Search

Background: No previous study has shown that the volume of calcium score is useful for evaluating the aorta when performing a partial clamp (PC). The purpose of this study was to examine the effect of different clamping strategies during off-pump coronary artery bypass grafting (OPCAB), in terms of the incidence of postoperative stroke using the calcium score of the ascending aorta. Methods: We retrospectively reviewed 339 patients, who underwent isolated OPCAB between August 2013 and March 2021. There were two groups of patients, depending on the procedure. A PC was used for proximal anastomoses in 130 (38.3%) patients. A clampless proximal facilitating anastomotic device (CFD) was used in 107 (31.5%) patients. We prescribed preoperative CT for all patients, and the Agatston score was used. Results: The calcium score significantly was higher in the CFD group than in the PC group (29.7 ± 66.5 vs. 1819.8 ± 2391.5, < 0.001). The number of distal anastomoses and operative time were not significantly different between the two groups. There was no mortality and three strokes occurred at the 30-day follow up. Two strokes occurred in the PC group (1.5%) and one in the CFD group (0.9%), which was not significantly different (P = 0.98). Conclusion: A PC does not increase postoperative stroke incidence compared with a CFD, when utilizing calcium score evaluation in OPCAB.

Background Acute type A aortic dissection is treated with an emergency procedure that uses ascending aortic replacement (AAR). However, to avoid a residual dissected aorta with a false lumen, total arch replacement (TAR) is required. The frozen elephant trunk (FET) technique is a promising surgical approach that promotes false lumen obliteration in a single step without increasing operative risk. Therefore, this retrospective single-center study aimed to evaluate the operative outcomes of AAR and TAR with FET. Methods Between 2007 and 2021, 143 patients with acute DeBakey type Ⅰ aortic dissection underwent a central repair using AAR (n = 95) or TAR with FET (n = 43). All perioperative variables, the duration of all-cause mortality, and aortic events defined as dilatation of the distal aorta > 5 cm, new occurrences of aortic dissection, distal aortic surgery, and distal aortic rupture were recorded. We compared these patients' perioperative variables and mid-term results with an additional focus on distal aortic events. Results Patient background data did not differ between the two groups. Perioperative results for the TAR with FET group vs the AAR group showed similar operative times (306 vs 298 min, P = 0.862), but the TAR group had longer cardiopulmonary bypass times (154 vs 179 min, P

Minimally invasive coronary artery bypass grafting is less invasive. Proximal anastomoses at the ascending aorta, in contrast, are technically difficult to perform because of the limited field of view. A man in his 60s undergoing haemodialysis required minimally invasive coronary artery bypass grafting for left anterior descending artery and circumflex arterial restenosis. We successfully performed minimally invasive coronary artery bypass grafting with a proximal graft anastomosis of the descending aorta. A thoracotomy was performed to extend the lateral approach to the descending aorta. We performed a minithoracotomy using three-dimensional endoscopy for internal thoracic artery harvesting. Endoscopic internal thoracic artery harvesting minimises incision length. The combination of endoscopic and lateral thoracotomy incisions in minimally invasive coronary artery bypass grafting enabled small and lateral thoracotomy incisions.

Although live-attenuated vaccines are contraindicated under immunosuppression, the immune status of patients with inflammatory bowel disease (IBD) has not been fully assessed prior to immunosuppressive therapy.To investigate antiviral serostatus against viruses requiring live vaccines for prevention in IBD patients undergoing immunosuppressive therapy.This multicenter study included IBD patients who were aged40 years and were treated with thiopurine monotherapy, molecular-targeted monotherapy, or combination therapy. Gender- and age-matched healthy subjects (HS) living in the same areas were included as control group. Antibody titers against measles, rubella, mumps, and varicella were measured by enzyme-linked immunosorbent assays.A total of 437 IBD patients (163 ulcerative colitis [UC] and 274 Crohn's disease [CD]) and 225 HS were included in the final analysis. Compared with HS, IBD patients had lower seropositivity rates for measles (IBD vs. HS = 83.91% vs. 85.33%), rubella (77.55% vs. 84.89%), mumps (37.50% vs. 37.78%), and varicella (91.26% vs. 96.44%). Gender- and age-adjusted seropositivity rates were lower in UC patients than in both CD patients and HS for measles (UC, CD, and HS = 81.60%, 85.29%, and 85.33%), rubella (76.40%, 78.23%, and 84.89%), mumps (27.16%, 43.70%, and 37.78%), and varicella (90.80%, 91.54%, and 96.44%); the difference was significant for all viruses except measles. Divided by the degree of immunosuppression, there were no significant differences in seropositivity rates among IBD patients.IBD patients, especially those with UC, exhibit reduced seropositivity rates and may benefit from screening prior to the initiation of immunosuppressive therapy.

