Nonlocal Spin Correlation as a Signature of Ising Anyons Trapped in Vacancies of the Kitaev Spin Liquid.

In the Kitaev chiral spin liquid, Ising anyons are realized as Z_{2} fluxes binding Majorana zero modes, which, however, are thermal excitations with finite decay rates. On the other hand, a lattice vacancy traps a Z_{2} flux even in the ground state, resulting in the stable realization of a Majorana zero mode in a vacancy. We demonstrate that spin-spin correlation functions between two vacancy sites exhibit long-range correlation arising from the fractionalized character of Majorana zero modes, in spite of the strong decay of bulk spin correlations. Remarkably, this nonlocal spin correlation does not decrease as the distance between two vacancy sites increases, signaling Majorana teleportation. Furthermore, we clarify that the nonlocal correlation can be detected electrically via the measurement of nonlocal conductance between two vacancy sites, which is straightforwardly utilized for the readout of Majorana qubits. These findings pave the way to the measurement-based quantum computation with Ising anyons trapped in vacancies of the Kitaev spin liquid.

Spin-Nernst Effect in Time-Reversal-Invariant Topological Superconductors.

We investigate the spin-Nernst effect in time-reversal-invariant topological superconductors, and show that it provides smoking-gun evidence for helical Cooper pairs. The spin-Nernst effect stems from asymmetric, in spin space, scattering of quasiparticles at nonmagnetic impurities, and generates a transverse spin current by the temperature gradient. Both the sign and the magnitude of the effect sensitively depend on the scattering phase shift at impurity sites. Therefore the spin-Nernst effect is uniquely suitable for identifying time-reversal-invariant topological superconducting orders.

Detection of early adenocarcinoma of the esophagogastric junction by spraying an enzyme-activatable fluorescent probe targeting Dipeptidyl peptidase-IV.

BACKGROUND: It is still difficult to detect and diagnose early adenocarcinoma of the esophagogastric junction (EGJ) using conventional endoscopy or image-enhanced endoscopy. A glutamylprolyl hydroxymethyl rhodamine green (EP-HMRG) fluorescent probe that can be enzymatically activated to become fluorescent after the cleavage of a dipeptidyl peptidase (DPP)-IV-specific sequence has been developed and is reported to be useful for the detection of squamous cell carcinoma of the head and neck, and esophagus; however, there is a lack of studies that focuses on detecting EGJ adenocarcinoma by fluorescence molecular imaging. Therefore, we investigated the visualization of early EGJ adenocarcinoma by applying EP-HMRG and using clinical samples resected by endoscopic submucosal dissection (ESD). METHODS: Fluorescence imaging with EP-HMRG was performed in 21 clinical samples resected by ESD, and the fluorescence intensity of the tumor and non-tumor regions of interest was prospectively measured. Immunohistochemistry was also performed to determine the expression of DPP-IV. RESULTS: Fluorescence imaging of the clinical samples showed that the tumor lesions were visualized within a few minutes after the application of EP-HMRG, with a sensitivity, specificity, and accuracy of 85.7, 85.7, and 85.7%, respectively. However, tumors with a background of intestinal metaplasia did not have a sufficient contrast-to-background ratio since complete intestinal metaplasia also expresses DPP-IV. Immunohistochemistry measurements revealed that all fluorescent tumor lesions expressed DPP-IV. CONCLUSIONS: Fluorescence imaging with EP-HMRG could be useful for the detection of early EGJ adenocarcinoma lesions that do not have a background of intestinal metaplasia.

Changes of Dyspeptic Symptom after Successful Eradication in Helicobacter pylori-Associated Dyspepsia.

