Cavity resonator for circularly polarized microwave irradiation mounted on a cryostat.

We have constructed a cylindrical cavity resonator with a hybrid coupler where circularly polarized microwaves can be irradiated to a sample. The polarity of the microwave can be switched by changing the input ports of the hybrid coupler. The cavity resonator is small enough to be mounted on a cryostat which enables us to change the sample temperature in a wide range. To demonstrate the performance of the cavity resonator mounted on a cryostat, Yttrium Iron Garnet (YIG) was used as a test sample. We succeeded in selectively exciting left and right circularly polarized modes with high polarization (>80%). We also evaluated the susceptibility tensor of YIG in the cryostat. The technique presented here would offer a new direction in the fields of spintronics and quantum information.

Rikkunshito simultaneously improves dyspepsia correlated with anxiety in patients with functional dyspepsia: A randomized clinical trial (the DREAM study).

BACKGROUND: Functional dyspepsia (FD), a heterogeneous disorder, involves multiple pathogenetic mechanisms. Developing treatments for FD has been challenging. We performed a randomized, placebo-controlled, double-blind clinical trial to determine the efficacy of rikkunshito, a Japanese herbal medicine, in FD patients. METHODS: FD patients (n = 192) who met the Rome III criteria without Helicobacter pylori infection, predominant heartburn, and depression were enrolled at 56 hospitals in Japan. After 2 weeks of single-blind placebo treatment, 128 patients with continuous symptoms were randomly assigned to 8 weeks of rikkunshito (n = 64) or placebo (n = 61). The primary efficacy endpoint was global assessment of overall treatment efficacy (OTE). The secondary efficacy endpoints were improvements in upper gastrointestinal symptoms evaluated by the Patient Assessment of Upper Gastrointestinal Disorders-Symptom Severity Index (PAGI-SYM), the Global Overall Symptom scale (GOS), and the modified Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease (m-FSSG), and psychological symptoms evaluated by the Hospital Anxiety and Depression Scale (HADS). KEY RESULTS: Rikkunshito increased OTE compared to placebo at 8 weeks (P = .019). Rikkunshito improved upper gastrointestinal symptoms (PAGI-SYM, GOS, and m-FSSG) at 8 weeks, especially postprandial fullness/early satiety (P = .015 and P = .001) and bloating (P = .007 and P = .002) of the PAGI-SYM subscales at 4 weeks and 8 weeks. Improvement of HADS at 8 weeks (P = .027) correlated with those of PAGI-SYM (r = .302, P = .001), GOS (r = .186, P = .044), and m-FSSG (r = .462, P < .001), postprandial fullness/early satiety (r = .226, P = .014), dyspepsia (r = .215, P = .019), and PDS (r = .221, P = .016). CONCLUSION & INFERENCES: Rikkunshito may be beneficial for FD patients to simultaneously treat gastrointestinal and psychological symptoms.

Evaluation of a Proton Pump Inhibitor for Sleep Bruxism: A Randomized Clinical Trial.

Bruxism is a repetitive jaw-muscle activity characterized by clenching or grinding of the teeth and/or bracing or thrusting of the mandible. Recent advances have clarified the relationship between gastroesophageal reflux and sleep bruxism (SB). However, the influence of pharmacological elimination of gastric acid secretion on SB has not been confirmed. The authors aimed to assess the efficacy of a proton pump inhibitor (PPI) on SB and to examine the gastrointestinal (GI) symptoms and endoscopic findings of the upper GI tract in SB patients. The authors performed a randomized double-blind placebo-controlled crossover study at Kagoshima University Hospital. Twelve patients with polysomnography (PSG)-diagnosed SB underwent an assessment of GI symptoms using the frequency scale for the symptoms of gastroesophageal reflux disease (FSSG) and esophagogastroduodenoscopy. At baseline (i.e., before interventions), the mean frequencies of electromyography (EMG) bursts and rhythmic masticatory muscle activity (RMMA) episodes were 65.4 ± 49.0 bursts/h and 7.0 ± 4.8 episodes/h, respectively, and at least 1 RMMA episode with grinding noise was confirmed in all participants. The mean FSSG score was 8.4 ± 5.6, and 41.7% of patients were diagnosed with gastroesophageal reflux disease. Mild reflux esophagitis was confirmed in 6 patients. PSG, including EMG of the left masseter muscle and audio-video recording, was performed on days 4 and 5 of administration of 10 mg of the PPI (rabeprazole) or placebo. PPI administration yielded a significant reduction in the frequency of EMG bursts, RMMA episodes, and grinding noise. No significant differences were observed regarding the swallowing events and sleep variables. Since the clinical application of PPI for SB treatment should remain on hold at present, the results of this trial highlight the potential application of pharmacological gastroesophageal reflux disease treatment for SB patients. Larger scale studies are warranted to corroborate these findings. (UMIN Clinical Trials Registry: UMIN000004577).

