Gastrointestinal stromal tumor with a novel mutation of KIT proto-oncogene

The majority of human gastrointestinal mesenchymal tumors are gastrointestinal stromal tumors (GISTs). Recent reports have shown the existence of gain-of-function mutations in the juxta-membrane domain of receptor tyrosine kinase (KIT) in GISTs. We present a 77-year-old woman with GIST diagnosed by positive immunostaining of cluster designation (CD) 34 and KIT. This case had a novel mutation at codon 576 located in the juxta-membrane domain of KIT. Our results indicate the importance of mutations in this KIT region and suggest the possibility of the existence of other types of mutations in this region in GISTs.     

Myocardial perfusion and fatty acid metabolism in patients with tako-tsubo-like left ventricular dysfunction

OBJECTIVES: We sought to assess myocardial perfusion and metabolism in patients with peculiar transient asynergy, which consisted of basal normokinesia and apical akinesia of the left ventricle (LV) at the same time. BACKGROUND: This asynergy has been widely called "tako-tsubo-like LV dysfunction" in Japan, but little is known about its pathophysiology. METHODS: We performed rest tallium-201 ((201)Tl) and iodine-123-beta-methyl-p-iodophenyl penta-decanoic acid ((123)I-BMIPP) dual-isotope myocardial single-photon emission computed tomography (SPECT) in 14 patients with tako-tsubo-like LV dysfunction. The LV was divided into 17 segments, and each segment was graded with scores between normal uptake (0) and defect (4). We also measured the Thrombolysis in Myocardial Infarction trial (TIMI) frame count in 28 patients and 20 control subjects. RESULTS: Early SPECT (5 +/- 3 days) revealed that the total defect score value with BMIPP was significantly higher than reduced uptake with (201)Tl (p < 0.01). Reduced uptake of BMIPP was observed in parallel with an apical akinetic region and usually involved uptake of (201)Tl. This discrepancy improved gradually during the follow-up period (29 +/- 6 days) (p = 0.36). Compared with control subjects, patients had a TIMI frame count that was significantly higher in all coronary arteries immediately after onset. This higher TIMI frame count decreased but was sustained even after resolution of tako-tsubo-like LV dysfunction. CONCLUSIONS: Our data suggest that myocardial fatty acid metabolism is more severely impaired than myocardial perfusion, in parallel with an apical akinetic region during the early phase, and that impaired multivessel coronary microcirculation is involved, at least in part, in tako-tsubo-like LV dysfunction.     

Milrinone-induced postconditioning reduces hepatic ischemia-reperfusion injury in rats: the roles of phosphatidylinositol 3-kinase and nitric oxide

Background

Ischemic postconditioning (PostC) protects the liver against ischemia-reperfusion (IR) injury. Milrinone, a phosphodiesterase 3 inhibitor, has been reported to exhibit preconditioning properties against hepatic IR injury; however, its PostC properties remain unknown. This study investigated whether milrinone has PostC properties against hepatic IR injury and the roles of phosphatidylinositol 3-kinase (PI3K) and nitric oxide synthase (NOS).

Materials and methods

Male Wistar rats were separated into six groups: (1) group S: animals that underwent sham operation without ischemia, (2) group C: ischemia followed by reperfusion with no other intervention, (3) group M: milrinone administered immediately after reperfusion, (4) group MW: wortmannin, a PI3K inhibitor, injected before milrinone administration, (5) group MN: l-NAME, a NOS inhibitor, injected before milrinone administration, and (6) group MD, milrinone administered 30 min after reperfusion. Except for group S, all groups underwent 1 h of warm ischemia of median and left lateral lobes, followed by 5 h of reperfusion. Biochemical liver function analysis and histologic examination were performed.

Results

Serum aspartate aminotransferase, alanine aminotransferase, and lactic dehydrogenase levels, histologic damage scores, and apoptotic rate in group M were significantly lower than those in group C. The inhibition of PI3K or NOS prevented this protective effect. Milrinone administered 30 min after reperfusion did not show obvious protective effects.

Conclusions

Milrinone-induced PostC protects against hepatic IR injury when it is administered immediately after reperfusion, and PI3K and NOS may play an important role in this protective effect.     

