Comparative evaluation of new and conventional classifications of magnifying endoscopy with narrow band imaging for invasion depth of superficial esophageal squamous cell carcinoma.

A new classification of magnifying endoscopy with narrow band imaging (ME-NBI) for diagnosing and staging superficial esophageal squamous cell carcinoma (SESCC) was proposed by the Japan Esophageal Society in 2011. This study aimed to compare the new classification with the conventional classifications (Inoue's classification and Arima's classification). This was a prospective analysis of data from a single cancer center involving 151 consecutive patients with 156 SESCCs that were endoscopically or surgically resected. Initially, only ME-NBI images were selected and reviewed independently by three experienced endoscopists. White light imaging (WLI) was then evaluated separately after an interval. The diagnostic performance of each classification and interobserver agreement were assessed, and the WLI findings that affect the diagnosis by the new classification were identified. The specificity for classifying invasive depth as epithelium (EP)/lamina propria mucosae (LPM) confined was higher with the new classification than with Inoue's classification (0.512 vs. 0.349; P = 0.02) and Arima's classification (0.512 vs. 0.279; P < 0.01). However, the sensitivity was lower (0.902 vs. 1.000; P < 0.01) compared with Arima's classification. The concordance rates of three evaluators (κ values) were 0.52 for the new classification, 0.50 for Inoue's classification, and 0.23 for Arima's classification. On multivariate analysis, thickness on WLI independently affected the accuracy of diagnosis with the new classification (OR 3.23; 95%CI, 1.30-8.03). The new classification is superior to conventional classifications with respect to specificity for diagnosing SESCC with depth EP/LPM. Thickness on WLI was a factor negatively affecting the diagnostic performance of the new classification.

Circulating microRNA-1290 as a novel diagnostic and prognostic biomarker in human colorectal cancer.

BACKGROUND: Circulating microRNAs (miRNAs) are attracting major interest as potential non-invasive biomarkers for colorectal cancer (CRC). This study aimed to identify a novel serum miRNA biomarker for the early detection and/or evaluating prognosis of CRC patients. PATIENTS AND METHODS: Comprehensive miRNA array analysis was carried out using serum samples from patients with colorectal neoplasia and healthy controls. Next, to verify whether the candidate miRNA possessed a secretory potential, we screened miRNA expression levels in culture medium from 2 CRC cell lines, followed by serum analysis from 12 stage IV CRC, 12 adenoma, and 12 control subjects. Thereafter, we validated expression of candidate miRNAs in 179 primary CRC tissues, as well as serum samples from an independent cohort of 211 CRCs, 56 adenomas, and 57 control subjects. RESULTS: Through microarray analysis, we identified significantly higher levels of miRNA-1290 (miR-1290) in serum from patients with colorectal adenomas and cancers. We verified miR-1290 overexpression in serum of CRC patients in a training cohort. In the validation cohort, serum miR-1290 levels were significantly up-regulated in patients with colorectal adenomas (P < 0.0001) and cancers (P < 0.0001). Serum miR-1290 levels could robustly distinguish adenoma [area under the curve (AUC) = 0.718] and CRC patients (AUC = 0.830) from normal subjects. High miR-1290 expression in serum and tissue was significantly associated with tumor aggressiveness and poor prognosis. Moreover, serum miR-1290 levels were an independent prognostic factor [hazard ratio (HR) = 4.51; 95% confidence interval (CI) = 1.23-23.69; P = 0.0096] and an independent predictor for tumor recurrence (hazard ratio = 3.92; 95% confidence interval = 1.11-25.14; P = 0.032) in CRC. CONCLUSIONS: Serum miR-1290 is a novel biomarker for early detection, recurrence, and prognosis in CRC.

Prospective evaluation of a transnasal endoscopy utilizing flexible spectral imaging color enhancement (FICE) with the Valsalva maneuver for detecting pharyngeal and esophageal cancer.

