than those in TSAs (61.6 ± 19.6 and 58.8 ± 4.7, respectively) (IGF2 DMR0, P = 0.038; LINE-1, P = 0.024). CONCLUSION: IGF2 DMR0 hypomethylation may be an infrequent epigenetic alteration in the SSA pathway. Hypomethylation of IGF2 DMR0 and LINE-1 may play a role in TSA pathway progression.

Exacerbation of bloody diarrhea as a side effect of mesalamine treatment of active ulcerative colitis.

Mesalamine has been used as the first-line therapy for the treatment of ulcerative colitis (UC) because of its efficacy and fewer side effects. However, earlier study showed that mesalamine occasionally causes diarrhea. We are presenting a patient with active UC in whom bloody diarrhea accompanied by abdominal pain and fever occurred and the symptoms were aggravated after administration of mesalamine. In order to clarify the reason of symptoms aggravation, drug lymphocyte stimulation test and rechallenge trial with mesalamine were performed. The results indicated the possibility that aggravation was related to allergic reaction and was dose-dependent. Furthermore, we examined colonoscopic views but there was no remarkable change in before and after rechallenge trial. Based on the above result, the patient was diagnosed with mesalamine intolerance. In order to differentiate whether the exacerbation of bloody diarrhea is due to the side effects of the mesalamine or a true relapse of UC, taking careful history before and after increasing mesalamine dosage as well as being aware of side effects of mesalamine are required. Clinicians should be aware of diarrhea as a side effect of mesalamine particularly after onset of mesalamine formulation, change in mesalamine formulation, or change in mesalamine dose.

[Sarcomatoid carcinoma of the liver: a case report and review of the literature].

A 66-year-old woman presented to our outpatient clinic with abdominal discomfort in April, 2008. Ultrasound revealed a hypo-echoic 10cm mass in the right hepatic lobe but no indication of chronic liver disease, with similar results in her history, on physical exam, and imaging. Serum testing did not identify any systemic disease. The mass was suspected to be intrahepatic cholangiocarcinoma and right hepatic lobectomy was performed. Histologic examination of the specimen revealed numerous spindle cells, and immunostaining confirmed a definitive diagnosis of sarcomatoid carcinoma of the liver. On subsequent review of the case, an abdominal CT performed 2.5 years earlier for unrelated symptoms had shown a 1cm faint low density area in the same location as the mass. The doubling time of this tumor was about 95 days.

[A case of primary retroperitoneal mucinous cystadenocarcinoma].

We encountered a case of primary retroperitoneal mucinous cystadenocarcinoma with ovarian-type stroma, an extremely rare condition. The patient was a 56-year-old woman with complaints of diarrhea, nausea, and abdominal fullness. Abdominal ultrasound revealed a nodular multi-cystic mass in the left lower quadrant of the abdomen. Subsequent contrast-enhanced CT and MRI determined it to be of retroperitoneal origin, consistent with a mucinous cystadenocarcinoma. Numerous small nodules were confirmed during the operation around the tumor suggesting local dissemination of the cancer and a left partial colectomy that included these nodules was performed. On histological examination, mucinous fluid was found trapped inside the cavity and poorly differentiated adenocarcinoma was observed in the solid portions. The ovarian-type stroma was confirmed in the layer beneath the epithelial lining and eventually a final diagnosis of mucinous cystadenocarcinoma was reached.

Genetic variants in surfactant, pulmonary-associated protein D (SFTPD) and Japanese susceptibility to ulcerative colitis.

BACKGROUND: Identifying culprit genes for a complex trait in a homogeneous population such as the Japanese remains challenging. We aimed to use previous achievements of genome-wide association studies to identify precise susceptibility loci for inflammatory bowel disease in Japanese people and to simultaneously investigate the replication of recently identified susceptibility loci. METHODS: An unrelated Japanese population of 174 Crohn's disease patients, 296 ulcerative colitis (UC) patients, and 394 healthy controls was consecutively enrolled in this study. Genotype and haplotype analyses focusing on susceptibility to inflammatory bowel disease were performed using 7 single nucleotide polymorphisms (SNPs) including 5 HapMap tag SNPs within surfactant, pulmonary-associated protein D (SFTPD) along with the 2 Caucasian susceptibility loci. We performed fine-scale mapping of trait-associated loci with the extension of a shattered coalescent process in a Bayesian framework. Epistasis on disease phenotypes was statistically explored with the interaction dendrogram. RESULTS: A minor allele G of rs911887 reached statistical significance for susceptibility to UC. The 2-allele haplotype GG comprising rs911887 and rs2243639 (Ala160Thr) within SFTPD was significantly associated with susceptibility to UC. A posterior density plot shows that trait-associated variants in the vicinity of rs911887 are likely to exist. An association between NKX2-3 and UC susceptibility was replicated and diverse evidence of epistasis in Japan was suggested. CONCLUSIONS: This preliminary study suggests that SFTPD is both a susceptibility gene and a disease-modifying gene for UC in Japanese. Replication of the causality and functional analyses of SFTPD is urgently warranted.

