High-density magnetic-vacancy inclusion in Co2MnGa single crystal probed by spin-polarized positron annihilation spectroscopy.

Co2MnGa is a Weyl semimetal exhibiting giant anomalous Hall and Nernst effects. Using spin-polarized positron annihilation spectroscopy, we examined a Bridgman-grown Co2MnGa single crystal with a nearly perfectL21-ordered structure and a reference Co2MnAl polycrystal with a Mn-Al-disorderedB2 structure. We found that a large amount of magnetic vacancies (more than 100 ppm) were included in the Co2MnGa crystal but not the Co2MnAl crystal. We discuss possible reasons for the inclusion of vacancies, the role of vacancies in the development of the ordered structure, and the electronic states associated with the vacancies. Toward the development of Co2MnGa-based devices, the manners for reducing vacancies as well as the influence of vacancies on the electrical transport properties should be considered.

Benign hilar bile duct strictures resected as perihilar cholangiocarcinoma.

BACKGROUND: Differentiation between perihilar cholangiocarcinoma (PHCC) and benign strictures is frequently difficult. The aim of this study was to investigate the incidence and long-term outcome of patients with tumours resected because of suspicion of PHCC, which ultimately turned out to be benign (malignancy masquerade). METHODS: Patients who underwent surgical resection with a diagnosis of PHCC between 2001 and 2016 were reviewed retrospectively. RESULTS: Among 707 consecutive patients, 685 had PHCC and the remaining 22 (3·1 per cent) had benign biliary stricture. All patients with benign disease underwent major hepatectomy, with no deaths. Preoperative histological assessment using bile duct biopsy or aspiration cytology had a high specificity (90 per cent), low sensitivity (62 per cent) and unsatisfactory accuracy (63 per cent). Despite the increasing use of histological assessment, the incidence of benign strictures resected did not decrease over time, being 0·9 per cent in 2001-2004, 4·0 per cent in 2005-2008, 3·8 per cent in 2009-2012 and 2·9 per cent in 2013-2016. The final pathology of benign strictures included IgG4-related sclerosing cholangitis (9 patients), hepatolithiasis (4), granulomatous cholangitis (3), non-specific chronic cholangitis (3), benign strictures after cholecystectomy (2), and a benign stricture possibly caused by parasitic infection (1). The 10-year overall survival rate for the 22 patients with benign stricture was 87 per cent, without recurrence of biliary stricture. CONCLUSION: The incidence of benign strictures resected as PHCC as a proportion of all resections was relatively low, at 3·1 per cent. Currently, unnecessary surgery for suspected PHCC is unavoidable.

ANTECEDENTES: La diferenciación entre colangiocarcinoma perihilar (perihilar colangiocarcinoma, PHCC) y estenosis benignas es con frecuencia difícil. El objetivo de este estudio fue investigar la incidencia y el resultado a largo plazo de los tumores resecados con sospecha diagnóstica de PHCC, que finalmente resultaron ser benignos (malignidad enmascarada). MÉTODOS: Se revisaron retrospectivamente los pacientes con diagnóstico de PHCC que se sometieron a resección quirúrgica entre 2001 y 2016. RESULTADOS: Entre 707 pacientes consecutivos, 685 pacientes presentaban PHCC y los 22 restantes (3,1%) tenían una estenosis biliar benigna. Todos los pacientes con patología benigna se sometieron a una hepatectomía mayor, sin mortalidad. La evaluación histológica preoperatoria mediante biopsia de conducto biliar o citología por aspiración tuvo una alta especificidad (90%), una baja sensibilidad (62%) y una exactitud diagnóstica insatisfactoria (63%). A pesar del uso creciente de la evaluación histológica, la incidencia de estenosis benignas resecadas no disminuyó con el tiempo, con un 0,9% en 2001-2004, un 4,0% en 2005-2008, un 3,8% en 2009-2012 y un 2,9% en 2013-2016. La patología final de las estenosis benignas incluyó colangitis esclerosante relacionada con IgG4 (n = 9), hepatolitiasis (n = 4), colangitis granulomatosa (n = 3), colangitis crónica no específica (n = 3), estenosis benignas tras una colecistectomía (n = 2) y una estenosis benigna posiblemente causada por una infección parasitaria (n = 1). Los resultados a largo plazo de los 22 pacientes con estenosis benigna fueron mejores (tasa de supervivencia a 10 años; 87,4%) sin recidiva de la estenosis biliar. CONCLUSIÓN: La incidencia de pacientes con estenosis benignas resecadas como PHCC en comparación con todas las resecciones fue relativamente baja, del 3,1%. Actualmente, la cirugía "innecesaria" por sospecha de PHCC es inevitable.

