Clinicopathological features of cytokeratin 5-positive pulmonary adenocarcinoma.

Cytokeratin 5 (CK5) is a marker for pulmonary squamous cell carcinoma; however, CK5 is sometimes present in pulmonary adenocarcinoma (ADC), and there is insufficient information regarding the clinicopathological features of CK5-positive ADC. We aimed to explore the clinicopathological characteristics of CK5-positive ADC using immunohistochemistry. We prepared the following two cohorts: a resected cohort containing 220 resected tumours for primarily studying the detailed morphological characteristics, and a tissue microarray (TMA) cohort containing 337 samples for investigating the associations of CK5 expression with other protein expressions, genetic and prognostic findings. CK5-positive ADC was defined to have ≥ 10% tumour cells and presence of CK5-positive tumour cells in the resected and TMA cohorts, respectively. CK5-positive ADCs were identified in 91 (16.3%) patients in the combined cohort. CK5-positive ADCs had male predominance (P = 0.012), smoking history (P = 0.001), higher stage (P < 0.001), histological high-grade components (P < 0.001), vascular invasion (P < 0.001), mucinous differentiation (P < 0.001), spread through airspaces (P < 0.001), EGFR wild-type (P < 0.001), KRAS mutations (P < 0.001), ALK rearrangement (P < 0.001) and ROS1 rearrangement (P = 0.002). In the resected cohort, more than half the CK5-positive ADCs (19 cases, 65.5%) showed mucinous differentiation; the remaining cases harboured high-grade components. In the TMA cohort, CK5-positive ADCs correlated with TTF-1 negativity (P = 0.002) and MUC5B, MUC5AC and HNF4alpha positivity (P < 0.001, 0.048, < 0.001). Further, CK5-positive ADCs had significantly lower disease-free and overall survival rates than CK5-negative ADCs (P < 0.001 for each). Additionally, multivariate analysis revealed that CK5 expression was an independent poor prognostic factor. CK5-positive ADCs showed aggressive clinical behaviour, with high-grade morphology and mucinous differentiation.

A multichannel gated neutron detector with reduced afterpulse for low-yield neutron measurements in intense hard X-ray backgrounds.

A design of multichannel gated photomultiplier tube (PMT) is presented for the 960-channel neutron time-of-flight detector at the Institute of Laser Engineering of Osaka University. This is important for the fusion science and the nuclear photonics where intense hard X-rays are generated from the interaction of ultra-short laser pulse of petawatt power density with matter. The hard X-rays often overload PMTs and cause signal-induced background noises called afterpulses, making the detection of subsequent neutrons impossible. For this reason, the PMTs are coupled with an electrical time-gating (ETG) system to avoid overloading. The ETG system disables the PMT by modulating the dynode potential during the primary X-ray flash. An after-pulsing suppression technique is demonstrated by applying a reverse bias voltage between the photocathode and the first dynode. The presented multichannel scheme provides a gate response time of 80 ns, a signal cutoff ratio of 2.5 × 102, and requires reasonably low power consumption.

Laparoendoscopic Single-site Plus 1-port Donor Nephrectomy: Division of Roles to Shorten Warm Ischemic Time.

BACKGROUND: In this study we present our new surgical procedure, laparoendoscopic single-site surgery plus 1 for donor nephrectomy (LESS+1-DN), which shortens warm ischemic time (WIT) and improves surgical outcomes. METHODS: From January 2013 to February 2017, 15 patients who underwent LESS-DN and 41 patients who underwent LESS+1-DN at our institution were evaluated retrospectively. Patients were divided into 3 groups: group A, 15 cases of LESS-DN; group B, the first 15 patients who underwent LESS+1-DN; and group C, 26 patients who underwent subsequent LESS+1-DN. To reduce WIT, we clearly defined the roles of the surgeon and first assistant in the 26 subsequent LESS+1-DN cases. The surgeon dissected the renal pedicle and harvested the kidney graft using a recovery bag and the first assistant held the recovery bag. RESULTS: The mean operative time in group C (213.7 minutes) was significantly shorter than that in groups A (253.3 minutes) and B (253.8 minutes). The WIT in group C (195.2 seconds) was significantly shorter than that in groups A (389.8 seconds) and B (313.2 seconds). Open conversion was required in 1 case in group A. None of the donors required conversion to open surgery and no perioperative complications occurred in groups B and C. Linear regression analysis of the LESS+1-DN operative times and consecutive case numbers demonstrated a shallow learning curve (R2 = 0.392, P < .05). CONCLUSION: Our new procedure that divides the roles of the operator and the first assistant contributed significantly to a shortening of WIT. Dividing roles can facilitate a safer laparoscopic donor nephrectomy.