BACKGROUND: Helicobacter pylori (H. pylori) gastritis could cause dyspepsia, and eradication is recommended as the first-line treatment. Patients who continuously have their symptoms under control > 6 months after eradication are defined as having H. pylori-associated dyspepsia (HPD), whereas patients who do not benefit from successful eradication are defined as having functional dyspepsia. OBJECTIVES: We assessed changes in dyspeptic symptoms after successful eradication of H. pylori by using a questionnaire. METHODS: We studied H. pylori-infected dyspeptic participants with abdominal symptom scores > 4 points on the Global Overall Symptom (GOS) scoring items and received eradication therapy. We evaluated their symptoms using the GOS questionnaire before their eradications, at 1-month and at 1-year check-ups after eradication therapy. RESULTS: Thirty dyspeptic participants (mean age 59.6 ± 15.3 years) answered every questionnaire. Fourteen participants (46.7%) had HPD, whereas 16 participants (53.3%) were non-HPD patients. The questionnaire at 1 month showed sensitivity of 64.3% (9/14) and specificity of 56.3% (9/16) for HPD. Approximately 60% of H. pylori-infected dyspepsia participants were identified as having HPD or non-HPD within 1 month after their eradications. CONCLUSIONS: Approximately 60% of HPD participants improved at 1 month after eradication. The questionnaire at 1 month helped diagnose HPD in advance and guided next treatment choice.

Chiral Higgs Mode in Nematic Superconductors.

Nematic superconductivity with spontaneously broken rotation symmetry has recently been reported in doped topological insulators, M_{x}Bi_{2}Se_{3} (M=Cu, Sr, Nb). Here we show that the electromagnetic (EM) response of these compounds provides a spectroscopy for bosonic excitations that reflect the pairing channel and the broken symmetries of the ground state. Using quasiclassical Keldysh theory, we find two characteristic bosonic modes in nematic superconductors: the nematicity mode and the chiral Higgs mode. The former corresponds to the vibrations of the nematic order parameter associated with broken crystal symmetry, while the latter represents the excitation of chiral Cooper pairs. The chiral Higgs mode softens at a critical doping, signaling a dynamical instability of the nematic state towards a new chiral ground state with broken time reversal and mirror symmetry. Evolution of the bosonic spectrum is directly captured by EM power absorption spectra. We also discuss contributions to the bosonic spectrum from subdominant pairing channels to the EM response.

Negative Thermal Magnetoresistivity as a Signature of a Chiral Anomaly in Weyl Superconductors.

We propose that the chiral anomaly of Weyl superconductors gives rise to negative thermal magnetoresistivity induced by emergent magnetic fields, which are generated by vortex textures of order parameters or lattice strain. We establish this scenario by combining the argument based on Berry curvatures and the quasiclassical theory of the Eilenberger equation with quantum corrections arising from inhomogeneous structures. It is found that the chiral anomaly contribution of the thermal conductivity exhibits characteristic temperature dependence, which can be a smoking-gun signature of this effect.

Preventive effect of mesenchymal stem cell culture supernatant on luminal stricture after endoscopic submucosal dissection in the rectum of pigs.

BACKGROUND: Mesenchymal stem cells (MSCs) are valuable in regenerative medicine, and MSC culture supernatant (MSC-CS) reportedly inhibits inflammation and fibrosis. We investigated whether colorectal luminal stricture develops after circumferential endoscopic submucosal dissection (ESD) in the colorectum, and whether the development of luminal stricture could be prevented by using MSC-CS enema. METHODS: In the first experiment, we performed circumferential ESD in the rectums or distal colons of pigs (n = 4 in each group). We sacrificed the pigs on Day 22 and measured the degree of luminal stricture. In the second experiment, we performed circumferential ESD in the rectums of pigs and administered an MSC-CS gel or a control gel enema after ESD for 4 days. We sacrificed the pigs on Day 8 (n = 3 in each group) or 22 (n = 3 in each group) to measure the degree of luminal stricture, and performed histological analysis. RESULTS: Severe luminal stricture was observed in the rectum but not in the distal colon. Moreover, fiber accumulation in the submucosa and hypertrophy of the muscularis propria were observed in the rectum but not in the distal colon. The degree of luminal stricture in the rectum was significantly lower in the MSC-CS group than in the control group. Furthermore, MSC-CS attenuated myofibroblast activation and hypertrophy of the muscularis propria on Day 22, and reduced inflammatory cell infiltration on Day 8. CONCLUSIONS: Luminal stricture after ESD developed only in the rectum because of the difference in myofibroblast activation and fiber accumulation. In addition, MSC-CS enema prevented luminal stricture after ESD, possibly by inhibiting the inflammatory reaction and fibrosis.