Clinical value of additional resection of a margin-positive distal bile duct in perihilar cholangiocarcinoma.

BACKGROUND: Little is known about the effect of additional resection for a frozen-section-positive distal bile duct margin (DM) in perihilar cholangiocarcinoma. METHODS: Patients who underwent surgical resection for perihilar cholangiocarcinoma between 2001 and 2015 were analysed retrospectively, focusing on the DM. RESULTS: Of 558 consecutive patients who underwent frozen-section examination for a DM, 74 (13·3 per cent) had a frozen-section-positive DM with invasive cancer or carcinoma in situ. Eventually, 53 patients underwent additional resection (bile duct resection in 44 and pancreatoduodenectomy in 9), whereas the remaining 21 patients did not. Ultimately, R0 resection was achieved in 30 of the 53 patients (57 per cent). No patient who underwent additional resection died from surgical complications. The 44 patients with additional bile duct resection had a 5-year overall survival rate of 31 per cent. Overall survival of the nine patients who had pancreatoduodenectomy was better, with a 10-year rate of 67 per cent. Survival of the 21 patients without additional resection was dismal: all died within 5 years. Multivariable analyses identified nodal status and additional resection as independent prognostic factors (lymph node metastasis: hazard ratio (HR) 2·26, 95 per cent c.i. 1·26 to 4·07; bile duct resection versus no additional resection: HR 0·32, 0·17 to 0·60; pancreatoduodenectomy versus no additional resection: HR 0·08, 0·02 to 0·29). CONCLUSION: Additional resection for frozen-section-positive DM in perihilar cholangiocarcinoma frequently yields R0 margins. It offers a better chance of long-term survival, and thus should be performed in carefully selected patients.

Proposal for a new classification for perihilar cholangiocarcinoma based on tumour depth.

BACKGROUND: The T system for distal cholangiocarcinoma has been revised from a layer-based to a depth-based approach in the current American Joint Committee on Cancer (AJCC) classification. In perihilar cholangiocarcinoma, tumour depth in the staging scheme has not yet been addressed. The aim of this study was to propose a new T system using measured tumour depth in perihilar cholangiocarcinoma. METHODS: Patients who underwent hepatectomy for perihilar cholangiocarcinoma between 2001 and 2014 were reviewed retrospectively. The vertical distance between the top of the tumour and deepest invasive cells was measured as invasive tumour thickness (ITT) by two independent pathologists. Log rank statistics were used to determine cut-off points, and the concordance (C) index was used to assess survival discrimination of each T system. RESULTS: ITT was measurable in all 440 patients, with a median value of 6·0 (range 0-45) mm. The median difference in ITT between observers was 0·6 (range 0-20) mm. Cut-off points for prognosis were 1, 5 and 8 mm. Five-year survival decreased with increasing ITT (P < 0·001): 67 per cent for ITT less than 1 mm (25 patients), 54·9 per cent for ITT 1 mm and over to less than 5 mm (138 patients), 43·4 per cent for ITT 5 mm and over to less than 8 mm (118 patients), and 32·2 per cent for ITT 8 mm and over (159 patients). The C-index of this classification was comparable to that of the current AJCC T classification (0·598 versus 0·589). CONCLUSION: ITT is a reliable approach for making a depth assessment in perihilar cholangiocarcinoma. A four-tier ITT classification with cut-off points of 1, 5 and 8 mm is an adequate alternative to the current layer-based T classification.