Full-layer mucosal histology in achalasia: Histological epithelial wave is characteristic in "pinstripe pattern"-positive achalasia.

BACKGROUND: Previously, the mucosal histology in achalasia has only been investigated using superficial biopsy or surgically resected esophageal specimens in end-stage cases. We investigated the histology of the full-layer mucosa in early and advanced achalasia. METHODS: Endoscopy was performed for the pinstripe pattern (PSP) (an early achalasia indicator) and dilation and thickening of the mucosa (advanced achalasia indicators). A mucosal entry site for peroral endoscopic myotomy was created using cap-fitted endoscopic mucosal resection to access the full-layer mucosa and the submucosa. KEY RESULTS: Mucosal histology was compared between 32 patients with achalasia and 15 controls. Histological esophagitis with findings of inflammatory cell infiltration and dilated intercellular spaces was observed more in patients with achalasia than in controls (87.5% vs 13.3%, P<.001; 84.4% vs 46.7%, P=.049). Muscularis mucosae (MM) atrophy and epithelial wave were only observed in achalasia (40.6% vs 0%, P=.005; 28.1% vs 0%, P=.043). Fibrosis was more common in achalasia, but without statistical significance (31.3% vs 20.0%, P=.503). In achalasia with endoscopic dilation and thickening of the mucosa, MM atrophy was observed histologically, and in cases involving endoscopic PSP, the histological epithelial wave was observed. CONCLUSIONS & INFERENCES: Histological findings of esophagitis were observed endoscopically even in early achalasia. Pinstripe pattern corresponds to the epithelial wave observed histologically in achalasia, whereas endoscopic findings in advanced achalasia correspond to MM atrophy. Appropriate management is necessary during early achalasia to prevent progression to advanced achalasia with more severe histological changes.

Changes in esophageal motility after endoscopic submucosal dissection for superficial esophageal cancer: a high-resolution manometry study.

The effect of endoscopic submucosal dissection (ESD) on esophageal motility remains unknown. Therefore, the aim of this study is to elucidate changes in esophageal motility after ESD along with the cause of dysphagia using high-resolution manometry (HRM). This is a before-and-after trial of the effect of ESD on the esophageal motility. Twenty patients who underwent ESD for superficial esophageal carcinoma were enrolled in this study. Patients filled out a questionnaire about dysphagia and underwent HRM before and after ESD. Results before and after ESD were compared. Data were obtained from 19 patients. The number of patients who complained of dysphagia before and after ESD was 1/19 (5.3%) and 6/19 (31.6%), respectively (P = 0.131). Scores from the five-point Likert scale before and after ESD were 0.1 ± 0.5 and 1.0 ± 1.6, respectively (P = 0.043). The distal contractile integral (DCI) before and after ESD and the number of failed, weak, or fragmented contractions were not significantly different. However, in five patients with circumferential ESD, DCI was remarkably decreased and the frequency of fail, weak, or fragmented contractions increased. Univariate regression analysis showed a relatively strong inverse correlation of ΔDCI with the circumferential mucosal defect ratio {P < 0.01, standardized regression coefficient (r) = -0.65}, the number of stricture preventions (P < 0.01, r = -0.601), and the number of stricture resolutions (P < 0.01, r = -0.77). This HRM study showed that impairment of esophageal motility could be caused by ESD. The impairment of esophageal motility was conspicuous, especially in patients with circumferential ESD and subsequent procedures such as endoscopic triamcinolone injection and endoscopic balloon dilatation. Impaired esophageal motility after ESD might explain dysphagia.