BACKGROUND/AIMS: This study evaluated the efficacy and safety of transnasal endoscopy (TNE) with flexible spectral imaging color enhancement (FICE) for detection of superficial cancer in the pharyngeal and esophageal regions for high-risk populations. METHODOLOGY: Patients who previously had head and neck or esophageal squamous cell carcinoma were enrolled. Screening was conducted using TNE with conventional white-light endoscopy (WLE) followed by FICE chromoendoscopy. For observation of the pharyngeal region, the Valsalva maneuver was employed. RESULTS: 99 patients were eligible. Six esophageal cancers were detected in four patients (4.0%). The sensitivity, specificity, and accuracy for the detection of cancer were 25.0% (95% CI, 3.4- 71.0), 97.8% (95% CI, 92.1-99.8), and 94.9 % (95% CI, 88.4-98.1), respectively for WLE; 100% (95% CI, 45.4%- 100%), 96.8% (95% CI, 90.7%-99.3%), and 96.9% (95% CI, 89.3%-99.1%), respectively for FICE chromoendoscopy. Pain in the nose and nasal hemorrhage were observed in 3 (3.0%) and 2 patients (2.0%), respectively. Following the Valsalva maneuver, endoscopic scores significantly increased from a mean of 1.1 (0.8-1.4) to 2.0 (1.3-2.6) (p<0.05). CONCLUSIONS: TNE with the Valsalva maneuver is a promising screening method for the pharyngeal and esophageal regions. TNE with FICE chromoendoscopy for detecting pharyngeal and esophageal cancer was more sensitive than WLE.

The effectiveness of fascial closure with antimicrobial-coated sutures in preventing incisional surgical site infections in gastrointestinal surgery: a systematic review and meta-analysis.

The aim of this study was to conduct a systematic review and meta-analysis of the efficacy of fascial closure using antimicrobial-sutures specifically for the prevention of surgical site infections (SSIs) in gastrointestinal surgery, as part of the revision of the SSI prevention guidelines of the Japanese Society of Surgical Infectious Diseases (JSSI). We searched CENTRAL, PubMed and ICHUSHI-Web in May 2023, and included randomized controlled trials (RCTs) comparing antimicrobial-coated and non-coated sutures for fascial closure in gastrointestinal surgery (PROSPERO No. CRD42023430377). Three authors independently screened the RCTs. We assessed the risk of bias and the GRADE criteria for the extracted data. The primary outcome was incisional SSI and the secondary outcomes were abdominal wall dehiscence and the length of postoperative hospital stay. This study was supported partially by the JSSI. A total of 10 RCTs and 5396 patients were included. The use of antimicrobial-coated sutures significantly lowered the risk of incisional SSIs compared with non-coated suture (risk ratio: 0.79, 95% confidence intervals: 0.64-0.98). In subgroup analyses, antimicrobial-coated sutures reduced the risk of SSIs for open surgeries, and when monofilament sutures were used. Antimicrobial-coated sutures did not reduce the incidence of abdominal wall dehiscence and the length of hospital stay compared with non-coated sutures. The certainty of the evidence was rated as moderate according to the GRADE criteria, because of risk of bias. In conclusion, the use of antimicrobial-coated sutures for fascial closure in gastrointestinal surgery is associated with a significantly lower risk of SSI than non-coated sutures.

Myeloid dendritic cells type 2 in allergic asthma.

BACKGROUND: Myeloid dendritic cells type 2 (mDC2s) are a new subtype of DCs identified in both the circulation and the lung and suggested to have a role in allergic asthma. METHODS: Circulating mDC2s were enumerated in 19 healthy, 18 atopic nonasthmatic, 18 mild atopic asthmatic, and 16 moderate/severe atopic asthmatic subjects using flow cytometry. RESULTS: The number of circulating mDC2s was significantly lower in atopic subjects compared with healthy controls and in asthmatic subjects compared with nonasthmatic subjects. There was a trend toward lower levels of circulating mDC2s with increasing allergy and asthma severity. The largest differences were seen in moderate/severe atopic asthmatics being 430.78 ± 48.91/ml compared with healthy controls being 767.05 ± 101.64/ml (P < 0.05). CONCLUSIONS: Circulating mDC2s are lower in atopic and asthmatic subjects, which suggests that these cells efflux from the blood into the airways in patients with allergic disease.

