Dynamic Properties of Heart Fragments from Different Regions and Their Synchronization.

The dynamic properties of the heart differ based on the regions that effectively circulate blood throughout the body with each heartbeat. These properties, including the inter-beat interval (IBI) of autonomous beat activity, are retained even in in vitro tissue fragments. However, details of beat dynamics have not been well analyzed, particularly at the sub-mm scale, although such dynamics of size are important for regenerative medicine and computational studies of the heart. We analyzed the beat dynamics in sub-mm tissue fragments from atria and ventricles of hearts obtained from chick embryos over a period of 40 h. The IBI and contraction speed differed by region and atrial fragments retained their values for a longer time. The major finding of this study is synchronization of these fragment pairs physically attached to each other. The probability of achieving this and the time required differ for regional pairs: atrium-atrium, ventricle-ventricle, or atrium-ventricle. Furthermore, the time required to achieve 1:1 synchronization does not depend on the proximity of initial IBI of paired fragments. Various interesting phenomena, such as 1:n synchronization and a reentrant-like beat sequence, are revealed during synchronization. Finally, our observation of fragment dynamics indicates that mechanical motion itself contributes to the synchronization of atria.

Indolent T-cell lymphoproliferative disorder of the stomach successfully treated by radiotherapy.

Successful treatment of indolent T-cell lymphoproliferative disorder of the gastrointestinal tract (ITLPDGI) by chemotherapy is rare and watchful waiting is often performed for asymptomatic patients. We report a case of ITLPDGI successfully treated by involved field radiotherapy (IFRT). The patient presented with slow ITLPDGI localised to the stomach with mild symptoms. IFRT (30 Gy/20f) was administered, after which endoscopy revealed resolution of lesions and blood vessel appearance, and absence of proliferating abnormal lymphocytes was confirmed by biopsy. The patient remains lymphoma-free 1 year post-treatment. Although long-term follow-up and additional cases are essential for the evaluation of IFRT as a treatment option for localised ITLPDGL, complete remission after relatively low-dose IFRT is promising, particularly as this has been rarely achieved by chemotherapy.

Peripheral T-cell lymphoma with gastrointestinal involvement and indolent T-lymphoproliferative disorders of the gastrointestinal tract.

The 2017 WHO classification includes a new provisional entity of indolent T-lymphoproliferative disorders of the gastrointestinal tract (ITLPD-GIT). We investigated GI involvement of peripheral T-cell lymphoma (PTCL). Eighty-two patients were diagnosed with PTCL during 2007-2017. Eleven patients (13 %) had histologically-confirmed GI tract involvement {3 monomorphic epitheliotropic intestinal lymphoma (MEITL), 3 extranodal NK-/T-cell lymphoma nasal type (ENKL), 2 PTCL, not otherwise specified, 1 adult T-cell leukemia-lymphoma, 2 ITLPD-GIT}. Three patients each had lesions in the small intestine and multiple lesions, two each in the stomach and colon, and one in the duodenum. Six of the 11 patients remained alive. No perforation/stenosis was observed after chemo-radiotherapy, although one patient with ENKL developed gastric bleeding during chemotherapy. One patient with ITLPD-GIT (CD4-/CD8+/Ki67Low) with a colonic lesion showing diffuse edema and multiple aphtha by endoscope and diarrhea, initially diagnosed with MEITL, had active but stable disease after various chemotherapies for 1 year and no therapy for the next 5 years. Another patient with ITLPD-GIT (CD4+/CD8+/Ki67Low) with a localized gastric lesion and slight epigastralgia was in remission for 1 year after radiation. In conclusion, about 10 % of PTCLs were complicated by GI tract lesions and most had a poor prognosis. ITLPD-GIT should be considered as a differential diagnosis based on histology and clinical course. Local complications after chemo/radiotherapy in PTCL with GI involvement were not frequent.

Usefulness of endoscopic ultrasound-guided fine needle aspiration for lymphadenopathy.