Genome-wide DNA markers to support genetic management for domestication and commercial production in a large rodent, the Ghanaian grasscutter (Thryonomys swinderianus).

Domestication and commercial production of the grasscutter, Thryonomys swinderianus, a large rodent, represents an important opportunity to secure sustainable animal protein for local communities in West Africa. To support production, DNA markers are required for population diversity assessment, pedigree analysis and marker-assisted selection. This study reports the application of double-digest RAD sequencing to simultaneously discover and genotype SNP markers in 24 wild and recently domesticated grasscutters. An initial panel of 1209 SNP loci was characterised from a total of more than 21 000 candidate loci containing single SNPs. This genome-wide resource represents the first application of its type to commercial production of a large rodent for food and advances the use of agricultural genomics in Ghana.

Muscle layer histopathology and manometry pattern of primary esophageal motility disorders including achalasia.

BACKGROUND: Histopathology of muscularis externa in primary esophageal motility disorders has been characterized previously. We aimed to correlate the results of high-resolution manometry with those of histopathology. METHODS: During peroral endoscopic myotomy, peroral esophageal muscle biopsy was performed in patients with primary esophageal motility disorders. Immunohistochemical staining for c-kit was performed to assess the interstitial cells of Cajal (ICCs). Hematoxylin Eosin and Azan-Mallory staining were used to detect muscle atrophy, inflammation, and fibrosis, respectively. KEY RESULTS: Slides from 30 patients with the following motility disorders were analyzed: achalasia (type I: 14, type II: 5, type III: 3), one diffuse esophageal spasm (DES), two outflow obstruction (OO), four jackhammer esophagus (JE), and one nutcracker esophagus (NE). ICCs were preserved in high numbers in type III achalasia (n=9.4±1.2 cells/high power field [HPF]), compared to types I (n=3.7±0.3 cells/HPF) and II (n=3.5±1.0 cells/HPF). Moreover, severe fibrosis was only observed in type I achalasia and not in other types of achalasia, OO, or DES. Four of five patients with JE and NE had severe inflammation with eosinophilic infiltration of the esophageal muscle layer (73.8±50.3 eosinophils/HPF) with no epithelial eosinophils. One patient with JE showed a visceral myopathy pattern. CONCLUSIONS & INFERENCES: Compared to types I and II, type III achalasia showed preserved ICCs, with variable data regarding DES and OO. In disorders considered as primary esophageal motility disorders, a disease category exists, which shows eosinophilic infiltration in the esophageal muscle layer with no eosinophils in the epithelium.

Observation of the flexoelectricity of a SrTiO3 single crystal by x-ray absorption and emission spectroscopies.

Flexoelectricity, defined as the spontaneous electric polarization in a dielectric material induced by a strain gradient, is investigated from the microscopic viewpoint by x-ray spectroscopy. A single crystal SrTiO3 sample was used as a test system in order to reveal the appearance of the electric dipole moment by simple bending of the crystal. The spectral change characteristic of ferroelectric transition in SrTiO3 was not observed in the Ti K-edge absorption spectra. Instead, the gradual decrease (increase) of the post-edge feature (pre-edge structure) by bending was qualitatively explained using theoretical calculations that assumed the presence of oxygen vacancies and a slight crystal distortion. This assumption is also supported by the broadening of a tiny charge-transfer peak in the Ti Kß resonant emission spectra. Therefore, it was revealed that the flexoelectric effect in SrTiO3 is easily drowned out through local imperfection induced by crystal deformations and cracks.

Risk assessment of recent Egyptian H5N1 influenza viruses.