Giant superconducting fluctuations in the compensated semimetal FeSe at the BCS-BEC crossover.

The physics of the crossover between weak-coupling Bardeen-Cooper-Schrieffer (BCS) and strong-coupling Bose-Einstein condensate (BEC) limits gives a unified framework of quantum-bound (superfluid) states of interacting fermions. This crossover has been studied in the ultracold atomic systems, but is extremely difficult to be realized for electrons in solids. Recently, the superconducting semimetal FeSe with a transition temperature Tc=8.5 K has been found to be deep inside the BCS-BEC crossover regime. Here we report experimental signatures of preformed Cooper pairing in FeSe, whose energy scale is comparable to the Fermi energies. In stark contrast to usual superconductors, large non-linear diamagnetism by far exceeding the standard Gaussian superconducting fluctuations is observed below T*∼20 K, providing thermodynamic evidence for prevailing phase fluctuations of superconductivity. Nuclear magnetic resonance and transport data give evidence of pseudogap formation at ∼T*. The multiband superconductivity along with electron-hole compensation in FeSe may highlight a novel aspect of the BCS-BEC crossover physics.

Possible observation of highly itinerant quantum magnetic monopoles in the frustrated pyrochlore Yb2Ti2O7.

The low-energy elementary excitations in frustrated quantum magnets have fascinated researchers for decades. In frustrated Ising magnets on a pyrochlore lattice possessing macroscopically degenerate spin-ice ground states, the excitations have been discussed in terms of classical magnetic monopoles, which do not contain quantum fluctuations. Here we report unusual behaviours of magneto-thermal conductivity in the disordered spin-liquid regime of pyrochlore Yb2Ti2O7, which hosts frustrated spin-ice correlations with large quantum fluctuations owing to pseudospin-1/2 of Yb ions. The analysis of the temperature and magnetic field dependencies shows the presence of gapped elementary excitations. We find that the gap energy is largely suppressed from that expected in classical monopoles. Moreover, these excitations propagate a long distance without being scattered, in contrast to the diffusive nature of classical monopoles. These results suggests the emergence of highly itinerant quantum magnetic monopole, which is a heavy quasiparticle that propagates coherently in three-dimensional spin liquids.

Variant parameter values-as defined by the Chicago Criteria-produced by ManoScan and a new system with Unisensor catheter.

BACKGROUND: Recently reported normal values for esophageal motility obtained by high-resolution manometry (HRM) using a system with a Unisensor catheter were significantly different from those obtained by the ManoScan(®) , which could result in a wrong diagnosis. To clarify whether these differences were due to system or subject differences, we compared the manometric parameter values between ManoScan and a new system with a Unisensor catheter (Starlet) in the same subjects. METHODS: A total of 103 volunteers without any symptoms related to esophageal motility disorders were recruited. Esophageal HRM was performed using both the ManoScan and the Starlet in all subjects. Data from the ManoScan were analyzed using ManoView, and data from the Starlet were analyzed by a program with e-sleeve function. Integrated relaxation pressure, distal contractile integral, contractile front velocity (CFV), intrabolus pressure, and distal latency were calculated by both analyzing programs, and the values of these parameters were compared between the two systems by a signed rank test. KEY RESULTS: Data from a total of 97 participants were analyzed. The values of all parameters, except CFV, measured by the Starlet were significantly higher than those obtained by the ManoScan (p < 0.01). CONCLUSIONS & INFERENCES: Both systems can measure esophageal motility appropriately; nevertheless, we confirmed that the two systems showed different values of the parameters defined by the Chicago criteria. These differences should be recognized to evaluate esophageal motility precisely.

Gastrointestinal symptoms in idiopathic pulmonary fibrosis patients treated with pirfenidone and herbal medicine.