Background: Stroke and paraplegia are serious complications of total aortic arch replacement (TAR). Hypothermic circulatory arrest and cerebral perfusion reduce the risk of neurologic complications, but longer circulatory arrest time remains a risk factor for such complications. We utilized a frozen elephant trunk (FET) with endo-balloon occlusion under mild systemic hypothermia, which allowed us to shorten circulatory arrest time. Methods: Between April 2007 and May 2020, 72 patients underwent elective TAR using antegrade cerebral perfusion (ACP). They were divided into 2 groups. 64 patients received conventional TAR with moderate systemic hypothermic (bladder temperature, 25–28°C) circulatory arrest (group C). We used a FET with endo-balloon occlusion and retrograde perfusion through the femoral artery for the newest 8 patients who had mild hypothermic (bladder temperature of 30°C) circulatory arrest (group B). Results: The mean operation time (257.5 ± 42.1 versus 327.8 ± 84.9 min, P = .023), CPB time (144.4 ± 28.1 versus 178.2 ± 26.4 min, P = .003), cardiac arrest time (75.5 ± 21.2 versus 95.7 ± 56.4 min, P < .001), SCP time (100.8 ± 25.5 versus 124 ± 23.2 min, P < .001), lower body circulation arrest time (17.2 ± 4.2 versus 62.5 ± 19.3 min, P < .001) were significantly shorter in the endo-balloon occlusion group. There were no perioperative neurological and renal complications or mortality in FET group. The new technique enabled a decrease in mechanical ventilation time (8.6 ± 1.4 versus 13.9 ± 5.7 min, P = .015) and hospital length of stay (9.7 ± 1.8 versus 18.3 ± 4.6 min, P = .005). Conclusion: FET using an endo-balloon occlusion with mild hypothermia is a safe and an effective approach in TAR.

Stent graft collapse due to aortic dissection is an extremely rare event. Although endovascular aneurysm repair (EVAR) and thoracic endovascular aortic repair (TEVAR) are increasingly being performed, various complications can occur. We report a case of collapse of a stent graft, which was used to repair an abdominal aortic aneurysm (AAA) after TEVAR for thoracic aortic aneurysm (TAA). A 72-year-old man with a 77 mm AAA and 60 mm TAA underwent EVAR and a TEVAR 2 months later, respectively. CT performed after the TEVAR showed thoracic aorta dissection with associated AAA stent graft collapse. The graft collapsed was due to superior mesenteric artery obstruction. An emergency TEVAR was performed, and the procedure improved the collapsed graft; however, the endoleak of the AAA stent graft persisted. The AAA expanded over several days, warranting an open repair. Our case provides an insight into the cautionary indications for endovascular therapy.

Although minimally invasive direct coronary artery bypass (MIDCAB) is a less invasive procedure, internal thoracic artery (ITA) harvesting is difficult. A 65-year-old woman was advised to undergo MIDCAB for recurrent in-stent restenosis. We harvested the ITA using three-dimensional endoscopy without robotics and determined the scope position using enhanced computed tomography. We changed the camera installation between the wound and the camera port, according to the harvesting site with a harmonic scalpel using the skeletonized technique. We harvested the ITA from the subclavian vein level superiorly to the xyphoid process level inferiorly.

Objective This study was performed to explore the association between circulating B-type natriuretic peptide (BNP) and other mortality-related factors in patients undergoing cardiovascular surgery. Methods In this observational study, multilevel linear regression analysis and multilevel survival analysis were performed to measure the log-transformed BNP (lnBNP) value at four time points in 197 patients with 788 repeated data measurements. Effects of the interaction between the time points and the two intervention groups (cardiac surgery and vascular surgery) were also investigated. Six models were evaluated to identify the best fit for the data. Stata/MP® version 14.2 (Stata Corp., College Station, TX, USA) was used to analyze the two-level variance component model fitting. Results There were significant differences in the fixed-effect parameters of lnBNP, such as the time point, age, body mass index, emergency operation, prognostic nutritional index, and estimated glomerular filtration rate. According to the multilevel survival analysis for all-cause death and vascular death, lnBNP significantly differed and was a common prognostic marker. Conclusion As lnBNP increased by 1 point, all-cause death increased 2.07 times and vascular death increased 3.10 times. lnBNP is an important prognostic predictor and quantitative biochemical marker in patients undergoing cardiovascular surgery.

Total anomalous pulmonary venous connection (TAPVC) is a rare congenital cardiac anomaly. There are a few reports of untreated TAPVC diagnosed in patients older than 60 years. Herein, we report the successful surgical treatment of TAPVC in a 70-year-old woman. A 70-year-old woman with TAPVC presented with symptoms of acute heart failure. We closed an atrial septal defect and performed tricuspid annuloplasty and commissurotomy of the pulmonary valve. Postoperative CT showed no residual shunt, and the pulmonary veins drained into the left atrium. She had an uneventful postoperative course. This report describes the case of the oldest known patient who underwent surgical treatment for TAPVC. Surviving into adulthood with little or no symptoms is uncommon in patients with TAPVC, and cases of late-onset TAPVC, such as our case, are rare. Nevertheless, close vigilance is necessary to prevent misdiagnosis in patients with this clinical presentation.