Prospective clinical study of endoscopic ultrasound-guided choledochoduodenostomy with direct metallic stent placement using a forward-viewing echoendoscope.

A prospective clinical study was conducted to evaluate the safety, feasibility, and efficacy of endoscopic ultrasound (EUS)-guided choledochoduodenostomy (CDS) with direct metallic stent placement using a prototype forward-viewing echoendoscope. The indication for EUS - CDS in this study was lower biliary obstruction only, and not failed endoscopic biliary drainage, because the aim was to evaluate EUS - CDS for first-line biliary drainage therapy. The technical and functional success rates were 94 % (17 /18) and 94 % (16 /17), respectively. Early complications (focal peritonitis) were encountered in two patients (11 %). No patients developed late complications. EUS - CDS with direct metallic stent placement using a forward-viewing echoendoscope was generally feasible and effective for malignant distal biliary tract obstruction. The forward-viewing echoendoscope was useful, especially for deploying the metallic stent.

TPI ASM8 reduces eosinophil progenitors in sputum after allergen challenge.

BACKGROUND: TPI ASM8 contains two modified phosphorothioate antisense oligonucleotides (AON), one targeting the common beta chain (ßc) of the IL-3/IL-5/GM-CSF receptors and the other targeting the chemokine receptor CCR3. Inhalation of TPI ASM8 significantly improves lung function and sputum eosinophilia after allergen inhalation challenge in asthmatics. OBJECTIVE: This study assessed whether TPI ASM8 reduces airway levels of haemopoietic progenitor cells. METHODS: This open-label study was conducted in 14 stable, allergic mild asthmatic subjects with early- and late-phase allergen-induced bronchoconstriction. Subjects underwent allergen challenges after 4-day treatment with placebo, 4 mg b.i.d. and 8 mg o.d. of TPI ASM8. Sputum was induced before, 7 and 24 h after allergen challenges for progenitor measurements. Treatments were separated by 2-3 weeks. RESULTS: TPI ASM8 reduced allergen-induced sputum eosinophils, and the early and late asthmatic responses (P<0.05). TPI ASM8 also reduced the number of CD34(+) CCR3(+) cells (P=0.004) and CD34(+) IL-5Rα(+) cells (P=0.016), and the proportion of CD34(+) cells expressing IL-5Rα (P=0.036). CONCLUSIONS AND CLINICAL RELEVANCE: TPI ASM8 was safe and well tolerated. The results of this study demonstrate blocking of CCR3 and ßc expression by TPI ASM8 significantly inhibits the accumulation of eosinophils and eosinophil progenitors in the airways after allergen challenge. Inhibition of airway progenitor cell accumulation presents a novel therapeutic target.

Sputum inflammatory cells and allergen-induced airway responses in allergic asthmatic subjects.

BACKGROUND: Allergen inhalation causes early and late bronchoconstrictor responses, airway hyperresponsiveness and airway inflammation in allergic asthmatics. The role of airway inflammatory cells in causing allergen-induced bronchoconstriction and airway hyperresponsiveness is controversial. The objective of this study was to examine the relationships between allergen-induced increases in airway inflammatory cells, early and late bronchoconstrictor responses and methacholine airway hyperresponsiveness. METHODS: Allergen inhalation challenge was conducted in 50 allergic asthmatics. Changes in the forced expired volume in 1 s (FEV(1%) ) were followed for 7 h, induced sputum was obtained at 7 and 24 h, and the provocative concentration of methacholine causing a 20% fall in FEV(1) (MCh PC(20) ) was measured at 24 h. RESULTS: There was a significant negative correlation between the baseline methacholine PC(20) and baseline sputum eosinophils (r = -0.512, P = 0.0001). Allergen-induced changes in methacholine PC(20) were also significantly negatively correlated to allergen-induced change in sputum eosinophils at 24 h (r = -0.434, P = 0.002), but not to changes in any other inflammatory cells. There were no significant correlations between sputum eosinophils or other inflammatory cells and the allergen-induced early or late asthmatic responses. CONCLUSION: Allergen-induced increases in airway eosinophils in asthmatic dual responders may contribute to allergen-induced changes in methacholine PC(20) , but not the late asthmatic responses.