Characteristics of nighttime reflux assessed using multichannel intraluminal impedance pH monitoring and a portable electroencephalograph.

Gastroesophageal reflux disease (GERD) is strongly associated with sleep disturbances. Although the mechanisms of this association have not been fully elucidated, nighttime reflux plays a central role. However, the detailed characteristics of nighttime reflux occurring during sleep are unknown. The aim of the present study was to examine the characteristics and prevalence of nighttime reflux in the natural sleep environment of GERD patients. Seventeen patients experiencing daily moderate-to-severe heartburn and/or regurgitation were studied using multichannel intraluminal impedance pH monitoring and electroencephalography off-proton pump inhibitor treatment. Nighttime reflux was divided based on reflux type (liquid or gas), acidity (acidic, weakly acidic, or alkaline) and extent (distal only or proximal migration) according to the standard criteria. Nighttime phases were divided as follows: recumbent-awake before falling asleep, nonrapid eye movement, rapid eye movement, awakening from sleep, and post-awakening in the morning. Among 184 nighttime refluxes, 43 (23%) occurred during recumbent-awake before falling asleep, 28 (15%) during nonrapid eye movement, 14 (8%) during rapid eye movement, 86 (46%) during awakening from sleep, and 13 (7%) during post-awakening in the morning. Liquid reflux was more common in awakening during sleep (92%), nonrapid eye movement (100%), and rapid eye movement (100%) compared with awakening before falling asleep (68%). The prevalence of proximal migration was significantly lower in nonrapid eye movement and rapid eye movement than in the other phases. There were no differences in acidity and bolus clearance time among the phases. Thirteen (65%) of 20 events with GERD symptoms had nighttime reflux, suggesting that only 7.1% (13 of 184) of nighttime refluxes were symptomatic. Nighttime reflux was observed in 48 (11%) of 425 awakening episodes during sleep. Different reflux patterns at each phase during nighttime might explain the pathogenesis of GERD and its related sleep disturbances.

Mechanisms of NLRP3 inflammasome activation and its role in NSAID-induced enteropathy.

Nonsteroidal anti-inflammatory drugs (NSAIDs) induce cytokines, including tumor necrosis factor-α and interleukins (ILs), in the small intestine via a Toll-like receptor 4 (TLR4)-dependent pathway, leading to intestinal ulceration. Activation of the inflammasome promotes pro-caspase-1 cleavage, leading to pro-IL-1ß maturation. We examined the role of NLRP3 inflammasome in NSAID-induced enteropathy. Small intestinal damage developed 3 h after indomethacin administration, accompanied by increases in IL-1ß and NLRP3 mRNA expression and mature caspase-1 and IL-1ß levels. In vivo blocking of IL-1ß using neutralizing antibodies attenuated indomethacin-induced damage, whereas exogenous IL-1ß aggravated it. NLRP3(-/-) and caspase-1(-/-) mice exhibited resistance to the damage with reduction of mature IL-1ß production. This resistance was abolished by exogenous IL-1ß. TLR4 deficiency prevented intestinal damage and inhibited upregulation of NLRP3 and IL-1ß mRNAs and maturation of pro-caspase-1 and pro-IL-1ß, whereas TLR4 activation by its agonists exerted opposite effects. Apyrase, an adenosine triphosphate (ATP) scavenger, or Brilliant Blue G, a purinergic P2X7 receptor antagonist, inhibited the damage as well as caspase-1 activation and IL-1ß processing, despite there being sufficient amounts of pro-IL-1ß and NLRP3. These results suggest that NLRP3 inflammasome-derived IL-1ß plays a crucial role in NSAID-induced enteropathy and that both TLR4- and P2X7-dependent pathways are required for NLRP3 inflammasome activation.