Pirfenidone is an antifibrotic agent for patients with pulmonary fibrosis, but this drug has adverse gastrointestinal (GI) effects. The first aim of this study was to assess GI symptoms due to pirfenidone by using a new questionnaire for reflux symptoms and dismotility symptoms. Whether adding herbal medicine of rikkunshi-to improved GI symptoms due to pirfenidone therapy was also investigated. This was a randomized controlled trial performed on 17 IPF patients. The patients were assigned to two groups, and the study period was 8 weeks. The pirfenidone group received pirfenidone therapy for 8 weeks with add-on rikkunshi-to from 4 weeks, while the control group did not receive either of these agents. To assess the effects of RK, plasma levels of acyl-ghrelin and des-acyl-ghrelin, serum KL-6 and surfactant protein-D, and pulmonary function tests were monitored. GI symptoms were most severe during the initial 2 weeks of pirfenidone therapy at a dose of 600 mg/day. Both reflux symptoms and dismotility symptoms deteriorated. Rikkunshi-to improved GI symptoms to the level prior to pirfenidone therapy. Plasma levels of des-acyl-ghrelin and acyl-/des-acyl-ghrelin ratio changed significantly at 8 weeks compared to 2 weeks. GI adverse events due to PFD were most severe in the first 2 weeks of treatment at a dose of 600 mg/day, and both reflux and dismotility symptoms deteriorated, but the drug was well tolerated at 1200 mg/day. Rikkunshi-to contributed to improvement of GI symptoms, but plasma ghrelin levels did not reflect the improvement of GI symptoms.

Uterine sutures at prior caesarean section and placenta accreta in subsequent pregnancy: a case-control study.

OBJECTIVE: To clarify the effects of uterine myometrial suture techniques at prior caesarean section on the incidence of pathologically diagnosed placenta accreta in placenta praevia with prior caesarean section (PPPC). DESIGN: Case-control study. SETTING: Eleven tertiary referral hospitals in central Japan. POPULATION: A total of 98 cases of placenta praevia, a history of one or more prior caesarean sections, and a history of uterine transverse incision and usage of only absorbable thread for myometrial sutures at the prior caesarean section. Exclusions were a history of myomectomy or Strassmann's operation. METHODS: Cases were grouped into a pathologically diagnosed placenta accreta group (38 cases) and a no accreta group (60 cases). Clinical characteristics including uterine suture methods at prior caesarean section were compared (single-layer versus double-layer closure; continuous versus interrupted sutures in the inner myometrial layer). MAIN OUTCOME MEASURE: The incidence of placenta accreta. RESULTS: No difference was found comparing single-layer with double-layer closure in the incidence of placenta accreta (37.1 versus 39.7%, P = 0.805); however, a significant difference was found comparing continuous with interrupted sutures (58.1 versus 29.9%, P = 0.008). Multivariable logistic regression analysis with stepwise selection for the eight factors meeting the criterion of P < 0.10 in univariate analysis was used, and four independent factors were selected, as follows: gravidity ≥ 3 (adjusted odds ratio, aOR, 3.4, 95% confidence interval, 95% CI, 0.99-11.6, P = 0.050); total praevia (versus non-total, aOR 18.4, 95% CI 3.2-107.0, P = 0.001); anterior/centre placenta (versus posterior, aOR 16.4, 95% CI 3.7-72.2, P < 0.001); and continuous sutures (versus interrupted, aOR 6.0, 95% CI 1.4-25.2, P = 0.015). CONCLUSIONS: In this limited study, a history of continuous sutures on the inner side of the uterine wall showed potential to influence the development of placenta accreta in PPPC patients.

Role of anatomical right hepatic trisectionectomy for perihilar cholangiocarcinoma.