Interleukin-18 production and pulmonary function in COPD.

Interleukin (IL)-18 production and pulmonary function were evaluated in patients with chronic obstructive pulmonary disease (COPD) in order to determine the role of IL-18 in COPD. Immunohistochemical techniques were used to examine IL-18 production in the lungs of patients with very severe COPD (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage IV, n = 16), smokers (n = 27) and nonsmokers (n = 23). Serum cytokine levels and pulmonary function were analysed in patients with GOLD stage I-IV COPD (n = 62), smokers (n = 34) and nonsmokers (n = 47). Persistent and severe small airway inflammation was observed in the lungs of ex-smokers with very severe COPD. IL-18 proteins were strongly expressed in alveolar macrophages, CD8+ T-cells, and both the bronchiolar and alveolar epithelia in the lungs of COPD patients. Serum levels of IL-18 in COPD patients and smokers were significantly higher than those in nonsmokers. Moreover, serum levels of IL-18 in patients with GOLD stage III and IV COPD were significantly higher than in smokers and nonsmokers. There was a significant negative correlation between serum IL-18 level and the predicted forced expiratory volume in one second in patients with COPD. In contrast, serum levels of IL-4, IL-13 and interferon-gamma were not significantly increased in any of the three groups. In conclusion, overproduction of interleukin-18 in the lungs may be involved in the pathogenesis of chronic obstructive pulmonary disease.

Transcranial magnetic stimulation over the cerebellum evokes late potential in the soleus muscle.

Transcranial magnetic stimulation (TMS) with a double cone coil placed over the left lateral side of the basal occiput was able to elicit late electromyographic (EMG) responses at the bilateral soleus muscles (SOL) averaged over 30 stimulation events, with a mean latency of approximately 100 ms. These EMG responses were detected using a low frequency bandpass filter with 0.05 Hz magnetic stimulation on ten healthy subjects in standing posture. As magnetic stimulation over the left basal occiput with a double cone coil can stimulate cerebellar structure, this late response seems to be conducted from the cerebellar structure to the SOL via an as yet unknown descending pathway. Here, we report new late EMG responses in relation to cerebellum or cerebellum related structures.

Resistance of the peripheral nerve to ischemia in diabetic patients--an electrophysiological study.

We studied the effect of ischemia on the excitability of the sensory fibers of the median nerve in 43 patients with non-insulin-dependent diabetes mellitus (NIDDM) by a double stimulation method. Ischemia caused significantly less reduction of nerve excitability in patients with poor glycemic control and in patients diseased for 5 years or longer than in the normal control group. Hyperexcitability after ischemia was markedly greater than normal among short-term, poorly controlled diabetics, and markedly less pronounced among long-term, poorly controlled diabetics. In many diabetic patients with normal conduction velocity or without sensory disturbance, post-ischemic hyperexcitability was remarkable. A study of nerve excitability may be useful as one means of detecting early-stage disturbance of the diabetic peripheral nerve.

Clinical utility of somatosensory evoked potentials in diabetes mellitus.

The posterior tibial nerve and median nerve somatosensory evoked potentials (PTN-SEPs and MN-SEPs) were investigated in 34 patients with diabetes mellitus (DM). We measured the latency of the first positive cortical potential (the cortical P37) of PTN-SEPs and that of the first negative cortical potential (the cortical N18) and Erb's potential of MN-SEPs. In 18 patients (52.9%), the cortical P37 latency was more than 3 SD longer than normal in the tibial nerve. There were positive correlations between the latency of cortical P37 and the duration of DM and the motor nerve conduction velocity of the posterior tibial nerve. Sensory action potentials of the posterior tibial nerve were not detectable in 21 patients, though cortical P37 potential was unambiguously recorded by stimulating the posterior tibial nerve even in those subjects. Diabetic retinopathy and nephropathy also tended to rise with increasing latency of cortical P37. The latency of cortical P37 is an important parameter in assessing diabetic neuropathy.