Nerve growth factor injected into the gastric ulcer base incorporates into endothelial, neuronal, glial and epithelial cells: implications for angiogenesis, mucosal regeneration and ulcer healing.

A previous study has demonstrated that locally administered growth factors such as epidermal growth factor, basic fibroblast growth factor and hepatocyte growth factor can accelerate healing of experimental gastric ulcers in rats. That study indicates that locally administered growth factors can exert potent biological effects resulting in enhanced gastric ulcers healing. However, the fate of injected growth factors, their retention and localization to specific cellular compartments have not been examined. In our preliminary study, we demonstrated that local injection of nerve growth factor to the base of experimental gastric ulcers dramatically accelerates ulcer healing, increases angiogenesis - new blood vessel formation, and improves the quality of vascular and epithelial regeneration. Before embarking on larger, definitive and time sequence studies, we wished to determine whether locally injected nerve growth factor is retained in gastric ulcer's tissues and taken up by specific cells during gastric ulcer healing. Gastric ulcers were induced in anesthetized rats by local application of acetic acid using standard methods; and, 60 min later fluorescein isothiocyanate-labeled nerve growth factor was injected locally to the ulcer base. Rats were euthanized 2, 5 and 10 days later. Gastric specimens were obtained and processed for histology. Unstained paraffin sections were examined under a fluorescence microscope, and the incorporation of fluorescein isothiocyanate-labeled nerve growth factor into various gastric tissue cells was determined and quantified. In addition, we performed immunostaining for S100ß protein that is expressed in neural components. Five and ten days after ulcer induction labeled nerve growth factor (injected to the gastric ulcer base) was incorporated into endothelial cells of blood vessels, neuronal, glial and epithelial cells, myofibroblasts and muscle cells. This study demonstrates for the first time that during gastric ulcer healing locally administered exogenous nerve growth factor is retained in gastric tissue and is taken up by endothelial, neural, muscle and epithelial cells. This is likely the basis for the therapeutic action of locally administered nerve growth factor and its stimulation of angiogenesis, tissue regeneration and gastric ulcer healing.

Enteric glial cells are associated with stress-induced colonic hyper-contraction in maternally separated rats.

BACKGROUND: Enteric glial cells (EGCs) play important roles in enteric integrity and regulation of gastrointestinal function. However, whether EGCs undergo pathophysiological changes in stress-associated gastrointestinal disorders is unknown. We investigated structural and functional alterations in colonic EGCs and their roles in colonic contraction in an irritable bowel syndrome (IBS) model. METHODS: As a chronic stress, male Wistar rats underwent 3-h maternal separation during postnatal days 2-14. As an acute stress, we used water-immersion stress (4 h) in adulthood (at 8 weeks). We quantitatively and morphologically evaluated enteric neurons and EGCs using whole-mount longitudinal muscle-myenteric plexus preparations. Colonic contraction was analyzed with electrical field stimulation (EFS). KEY RESULTS: Glial fibrillary acidic protein (GFAP) expression and the number of total, cholinergic, and nitrergic neurons were unchanged in maternally separated rats with acute stress (combined stress: an IBS model) compared with controls. However, the density of GFAP-positive EGC processes that apparently overlapped with the neurons and the extent of bulbous swelling of terminals increased according to the stress intensity: control, acute stress, maternal separation, and combined stress. EFS-induced colonic contractions were significantly greater in the combined stress rats than in controls. Higher dose of fluorocitrate, a selective inhibitor of EGC metabolism, was required to inhibit both EFS-induced contraction and EGCs activation in the combined stress rats than in controls. CONCLUSIONS & INFERENCES: Colonic EGCs exhibited structural alterations according to the stress intensity. EGCs were associated with stress-induced colonic hyper-contraction in the combined stress rats, which may underlie the pathogenesis of IBS.

Basophil infiltration in eosinophilic oesophagitis and proton pump inhibitor-responsive oesophageal eosinophilia.