Highly pathogenic avian influenza (HPAI) viruses of the H5N1 subtype are enzootic in poultry populations in different parts of the world, and have caused numerous human infections in recent years, particularly in Egypt. However, no sustained human-to-human transmission of these viruses has yet been reported. We tested nine naturally occurring Egyptian H5N1 viruses (isolated in 2014-2015) in ferrets and found that three of them transmitted via respiratory droplets, causing a fatal infection in one of the exposed animals. All isolates were sensitive to neuraminidase inhibitors. However, these viruses were not transmitted via respiratory droplets in three additional transmission experiments in ferrets. Currently, we do not know if the efficiency of transmission is very low or if subtle differences in experimental parameters contributed to these inconsistent results. Nonetheless, our findings heighten concern regarding the pandemic potential of recent Egyptian H5N1 influenza viruses.

Use of a Latent Topic Model for Characteristic Extraction from Health Checkup Questionnaire Data.

OBJECTIVES: When patients complete questionnaires during health checkups, many of their responses are subjective, making topic extraction difficult. Therefore, the purpose of this study was to develop a model capable of extracting appropriate topics from subjective data in questionnaires conducted during health checkups. METHODS: We employed a latent topic model to group the lifestyle habits of the study participants and represented their responses to items on health checkup questionnaires as a probability model. For the probability model, we used latent Dirichlet allocation to extract 30 topics from the questionnaires. According to the model parameters, a total of 4381 study participants were then divided into groups based on these topics. Results from laboratory tests, including blood glucose level, triglycerides, and estimated glomerular filtration rate, were compared between each group, and these results were then compared with those obtained by hierarchical clustering. RESULTS: If a significant (p < 0.05) difference was observed in any of the laboratory measurements between groups, it was considered to indicate a questionnaire response pattern corresponding to the value of the test result. A comparison between the latent topic model and hierarchical clustering grouping revealed that, in the latent topic model method, a small group of participants who reported having subjective signs of urinary disorder were allocated to a single group. CONCLUSIONS: The latent topic model is useful for extracting characteristics from a small number of groups from questionnaires with a large number of items. These results show that, in addition to chief complaints and history of past illness, questionnaire data obtained during medical checkups can serve as useful judgment criteria for assessing the conditions of patients.

Prediction model for glucose metabolism based on lipid metabolism.

OBJECTIVES: We developed a robust, long-term clinical prediction model to predict conditions leading to early diabetes using laboratory values other than blood glucose and insulin levels. Our model protects against missing data and noise that occur during long-term analysis. METHODS: RESULTS of a 75-g oral glucose tolerance test (OGTT) were divided into three groups: diabetes, impaired glucose tolerance (IGT), and normal (n = 114, 235, and 325, respectively). For glucose metabolic and lipid metabolic parameters, near 30-day mean values and 10-year integrated values were compared. The relation between high-density lipoprotein cholesterol (HDL-C) and variations in HbA1c was analyzed in 158 patients. We also constructed a state space model consisting of an observation model (HDL-C and HbA1c) and an internal model (disorders of lipid metabolism and glucose metabolism) and applied this model to 116 cases. RESULTS: The root mean square error between the observed HbA1c and predicted HbA1c was 0.25. CONCLUSIONS: In the observation model, HDL-C levels were useful for prediction of increases in HbA1c. Even with numerous missing values over time, as occurs in clinical practice, clinically valid predictions can be made using this state space model.

Morphology and distribution of lamellar corpuscles in the mesentery of the cat.

Mesentery samples obtained from 13 mixed breed cats were stereoscopically and microscopically examined and yielded the following results. In the mesentery, lamellar corpuscles were densely distributed around blood vessels, with a mean number of 182.2 ± 20.9 and mean maximum and minimum diameters of 0.98 ± 0.18 mm and 0.54 ± 0.08 mm, respectively. While most lamellar corpuscles were isolated, some complex lamellar corpuscles were found in the mesentery. Lamellar corpuscles in the mesentery appear to serve more as internal receptors that detect changes in the internal environment than as external receptors. In addition, those found around blood vessels in the mesentery are likely to be involved in blood pressure regulation.

Preclinical anticancer effects and toxicologic assessment of hepatic artery infusion of fine-powder cisplatin with lipiodol in vivo.

