Polymorphism at rs9264942 is associated with HLA-C expression and inflammatory bowel disease in the Japanese.

An expression quantitative trait locus (eQTL) single-nucleotide polymorphism (SNP) at rs9264942 was earlier associated with human leukocyte antigen (HLA)-C expression in Europeans. HLA-C has also been related to inflammatory bowel disease (IBD) risk in the Japanese. This study examined whether an eQTL SNP at rs9264942 could regulate HLA-C expression and whether four SNP haplotypes, including the eQTL SNP at rs9264942 and three SNPs at rs2270191, rs3132550, and rs6915986 of IBD risk carried in the HLA-C*12:02~B*52:01~DRB1*15:02 allele, were associated with IBD in the Japanese. HLA-C expression on CD3e+CD8a+ lymphocytes was significantly higher for the CC or CT genotype than for the TT genotype of rs9264942. The TACC haplotype of the four SNPs was associated with a strong susceptibility to ulcerative colitis (UC) but protection against Crohn's disease (CD) as well as with disease clinical outcome. While UC protectivity was significant but CD susceptibility was not for the CGTT haplotype, the significance of UC protectivity disappeared but CD susceptibility reached significance for the CGCT haplotype. In conclusion, our findings support that the eQTL SNP at rs9264942 regulates HLA-C expression in the Japanese and suggest that the four SNPs, which are in strong linkage disequilibrium, may be surrogate marker candidates of a particular HLA haplotype, HLA-C*12:02~B*52:01~DRB1*15:02, related to IBD susceptibility and disease outcome.

Association between lower air pressure and the onset of ischemic colitis: a case-control study.

OBJECTIVE: Ischemic colitis (IC) often affects the elderly. Proarteriosclerotic factors, such as hypertension and smoking, and cardiovascular disease are considered major contributors to IC. Although a possible link between certain cerebrocardiovascular disorders and meteorological phenomena has been reported, the relationship between IC onset and weather changes remains uninvestigated. This study examined whether specific meteorological factors were associated with the occurrence of IC. PATIENTS AND METHODS: We retrospectively enrolled 303 patients who had been diagnosed with IC between January 2003 and June 2010 at Suwa Red Cross Hospital in Nagano Prefecture, Japan. The meteorological data of the days on which IC patients visited the hospital (IC+ days) were compared with those of the days on which IC patients did not (IC- days). RESULTS: Univariate analysis indicated that IC+ days had significantly lower air pressure (P<0.001), depressed air pressure from the previous day (P<0.001), and fewer daylight hours (P<0.001), as well as higher air temperature (P=0.017), air humidity (P=0.004), wind velocity (P<0.001), and rainfall (P=0.012) compared with IC- days. Multivariate logistic regression analysis of the meteorological data showed that air pressure (odds ratio: 0.935, P<0.001) and change in air pressure from the previous day (odds ratio: 0.934, P<0.001) were related to onset of IC. CONCLUSION: Lower air pressure and decrease in air pressure from the previous day are possible novel factors associated with the development of IC.

[A Case of Chordoma of the Sacrum Treated with Pazopanib].

A-70-year-old man with chordoma of the sacrum was treated with pazopanib (initially 400 mg/day, upto 800 mg/day). After 2 months of treatment, a significant tumor reduction was achieved and the patient was able to sit down easily. Therefore, the pazopanib therapy was continued. He had 14 months of progression-free survival.

Reduced expression of αGlcNAc in Barrett's oesophagus adjacent to Barrett's adenocarcinoma--a possible biomarker to predict the malignant potential of Barrett's oesophagus.

AIMS: Gastric gland mucin contains O-glycans exhibiting terminal α1,4-linked N-acetylglucosamine residues (αGlcNAc). Recently we demonstrated that mice deficient in αGlcNAc in gastric gland mucin develop gastric adenocarcinoma spontaneously, indicating that αGlcNAc is a tumour suppressor for gastric cancer. However, the role of αGlcNAc in Barrett's oesophagus (BO) remains unknown. In this study, we investigated whether reduced αGlcNAc expression in BO is associated with development of Barrett's adenocarcinoma (BAC). METHODS AND RESULTS: Thirty-five BO lesions adjacent to BAC were examined by immunohistochemistry for αGlcNAc, MUC6 and CDX2. As controls, 35 BO lesions without BAC obtained from patients with oesophageal squamous cell carcinoma were also analysed. Expression of αGlcNAc relative to its scaffold MUC6 in BO adjacent to BAC was reduced significantly compared to control BO. Decreased αGlcNAc expression in BO adjacent to BAC was particularly significant in patients with smaller tumour size (<20 mm) and minimal invasion of tumour cells to the superficial muscularis mucosae. There was also a significant inverse correlation between αGlcNAc and CDX2 expression in BO adjacent to BAC. CONCLUSIONS: Decreased expression of αGlcNAc compared with MUC6 in BO is a possible hallmark in predicting BAC development.