BACKGROUND: The features of proton pump inhibitor-responsive oesophageal eosinophilia (PPI-REE) are similar to those of eosinophilic oesophagitis (EoE), but PPI-REE demonstrates symptomatic and histological responses to PPI therapy. Several studies have shown that basophils play a crucial role in the pathogenesis of allergic diseases. AIM: To identify and compare basophil infiltration in the oesophageal epithelium in patients with EoE, PPI-REE, gastroesophageal reflux disease (GERD) and normal oesophagus (controls). METHODS: Biopsy specimens from 43 patients, including 12 with EoE, 11 with PPI-REE, 10 with GERD and 10 normal oesophagus, were analysed. Immunohistochemistry was performed to quantify the number of basophils and mast cells in the oesophageal epithelium. Double immunofluorescence staining for thymic stromal lymphopoietin (TSLP) and basophils was performed. Patients with EoE were treated with swallowed fluticasone. RESULTS: There were no differences in clinical, endoscopic or histological features between patients with EoE and PPI-REE. There were more basophils and mast cells in patients with EoE and PPI-REE than in patients with GERD and control subjects. Basophil infiltration of the oesophageal epithelium in patients with EoE was higher than that in patients with PPI-REE (3.6 ± 2.8 per high power field vs. 1.2 ± 0.9 per high power field respectively; P = 0.02); however, there was no significant difference in mast cell infiltration between the two groups. TSLP was highly expressed in the oesophageal epithelium in areas infiltrated by basophils. Steroid therapy significantly decreased intraepithelial basophils in patients with EoE. CONCLUSION: Basophils may play an important role in the pathogenesis of eosinophilic oesophagitis.

Proteoglycan expression is influenced by mechanical load in TMJ discs.

The expression and assembly of the extracellular matrix are profoundly associated with adaptive and pathological responses of the temporomandibular joint (TMJ). To better understand the adaptive responses of the TMJ disc to mechanical loading, we examined the expression of 2 modular proteoglycans and 10 small leucine-rich proteoglycans (SLRPs) at the mRNA and protein levels and determined the contents of proteoglycan-related glycosaminoglycans (GAGs) in rat TMJ discs in response to altered mechanical loading caused by an incisal bite plane. One hundred thirty 7-week-old male Wistar rats were assigned to control and bite plane groups. TMJ disc thickness and the intensity of toluidine blue staining of metachromasia increased in the posterior band after 2 weeks of wearing the bite plane. GAG content increased significantly in the bite plane group after 2 weeks. Quantitative real-time RT-PCR (reverse transcription polymerase chain reaction) analysis indicated that biglycan and chondroadherin mRNA levels increased after 2 weeks and that the level of decorin mRNA increased at 4 weeks. Versican mRNA levels increased after 3 weeks, particularly for the V0 and V1 versican isoforms, which carry more GAG attachment sites than do the V2 and V3 isoforms. Western analysis demonstrated a corresponding increase in the levels of versican, biglycan, and decorin core proteins at 4 weeks in the bite plane group. These results indicate that mechanical loading differentially influences proteoglycan mRNA expression and protein accumulation in the TMJ disc. The change in proteoglycan mRNA and protein levels may lead to the modulation of matrix-matrix and cell-matrix interactions and has important biological significance for adaptation to complicated biomechanical requirements and for tissue maintenance in the TMJ disc.

Effect of heat stress soon after muscle injury on the expression of MyoD and myogenin during regeneration process.

Heat stress could promote skeletal muscle regeneration. But, in the regeneration process, effects of heat stress on myogenic cells and the regulating factors is unknown. Therefore, Influences of heat stress soon after injury on distribution of the myogenic cells and chronological changes in expression of MyoD and myogenin were examined. The first peak of MyoD expression was temporally correlated with the time when proliferating satellite cells began to appear, and the rapid decline of the MyoD expression from the first peak, with the appearance time of myoblasts, respectively in both the non-Heat and Heat groups. The first peak of myogenin expression was temporally correlated with the time when multinuclear cells began to form in the both groups. Due to the heat stress, proliferation and differentiation of myogenic cells and chronological changes in these factors were accelerated one day earlier than in the non-Heat group. As MyoD and myogenin are regulating factor of proliferation and differentiation, heat stress soon after the muscle injury could accelerate the proliferation and differentiation of myogenic cells and the expression of their regulating factors MyoD and myogenin.

Randomised clinical trial: prevention of recurrence of peptic ulcers by rabeprazole in patients taking low-dose aspirin.