[Comparison of clinical results between TUR-P and holmium laser enucleation of the prostate (HoLEP) based on the initial experience].

OBJECTIVE: We compared the surgical results between holmium laser enucleation of the prostate (HoLEP) and transurethral resection of the prostate (TUR-P) for the treatment of men with benign prostatic hyperplasia (BPH). METHODS: A total of 87 patients with symptomatic BPH were analysed. HoLEP was performed on 46 men (mean age 68.2 +/- 7.5 years old) from December 2005 to February 2007, and TUR-P was performed on 41 men (mean age 69.2 +/- 7.3 years old) from April 2004 to March 2006. RESULTS: Both groups were comparable in terms of age, pre-operative IPSS, QOL index, urodynamic study results and prostate volume. During operation, decrease in hemoglobin was less in the HoLEP group than in the TUR-P group (1.15 +/- 1.2 vs 1.91 +/- 1.3 g/dl p < 0.05). The operation time was significantly longer in the HoLEP group than in the TUR-P group (161.9 +/- 65.0 vs. 118.3 +/- 36.9 minutes p < 0.001). Mean resected weight was 29.3 +/- 13.3 g (10-55) in the TUR-P group and 34.8 +/- 33.4 g (5-148) in the HoLEP group (p = 0.337). The catheterization period (52.1 +/- 29.6 vs. 115.2 +/- 27.5 hour p < 0.001) and hospital stay (6.6 +/- 2.3 vs. 9.4 +/- 2.2 days p < 0.001) were significantly shorter in the HoLEP group than in the TUR-P group. At follow up, Qmax, average flow rate and post void residual urine (PVR) in two groups improved significantly, and these parameters were not significantly different between the groups after 3 months. CONCLUSIONS: Both TUR-P and HoLEP were effective in relieving BOO. The estimated blood loss, a catheterization time and hospitalization were less or shorter in the HoLEP group. HoLEP may be a good alternative to the conventional transurethral electrocautery resection of the prostate for symptomatic BPH.

Quantitative analysis for human glucocorticoid receptor alpha/beta mRNA in IBD.

We have previously reported that in peripheral blood mononuclear cells (PBMC), the augmented expression of the beta isoform of the human glucocorticoid receptor (hGRbeta), as a putative dominant negative regulator of glucocorticoid action, is associated with glucocorticoid (GC) unresponsiveness of UC patients. In this study, we quantified the levels and serial changes of hGR transcripts in PBMC of IBD patients by a real-time fluorescence monitoring of PCR. As results, relative hGRbeta mRNA expression was significantly higher in the active stage of UC than in inactive periods of UC or CD patients. Longitudinal analysis revealed that hGRbeta mRNA expression in UC was increased after the relapse of inflammation, suggesting that the overproduction of cytokines during inflammation may be responsible. In in vitro culture experiments of human lymphoid cell (CEM) and human PBMC, IL-7, and IL-18 increased hGRbeta mRNA expression in these cells but GC itself did not. Through these analyses, it is indicated that the inflammatory cytokines altered the splicing condition of the primary transcript of hGR gene in IBD patients.

Minute findings by magnifying colonoscopy are useful for the evaluation of ulcerative colitis.

BACKGROUND: Colonoscopy has an important role in the diagnosis of ulcerative colitis. However, colonoscopic findings are inadequate for the prediction of relapse without histologic examination. In this study, the role of magnifying colonoscopy in ulcerative colitis was evaluated. METHODS: One hundred sixteen magnifying colonoscopy observations were made in 61 patients with ulcerative colitis between January 1994 and October 1998. A simple classification of magnifying colonoscopic findings into 5 categories was devised as follows: regularly arranged crypt openings, villous-like, minute defects of epithelium, small yellowish spots, and coral reef-like appearance. The colonoscopic findings by classification were compared with histopathologic findings, and the usefulness of the classification for predicting relapse was prospectively analyzed in 18 patients. RESULTS: Compared with grade as determined by conventional colonoscopy, there was a better correlation between the classification of findings by magnifying colonoscopy and histopathologic findings (r(2) = 0.665, 0.807, respectively). Of 18 patients studied prospectively, 7 of 9 with minute defects of epithelium relapsed within 6 months, and the cumulative nonrelapsing rate was significantly lower in patients with minute defects of epithelium compared with those without minute defects of epithelium (p = 0.0059). Moreover, minute defects of epithelium was found to be a significant independent predictive factor for relapse (multivariate analysis, Cox proportional hazards model; p = 0.0203). CONCLUSIONS: Our proposed classification of magnifying colonoscopic findings in patients with ulcerative colitis is useful for the evaluation of disease activity and for the prediction of periods of remission.