We report a rare case of lung adenocarcinoma combined with minute pulmonary meningothelial-like nodule (MPMN) in a young adult. A 39-year-old woman was referred to our department for abnormal shadow of the right lower lobe. Chest computed tomography (CT) showed a mass shadow, 11 mm in size, in right S6. Since fluorodeoxyglucose-positron emission tomography (FDG-PET) demonstrated a lesion with FDG activity, with an increased uptake value of 2.2, this lesion was suspected to be a lung cancer. Wedge resection of right S6 was performed via thoracoscopy. The intraoperative pathological diagnosis was invasive lung adenocarcinoma, and additional right S6 segmentectomy and lymph node dissection (ND1a) was performed. The final pathological diagnosis of the tumor was adenocarcinoma of the lung, and MPMN was incidentally found by pathology in reseced specimen.

We presented an extremely rare case of a 38-year-old female’s venous aneurysm of left cephalic vein with unique histopathological features, displaying variably thinned medial wall with focal, markedly reduced or absent smooth muscle cells and elastic fibers, most likely leading to the venous dissection with an intimal tear and many medial blood-filled vascular channels. We propose that those venous dissection-like findings would be a new feature especially from the clinicopathological viewpoints and might be considered in the classification of venous aneurysm. Further prospective studies are needed to validate the presence and significance of venous dissecting aneurysm as a new histopathological entity, after collecting and investigating a larger number of venous aneurysm cases examined. This short report could interest the scientific community, taken together with potentially specific findings of new entity, venous dissecting aneurysm.

Background and aim This study analyzed inflammatory bowel disease activity for 2 years after the Great East Japan Earthquake. Methods We compared the relapse rates of patients with ulcerative colitis or Crohn's disease 1 and 2 years after the earthquake with rates immediately after the earthquake. To evaluate continuous disease courses, we also performed multivariate time-to-event analyses from the time of the earthquake to the onset of additional treatments. Results Of 903 patients with ulcerative colitis or Crohn's disease in our previous study, we could evaluate 2-year courses in 677 patients (394 ulcerative colitis and 283 Crohn's disease). Compared with the relapse rates of ulcerative colitis and Crohn's disease immediately after the earthquake (15.8% and 7.0%, respectively), those in the corresponding periods in 2012 (2.5% and 1.1%, respectively) and 2013 (2.3% and 2.5%, respectively) significantly decreased. There were 226 patients who required additional treatments after the earthquake. Multivariate time-to-event analyses revealed that only patients who had experienced the death of family members or friends were likely to need additional treatments (hazard ratio = 1.77, 95% confidence interval = 1.25-2.47). No other factors had a significant influence. Conclusions The relapse rates 1 and 2 years after the earthquake significantly decreased. The factors that influenced long-term relapse were different from those that influenced short-term relapse.

Background Paradoxical inflammations during anti-TNF-α therapy are defined as adverse effects such as psoriasiform skin lesions, uveitis and sarcoidosis-like granulomas induced by immune reactions, not by infectious agents. Here, we report a very rare case of the simultaneous development of sarcoidosis and cutaneous vasculitis in a patient with refractory Crohn’s disease during infliximab therapy and both of which resolved spontaneously without the cessation of infliximab. Case presentation In September 2000, 23-year old Japanese male was diagnosed with Crohn’s disease. Prednisolone in combination with mesalazine was introduced at first and succeeded for almost one year. In June 2002, since his gastrointestinal symptoms relapsed and were refractory, infliximab (IFX) therapy 5 mg/kg was introduced. In February 2011, because he had repeated arthralgia almost every intravenous IFX administration, IFX was increased to 10 mg/kg under the diagnosis of a secondary failure of IFX. In December 2012, he complained of slight dry cough and an itchy eruption on both lower limbs, and he was referred to our hospital due to the appearance of bilateral hilar lymphadenopathy on chest X-ray examination. Chest computed tomogram revealed bilateral hilar lymphadenopathy and fine reticulonodular shadows on the bilateral upper lungs. Serum calcium, angiotensin-converting enzyme and soluble interleukin 2 receptor levels were not elevated, but the titer of antinuclear antibody was considerably elevated. Mycobacterium infection was carefully excluded. Trans-bronchial lung biopsy showed non-caseating epithelioid cell granulomas compatible with sarcoidosis. The skin biopsy of the right limb was diagnosed as leukocytoclastic vasculitis. The patient was diagnosed as having a series of paradoxical inflammations during anti-TNF-α therapy. Since his paradoxical inflammations were not severe and opportunistic infections were excluded, IFX was cautiously continued for refractory Crohn’s disease. Nine months later, not only his intrathoracic lesions but also his cutaneous lesions had spontaneously resolved. Conclusion Physicians caring for patients with anti-TNF-α therapy should know that, based on a careful exclusion of infectious agents and thoughtful assessment of the patient’s possible risks and benefits, paradoxical inflammations can be resolved without the cessation of anti-TNF-α therapy.