BACKGROUND: Few studies have evaluated the effects of rabeprazole on low-dose aspirin (LDA)-induced gastroduodenal injuries. AIM: To conduct a randomised, double-blind, triple-dummy, active-controlled, multicentre trial, named the PLANETARIUM study, to assess the efficacy, dose-response relationship and safety of rabeprazole for peptic ulcer recurrence in Japanese patients on long-term LDA therapy. METHODS: Eligible patients had a history of endoscopically confirmed peptic ulcers and were receiving long-term LDA (81 or 100 mg/day) therapy for cardiovascular or cerebrovascular protection. Subjects were randomly segregated into three groups receiving rabeprazole 10 mg once daily (standard dose in Japan), rabeprazole 5 mg once daily, or teprenone (geranylgeranylacetone; mucosal protective agent commercially available in Japan) 50 mg three times per day as an active control. The primary endpoint was recurrence of peptic ulcers over 24 weeks. RESULTS: Among 472 randomised subjects, 452 subjects (n = 151, 150, 151, respectively) constituted the full analysis set. The cumulative recurrence rates of peptic ulcers over 24 weeks in the 10- and 5-mg rabeprazole groups were 1.4% and 2.8%, respectively, both of which were significantly lower than that in the teprenone group (21.7%). The cumulative occurrence rate of bleeding ulcers over 24 weeks in the teprenone group was 4.6%, while bleeding ulcers were not observed in the 10- or 5-mg rabeprazole groups. Rabeprazole was well tolerated at both doses. CONCLUSION: Rabeprazole prevents the recurrence of peptic ulcers with no evidence of a major dose-response effect in subjects on low-dose aspirin therapy.

Telaprevir impairs renal function and increases blood ribavirin concentration during telaprevir/pegylated interferon/ribavirin therapy for chronic hepatitis C.

We aimed to examine the relationship between renal dysfunction and anaemia that may develop during combination therapy involving pegylated interferon, ribavirin and telaprevir (PEG-IFN/RBV/TVR) for the treatment of chronic hepatitis C. Sixty-eight patients with genotype 1b high viral loads were treated with PEG-IFN/RBV/TVR. Peg-IFN and RBV doses were administered according to body weight. TVR was prescribed at 2250 mg/day for 44 patients and at 1500 mg/day for 24 patients who had low haemoglobin level (<12 g/dL). When anaemia had developed, the RBV dose was decreased. The serum TVR concentration at day 8 was measured, and the serum RBV concentration was measured serially. The estimated glomerular filtration rate (eGFR) was estimated to assess renal function. At week 1, serum TVR concentration was not correlated with a decrease in eGFR; however, the TVR dose, on a weight basis (mg/kg), and eGFR were correlated (r = 0.2691; P = 0.0265). Moreover, there was a negative correlation between eGFR and RBV serum concentration (r = −0.3694; P = 0.0025), and the serum RBV concentration and decrease in the haemoglobin were significantly correlated from week 1 to week 8. In triple therapy, the TVR dose per weight is correlated with a decline in renal function. Thus, the serum concentration of RBV increases, with a concomitant decrease in haemoglobin. It is important to adjust the doses of TVR and RBV to avoid excessive serum RBV levels and the development of severe anaemia, to achieve a good clinical effect.

Real-time estimation of tongue movement based on suprahyoid muscle activity.

In this study, we introduce a real-time method for tongue movement estimation based on the analysis of the surface electromyography (EMG) signals from the suprahyoid muscles, which usual function is to open the mouth and to control the position of the hyoid, the base of the tongue. Nine surface electrodes were affixed to the underside of the jaw and their signals were processed via multi-channel EMG system. The features of the EMG signals were extracted by using a root mean square (RMS) method. The dimension of the variables was reduced additionally from 108 to 10 by applying the Principal Component Analysis (PCA). The feature quantities of the reduced dimension set were associated with the tongue movements by using an artificial neural network. Results showed that the proposed method allows precise estimation of the tongue movements. For the test data set, the identification rate was greater than 97 % and the response time was less than 0.7 s. The proposed method could be implemented to facilitate novel approaches for alternative communication and control of assistive technology for supporting the independent living of people with severe quadriplegia.

Successful treatment of both acute leukemia and active Crohn's disease after allogeneic hematopoietic stem cell transplantation using reduced-intensity conditioning with fludarabine and busulfan: a case report.