Comparative study of evoked potentials in multiple sclerosis and neuro-Behçet's syndrome.

We studied somatosensory evoked potentials (SEPs) and brainstem auditory evoked potentials (BAEPs) in Japanese patients with multiple sclerosis (MS) and those with neuro-Behcet's disease (NB). Abnormal cortical P37 of posterior tibial nerve SEPs or cervical N13 of median nerve SEPs were more frequently found in the MS patients than in the NB patients. On the other hand, prolongation of the central conduction time of median nerve SEPs or abnormal BAEPs were more common in NB than in MS. The present data showed that lesions were mainly present in the spinal cord in MS and in the brainstem in NB. SEPs and BAEPs were considered of great value for detecting the involvement of the central nervous system in MS and NB and distinguishing between these diseases.

Abnormal brainstem evoked potentials in diabetes mellitus. Evoked potential testings and magnetic resonance imaging.

Brainstem auditory evoked potentials (BAEPs) and median nerve somatosensory evoked potentials (MN-SEPs) were measured in 53 diabetic patients. Magnetic resonance imaging (MRI) was performed 12 patients with abnormal BAEPs and/or MN-SEPs in order to confirm the existence of lesions in the central nervous system. Twenty-six percent of the diabetic patients had abnormal BAEPs and three had a prolongation of the central conduction time in the MN-SEPs. MRI findings of ten of the 12 patients with abnormal BAEPs or MN-SEPs showed multiple small lesions in the pons, thalamus, and centrum semiovale etc. Two of them showed small lesion in the pontine basis which could induce prolonged interpeak latencies of BAEPs. Our MRI study might suggest that abnormal brainstem evoked potentials in diabetic patients were induced by diabetic macroangiopathy or microangiopathy.

Abnormal evoked potentials of Kearns-Sayre syndrome.

We examined eight patients with Kearns-Sayre syndrome (KSS) to investigate a dysfunction in the central nervous system (CNS) using PTN-SEP, MN-SEP and BAEP. We found a significant increase in the P37 latency of PTN-SEPs and the central conduction time of MN-SEPs, and interpeak latencies of BAEPs. Delayed SEPs or BAEPs were caused by a dysfunction of the somatosensory or lateral lemniscus pathways which could be related to mitochondrial abnormalities in the CNS. Long-term therapy with CoQ showed an improvement of the latencies of SEPs after about half a year from the start of CoQ therapy in our patients. The improvement of the latencies of SEPs were preserved during CoQ therapy. It could be demonstrated that CoQ therapy had the beneficial effects on abnormal functions of the CNS in patients with KSS.

Skin hemodynamics during change from supine to lateral position.

The purpose of this study was to identify the skin hemodynamics during the position change from supine to lateral in patients with neurodegenerative diseases. The participants were 19 patients with neurodegenerative diseases and 12 healthy volunteers. The alteration in the total concentration of oxyhemoglobin and deoxyhemoglobin, indicative of change in blood volume, was measured in the skin of the left flank by using a portable noninvasive tissue oxygen monitor by near-infrared spectroscopy. The positions were changed from the left and right lateral with a return to the supine between each procedure. In healthy volunteers, total hemoglobin concentration (skin blood volume) increased when the position changed from supine to left lateral and decreased when changed from supine to right lateral. The decreased skin blood volume gradually recovered after a change from the supine to the right lateral position in healthy volunteers. However, it did not recover in three sporadic olivopontocerebellar atrophy (OPCA) patients with marked autonomic dysfunction and one Parkinsonian patient with severe orthostatic hypotension. Our study identified that the intracutaneous blood was changing dynamically during the position change from supine to lateral and was regulated by autonomic nerve function.