Background/Aims: Several earlier studies on factors predicting the long-term outcome of ulcerative colitis only encompassed treatment failure for one severe episode, or suffered from a lack of multivariate analyses. We aimed to identify factors assessable at diagnosis or after the first induction therapy which predicted relapse or later colectomy in patients with mild to severe ulcerative colitis. Methods: Clinical parameters (age, sex, disease extent, and disease activity at diagnosis) and laboratory data (hemoglobin, albumin, C-reactive protein, and erythrocyte sedimentation rate at diagnosis and 4 weeks after the first induction therapy) were evaluated in 296 patients (median follow-up 87 months). Factors predicting relapse and later colectomy were sought using the Cox proportional hazard model. Results: The presence of moderate or severe disease at diagnosis were significant predictors of relapse [adjusted hazard ratio (95% CI) 2.07 (1.48–2.89) and 1.70 (1.06–2.72), respectively] and later colectomy [3.40 (1.09–10.54) and 6.77 (1.92–23.86)]. After the first induction therapy, hemoglobin and albumin were associated with relapse [0.87 (0.76–0.99) and 0.58 (0.41–0.83)] and later colectomy [0.60 (0.47–0.77) and 0.11 (0.06–0.22)]. Conclusion: Relapse and later colectomy were associated with (1) disease activity at diagnosis and (2) lower levels of hemoglobin and albumin after the first induction therapy.

The main goal of Crohn's disease (CD) treatment at present is to induce and maintain remission for as long as possible, and several approaches have been used as induction and maintenance therapies. There are no reports that have compared the effects on mid- and long-term prognosis among the induction and maintenance therapies, especially between infliximab, a chimeric antibody to tumor necrosis factor-α, and nutritional therapies. A total of 262 CD patients with induced remission were enrolled in the cohort study. Patients who failed to achieve remission, and patients who were lost to follow-up within 12 months were excluded. Induction therapies for CD included total elemental enteral nutrition, total parenteral nutrition, infliximab, prednisolone, and surgical resection. Maintenance therapies included home elemental diet, 5-aminosalicylates, immunomodulators, and scheduled infliximab therapy. We evaluated the possible predictive factors of relapse and surgical recurrence including the clinical backgrounds of the patients and medical therapies, using the Cox multivariate hazard analysis. The main factors that strongly affected the first relapse were scheduled infliximab therapy (hazard ratio (HR) = 0.24, p < 0.0001), surgical induction (HR = 0.19, p < 0.0001) and high frequency of previous relapse (HR = 2.56, p = 0.002). Penetrating (HR = 3.33, p = 0.009) and stricturing (HR = 6.60, p < 0.0001) disease behavior were main risk factors of surgical recurrence. Scheduled infliximab therapy is the most effective maintenance therapy in a real clinical setting with respect to the mid- and long-term prognosis.

Emerging evidence shows a beneficial effect of estrogens for Parkinson's disease, yet the exact potency of these compounds implicated remain obscured. In this study, we investigated the neuroprotective effect of 17β-estradiol and estrone against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced striatal toxicity in mice. The neuroprotective effects of both compounds were evaluated by HPLC and Western blot analyses 5 days after the last of 4 consecutive injections of MPTP at 1-h intervals to mice. Subacute treatment (10 days) with estrone or 17β-estradiol at low doses (0.05 and 0.2 mg/kg) showed no significant changes against MPTP-induced damage of striatal dopamine terminals in mice. Furthermore, acute treatment with estrone at high doses (0.5 and 2.0 mg/kg) showed no significant alterations against MPTP-induced damage of striatal dopamine terminals in mice. In contrast, acute treatment with 17β-estradiol at high doses exhibited a neuroprotective effect against the damage of striatal dopamine terminals in both male and female mice after MPTP treatments. The results demonstrate that estrogen therapy with high doses may have a neuroprotective effect on the damage of striatal dopamine terminals in the MPTP-induced mice. These findings may lead to be development of estrogen therapy for the prevention and treatment of Parkinson's disease.

The human leukocyte antigen (HLA) region has been implicated in the disease susceptibility of inflammatory bowel disease by several linkage and association studies. In Caucasians, HLA-DRB1 has been reported to determine the clinical phenotypes of ulcerative colitis (UC). Others and we previously reported that HLA-DRB1*1502 was strongly associated with UC in the Japanese population. However, the contribution of HLA-DRB1 to the clinical phenotypes in Japanese UC has not been elucidated yet. The aim of this study was to determine whether HLA-DRB1 alleles were associated with the clinical phenotypes in Japanese patients with UC. A total of 353 patients with UC were recruited. Patients were classified into subgroups by sex, age at diagnosis, disease extent, need for steroid therapy or need for surgical treatment. The allele frequency of HLA-DRB1*08 was significantly higher in patients whose disease extended beyond the rectum (left-sided and extensive UC) than in those with proctitis [odds ratio (OR) = 2.20, Pc = 0.043). The allele frequency of HLA-DRB1*09 was significantly higher in patients with UC diagnosed at the age of 40 years or older than in those with UC diagnosed before the age of 40 years (OR = 2.31, Pc = 0.022). Besides these positive associations, no significant differences were found in the allele frequencies between the other subgroups. We conclude that HLA-DRB1*09 is associated with the age at diagnosis and HLA-DRB1*08 is associated with the disease extent of UC in Japanese. These results indicate that HLA-DRB1 is not only associated with the overall UC susceptibility but also associated with the clinical phenotypes in Japanese.