Oral administration of conditioned medium obtained from mesenchymal stem cell culture prevents subsequent stricture formation after esophageal submucosal dissection in pigs.

BACKGROUND AND AIMS: Endoscopic submucosal dissection (ESD) for esophageal cancer often causes postoperative stricture when more than three fourths of the circumference of the esophagus is dissected. Mesenchymal stem cells are a valuable cell source in regenerative medicine, and conditioned medium (CM) obtained from mesenchymal stem cells reportedly inhibits inflammation. In this study we evaluated whether CM could prevent esophageal stricture after ESD. METHODS: We resected a semi-circumference of pig esophagus by ESD. We prepared CM gel by mixing with 5% carboxymethyl cellulose and endoscopically applied it onto the wound bed immediately after ESD and on days 8 and 15 (weekly CM group) or administered it orally from days 1 to 4 (daily CM group). We also injected triamcinolone acetonide into the remaining submucosa immediately after ESD (steroid group). We killed the pigs on day 8 or day 22 to measure the stricture rate and to perform histologic analysis. RESULTS: Stricture rate in weekly and daily CM groups and steroid groups were significantly lower than in the control group on day 22. Moreover, CM significantly attenuated the number of activated myofibroblasts and fiber thickness on day 22. CM also significantly decreased the infiltration of neutrophils and macrophages compared with the control group on day 8. CONCLUSIONS: CM gel prevents esophageal stricture formation by suppressing myofibroblast activation and fibrosis after the infiltration of neutrophils and macrophages. Oral administration of CM gel is a promising treatment for the prevention of post-ESD stricture.

Gastric mucosal cracked and cobblestone-like changes resulting from proton pump inhibitor use.

BACKGROUND AND AIM: Use of proton pump inhibitors (PPI) is histologically associated with oxyntic gland dilatations. Two interesting mucosal changes are often detected endoscopically in patients who use PPI: gastric cracked mucosa (GCM) and gastric cobblestone-like mucosa (GCSM). The aim of the present study was to clarify the relationship between PPI use and these mucosal changes. METHODS: This was a single-center observational study. All successive subjects who underwent a routine esophagogastroduodenoscopy (EGD) between August and November 2014 in Hokkaido University Hospital were enrolled. Endoscopists carried out the assessment blinded to the use of PPI and checked for GCSM and GCM using original diagnostic criteria for GCM and GCSM. Subjects were divided into two groups: those who used PPI (PPI group) and those who did not (control group). Endoscopic findings and backgrounds were compared between the two groups. RESULTS: A total of 538 patients were analyzed (control group: 374 patients, men/women: 204/170, median age: 65.2 years; PPI group: 164 patients, men/women: 89/75, median age: 67.1 years). GCM was detected in 54 (10.0%) subjects, and GCSM was detected in 18 (3.3%) subjects. There was a significant difference in the prevalence rate of GCM between the control group (14/374, 3.7%) and the PPI group (40/164, 24.4%) (P < 0.01). GCSM was significantly more prevalent in the PPI group (15/164, 9.1%) than in the control group (3/374, 0.8%) (P < 0.01). CONCLUSION: Novel GCM and GCSM endoscopic findings in the corpus area seem to be strongly associated with PPI use.

Fluorescent imaging of superficial head and neck squamous cell carcinoma using a γ-glutamyltranspeptidase-activated targeting agent: a pilot study.