Clinical characteristics of young-onset ischemic colitis.

BACKGROUND: Ischemic colitis (IC) typically develops in the elderly, where hypertension, cerebrocardiovascular disease, and past history of abdominal surgery are regarded as risk factors. Although there have been reports of younger patients with IC, its clinical features remain unclear. AIM: The aim of this study was to clarify the clinical characteristics of IC in young adults. METHODS: Three hundred fifty-nine patients were diagnosed as having IC at five hospitals across Nagano prefecture, Japan. Clinical data were compared between the young patient group [20-45 years, n = 53 (15%)] and the elderly patient group [>45 years, n = 306 (85%)], as well as with age- and gender-matched healthy individuals (n = 156). RESULTS: The presence of a smoking habit and hyperuricemia were significantly higher in the young patient group compared with the elderly patient group (42 vs. 19%, P = 0.001 and 8 vs. 1%, P = 0.019, respectively), which was confirmed by multiple logistic regression analysis (P = 0.001, odds ratio 3.239 and P = 0.028, odds ratio 16.907, respectively). Additionally, multiple logistic regression analysis of the young IC patient group and age- and gender-matched healthy individuals demonstrated that these two factors were strongly associated with IC development (P = 0.008, odds ratio 2.49 for smoking habit and P = 0.039, odds ratio 6.37 for hyperuricemia). CONCLUSIONS: High prevalences of a smoking habit and hyperuricemia are characteristic features of IC in the young adult population.

[A case of rectal mucosa-associated lymphoid tissue lymphoma (MALT) successfully treated by radiation therapy].

A 33-year-old woman had hematochezia for 5 months. A total colonoscopy showed an easily-bleeding elevated lesion with a nodular lesion in the lower rectum. Histological findings of a conventional biopsy from the lesion showed MALT (mucosa-associated lymphoid tissue) lymphoma and she was diagnosed as stage I. The monoclonality of B-cells was not detected by polymerase chain reaction products for immunoglobulin heavy chain. We selected antibiotic therapy because Helicobacter pylori was detected in culture of the patient's gastric biopsy specimens. The antibiotic therapy was successful, but her symptoms worsened. We therefore gave her with 30 Gy radiation therapy. She recovered a month after the radiation. Histological complete remission was confirmed 4 months after the radiation. Adverse events of the radiation therapy included anal pain for 1 month and premature ovarian failure. Radiation therapy may be useful for localized rectal MALT lymphoma.

[A case of acute pancreatitis after extracorporeal shock wave lithotripsy for renal pelvic calculus].

A 62-year-old man was admitted to receive extracorporeal shock wave lithotripsy (ESWL) for a right renal pelvic calculus. During the operation, the patient complained of right upper quadrant pain. Later in the day, laboratory data showed elevated serum amylase levels, and abdominal CT revealed an enlarged pancreas. These findings led to a diagnosis of acute pancreatitis. The following day, urine output had decreased, and pleural and ascitic fluid had accumulated. For these reasons, the patient was transferred to our hospital to receive combination therapy, including arterial infusion therapy with protease inhibitors, antibiotics and continuous hemodiafiltration. The condition of the patient improved, and he was discharged on day 30. Acute pancreatitis should be considered as an early complication after ESWL for urinary tract calculus.

[A case of peritoneal serous papillary adenocarcinoma].

A78-year-old female was admitted to our hospital with anorexia due to ascites. We were not able to diagnose by cytological diagnosis. For a definite diagnosis she underwent an open biopsy. Histological findings revealed observable papillary adenocarcinoma with psammoma body, carcinoma cells were positive for Ber-EP4 on immunostaining, and ovaries were normal. Thus, we made a diagnosis of peritoneal serous papillary adenocarcinoma. She was treated by intraperitoneal administration of CDDP(20 mg/day: day 1, every four weeks). Ascites vanished and CA125 was within the normal range. There was no recurrence after 3 years, but Virchow's lymph node metastasis occurred. The patient is still alive 12 months after metastasis with CDDP intraperitoneal administration.

[A case of advanced gastric cancer successfully treated by surgery after chemotherapy with S-1/CDDP].

A-46-year-old male with advanced-stage IV multicentric gastric cancer was treated with S-1/CDDP as neoadjuvant chemotherapy. S-1 (initially 100 mg/day, up to 120 mg/day) was orally administered for 3 weeks (day 1-21) followed by 1 drug-free week as a course, and CDDP (initially 60 mg/day, up to 100 mg/day) was administered by intravenous drip on day 8. After the fourth course, a significant tumor reduction was obtained and curative surgery was performed. Thereafter, S-1 therapy was continued. There has not been any recurrence for 19 months postoperatively.

[Internal iliac artery aneurysm rupture with aorto-enteric fistula after reconstruction of abdominal aortic aneurysm: report of a case].