Background: 5-Aminosalicylic acid (5-ASA) is known to be effective in the treatment of active ulcerative colitis (UC). The aim of the current study was to investigate the effect of 5-ASA enemas, as a maintenance therapy for UC, when administered twice weekly as a weekend treatment regimen, compared to daily oral 5-ASA alone. We hypothesized that the weekend enema therapy would be better tolerated by patients who worked or attended school. Methods: Between January 2004 and August 2005, patients with UC, in whom remission of the condition had just been induced, were randomly assigned to either: the weekend 5-ASA enema group (n = 11), who received 1 g 5-ASA enemas twice a week on Saturday and Sunday plus oral 5-ASA 3 g/day for 7 days, or to the daily oral 5-ASA use only group (n = 13), who received only oral 5-ASA 3 g/day for 7 days. The primary endpoint of the study was defined as the incidence of relapse. The study was stopped after 24 patients had been enrolled because an interim analysis showed a significant benefit of the weekend 5-ASA enema group. Results: In the weekend enema group, 2 patients (18.2%) had relapses compared with 10 (76.9%) in the oral 5-ASA only group. The multivariate hazard ratio of relapse associated with weekend 5-ASA enema, relative to the oral alone group, was 0.19 (95% confidence interval, 0.04–0.94). Conclusions: This study demonstrated the beneficial effects of adding weekend 1 g 5-ASA enema to daily 3 g oral 5-ASA as maintenance therapy for UC. (Inflamm Bowel Dis 2007)

We investigated the alteration of oligodendrocytes in comparison with that of astrocytes and microglia in the mouse striatum after MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropridine) treatment under the same conditions using Western blot analysis and Immunohistochemistry. In our Western blot analysis, four administrations of MPTP at 2-h intervals to mice produced the remarkable loss of TH (tyrosine hydroxylase) protein levels in the striatum after 3 and 7 days. In contrast, GFAP (glial fibrillary acidic protein) and Iba-1 protein in the striatum showed a significant increase of GFAP and Iba-1 protein levels 3 and 7 days after MPTP treatment. On the other hand, the levels of CNPase (2', 3'-cyclic nucleotide 3'-phosphodiesterase) protein were decreased significantly in the striatum 3 and 7 days after MPTP treatment. In our immunohistochemical study, a significant decrease in the area of expression of CNPase-positive profiles was observed in the striatum 3 and 7 days after MPTP treatment. These results demonstrate that oligodendrocytes in the striatum are damaged after MPTP treatment. Thus our present findings provide valuable information for the pathogenesis of Parkinson's disease.

This study was designed to investigate retrospectively the efficacy and safety of endoscopic balloon dilation for intestinal strictures in Crohn’s disease. Sixteen patients with 20 strictures were treated. The stricture sites were as follows: at the ileocolonic (n = 6) or ileoileal (n = 1) anastomosis, in the colon (n = 10), ileum (n = 2), and at the ileocecal valve (n = 1). The dilations were performed with through-the-scope balloons, with diameters of 15 to 20 mm on inflation and lengths of 30 to 80 mm. In 15 of 16 patients, the strictures were successfully dilated and the symptoms caused by the strictures disappeared after the first session. The patients were followed for a median of 38.5 months. Repeat symptomatic stricture formation occurred after a mean of 19.7 months in seven patients. Four patients needed second-round dilation and three patients were treated surgically. Complications occurred in four patients who had primary strictures: bleeding in one, high fever in one, and colorectal perforation in two. One of the patients complicated with colorectal perforation was treated surgically, and the other was treated conservatively. The cumulative nonsurgical rates for the dilation strictures were 93 percent at 12 months and 65 percent at 36 months, respectively. Three patients were treated surgically because of strictures or fistulas that were not related to the procedure of dilation. As a whole, the cumulative nonsurgical rates were 81 percent at 12 months and 46 percent at 36 months. Nine patients (56.3 percent) were able to avoid surgery. Using endoscopic balloon dilation, it may be possible to avoid or postpone surgery. Primary strictures seem to have increased risk of perforation.