Lymphadenopathy may be difficult to diagnose using imaging results alone. Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) may help to diagnose and determine the appropriate management of lymphadenopathy. EUS-FNA has been used as a safe and less invasive method for obtaining pathologic specimens from extraluminal lesions using endoscopic ultrasound. The present study evaluated the usefulness of EUS-FNA for lymphadenopathy. Between July 2013 and December 2016, 72 patients undergoing EUS-FNA for lymphadenopathy that could not be diagnosed solely using imaging were included. The present study evaluated the sensitivity, specificity, positive and negative predictive value, overall accuracy, helpfulness in determining the management of lymphadenopathy and EUS-FNA-associated complications. Of the 72 included patients, 8 were diagnosed with benign (inflammatory or reactive) lymphadenopathy. The diagnostic sensitivity, specificity, positive and negative predictive value, and overall accuracy were 95.3, 100, 100, 72.7 and 95.8%, respectively. While EUS-FNA of metastatic nodes identified the origin in the majority of cases, the procedure resulted in a different histopathological diagnosis from the previous image-based diagnosis in 9 patients. Consequently, 2 patients with testicular cancer were administered bleomycin, etoposide, and cisplatin. An individual with GIST was administered imatinib, and a patient with prostate cancer was administered degarelix (antihormon drug). A total of 5 other patients received palliative medicine due to the change in diagnosis. EUS-FNA also helped determine the appropriate cancer management plan in other patients; specifically, based on the cytology of the metastatic lymph node, EUS-FNA helped determine the cancer stage, and to identify recurrence or the primary cancer from which tissue could not be collected. No EUS-FNA-associated symptoms were reported. To conclude, the present study suggested that EUS-FNA of suspected metastatic lymph nodes appears safe and useful for cancer staging and diagnosing recurrence. It may also useful for diagnosing patients whose collection of samples from the original cancer appeared impractical. EUS-FNA for lymphadenopathy that may not be diagnosed with imaging alone may assist in diagnosis and help to determine the appropriate management strategy.

Endoscopic removal of laser-cut covered self-expandable metallic biliary stents: A report of six cases.

Covered self-expandable metallic stents (CSEMS) may provide palliative drainage for unresectable distal malignant biliary strictures. Laser-cut CSEMS allows easy positioning due to its characteristic of minimal stent shortening. Endoscopic stent removal is sometimes recommended for recurrent biliary obstruction (RBO). However, there are no previous reports of endoscopic removal of laser-cut CSEMS. The current study presents data from 6 patients who were placed a laser-cut CSEMS for unresectable distal malignant biliary strictures, and later endoscopic stent removal was attempted for RBO at the present institute. The duration of stent placement, the procedural success rate, the procedural duration, and accidental complications were evaluated. The mean duration of stent placement was 156±37.9 days (range, 117-205). The procedural success rate was 100%. The mean procedural duration was 11.8±7.5 min (range, 5-24). No complications were reported. Laser-cut CSEMS were safely removed from all patients. The present case report is the first to demonstrate that Endoscopic stent removal of laser-cut CSEMS was safely performed.

Increased neutrophil-to-lymphocyte ratio is a novel marker for nutrition, inflammation and chemotherapy outcome in patients with locally advanced and metastatic esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is one of the most common types of cancer, and its progression is strongly influenced by the presence of inflammation. Recently, there has been growing interest in the host inflammatory response, and increasing evidence has indicated that the neutrophil-to-lymphocyte ratio (NLR), a useful marker of systemic inflammation, may be an effective prognostic indicator in various types of malignant diseases. In the present study, 260 patients with ESCC were enrolled, including 110 who received chemoradiation therapy (CRT) involving irradiation and chemotherapy of 5-fluorouracil and cisplatin, and 150 received chemotherapy using 5-fluorouracil and cisplatin (FP). The patients of each group were both divided into two groups according to their NLR: High NLR (NLR>3.0) and low NLR (NLR≤3.0). Serum levels of prealbumin and retinol binding protein, which are nutritional parameters, were both significantly inversely correlated with NLR in patients treated with CRT, and patients treated with FP. Levels of CRP, a marker of inflammation, were significantly correlated with NLR, and stimulation indices, markers of immune reactions, were inversely correlated with NLR in both of CRT patients and FP patients. In patients treated with CRT, a partial response was significantly higher in patients with a low NLR and with progressive disease compared to those with a high NLR. In patients treated with FP, a partial response was also significantly higher in patients with a low NLR and with progressive disease compared to those with a high NLR. The overall survival of patients with CRT and FP were both significantly worse in patients with a high NLR than in those with a low NLR. NLR may serve as a useful marker of the tumor response, immune suppression, malnutrition and prognosis upon CRT or FP in patients with locally advanced or metastatic ESCC.