An 84-year-old male was admitted to our hospital due to diarrhea. Fourteen years ago, he underwent a graft replacement for an abdominal aortic aneurysm. Three years ago, he was pointed out left internal iliac artery aneurysm about 8cm in diameter. During the hospital stay, he experienced sudden massive hematochezia. Colonoscopic examination revealed a fistula at the rectum. Abdominal CT showed left internal iliac artery aneurysm with aorto-enteric fistula (AEF). An emergent aneurysmectomy and Hartmann's procedure was performed and the patient recovered. This case might show the usefulness of colonoscopy and CT for early diagnosis of secondary AEF. Early diagnosis and surgical treatment are necessary to recover from secondary AEF.

Possible relationship between Helicobacter pylori infection and cap polyposis of the colon.

BACKGROUND: Cap polyposis is a rarely encountered disease characterized by multiple distinctive inflammatory colonic polyps located from the rectum to the distal colon. The etiology of this disease is still unknown, and no specific treatment has been established. AIM: We report three cases of cap polyposis that were cured following eradication therapy for Helicobacter pylori infection. METHODS AND RESULTS: Three women were referred to Shinshu University Hospital because of mucoid and/or bloody diarrhea. Laboratory data showed hypoproteinemia in all cases; markers of inflammation such as C-reactive protein were negative. Colonoscopy revealed multiple sessile polyps with mucus adherent on the apices of the mucosal folds in the rectum and/or the sigmoid colon. The intervening mucosa was normal. Microscopic examinations of biopsy specimens taken from sessile polyps revealed inflamed mucosa with elongated tortuous crypts attenuated towards the mucosal surface. A granulation tissue 'cap' was observed on the surface of the mucosa. Various treatments were unsuccessful, including administration of metronidazole or prednisolone, avoidance of straining at defecation, and surgical or endoscopic resection. All were diagnosed with H. pylori infection in the stomach. Helicobacter pylori was not detected in the biopsy specimens from the colonic inflammatory polyps by immunohistochemical study using polyclonal anti-H. pylori antibody. After successful eradication therapy the clinical symptoms improved. Disappearance of cap polyposis was confirmed by colonoscopy in all three cases. CONCLUSION: We speculate that H. pylori infection might play a role in the pathogenesis of cap polyposis.

Recurrent gastric hemorrhaging with large submucosal hematomas in a patient with primary AL systemic amyloidosis: endoscopic and histopathological findings.

A 64-year-old woman who suffered intractable gastric ulcers with hemorrhaging showed huge submucosal hematomas in her stomach on the endoscopic examination. Since gastric mucosal biopsy revealed amyloid deposition and IgG lambda type M protein was detectable in her serum, she was diagnosed as having primary AL systemic amyloidosis. The gastric hemorrhages did not improve despite intensive medication, so total gastrectomy was performed, resulting in an unfavorable outcome. Massive deposition of amyloid with A lambda immunoreactivity was seen on the submucosal vessels in her stomach. This is a rare primary AL systemic amyloidosis case showing recurrent and fatal gastric submucosal hematomas.

Autoimmune pancreatitis is closely associated with gastric ulcer presenting with abundant IgG4-bearing plasma cell infiltration.

BACKGROUND: Autoimmune pancreatitis is characterized by high serum IgG4 concentrations and lymphoplasmacytic infiltration. Because of the diversity of extrapancreatic involvement in this disease, the present study sought to identify other associated GI-tract lesions. METHODS: EGD findings were compared between a group of 23 patients with autoimmune pancreatitis undergoing ERCP for obstructive jaundice and 230 age- and gender-matched control patients. To clarify the histopathologic differences found between these two groups, the histopathologic findings (Updated Sydney System) and the immunohistochemistry of each IgG subclass were compared between 8 patients with autoimmune pancreatitis and gastric ulcer, and 23 control patients with gastric ulcer from which biopsy specimens had been obtained. RESULTS: Gastric ulcer was found significantly more frequently in patients with autoimmune pancreatitis compared with control patients (34.8% vs. 13.5%; p=0.007). There was no significant difference between the groups with respect to the frequency of other GI lesions. Four of 8 gastric ulcers in patients with autoimmune pancreatitis were linear, with the long axis perpendicular to the incisura on the lesser curvature of the stomach. The activity score for the gastric lesions was significantly lower in patients with autoimmune pancreatitis compared with control patients (mean score 0.38 vs. 1.08; p=0.012). There were no significant differences in histopathologic findings with respect to inflammation, atrophy, metaplasia, or Helicobacter pylori scores between the two groups. IgG4-bearing plasma cells were significantly more abundant in gastric lesions in patients with autoimmune pancreatitis compared with those in control patients (mean score 1.75 vs. 0.39; p=0.0008). CONCLUSIONS: Autoimmune pancreatitis is closely associated with gastric ulcer with abundant IgG4-bearing plasma cell infiltration.