We conducted an in vivo study to evaluate the anticancer effect and toxicity of fine-powder cisplatin suspended in lipiodol (fCDDP/LPD suspension) after a single administration of three different doses to rats via the intrahepatic artery after transplantation of rat ascites hepatoma cells. The toxicity of the fCDDP/LPD suspension was also assessed in the same protocol in noncancer-bearing rats and the observed toxicologic changes were compared among groups administered saline (Sal), an aqueous solution of fCDDP (fCDDP/Sal solution), and LPD alone. In parallel with the toxicity test, plasma CDDP concentrations were compared between the fCDDP/LPD suspension and fCDDP/Sal solution. The mean weight of the tumors in the fCDDP/LPD suspension groups was significantly less than in the LPD-alone group. The pathologic changes in the liver observed in the fCDDP/LPD suspension group increased with dose, were more marked compared with those in the fCDDP/Sal solution and LPD-alone groups, and were reversible. No other toxicologic effects were observed. The concentration of CDDP in the plasma in the fCDDP/LPD suspension group was slightly lower than that in the fCDDP/Sal solution group. In conclusion, the results indicate that the fCDDP/LPD suspension has sufficient anticancer efficacy and tolerability for use in the clinical treatment of hepatocellular carcinoma.

Erythromelalgia associated with Clitocybe acromelalga intoxication.

CONTEXT: Erythromelalgia is a rare disorder characterized by reddening, severe burning pain, and swelling of the extremities. Food poisoning by Clitocybe acromelalga, a poisonous mushroom, is known to induce erythromelalgia; however, its treatment protocol remains unclear. We describe here three cases of erythromelalgia following the consumption of C. acromelalga with varying clinical courses. CASE DETAILS: Of the three patients, the first patient presented 22 days after the onset of erythromelalgia; although he was treated with aspirin, numbness in the limbs persisted as sequela. Patient 2 presented at 3 days after the symptomatic onset and was immediately treated with high-dose intravenous nicotinic acid, with a dramatic symptomatic improvement. Patient 3, who had milder symptoms, spontaneously recovered within a week without any treatment. DISCUSSION: The clinical manifestations and varying clinical courses associated with C. acromelalga toxicity are discussed here, with the pathogenesis of this mycotoxin and a potential treatment. Detailed interviews of such patients are important, particularly because of the remarkably slow course of this mycotoxin as compared with common food poisonings. Treatment with intravenous nicotinic acid was associated with improvement in one patient. We believe that this painful disorder might thus be treatable, although the mechanism underlying the treatment remains unclear.

Scanning electron microscopic study for pore formation of the greater omentum of cats.

The greater omentum of the cats is said to have a lace-like structure. However, there are only a few descriptions on whether pores exist, and there are not many morphological studies on this meshwork. In this study, the greater omentum of the cats was observed at each age of development using a scanning electron microscope. The greater omentum of the cats immediately after birth was found to be continuous, and no pores were observed. Also, development of microvilli was observed in the mesothelial cells on the surface of the greater omentum. In young cats at 3 months of age, small pores were sporadically observed, and at the ages of 6-12 months, there were more and larger pores. It was estimated that the pores on the greater omentum are formed in the process of moving from the movement of organs, such as the stomach, intestines and diaphragm, and the presence of these pores enables the passage of ascites between the omental bursa, the greater omentum and the serosal cavity of the wall without flowing through the omental foramen.

Successful treatment of wound breakdown caused by pyoderma gangrenosum after total knee arthroplasty.

Pyoderma gangrenosum is a rare ulcerative disorder of the skin of unknown etiology. We present a case of pyoderma gangrenosum that occurred following total knee arthroplasty, which was initially misdiagnosed as severe wound infection. Repeated debridement procedures resulted in a large soft tissue defect around the anterior knee joint. The patient was treated successfully with a latissimus dorsi musculocutaneous flap under immunosuppressive therapy. Pyoderma gangrenosum is often misdiagnosed as an infected wound, but the treatment for theses differential diagnoses is completely different. When a lesion is refractory to thorough treatment for infection, a diagnosis of pyoderma gangrenosum should be considered.

Marked difference between adults and children in Bordetella pertussis DNA load in nasopharyngeal swabs.