BACKGROUND: Right-sided hepatectomy is often selected for perihilar cholangiocarcinoma because the extrahepatic portion of the left hepatic duct is longer than that of the right hepatic duct. However, the length of resected left hepatic duct in right-sided hepatectomy has not been reported. METHODS: Patients who underwent right-sided hepatectomy for perihilar cholangiocarcinoma were reviewed retrospectively. Trisectionectomies were performed according to a previously reported technique of anatomical right hepatic trisectionectomy. Right hepatectomy was performed according to standard operative procedures. The length of resected left hepatic duct was measured. RESULTS: Thirty-three patients underwent right trisectionectomy and 141 had a right hemihepatectomy. Patients having a trisectionectomy had more advanced tumours and so required combined portal vein resection more frequently. Duration of surgery and blood loss were similar in the two groups. Morbidity and mortality rates tended to be higher following hemihepatectomy than after trisectionectomy. The mean(s.d.) length of resected left hepatic duct was significantly greater in trisectionectomy than in hemihepatectomy (25·0(6·9) versus 14·8(5·3) mm; P < 0·001). In patients with Bismuth type IV tumours, the percentage of negative left hepatic duct margins was significantly higher for trisectionectomy than for hemihepatectomy (89 versus 57 per cent; P = 0·021). Achievement of R0 resection was similar and survival did not differ between the two groups, despite different tumour load. CONCLUSION: Compared with right hemihepatectomy, anatomical right hepatic trisectionectomy provides a greater length of resected hepatic duct, leading to a high proportion of negative proximal ductal margins even in patients with Bismuth type IV tumours.

Total spondylectomy following carbon ion radiotherapy to treat chordoma of the mobile spine.

The main form of treatment of a chordoma of the mobile spine is total en bloc spondylectomy (TES), but the clinical results are not satisfactory. Stand-alone carbon ion radiotherapy (CIRT) for bone and soft-tissue sarcomas has recently been reported to have a high rate of local control with a low rate of local recurrence. We report two patients who underwent TES after CIRT for treating a chordoma in the lumbar spine with good medium-term outcomes. At operation, there remained histological evidence of viable tumour cells in both cases. After the combination use of TES following CIRT, neither patient showed signs of recurrence at the follow-up examination. These two cases suggest that CIRT should be combined with total spondylectomy in the treatment of chordoma of the mobile spine.

Monosodium glutamate stimulates secretion of glucagon-like peptide-1 and reduces postprandial glucose after a lipid-containing meal.

BACKGROUND: Monosodium l-glutamate (MSG) is known to influence the endocrine system and gastrointestinal (GI) motility. The mechanism of postprandial glycemic control by food in the GI tract is mostly unknown and of great interest. AIM: To investigate the effect of MSG on glucose homeostasis, incretin secretion and gastric emptying in humans after a lipid-containing meal. METHODS: Thirteen healthy male volunteers (mean age, 25.5 years) and with no Helicobcter pylori infection were enrolled. A 400 mL (520 kcal) liquid meal with MSG (2 g, 0.5% wt:vol) or NaCl (control) was ingested in a single-blind placebo-controlled cross-over study. Blood glucose, serum insulin, plasma glucagon, plasma glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide were measured. Gastric emptying was monitored by a 13C acetate breath test. Postprandial symptoms were assessed on a visual analogue scale. RESULTS: The 30-min postprandial glucose concentration was significantly reduced by adding MSG to the test meal. The area under the glucose concentration vs. time curve (0-60 min) was also significantly reduced by adding MSG (40.6 ± 3.51 mg·1 hr/dL with MSG vs. 49.2 ± 3.86 mg·1 hr/dL with NaCl, P = 0.047), whereas, the 30-min postprandial plasma GLP-1 level was significantly increased (58.1 ± 15.8 pmol/L with MSG vs. 13.4 ± 15.8 pmol/L with NaCl, P = 0.035). MSG did not affect the half gastric emptying time or postprandial symptoms. CONCLUSIONS: Monosodium l-glutamate improved early postprandial glycaemia after a lipid-containing liquid meal. This effect was not associated with a change in gastric emptying, but was possibly related to stimulation of glucagon-like peptide-1 secretion.

A case report of placental mesenchymal dysplasia with an increased VEGF-D expression.