BACKGROUND: A 32-year-old man diagnosed with acute myelomonocytic leukemia (M4) concurrently had active Crohn's disease (CD) that was refractory to azathioprine and anti-tumor necrosis factor. CASE REPORT: He underwent an allogeneic bone marrow transplantation from a one HLA-DR allele-mismatched unrelated donor to achieve the first complete remission of leukemia. The conditioning regimen consisted of fludarabine (180 mg/m(2)) and busulfan (8.0 mg/kg) without T-cell depletion. Graft-versus-host disease (GVHD) prophylaxis included tacrolimus and mycophenolate mofetil. Cefotaxime was prescribed for a secondary bacterial infection in a perianal abscess before the start of conditioning chemotherapy. Although low-grade diarrhea persisted, there were no signs of either acute GVHD or CD in the mucosal biopsy specimens on day 24. Complete remission of leukemia and near remission of CD were sustained for 20 months after transplantation without any immunosuppressive drug. CONCLUSIONS: Allogeneic heamtopoietic stem cell transplantation with reduced-intensity conditioning is a possible therapeutic option for patients with severe and/or refractory CD.

Tuberculosis diagnostic pathway in a municipality in south-eastern Brazil.

OBJECTIVE: To analyse the pathway taken by tuberculosis (TB) patients from the first contact with the health services and the diagnosis of TB disease. METHOD: In a survey conducted in a south-eastern municipality of Brazil prioritised for TB control, a structured questionnaire was applied to 100 TB patients under treatment; secondary data recorded in two information systems were also collected for analysis. Diagrams were constructed to represent the patient pathway through the health services up to diagnosis. RESULTS: The emergency services were the point of entry into care for the majority of the patients. Those who first attended primary health care (PHC) centres needed to visit other health services for diagnosis. CONCLUSION: Our study shows that multiple visits to multiple health services are required for the majority of patients to be diagnosed with TB. It is necessary to reinforce the referral path established for TB diagnosis and communication among providers, who should play a clear role in obtaining early diagnosis.

Randomised clinical trial: rabeprazole improves symptoms in patients with functional dyspepsia in Japan.

BACKGROUND: The efficacy of proton pump inhibitors (PPIs) for treating functional dyspepsia (FD) is not well established. AIM: This study, named the SAMURAI study, aimed to assess the efficacy and dose-response relationship of rabeprazole in Japanese patients with FD in a multicentre, double-blinded, randomised, placebo-controlled trial. METHODS: Investigated FD was diagnosed using the Rome III criteria. Subjects who did not respond to 1 week of single-blind placebo treatment in a run-in period were randomly assigned to 8 weeks of double-blind treatment with rabeprazole 10 mg, 20 mg, 40 mg or placebo, once daily. Dyspeptic symptoms were assessed by a dyspepsia symptom questionnaire (7-point Likert scale) and symptom diary. RESULTS: Of 392 subjects entered into the run-in period, 338 were randomly assigned. Although there was no significant difference between placebo and rabeprazole groups in complete symptom relief for four major dyspeptic symptoms, the satisfactory symptom relief of rabeprazole 20 mg was significantly higher than placebo according to the dyspepsia symptom questionnaire (45.3% vs. 28.2%, P = 0.027) and the symptom diary assessment (48.7% vs. 30.0%, P = 0.016). The efficacy was not influenced by syndrome type or Helicobacter pylori status. No statistically significant differences in the incidence of adverse events were seen among treatment groups. CONCLUSIONS: Rabeprazole 20 mg once daily but not 10 or 40 mg significantly provides satisfactory symptom relief for functional dyspepsia (ClinicalTrials.gov, Number NCT01089543).

Etiology of recurrent acute pancreatitis, with special emphasis on pancreaticobiliary malformation.