BACKGROUND: Detecting superficial head and neck squamous cell carcinoma (HNSCC) by endoscopy is challenging because of limited morphological hallmarks, and iodine cannot be applied to head and neck lesions due to severe mucosal irritation. γ-glutamyltranspeptidase (GGT), a cell surface enzyme, is overexpressed in several cancers, and it has been reported that γ-glutamyl hydroxymethyl rhodamine green (gGlu-HMRG), a fluorescent targeting agent which can be enzymatically activated and becomes fluorescent after cleavage of a GGT-specific sequence, can be activated within a few minutes after application to animal models. We investigated whether early HNSCC can be detected by applying gGlu-HMRG to clinical samples. METHODS: gGlu-HMRG was applied to four HNSCC cell lines, and fluorescence was observed by fluorescence microscopy and flow cytometry. Immunohistological examination was performed in three recent cases of endoscopic submucosal dissection (ESD) to investigate GGT expression. Fluorescence imaging with gGlu-HMRG in eight clinical samples resected by ESD or surgery was performed, and fluorescence intensity of tumor and normal mucosa regions of interest (ROI) was prospectively measured. RESULTS: All four gGlu-HMRG-applied cell lines emitted green fluorescence. Immunohistological examination demonstrated that GGT was highly expressed in HNSCC of the recent three ESD cases but barely in the normal mucosa. Fluorescence imaging showed that iodine-voiding lesions became fluorescent within a few minutes after application of gGlu-HMRG in all eight resected tumors. Tumor ROI fluorescence intensity was significantly higher than in the normal mucosa five minutes after gGlu-HMRG application. CONCLUSIONS: Fluorescence imaging with gGlu-HMRG would be useful for early detection of HNSCC.

Multicenter randomized controlled study to assess the effect of prophylactic clipping on post-polypectomy delayed bleeding.

BACKGROUND AND AIM: Prophylactic clipping has been widely used to prevent post-procedural bleeding in colon polypctomy. However, its efficiency has not been confirmed and there is no consensus on the usefulness of prophylactic clipping. The aim of the present study was to evaluate the preventive effect of prophylactic clipping on post-polypectomy bleeding. METHODS: A multicenter randomized controlled study was conducted from January 2012 to July 2013 in Japan. Patients who had polyps <2 cm in diameter were divided into a clipping group and a non-clipping group by cluster randomization. After endoscopic polypectomy, patients allocated to the clipping group underwent prophylactic clipping, whereas the procedure was completed without clipping in patients allocated to the non-clipping group. Occurrence of post-polypectomy bleeding was compared between the two groups. RESULTS: Seven hospitals participated in this study. A total of 3365 polyps in 1499 patients were evaluated. The clipping group consisted of 1636 polyps in 752 patients, and the non-clipping group consisted of 1729 polyps in 747 patients. Post-polypectomy bleeding occurred in 1.10% (18/1636) of the cases in the clipping group, and in 0.87% (15/1729) of those in the non-clipping group. The difference was -0.22% (95% confidence interval [CI]: -0.96, 0.53). Upper limit of the 95% CI was lower than the non-inferiority margin (1.5%), and we could thus prove non-inferiority of non-clipping against clipping. CONCLUSION: Prophylactic clipping is not necessary to prevent post-polypectomy bleeding for polyps <2 cm in diameter.

Technical difficulty according to location, and risk factors for perforation, in endoscopic submucosal dissection of colorectal tumors.

BACKGROUND: Colorectal endoscopic submucosal dissection (ESD) is a widely accepted treatment for colorectal tumors, but is technically more difficult and has a higher risk of complications such as perforation than gastric ESD. Few studies have investigated the factors associated with technical difficulty and perforation in colorectal ESD. This study aimed to evaluate the technical difficulty according to location, and the risk factors for perforation, in colorectal ESD. METHODS: This retrospective study included 134 consecutive colorectal tumors treated by ESD in 122 patients at the Division of Endoscopy of Hokkaido University Hospital and the Department of Gastroenterology of Kitami Red Cross Hospital from November 2011 to February 2013. To evaluate the technical difficulty of performing ESD for colorectal tumors at specific locations, the en bloc R0 resection rate, specimen diameter, procedure speed, and procedure time were compared among tumor locations using the χ (2) test or analysis of variance. Risk factors for perforation were identified by multiple logistic regression analysis. RESULTS: The en bloc R0 resection rate was 86.6 % (116/134), the mean tumor diameter was 27.1 mm, and the mean procedure time was 63.5 min. The mean speed of procedures was significantly slower in the sigmoid colon (24.7 min/cm(2)) than in other areas. Perforation occurred in nine cases (6.7 %). Submucosal fibrosis was the only factor independently associated with perforation (odds ratio 5.684, 95 % confidence interval 1.307-24.727). CONCLUSIONS: ESD was slower for sigmoid colon tumors than for tumors in other areas, suggesting that ESD was technically more difficult in the sigmoid colon than in other colorectal areas. Submucosal fibrosis was independently associated with perforation during colorectal ESD.