The pathogenesis of placental mesenchymal dysplasia (PMD) remains unclear. This report presents a case of PMD with a female fetus complicated with intrauterine growth restriction (IUGR). The ultrasound findings were similar to molar pregnancies, but PMD was suspected based on the presence of low ß-hCG levels and a normal karyotype. After delivery, pathological examination of the placenta showed dilated villi and thick-walled vessels lacking trophoblast proliferation, which thus led to a diagnosis of PMD. The VEGF-D (Xp22.31) mRNA expression was found to have increased in the abnormal villi. Whether this is an incidental or X-linked gene specific event in, IUGR complicated, PMD pathogenesis warrants further investigation of VEGF-D expression in PMD.

Cascade stomach is associated with upper gastrointestinal symptoms: a population-based study.

BACKGROUND: Cascade stomach (CS) is recognized by characteristic findings on barium studies. We prospectively investigated the relationship between CS and upper gastrointestinal (GI) symptoms. METHODS: In subjects undergoing health screening, CS was diagnosed by barium studies. Consecutive persons (500 men and 127 women) with CS were identified and the same number of age-matched subjects without CS were selected as controls. Upper GI symptoms were classified as reflux symptoms, dyspepsia symptoms, or epigastralgia symptoms. Then, we prospectively analyzed barium studies to classify the gastric morphology and also assessed upper GI symptoms in consecutive 5008 men and 2736 women. KEY RESULTS: BMI was significantly higher in men with CS than in controls, and also in women with CS than in controls. Upper GI symptoms were significantly more frequent in the CS group than the controls among both men and women, especially reflux symptoms. In men, logistic regression analysis identified CS as an independent risk factor for upper GI symptoms (odds ratio = 1.771, P = 0.005) and for reflux symptoms (odds ratio = 2.07, P = 0.009). In women, CS was also significantly related to upper GI symptoms (odds ratio = 2.544, P = 0.020). The prevalence of CS was significantly higher (P < 0.0001) among symptomatic men than among those with no symptoms. CONCLUSIONS & INFERENCES: Gastric morphology is related to upper GI symptoms in both men and women. Cascade stomach should be reconsidered as a pathophysiological factor associated with upper GI symptoms.

Propeptide processing and proteolytic activity of proenzymes of the staphylococcal and enterococcal GluV8-family protease.

Proenzymes with various lengths of propeptides have been observed in GluV8 from Staphylococcus aureus and GluSE from S. epidermidis. However, the production mechanism of these proenzymes and roles of truncated propeptides have yet to be elucidated. Here we demonstrate that shortening of propeptide commonly occurs in an auto-catalytic manner in GluV8-family members, including those from coagulase negative Staphylococci and Enterococcus faecalis. Accompanied with propeptide shortening, the pro-mature junction (Asn/Ser_1-Val1) becomes more susceptible towards the hetero-catalytic maturation enzymes. The auto-catalytic propeptide truncation is not observed in Ser169Ala inert molecules of GluV8-family members. A faint proteolytic activity of proenzymes from Staphylococcus caprae and E. faecalis is detected. In addition, proteolytic activity of proenzyme of GluV8 carrying Arg-3AlaAsn.1 is demonstrated with synthetic peptide substrates LLE/Q-MCA. These results suggest that GluV8-family proenzymes with shortened propeptides intrinsically possess proteolytic activity and are involved in the propeptide shortening that facilitates the final hetero-catalytic maturation.

Prospective study of biliary cytology in suspected perihilar cholangiocarcinoma.