The two-row malting barley cultivar 'New Sachiho Golden' with null lipoxygenase-1 improves flavor stability in beer and was developed by marker-assisted selection.

Lipoxygenase-1 (LOX-1) null 'New Sachiho Golden' is a two-row malting barley (Hordeum vulgare L.) cultivar released in 2015 that was developed at the Tochigi Prefectural Agricultural Experimental Station by backcross breeding using the high-yield leading cultivar 'Sachiho Golden' as a recurrent parent and the LOX-1 null mutant 'Daikei LM1' as a non-recurrent parent. To develop 'New Sachiho Golden' we used a simple LOX activity assay and marker-assisted selection. This is the first LOX-1 null malting barley cultivar in Japan that is resistant to barley yellow mosaic virus (types I-III). Agronomic characteristics and malting qualities of 'New Sachiho Golden' were similar to those of 'Sachiho Golden', except that 'New Sachiho Golden' had no LOX activity in ungerminated grains and had clearly lower LOX activity during malting than 'Sachiho Golden'. The concentrations of a trans-2-nonenal (T2N) precursor in wort and beer made from 'New Sachiho Golden' were significantly lower than in those made from 'Sachiho Golden', both before and after storage.

Status of the gastric mucosa with endoscopically diagnosed gastrointestinal stromal tumor.

Background. Since gastrointestinal stromal tumor (GIST) is a mesenchymal submucosal tumor, the endosonographic, CT, and MRI features of gastric GISTs have been widely investigated. However, the GIST-bearing gastric mucosa status has not been reported. Objective. To characterize the GIST-bearing gastric mucosa status in terms of the degree of inflammation and atrophy, assessed endoscopically. Subjects and Methods. The subjects were 46 patients with submucosal tumors (histologically proven gastric GISTs) who had undergone upper gastrointestinal endoscopy in our hospital between April 2007 and September 2012. They were retrospectively evaluated regarding clinicopathological features, the endoscopically determined status of the entire gastric mucosa (presence or absence and degree of atrophy), presence or absence and severity of endoscopic gastritis/atrophy (A-B classification) at the GIST site, and presence or absence of H. pylori infection. Results. Twenty-three patients had no mucosal atrophy, but 17 and 6 had closed- and open-type atrophy, respectively. Twenty-six, 5, 12, 1, 1, and 1 patients had grades B0, B1, B2, B3, A0, and A1 gastritis/atrophy at the lesion site, respectively, with no grade A2 gastritis/atrophy. Conclusion. The results suggest that gastric GISTs tend to arise in the stomach wall with H. pylori-negative, nonatrophic mucosa or H. pylori-positive, mildly atrophic mucosa.

Is narrow-band imaging useful for histological evaluation of gastric mucosa-associated lymphoid tissue lymphoma after treatment?

BACKGROUND AND AIM: Endoscopic diagnosis of stomach mucosa-associated lymphoid tissue (MALT) lymphoma is often difficult because few specific findings are indicated. Even when MALT lymphoma is suspected by endoscopy, it is still difficult to make a definitive diagnosis by biopsy because lymphoma cells sometimes distribute unevenly. We previously reported that a tree-like appearance (TLA) is a characteristic finding of MALT lymphoma by narrow-band imaging (NBI) magnifying endoscopy and it is valuable in the selection of an optimal biopsy site in MALT lymphoma. Here, we study the frequency of TLA and evaluate the relationship between the response to eradication therapy and TLA in MALT lymphoma. METHODS: We retrospectively examined the clinical background, endoscopic findings, response to eradication therapy, and Helicobacter pylori infection status of 16 patients diagnosed with MALT lymphoma who were referred to our hospital from April 2007 to August 2012. The regimen for eradicationtherapy consisted of rabeprazole, with amoxicillin and clarithromycin, all given for 7 days. RESULTS: TLA was found in 75% (12/16) and H. pylori infection in 75% (12/16) of patients diagnosed with MALT lymphoma by NBI magnifying endoscopy. In all complete regression (CR) patients after eradication treatment, the TLA finding had disappeared (100%); however, in the non-CR patients, TLA remained the same as before the eradication therapy (P=0.002). CONCLUSION: These results suggest that NBI magnifying endoscopy may be useful not only in the diagnosis but also in the evaluation of the response to eradication therapy of MALT lymphoma of the stomach.