PURPOSE: This study was aimed to investigate etiology and clinical profiles of recurrent acute pancreatitis (RAP), particularly from the morphology of the pancreaticobiliary duct system. MATERIAL AND METHODS: Pancreaticobiliary morphology was examined in 230 of 381 patients with acute pancreatitis (AP) using endoscopic retrograde cholangiopancreatography. We analyzed factors associated with RAP including the pancreaticobiliary duct system. RESULTS: RAP was diagnosed in 74 patients (19%). Major etiologies of RAP were alcoholic (38%), idiopathic (26%) and pancreaticobiliary malformation (22%). Patients with alcoholic RAP were significantly younger (47.2±11.6 years) than those with gallstone RAP (67.3±16.8; p<0.05). RAP with pancreaticobiliary malformation (male-to-female ratio: 1:4.3; p<0.01) and gallstone RAP (1:1.7; p<0.05) occurred predominantly in females in comparison with alcoholic RAP (1:0.2). Recurrence rate was 80% for AP with pancreaticobiliary malformation, significantly higher than for the others (p<0.01). Pancreas divisum was suspected as the etiology of mild RAP in 7 patients. Four RAP patients with pancreas divisum underwent endoscopic minor papilla sphincterotomy and improved. Pancreaticobiliary maljunction with biliary dilatation (choledochal cyst) was suspected as the etiology of mild RAP in 3 patients. The 3 RAP patients with choledochal cyst underwent prophylactic flow diversion surgery with complete resection of the dilated common bile duct, and achieved improvement. High confluence of pancreaticobiliary ducts was suspected as the etiology of mild RAP in 6 patients. CONCLUSION: Pancreaticobiliary malformation is one of the major causes of RAP. As some of them benefit from endoscopic or surgical treatment, morphology of the pancreaticobiliary duct system should be examined where possible in RAP patients.

Locoregional mitomycin C injection for esophageal stricture after endoscopic submucosal dissection.

This prospective study aimed to evaluate the feasibility and safety of locoregional mitomycin C (MMC) injection to treat refractory esophageal strictures after endoscopic submucosal dissection (ESD) for superficial esophageal carcinoma. Patients with dysphagia and strictures that were refractory to repeated endoscopic balloon dilation (EBD) were eligible. After EBD, MMC was injected into the dilated site. Between June 2009 and August 2010, five patients were recruited. The treatment was performed once in two patients and twice in three patients with recurrent dysphagia or restenosis. In all patients, passing a standard endoscope through the site was easy and the dysphagia grade improved (grade 3→1 in 3 patients, grade 4→2 in 2 patients). No serious complications were noted. During the observation period of 4.8 months, neither recurrent dysphagia nor re-stricture appeared in any of the patients. The combination of locoregional MMC injections and EBD is feasible and safe for the treatment of esophageal strictures after ESD.Recently, endoscopic submucosal dissection (ESD) has been developed and accepted as a new endoscopic treatment for gastrointestinal tumors. ESD is a promising treatment for superficial esophageal carcinoma (SEC), and it has a reliable en bloc resection rate. However, the application of ESD for widespread lesions is challenging because of the high risk of the development of severe strictures, which lead to a low quality of life after ESD. Although endoscopic balloon dilation (EBD) is effective for benign strictures, it needs to be performed frequently until the dysphagia disappears 1. Mitomycin C (MMC), which is a chemotherapeutic agent derived from some Streptomyces species 2, reduces scar formation when topically applied to a surgical lesion. MMC has been applied to treat strictures in a variety of anatomical locations, including a variety of organs 3. The aim of this study was to prospectively evaluate both the feasibility and the safety of locoregional MMC injection therapy in patients with refractory esophageal strictures after ESD for SEC.

Small intestinal injury caused by NSAIDs/aspirin: finding new from old.

Small intestinal injury caused by non-steroidal anti-inflammatory drugs (NSAIDs) or aspirin is an epoch making topic in clinical field with the aid of new devices, capsule endoscopy and double balloon enteroscopy to look at small intestine directly. However, the injury has been reported in animals since more than 40 years ago. Proposed mechanisms are impairment of mucosal defense through inhibition of cyclooxygenase (COX) resulting in deficiency of prostaglandins, and mitochondrial disorder. Possible aggressive factors are NSAIDs/aspirin themselves, bile, and enterobacteria. Translocation of enterobacteria through the mucosa impaired integrity may be the first step of the injury. Bacterial lipopolysaccharides stimulate toll-like receptor-4 in macrophages, which increases proinflammatory cytokines through MyD88 signaling pathway. Finally neutrophils are activated and the small intestinal mucosa is injured with the attacks of NSAIDs/aspirin themselves, bile, and proteolytic enzymes and active oxygen species released by neutrophils. Candidates of treatment tools are prostaglandin derivatives, mucoprotective drugs, probiotics, and mitochondrial protective drugs such as metronidazole and cyclosporin A. Further clinical studies are needed to elucidate the effect in humans.