Ulcerative colitis (UC) is a multifactorial disorder with both genetic and environmental factors. HLA-B*52 and DRB1*1502 are reported to be strongly associated with UC in Japan. However, the actual susceptible gene has not been identified yet. In this study, to map precisely the susceptible locus for UC, we performed association mapping in the chromosome 6p using 24 microsatellite markers distributed over 16 Mb. A total of 183 patients with UC and 186 healthy controls (HC) were included in this study. In all, 15 markers around the human leukocyte antigen (HLA) region showed statistical significance in the genotypic differentiation test concerned with the allelic distribution between the UC and HC. Especially, the markers between the centromeric region of HLA class I and the telomeric region of class III showed remarkably low P-values and the allele239 of C2-4-4 in class I marker showed the strongest association (Pc=2.9 x 10(-9): OR=3.74, 95% CI=2.50-5.60). Furthermore, we found strong linkage disequilibrium (LD) between the allele239 of C2-4-4 and HLA-B*52 in haplotype analysis. These results provide evidence that, in Japanese, important determinants of disease susceptibility to UC may exist in HLA, especially between the centromeric region of class I and the telomeric region of class III, under the strong LD with HLA-B*52.

A 73-year-old male was referred to our hospital for abdominal pain, diarrhea and general fatigue lasting for 3 weeks. Physical examination of the abdomen revealed a firm mass in the left abdominal region. Computed tomography revealed a mass around the descending colon. Colonoscopy and barium enema revealed poor extensibility of the lumen with edematous mucosa, and narrowing of the descending colon with rugged mucosal surface. Because of the clinical symptoms and findings, the patient was diagnosed clinically as suffering from panniculitis of the descending colon. He underwent the left hemi-colectomy with side-to-side colo-colostomy after making of a loop ileostomy. Histological analysis of the resected colon showed an infiltration of inflammatory cells, predominantly lymphocytes, into veins and venules of the submucosa, muscularis propria and fat tissue of the colonic mesentery, with an involvement of all layers of the vessel wall. Arteries were escaped from inflammatory changes. The histopathological diagnosis of enterocolic phlebitis and venulitis was made because of these findings.

Objective Telomere shortening is correlated with cell turnover and aging, but it has been recently suggested to occur not only by aging but by several biochemical factors of metabolic disorders predisposing to atherosclerosis. Patients and Methods We compared telomere length of peripheral blood mononuclear cells of patients with the metabolic disorders, hypercholesterolemia (HC) and diabetes mellitus (DM), according to the presence or absence of coronary diseases. Results The results demonstrated that HC and/or DM patients with coronary diseases have significantly shorter telomere length than healthy controls (p=0.0014). Conclusion Telomere shortening may be involved in the mechanisms that promote coronary diseases under some circumstances of metabolic disorders.(Internal Medicine 42: 150-153, 2003)

Telomerase acitivity can be induced in human B lymphocytes by in vitro stimulation of their antigen receptors. To determine whether telomerase activity is induced in vivo, we analyzed telomerase activity in B lymphocytes from the mesenteric lymph nodes of patients with inflammatory bowel disease (IBD), whose lymph nodes are well known to be strongly stimulated, and from those of noninflamed controls. Seven IBD patients and 4 noninflamed controls were enrolled. Telomerase activity was assayed by telomeric repeat amplification protocol with minor modifications. The mesenteric lymph nodes from patients with IBD had stronger telomerase activity than those from controls or peripheral mononuclear cells. Isolation of CD19+ B lymphocytes from these lymph nodes showed that this strong activity resides in this lymphocytes subpopulation. This study provides the evidence that telomerase activity is induced in human B lymphocytes in human inflammatory disease.

Inflammatory bowel disease (IBD) is a multifactorial disease with a significant genetic background. Evidence is accumulating that molecules such as CD14, which interact with luminal bacterial constituents, are involved in the pathogenesis. It has recently been shown that the T allele of the 5'-flanking region of the CD14 gene at position -159 is related to high expression of CD14. In further exploring the genetic background of IBD, we investigated this novel polymorphism of CD14 gene in patients with ulcerative colitis or Crohn disease.DNA was obtained from 101 patients with ulcerative colitis, 82 with Crohn disease and 123 healthy controls. All were typed for the promoter polymorphism of the CD14 gene at position -159 by restriction fragment length polymorphism analysis. Serum samples were obtained from 105 healthy controls and serum sCD14 levels were measured.T allele frequencies were 57.4%, 48.2% and 44.7% in ulcerative colitis, Crohn disease and healthy controls, respectively. The T allele and T/T genotype frequencies were significantly higher in ulcerative colitis patients than in healthy controls (P = 0.0074, OR = 1.67, 95% CI = 1.15-2.42, P = 0.022, OR= 1.96 95% CI: 1.10-3.48, respectively). The sCD14 level was significantly higher in TT genotype populations than CC (P = 0.0205).The promoter polymorphism of the CD14 gene at -159T plays a significant role in regulating the CD14 expression and is positively associated with ulcerative colitis, and this polymorphism may confer a genetic predisposition to ulcerative colitis. The results also support the concept that bacterial constituents may be involved in the pathogenesis of ulcerative colitis.