Comorbid irritable bowel syndrome symptoms and headache have greater association with anxiety than depression: Annual health check-up survey results

High rates of co-existing irritable bowel syndrome (IBS) and headache have been reported in western countries. We investigated that comorbidity in individuals in Japan, along with anxiety and depression in subjects with and without IBS symptoms and/or headache.This cross-sectional study was performed from April 2012 to January 2013 at the Matsue Seikyo General Hospital Health Check Center. Questionnaires concerning symptoms related to IBS (Rome III) and headache, as well as anxiety/depression score were sent to individuals scheduled to undergo an annual health check-up, then returned during the visit and analyzed in a blinded manner.A total of 2885 individuals returned completed questionnaires and were enrolled, of whom 218 (7.6%) met the IBS criteria. The rates of co-existing headache in subjects with and without IBS symptoms were 44.0% (96/218) and 22.9% (611/2667), respectively, indicating a significantly higher rate of co-existing headache in subjects with as compared to without IBS (odds ratio [OR] 2.65, P < .001). Furthermore, the percentage of subjects with anxiety along with comorbid IBS symptoms and headache was significantly greater as compared to those with IBS (OR 3.01, P = .001) or headache (OR 2.41, P < .001) alone. Unlike anxiety, the percentage of subjects with depression was not significantly different among the IBS/non-headache, non-IBS/headache, and IBS/headache groups.Subjects with IBS symptoms had a higher rate of co-existing headache as compared to those without IBS. Furthermore, those with comorbid IBS symptoms and headache had a greater association with anxiety than with depression, as compared to those with only IBS or headache.     

Prevalence and risk factors for lymph node metastasis after noncurative endoscopic resection for early gastric cancer: a systematic review and meta-analysis

Background

Additional surgery for all patients with noncurative resection after endoscopic resection (ER) for early gastric cancer (EGC) may be excessive due to the relatively low rate of lymph node metastasis (LNM) in such patients. However, the prevalence and risk factors for LNM after noncurative ER have not been consistent across studies.

Methods

We performed a systematic review of electronic databases through August 10, 2018 to identify cohort studies with patients who underwent additional surgery after noncurative ER for EGC. The prevalence of LNM in such patients was extracted for all studies. Odds ratios (ORs) were combined using random-effects meta-analyses to assess the risk of LNM, when possible.

Results

We identified 24 studies comprising 3877 patients with 311 having LNM (pooled prevalence, 8.1%). The risk of LNM was significantly increased in lymphatic invasion (OR [95% confidence interval] = 4.22 [2.88–6.19]), lymphovascular invasion (LVI) (4.17 [2.90–5.99]), vascular invasion (2.38 [1.65–3.44]), positive vertical margin (2.16 [1.59–2.93]), submucosal invasion depth of ≥ 500 μm (2.14 [1.48–3.09]), and tumor size > 30 mm (1.77 [1.31–2.40]). In contrast, there was no significant association between undifferentiated-type or ulceration (scar) and LNM. When studies were restricted to those that evaluated the adjusted OR, the risk of vascular invasion for LNM did not reach statistical significance.

Conclusions

Several pathological factors, most notably lymphatic invasion and LVI, were associated with LNM in patients with noncurative resection after ER for EGC. Lymphatic and vascular invasion should be assessed separately instead of LVI (PROSPERO CRD42018109996).

     

Clinical impact of vonoprazan-based dual therapy with amoxicillin for H. pylori infection in a treatment-naïve cohort of junior high school students in Japan

Background

Although 7-day triple therapy, consisting of vonoprazan, amoxicillin (AMO), and clarithromycin (CLA), is recommended for Helicobacter pylori (H. pylori) eradication in adults. However, the importance of reducing antibiotic use in pediatric patients is well recognized. Therefore, our aim was to compare the effectiveness and safety of vonoprazan and AMO (VA) dual therapy to vonoprazan-based (VAC) triple therapy for H. pylori eradication in a cohort of treatment-naïve junior high school students in Japan.