Stable Skyrmions in SU(2) gauged Bose-Einstein condensates.

We demonstrate that the three-dimensional Skyrmion, which has remained elusive so far, spontaneously appears as the ground state of SU(2) symmetric Bose-Einstein condensates coupled with a non-Abelian gauge field. The gauge field is a three-dimensional analogue of the Rashba spin-orbit coupling. Upon squashing the SO(3) symmetric gauge field to one- or two-dimensional shapes, we find that the ground state continuously undergoes a change from a three-dimensional to a one- or two-dimensional Skyrmion, which is identified by estimating winding numbers and helicity. All of the emerged Skyrmions are physically understandable with the concept of the helical modulation in a unified way. These topological objects might potentially be realizable in two-component Bose-Einstein condensates experimentally.

Symmetry protected topological order and spin susceptibility in superfluid 3He-B.

We here demonstrate that the superfluid (3)He-B under a magnetic field in a particular direction stays topological due to a discrete symmetry, that is, in a symmetry protected topological order. Because of the symmetry protected topological order, helical surface Majorana fermions in the B phase remain gapless and their Ising spin character persists. We unveil that the competition between the Zeeman magnetic field and dipole interaction involves an anomalous quantum phase transition in which a topological phase transition takes place together with spontaneous symmetry breaking. Based on the quasiclassical theory, we illustrate that the phase transition is accompanied by anisotropic quantum criticality of spin susceptibilities on the surface, which is detectable in NMR experiments.

Proton Pump Inhibitor-Associated Large Hyperplastic Polyp in Non-Helicobacter pylori-Infected Stomach.

A proton pump inhibitor (PPI)-associated hyperplastic polyp (HP) in the non-Helicobacter pylori-infected stomach is rare, and its endoscopic features remain poorly described. A 42-year-old man with tarry stool was referred to our hospital for examination and treatment. He had taken PPI for 14 years and was confirmed to be H. pylori-negative. Transnasal endoscopy revealed bleeding from a 20-mm, reddish pedunculated polyp with a nodular surface, located in the greater curvature of the upper gastric body. Endoscopic mucosal resection was performed, and the lesion was diagnosed as an HP. To our knowledge, this report represents a valuable addition to the HP literature describing a rare case of PPI-associated large HP in the non-H. pylori-infected stomach.

Collision Tumor of the Stomach.

Collison tumor of the stomach is rare, and its endoscopic and pathological features remain poorly described. A 70-year-old woman was referred to our hospital for examination and treatment of undifferentiated gastric cancer. Esophagogastroduodenoscopy revealed a whitish, superficial elevated lesion in contact with a reddish, superficial depressed lesion from the anterior wall of the gastric angle and antrum to the lesser curvature. Laparoscopic distal gastrectomy was performed for preoperative diagnosis of suspected early gastric cancer presenting as a differentiated and undifferentiated collision tumor, which led to the lesion being diagnosed as collision tumor, tub1-tub2+por1-sig, pT1a (M), ly0, v0, N0, stage IA. To our knowledge, this report represents a valuable addition to the collision tumor literature describing a rare case of preoperatively diagnosed collision tumor of the stomach.

Efficacy and feasibility of combination chemotherapy with S-1 and cisplatin (2 weeks regimen) for advanced gastric cancer.