PURPOSE: Two pathways have been proposed for the development of colorectal cancers: loss of heterozygosity and replication error. Colorectal cancers arising through the replication error pathway, like most hereditary nonpolyposis colorectal cancers, show microsatellite instability. It has been also reported that telomere shortening frequently occurs in colorectal cancers and that telomerase is often activated strongly in them. The aim of this study was to examine whether any relationships can be found among microsatellite instability, telomere length, and telomerase activity in colorectal cancers. METHODS: Genomic DNA was extracted from 55 invasive cancers and corresponding normal mucosas. Five microsatellite loci were analyzed by polymerase chain reaction. Telomere length was examined by Southern blot analysis. Telomerase activity was assayed by telomeric repeat amplification protocol with minor modifications. RESULTS: Microsatellite instability was found in 8 (14.5 percent) of 55 tumors, and all of them showed short telomeres. Furthermore, four high-frequency microsatellite instability tumors that showed microsatellite instability at more than two loci exhibited remarkably short telomeres. The microsatellite instability correlated significantly with frequency of telomere shortening (P=0.0183; Fisher's exact probability test), but not with strength of telomerase activity. CONCLUSION: The relationship identified by this study between microsatellite instability and telomere shortening might suggest some association between the DNA mismatch repair system and the telomere maintenance mechanism in colorectal cancers.

Background & Aims: Tumor necrosis factor (TNF) is considered to play an important role in the pathogenesis of Crohn's disease (CD). Recently, 3 polymorphisms in the 5'-flanking region of the TNF gene at positions −1031, −863, and −857, which are related to high transcriptional promoter activity, have been identified in the Japanese population. In an effort to understand potential genetic association with CD, we evaluated patients diagnosed with CD and ulcerative colitis (UC) in the presence of other novel polymorphisms. Methods: Blood samples were obtained from 103 patients with CD and 76 patients with UC. Polymorphisms in the TNF gene at their respective positions were analyzed by direct sequencing, and the allele frequencies were compared with those determined previously in a healthy Japanese population. Results: Allele frequencies of −1031C, −863A, and −857T in normal controls were 16.0%, 14.0%, and 17.7%, respectively. Polymorphic allele frequencies at positions −1031, −863, and −857 were 24.3%, 21.8%, and 27.2% in CD and 11.8%, 11.2%, and 11.8% in UC, respectively. The frequencies at all 3 positions were significantly higher in CD patients than in UC patients or healthy controls. Among the subgroups of CD, small bowel disease showed the highest frequencies. Conclusions: Although the findings need to be confirmed in other populations with larger numbers of patients, TNF gene polymorphisms −1031C, −863A, and −857T are positively associated with CD; they may influence not only the susceptibility to CD but also the disease location. GASTROENTEROLOGY 1999;117:1062-1068

Telomere length in human somatic cells gradually decreases with the number of cell divisions and is regarded as a marker of somatic cell turnover. Mucosal cells of the affected colon show rapid turnover in individuals with active ulcerative colitis (UC). Telomere length was determined by Southern blot analysis of terminal restriction fragments (TRFs) from the colonic mucosa of 17 patients with UC in remission, two of whom showed dysplasia, and 17 control subjects without colitis. For each individual, mean TRF length was compared between rectal mucosa and unaffected cecal mucosa. The mean TRF length of the rectal mucosa was significantly less than that of cecal mucosa in UC patients (7.87 +/- 0.36kb versus 8.77 +/- 0.21 kb; P = 0.0015, Wilcoxon signed rank test), whereas no significant difference was detected in the control subjects. The extent of telomere shortening was 10.6 +/- 3.35% in UC patients, compared with 0.8 +/- 0.64% in noncolitis controls (P = 0.0024, Mann-Whitney U-test). Four UC patients, two of whom had dysplasia, showed telomere shortening of more than 20% in the rectal mucosa. These observations suggest that telomere shortening in the colonic mucosa of individuals with UC may represent the history of mucosal inflammation during disease of long duration, and that it may contribute to aneuploidy in UC.

テロメアはヒト体細胞において一細胞分裂ごとに短縮することより,細胞分裂回数を数えるマーカーと考えられている.この特徴を利用して,潰瘍性大腸炎の発癌リスク評価を試みた.またテロメラーゼはde novoでテロメアを伸長させる酵素で,大腸癌においても9割以上で高発現を示すことより,診断マーカー,治療の標的として有望である.臨床検体を用いたテロメラーゼ活性の検出法として,従来からのTRAP法と新規に開発したhTERT遺伝子のin situ hybridization法について,その結果と特徴について記述した.