BACKGROUND: The diagnostic value of biliary cytology for hilar bile duct stricture is uncertain. This study prospectively examined three methods for the evaluation of biliary cytology in a consecutive group of patients. METHODS: Preoperative bile sampling by aspiration through a drainage catheter (aspiration samples), saline flush through a drainage catheter (saline samples) or direct sampling from a drainage bag (bag samples) was performed in consecutive patients with suspected perihilar cholangiocarcinoma who underwent resection after endoscopic nasobiliary drainage or percutaneous transhepatic biliary drainage. All bile sampling was performed three times on separate days. The accuracy of cytology in the diagnosis of carcinoma was determined. RESULTS: Of 100 consecutive patients with hilar strictures, 97 had histologically proven cholangiocarcinoma. The proportion of these 97 patients who had a positive finding on cytology in at least one of three sampling sessions was 55 per cent for aspiration samples, 48 per cent for bag samples and 38 per cent for saline samples (P = 0·021, aspiration versus saline). Tumour length correlated significantly with overall positivity. For aspiration samples, sensitivity was 55 per cent, specificity was 100 per cent and accuracy 56·0 per cent. CONCLUSION: For biliary cytology, sampling by catheter aspiration is more effective than catheter flushing or sampling from a drainage bag. Repeated sampling increases sensitivity. Biliary cytology has modest diagnostic yield, but is easy to perform, highly specific, and can provide a definitive diagnosis.

Increase of weakly acidic gas esophagopharyngeal reflux (EPR) and swallowing-induced acidic/weakly acidic EPR in patients with chronic cough responding to proton pump inhibitors.

BACKGROUND: Gastro-esophageal reflux disease (GERD)-related chronic cough (CC) may have multifactorial causes. To clarify the characteristics of esophagopharyngeal reflux (EPR) events in CC patients whose cough was apparently influenced by gastro-esophageal reflux (GER), we studied patients with CC clearly responding to full-dose proton pump inhibitor (PPI) therapy (CC patients). METHODS: Ten CC patients, 10 GERD patients, and 10 healthy controls underwent 24-h ambulatory pharyngo-esophageal impedance and pH monitoring. Weakly acidic reflux was defined as a decrease of pH by >1 unit with a nadir pH >4. In six CC patients, monitoring was repeated after 8 weeks of PPI therapy. The number of each EPR event and the symptom association probability (SAP) were calculated. Symptoms were evaluated by a validated GERD symptom questionnaire. KEY RESULTS: Weakly acidic gas EPR and swallowing-induced acidic/weakly acidic EPR only occurred in CC patients, and the numbers of such events was significantly higher in the CC group than in the other two groups (P < 0.05, respectively). Symptom association probability analysis revealed a positive association between GER and cough in three CC patients. Proton pump inhibitor therapy abolished swallowing-induced acidic/weakly acidic EPR, reduced weakly acidic gas EPR, and improved symptoms (all P < 0.05). CONCLUSIONS & INFERENCES: Most patients with CC responding to PPI therapy had weakly acidic gas EPR and swallowing-induced acidic/weakly acidic EPR. A direct effect of acidic mist or liquid refluxing into the pharynx may contribute to chronic cough, while cough may also arise indirectly from reflux via a vago-vagal reflex in some patients.

Mechanism of gastroesophageal reflux in patients with obstructive sleep apnea syndrome.

BACKGROUND: It has been reported that the prevalence of gastroesophageal reflux (GER) disease is high in patients with obstructive sleep apnea (OSA). End-inspiratory intra-esophageal pressure decreases progressively during OSA, which has been thought to facilitate GER in OSA patients. The aim of our study was to clarify the mechanisms of GER during sleep (sleep-GER) in OSA patients. METHODS: Eight OSA patients with reflux esophagitis (RE), nine OSA patients without RE, and eight healthy controls were studied. Polysomnography with concurrent esophageal manometry and pH recording were performed. KEY RESULTS: Significantly more sleep-GER occurred in OSA patients with RE than without RE or in controls (P < 0.05). The severity of OSA did not differ between OSA patients with RE and without RE. Sleep-GER was mainly caused by transient lower esophageal sphincter relaxation (TLESR), but not by negative intra-esophageal pressure during OSA. During OSA gastroesophageal junction pressure progressively increased synchronous to intra-esophageal pressure decrease. OSA patients had significantly more TLESR events during sleep related to preceding arousals and shallow sleep, but the number of TLESR events was not related to RE. CONCLUSIONS & INFERENCES: In OSA patients, sleep-GER was mainly caused by TLESR, but not by negative intra-esophageal pressure due to OSA.