Quick lateral movements of the trunk in a seated position reflect mobility and activities of daily living (ADL) function in frail elderly individuals.

A novel and safe performance test for measuring mobility is described. The test, which we have named the Seated Side Tapping test (Side Tapping test), requires the subjects to move their bodies laterally to the left and right in turn as quickly as possible whilst remaining in a seated position. We examined the associations between the results of the new test and those of other mobility tests, ADL, and the use of walking aids. The participants were 75 frail elderly people who were receiving rehabilitation services. Gait speed and the timed up and go (TUG) test were employed as mobility tests, and the participants' use of walking aids was recorded. The ADL score was assessed using the Barthel Index. Significant correlations were found between the side tapping test and gait speed (r=-0.59, p<0.01), and TUG (r=0.63, p<0.01). This test also revealed significant relationships with the ADL scores and the use of walking aids. These results indicate that an ability to perform quick lateral trunk movements in a seated position reflects their mobility during standing. Thus, we concluded that since the side tapping test is simple and safe, it is useful for detecting mobility impairments, ADL levels, and the need for walking aids, especially in frail elderly individuals.

Usefulness of the DL in ME with NBI for determining the expanded area of early-stage differentiated gastric carcinoma.

AIM: To investigate whether magnifying endoscopy with narrow band imaging (ME-NBI) is useful for evaluating the area of superficial, depressed- or flat-type differentiated adenocarcinoma of the stomach. METHODS: This procedure was performed in Saitama Medical University International Medical Center, Japanese Red Cross Kumamoto Hospital and Kitakyushu Municipal Medical Center. The subjects were 31 patients in whom biopsy findings, from superficial, depressed- or flat-type gastric lesion, suggested differentiated adenocarcinoma in the above 3 hospitals between January and December 2009. Biopsy was performed on the lesion and non-lesion sides of a boundary (imaginary boundary) visualized on ME-NBI. The results were pathologically investigated. We evaluated the accuracy of estimating a demarcation line (DL) on ME-NBI in comparison with biopsy findings as a gold standard. RESULTS: The DL that could be recognized at 2 points on the orifice and anal sides of each lesion during ME-NBI was consistent with the pathological findings in 22 patients with 0-IIc lesions, 7 with 0-IIb lesions, and 2 with 0-IIb + IIc lesions, showing an accuracy of 100%. CONCLUSION: The results suggest the usefulness of ME-NBI for evaluating the area of superficial, depressed- and flat-type differentiated adenocarcinoma of the stomach.

Possibilities of interventional endoscopic ultrasound.

Since endoscopic ultrasound (EUS) was developed in the 1990s, EUS has become widely accepted as an imaging tool. EUS is categorized into radial and linear in design. Radial endoscopes provide cross-sectional imaging of the mediastinum, gastrointestinal tract, liver, spleen, kidney, adrenal gland, and pancreas, which has highly accuracy in the T and N staging of esophageal, lung, gastric, rectal, and pancreatic cancer. Tumor staging is common indication of radial-EUS, and EUS-staging is predictive of surgical resectability. In contrast, linear array endoscope uses a side-viewing probe and has advantages in the ability to perform EUS-guides fine needle aspiration (EUS-FNA), which has been established for cytologic diagnosis. For example, EUS-FNA arrows accurate nodal staging of esophageal cancer before surgery, which provides more accurate assessment of nodes than radial-EUS imaging alone. EUS-FNA has been also commonly used for diagnose of pancreatic diseases because of the highly accuracy than US or computed tomography. EUS and EUS-FNA has been used not only for TNM staging and cytologic diagnosis of pancreatic cancer, but also for evaluation of chronic pancreatitis, pancreatic cystic lesions, and other pancreatic masses. More recently, EUS-FNA has developed into EUS-guided fine needle injection including EUS-guided celiac plexus neurolysis, celiac plexus block, and other "interventional EUS" procedures. In this review, we have summarized the new possibilities offered by "interventional EUS".