Endoscopic resection has become a major curative treatment for early colorectal carcinoma without lymph node metastasis. However, lymph node metastasis, a poor prognostic factor in colorectal carcinoma, occurs in about 10% of the patients with submucosal invasive colorectal carcinoma. Therefore, it is important to identify a high-risk factor for lymph node metastasis in submucosal invasive colorectal carcinoma. This study was designed to identify the relationship between tumor budding with β-catenin expression and lymph node metastasis in submucosal invasive colorectal carcinoma. We investigated the immunohistochemistry of tumor budding in the 142 patients who underwent surgical resection for submucosal invasive colorectal carcinomas between 1984 and 1999 and the expression pattern of β-catenin in budding tumor cells. Accordingly, all the patients were followed up for at least 10 years or until death. Among the 142 patients, lymph node metastasis was detected in 14 patients (9.9%). Univariate analysis showed that tumor budding with ≥ 5 tumor cells or cell clusters with expression of β-catenin in the nucleus was significantly associated with lymph node metastasis (P = 0.005). In contrast, tumor budding detected by hematoxylin and eosin staining was not associated with lymph node metastasis. Multivariate logistic regression analysis showed that tumor budding with ≥ 5 tumor cells or cell clusters with expression of β-catenin in the nucleus was a significant risk factor for lymph node metastasis (odds ratio, 7.124; 95% confidence interval, 1.407-36.062). Thus, tumor budding associated with β-catenin expression is a risk factor for lymph node metastasis in submucosal invasive colorectal carcinoma.

Background Intestinal microbiota contributes to the pathogenesis of Crohn's disease. Elemental diet and total parenteral nutrition are effective therapies for Crohn's disease; however, changes of microbiota as a result of both treatments have not been fully elucidated. Aim To elucidate changes of faecal microbiota in Crohn's disease patients treated with elemental diet and total parenteral nutrition. Methods Stool samples were collected from 33 active Crohn's disease patients and 17 healthy subjects, and recollected after elemental diet (8 patients) and total parenteral nutrition (9 patients). Terminal restriction fragment length polymorphism analysis of bacterial 16srDNA was performed to evaluate the whole microbiota. Specific quantitative PCR was then used to determine populations of predominant bacterial groups. Results In Crohn's disease patients, the number of terminal restriction fragments, which reflects bacterial species, was significantly lower. Populations of total bacteria and Bifidobacterium were significantly lower and the ratio of Enterococcus was higher. The number of terminal restriction fragments was significantly decreased after total parenteral nutrition, but not after elemental diet. Population of Bacteroides fragilis significantly decreased after elemental diet, while population of Enterococcus significantly increased after total parenteral nutrition. Conclusion Faecal microbiota in Crohn's disease patients was markedly different from healthy subjects. Species diversity was reduced by total parenteral nutrition, but not by elemental diet.

Recently, a genome-wide association study for ulcerative colitis (UC) in the UK population was reported, and several susceptibility loci including the human leukocyte antigen (HLA) region were identified. The strongest association in the HLA region was found at a 400 kb haplotype block containing HLA-DRB1. In Japanese population, previous study suggested the association between UC and HLA-B*52; however, HLA typing was determined using serotyping with the small sample size. The purpose of this study was to perform an association study in HLA-B by genotyping. A total of 320 patients with UC and 322 healthy controls were recruited in this case-control study. All subjects were Japanese. Genotyping of HLA-B was performed by polymerase chain reaction using a sequence-specific primer. When the allele frequencies were compared, significant associations were found with B*52 [odds ratio (OR) = 3.65, P = 1.6 x 10(-17), P(c) = 3.7 x 10(-16)] and B*4002 (OR = 0.52, P = 0.00030, P(c) = 0.0068). The allele frequency of B*52 was significantly higher in patients diagnosed before 40 years of age than in those diagnosed after 40 years (OR = 1.79, P = 0.010, P(c) = 0.020). A combination association map of Japanese UC using our current and previous studies showed two equal peaks of association on HLA-DRB1 and HLA-B, indicating the possible existence of two casual variants in the HLA region inside and outside the 400 kb block found in UK. We conclude that HLA-B contributes to the susceptibility to Japanese UC, especially cases with younger age of onset. The strength of association for HLA-B was equal to that for HLA-DRB1 in Japanese UC, in contrast to the UK population.

TNFSF15 is a susceptibility gene for Crohn's disease (CD). It remains to be elucidated how the associated single nucleotide polymorphisms (SNPs) in TNFSF15 affect the susceptibility to CD. Because there are no non-synonymous SNPs in TNFSF15, we speculated that one or more of the SNPs associated with CD may act as cis-regulatory SNPs. To reveal the effects of the SNPs on the transcriptional activity of TNFSF15, we first examined the allelic expression imbalance of TNFSF15 in peripheral blood mononuclear cells (PBMCs). When PBMCs stimulated by phytohemagglutinin (PHA) were examined, the allelic ratio of mRNA transcribed from the risk haplotype to the non-risk haplotype increased, compared with the ratio without stimulation. When peripheral blood T cells and Jurkat cells stimulated by phorbol 12-myristate 13-acetate + ionomycin were examined, an allelic expression imbalance similar to that observed in PBMCs stimulated by PHA was confirmed. The promoter assay in stimulated Jurkat cells showed that the luciferase activity of the promoter region (-979 to +35) of the risk haplotype was significantly higher than that of the non-risk haplotype, and deletion and mutagenesis analysis demonstrated that this difference resulted from the -358T/C SNP. The promoter activity of -358C (risk allele) was higher than that of -358T (non-risk allele) in stimulated T cells. This effect of -358T/C on the transcriptional activity in stimulated T cells may confer susceptibility to CD.