Bordetella pertussis is the aetiologic agent of whooping cough, a common cause of severe respiratory illness in children and prolonged mild cough in adults. To understand some of the reasons for differences in clinical symptoms between adults and children, we measured B. pertussis DNA loads in nasopharyngeal swabs (NPS) from 19 adults and 40 children (including 14 infants) by quantitative IS481 real-time PCR. All cases had been pre-diagnosed with the B. pertussis-specific loop-mediated isothermal amplification method. The mean PCR threshold cycles for adult and child NPS were 34.9 and 27.1, respectively, indicating a significantly lower B. pertussis DNA load in adults than in children (p <0.001). Moreover, adults had very low DNA loads during both early and later stages of the disease. When corresponding bacterial loads in NPS were calculated for B. pertussis Tohama cells using a standard curve, the mean number of bacterial cells taken with a rayon-tipped swab from an adult, older child and infant was estimated to be 320 (95% CI 120-910), 2.1 × 104(95% CI 5.3 × 10³ to 8.3 × 104) and 1.1 × 106 cells (95% CI 1.2 × 105 to 8.9 × 106), respectively. This indicates that the B. pertussis load in NPS is closely correlated with patient age. Our observations suggest that adult pertussis is characterized by a lower bacterial load in the nasopharynx, resulting in milder symptoms and negative cultures.

Testing the druggable endothelial differentiation gene 2 knee osteoarthritis genetic factor for replication in a wide range of sample collections.

OBJECTIVES: To replicate a previously reported association with osteoarthritis (OA) of the promoter single nucleotide polymorphism (SNP) rs10980705 in the endothelial differentiation gene 2 (EDG2). METHODS: Five collections of samples, four from Europe and one from China, were studied. They included patients with 3 OA phenotypes: 1501 with knee OA, 1497 with hip OA and 376 with generalised OA. A total of 2521 controls were also studied. Allele and genotype frequencies of the rs10980705 SNP were analysed in each individual sample collection and in pooled data. In addition, a meta-analysis to incorporate results from the original Japanese report was performed. RESULTS: The association of the rs10980705 SNP with knee OA was not replicated in any of the five sample collections studied or in their combined analysis (odds ratio (OR) 1.10, 95% CI 0.98 to 1.22; p = 0.10). Meta-analysis of all data, including the original Japanese study, did show association with knee OA (OR 1.15, 95% CI 1.06 to 1.26; p = 0.002) but the effect was accounted for by the Japanese data and was less significant than the original report. No association was found with hip OA or with generalised OA. CONCLUSIONS: The original report of a promising genetic association between a druggable G-protein coupled receptor, EDG2, and knee OA has not been replicated. This lack of replication could be due to a modest effect of the promoter polymorphism that will require even larger studies (the winners curse) although a more pronounced effect in the Asian population vs Europeans cannot be excluded.

Neuroendoscopic trans-third ventricle approach for lesions of the ventral brainstem surface.

Due to the establishment in recent years of neuroendoscopic third ventriculostomy (ETV), it has become possible during ETV to observe the ventral brainstem surface--particularly the prepontine cistern--in a minimally invasive manner via the third ventricular base with a neuroendoscope. As an adaptation of that technique in this study, we investigated a neuroendoscopic trans-third ventricle approach (ETTVA), which accesses lesions of the ventral brainstem surface with a neuroendoscope inserted via the stoma of the third ventricular floor. Our study included 6 cases, including one case each of neurenteric cyst, chordoma, pontine glioma (astrocytoma), ecchordosis physaliphora, endodermal cyst, and cystic schwannoma. Surgical operations performed by ETTVA included 3 cases of tumor resection, 2 cases of tumor biopsy, and 1 case of cyst puncture and aspiration. There were no complications accompanying ETTVA. Out of the 6 cases, only 1 required additional surgical treatment following ETTVA surgery. In the other 5 cases, no additional surgical procedures were performed. This study showed that ETTVA allowed access to the prepontine cistern quickly and in a minimally invasive manner. In selected cases, ETTVA can offer a new approach to these lesions.