A case of gastric mucosa-associated lymphoid tissue lymphoma in which magnified endoscopy with narrow band imaging was useful in the diagnosis.

Recently, we reported a case of gastric mucosa-associated lymphoid tissue (MALT) lymphoma presenting with unique vascular features. In the report, we defined the tree-like appearance (TLA) on the images of abnormal blood vessels which resembled branches from the trunk of a tree in the shiny mucosa, in which the glandular structure was lost. The 67-year-old female was diagnosed with gastric MALT lymphoma. The patient received eradication therapy for H. pylori. Conventional endoscopy revealed multiple ill-delineated brownish depressions in the stomach and cobblestone-like mucosa was observed at the greater curvature to the posterior wall of the upper gastric body 7 mo after successful eradication. Unsuccessful treatment of gastric MALT lymphoma was suspected on conventional endoscopy. Conventional endoscopic observations found focal depressions and cobblestone-like appearance, and these lesions were subsequently observed using magnified endoscopy combined with narrow band imaging to identify abnormal vessels presenting with a TLA within the lesions. Ten biopsies were taken from the area where abnormal vessels were present within these lesions. Ten biopsies were also taken from the lesions without abnormal vessels as a control. A total of 20 biopsy samples were evaluated to determine whether the diagnosis of MALT lymphoma could be obtained histologically from each sample. A positive diagnosis was obtained in 8/10 TLA (+) sites and in 2/10 TLA(-) sites. Target biopsies of the site with abnormal blood vessels can potentially improve diagnostic accuracy of gastric MALT lymphoma.

Diagnosis of boundary in early gastric cancer.

Endoscopic submucosal dissection (ESD) is an advanced therapeutic endoscopic technique, which allowsresection of larger superficial tumors in the esophagus, stomach, and colon. Precise diagnosis of the boundary between tumor and the non-tumorous surrounding portion is especially important before starting ESD, because too much resection can potentially take more time and can induce a higher complication rate, while too little resection can result in a non-curative resection. The boundary diagnosis is often difficult for early gastric cancer, mainly because of the underlying condition of chronic gastritis. Due to recent developments in endoscopy, including magnified endoscopy and narrow band endoscopy, the boundary diagnosis is becoming easy and more accurate.We have also applied magnified endoscopy combined with narrow band imaging to fresh specimens immediately after resection using thetiling method and XY stage.

Prospective study of the evaluation of the usefulness of tumor typing by narrow band imaging for the differential diagnosis of gastric adenoma and well-differentiated adenocarcinoma.

BACKGROUND AND AIM: Presently, the differential diagnosis of gastric adenoma and well-differentiated adenocarcinoma by endoscopy is very difficult. We carried out magnifying endoscopy with narrow band imaging (NBI) in lesions that required discrimination between gastric adenoma and well-differentiated adenocarcinoma, and prospectively evaluated whether the tumor typing that we propose is useful for their differential diagnosis. METHODS: The materials were 93 lesions that required differential diagnosis between gastric adenoma and well-differentiated adenocarcinoma among the gastric epithelial tumors for which endoscopic treatment was planned at three facilities during the 14 months between November 2008 and December 2009. According to the typing method proposed by our facility based on images of the mucosal ultrastructure and microvessels obtained by magnified endoscopy combined with NBI, type I-II and type III-V lesions were diagnosed as gastric adenoma and well-differentiated adenocarcinoma, respectively, before endoscopic treatment, and the accuracy of the diagnoses were prospectively examined by comparing them with the postoperative pathological findings. RESULTS: Of the 93 lesions, 87 could be typed into the five types of our typing method, but six lesions could not be classified. The 87 lesions consisted of 16 type I, 12 type II, 29 type III, 27 type IV, and three type V lesions. The percentages of accurate preoperative diagnoses of types I-II as adenoma and types III-V as well-differentiated adenocarcinoma were 79% and 93%, respectively. CONCLUSIONS: The tumor typing based on NBI was useful for the endoscopic differentiation of gastric adenoma and well-differentiated adenocarcinoma.

Short term results of endoscopic submucosal dissection in superficial esophageal squamous cell neoplasms.