Methods

This was a prospective observational study of second-year junior high-school students in Yurihonjo and Nikaho Cities, Japan. Between 2015 and 2017, 161 students were treated with VAC-triple therapy (20 mg vonoprazan, 750 mg AMO, and 200 mg CLA, twice a day for 7 days), while 60 students were treated with VA-dual therapy (20 mg vonoprazan and 750 mg AMO, twice a day for 7 days) since 2018. The success rate of H. pylori eradication and drug-related adverse events were compared between the two therapy groups. Intention-to-treat (ITT) and per-protocol (PP) analyses were performed.

Results

Groups were comparable at baseline. The ITT and PP eradication rates were 85.0% (95% confidence interval [CI] 75.8–94.2%) and 86.4% (95% CI 77.4–95.5%), respectively, with VA-dual therapy and 82.0% (95% CI 76.0%–87.9%) and 84.1% (95% CI 78.3–89.8%), respectively, with VAC-triple therapy. VA-dual therapy was non-inferior to VAC-triple therapy (ITT, p = 0.018; PP, p = 0.020). The adverse event rate was 10.0% with VA-dual therapy and 19.8% with VAC-triple therapy (p = 0.108).

Conclusions

The effectiveness of VA-dual therapy was comparable to that of VAC-triple therapy in H. pylori treatment-naïve junior high school students, while reducing the use of antibiotics.

     

Effects of endoscopic sinus surgery on nasal spray deposition using dye-based methods for humans and a human silicone sinonasal cavity model

ObjectiveWe have evaluated that the deposition patterns of corticosteroid nasal spray in the sinonasal cavity of both post-operated human cases, which were further compared with a computed tomography-based sinonasal airway model.MethodsFifty-one patients with chronic rhinosinusitis following an endoscopic sinus surgery were enrolled in this study. Nasal spray mometasone furoate hydrate (Nasonex®) containing 0.1% indigocarmine was applied to the patients' nasal cavities and the sinonasal cavity was observed by endoscopy and video documentation. A single plaster sinonasal model was used to quantify the sinonasal deposition of nasal sprays containing 10% red ink solution using 12 round paper strips.ResultsThe predominant areas of the spray deposition of the operated sinonasal cavities were recognized in the ethmoid sinus and the olfactory cleft in the human study. The droplets were mainly deposited in the inferior turbinate followed by the posterior part of the ethmoid sinus, the olfactory cleft, and anterior part of the ethmoid sinus in a sinonasal model.ConclusionThe corticosteroid nasal spray efficiently reached the olfactory cleft and the ethmoid sinus in post-operative conditions, which was demonstrated by post-operated human cases and a computed tomography-based sinonasal airway model.     

Cloning and Characterization of a Unique Cytotoxic Protein Parasporin-5 Produced by Bacillus thuringiensis A1100 Strain

Parasporin is the cytocidal protein present in the parasporal inclusion of the non-insecticidal Bacillus thuringiensis strains, which has no hemolytic activity but has cytocidal activities, preferentially killing cancer cells. In this study, we characterized a cytocidal protein that belongs to this category, which was designated parasporin-5 (PS5). PS5 was purified from B. thuringiensis serovar tohokuensis strain A1100 based on its cytocidal activity against human leukemic T cells (MOLT-4). The 50% effective concentration (EC₅₀) of PS5 to MOLT-4 cells was approximately 0.075 μg/mL. PS5 was expressed as a 33.8-kDa inactive precursor protein and exhibited cytocidal activity only when degraded by protease at the C-terminal into smaller molecules of 29.8 kDa. Although PS5 showed no significant homology with other known parasporins, a Position Specific Iterative-Basic Local Alignment Search Tool (PSI-BLAST) search revealed that the protein showed slight homology to, not only some B. thuringiensis Cry toxins, but also to aerolysin-type β-pore-forming toxins (β-PFTs). The recombinant PS5 protein could be obtained as an active protein only when it was expressed in a precursor followed by processing with proteinase K. The cytotoxic activities of the protein against various mammalian cell lines were evaluated. PS5 showed strong cytocidal activity to seven of 18 mammalian cell lines tested, and low to no cytotoxicity to the others.