OBJECTIVE: Although combination chemotherapy with 3 weeks of S-1 and cisplatin is effective for advanced gastric cancer, the toxicities of S-1 which mostly occur during the third week of administration are a major problem. To achieve fewer adverse effects with S-1 and higher dose intensity of cisplatin, we performed combination chemotherapy with 2 weeks of S-1 and cisplatin as first line. The aim of this retrospective study was to analyse the efficacy and feasibility of this regimen. METHODS: S-1 (40-60 mg depending on patient's body surface area) was given orally twice daily for 2 consecutive weeks, and 70 mg/m(2) cisplatin was given intravenously on day 8, followed by a 2-week rest period. RESULTS: Forty-eight patients received a total of 184 courses of chemotherapy. Overall response rate was 40.6% and median survival time was 411 days. Dose intensities were 257.6 mg/m(2)/week for S-1 and 16.4 mg/m(2)/week for cisplatin. The incidences of grade 3/4 haematological toxicities were leucopenia (19%), neutropenia (29%) and anaemia (17%), and those of grade 3 non-haematological toxicities were anorexia (31%) and nausea (21%). The rate of treatment discontinuation owing to toxicity was 10%. CONCLUSIONS: This regimen may be effective as an alternative therapy to 3 weeks of S-1 and cisplatin to reduce the toxicity of chemotherapy for advanced gastric cancer.

[A case of metastatic gastric endocrine cell carcinoma which could be curably resected after chemotherapy with S-1/CDDP].

Gastric endocrine cell carcinoma is known to be highly malignant with a poor prognosis, and no standard treatment has been established. We experienced a case of endocrine cell carcinoma of the stomach with liver and lymph node metastases. The lesions became resectable at curability B after chemotherapy with S-1/cisplatin (CDDP). A 59-year-old man, who had no specific complaint, had gastrointestinal endoscopy for screening. A 30-mm tumor was found at the greater curvature of the lower body of the stomach, and was histologically diagnosed as an endocrine cell carcinoma from the biopsy specimen. A computed tomography (CT) scan and abdominal magnetic resonance imaging (MRI) showed masses at S5 and S6 of the liver, and No. 4 lymph node enlargement. Diagnosed as gastric endocrine cell carcinoma with liver and lymph node metastases, he was referred to our hospital. We started chemotherapy with a daily dose of S-1 administered on days 1 to 14 and CDDP of 70 mg/m(2) on day 8, every 4 weeks. After three courses of treatment, the primary lesion became a small scar and the metastatic lesions vanished from the CT and MRI. Then we performed distal gastrectomy with lymph node dissection and partial liver resectomy. Histological findings revealed no cancer cells, except for a few cells in the S5 liver lesion.

Rapid detection of superficial head and neck squamous cell carcinoma by topically spraying fluorescent probe targeting dipeptidyl peptidase-IV.

BACKGROUND: A fluorescent probe glutamylprolyl hydroxymethyl rhodamine green (EP-HMRG), which becomes fluorescent after cleavage by dipeptidyl peptidase-IV (DPP-IV), has been reported to be useful for the detection of esophageal cancer. Thus, we investigated whether head and neck squamous cell carcinoma (HNSCC) can be detected by spraying EP-HMRG. METHODS: Fluorescence imaging of 17 cases of HNSCCs resected using endoscopic or surgical resection was performed ex vivo after spraying EP-HMRG, and then the fluorescence intensity of the tumors and normal mucosa were measured. RESULTS: Iodine-voiding lesions became fluorescent within a few minutes after the application of EP-HMRG in 12 resected tumors without a history of radiotherapy but this was not observed in the normal mucosa. Fluorescence intensity in tumor lesions was significantly higher than normal lesions. However, 5 other tumors that developed after radiotherapy did not have sufficient contrast against normal mucosa. CONCLUSION: Fluorescence imaging with EP-HMRG would be useful for rapid detection of superficial HNSCC without a history of radiotherapy.