AIM: To evaluate the efficacy of endoscopic submucosal dissection for superficial esophageal squamous cell neoplasms. METHODS: Between July 2007 and March 2009, 27 consecutive superficial esophageal squamous cell neoplasms in 25 enrolled patients were treated by endoscopic submucosal dissection. The therapeutic efficacy, complications, and follow-up results were assessed. RESULTS: The mean size of the lesions was 21 ± 13 mm (range 2-55 mm); the mean size of the resection specimens was 32 ± 12 mm (range 10-70 mm). The en block resection rate was 100% (27/27), and en block resection with tumor-free lateral/basal margins was 88.9% (24/27). Perforation occurred in 1 patient who was managed by conservative medical treatments. None of the patients developed local recurrence or distant metastasis in the follow-up period. CONCLUSION: Endoscopic submucosal dissection is applicable to superficial esophageal squamous cell neoplasms with promising results.

[A case of gastric xanthogranuloma associated with early gastric cancer].

A 67-year-old man complaining of epigastric pain was referred for evaluation. Upper gastrointestinal endoscopy and CT revealed two extraluminal tumors in the posterior wall of the gastric body. Both of the lesions were remarkably reduced two months after the evaluation, but early gastric cancer was diagnosed on the mucosal side of the gastric body at that time. The patient underwent a distal gastrectomy, with resection of both of the extraluminal tumors. The posterior wall of the stomach was thickened and had a yellowish tumor which was diagnosed as xanthogranuloma. We report this very rare case of synchronous xanthogranuloma and gastric carcinoma.

Usefulness of anti-ulcer drugs for the prevention and treatment of peptic ulcers induced by low doses of aspirin.

AIM: To investigate the usefulness of anti-ulcer drugs for the prevention and treatment of low-dose aspirin-induced peptic ulcer. METHODS: Upper gastrointestinal endoscopy was performed in 68 patients receiving daily low-dose aspirin (81 or 100 mg/day). The endoscopic findings were classified according to the Lanza score, and the scores were compared between groups categorized according to the concomitant use of anti-ulcer drugs and the types of drugs used. In another study, 31 hemorrhagic peptic ulcer patients who had been receiving low-dose aspirin were enrolled. The patients were randomly classified into the proton pump inhibitor (PPI)-treated group and the H2 receptor antagonist (H2RA)-treated group. The administration of low-dose aspirin was continued concomitantly, and endoscopic examinations were performed 8 wk later. RESULTS: The Lanza scores (mean +/- SD) of the gastro-mucosal lesions were 1.0 +/- 1.9 and 1.9 +/- 2.3 in 8 and 16 patients receiving prevention therapy with a PPI and an H2RA, respectively. Both scores were significantly smaller than the scores in 34 patients who were not receiving prevention therapy (4.7 +/- 1.0) and in 10 patients receiving cytoprotective anti-ulcer drugs (4.3 +/- 1.6). In the prospective study, 18 and 13 patients received a PPI and an H2RA, respectively. Endoscopic examinations revealed that the tissue in the region of the gastro-mucosal lesions had reverted to normal in all patients in the PPI-treated group and in 12 patients (92%) in the H2RA-treated group; no significant differences were observed between the groups. CONCLUSION: H2RA therapy was effective for both the prevention and treatment of low-dose aspirin-induced peptic ulcer, similar to the effects of PPIs, while cytoprotective anti-ulcer drugs were ineffective in preventing ulceration.

[A case of Epstein-Barr virus (EBV) associated remnant gastric carcinoma arising 7 years after distal gastrectomy for EBV associated gastric carcinoma].

A 52-year-old man undergoing distal gastrectomy for gastric cancer in July 1998 was found to have a 0-IIa type gastric tumor near EC junction in January 2005. Histological examination showed the tumor was moderately differentiated adenocarcinoma. As the tumor was diagnosed as mucosal cancer, endoscopic mucosal dissection was performed. But pathological findings showed the depth of cancer cell invasion into deep submucosal layer. Then total resection of remnant stomach was performed. Both tumors were diagnosed as EBV-associated carcinoma. It is speculated that the mucosa changing after initial operation would give risk to a new occurrence of EBV-associated remnant gastric carcinoma. And then follow up after operation is important. Although some cases of EBV-associated remnant gastric carcinoma is found for short period after the primary surgery, our case second primary cancer was found 7 year after primary surgery. Long term follow-up by Endoscopy seems to be important.