Prognostic Evaluation of HER2-positive Early Breast Cancers Using Clinico-pathological Criteria.

Background/Aim: HER2-positive breast carcinomas (BCs) generally behave more aggressively and show higher cytological and histological grade than HER2-negative BCs. However, the clinical properties of HER2-positive early BCs have not been studied extensively. Hence, the therapeutic significance of neoadjuvant chemotherapy (NAC) for this BC remains debatable. Patients and Methods: We retrospectively examined the clinicopathological features of 94 HER2-positive early BCs who perioperatively received anti-HER2 drugs, without undergoing NAC prior to surgery. Results: The patients' five year-disease free survival (DFS) and overall survival (OS) rates were 95.6% and 100%, respectively. Univariate analysis demonstrated significant differences in distant metastasis-free survival (DMFS) between clinical and pathological tumor stages (T stages). Pathological T1 stage and clinical T1 stage tumors showed significantly higher DMSF than pT2-3 and cT2-3 (p=0.0002 and 0.0294). Multivariate analysis disclosed no significant differences in DFS, OS, and DMFS with respect to preoperative clinical tumor stage, patient age, type of surgery, postoperative therapy, and pathological factors. Recurrences occurred in nine patients: four (4.3%) and five (5.3%) patients showed local and distant recurrences, respectively. One patient with cT2 BC died of disease. Interestingly, four of the five BCs with distant recurrence pathologically demonstrated lymph vessel invasion. The prognoses of patients with HER2-positive stage cT1/2N0M0 BC were highly favorable. Conclusion: The indications for NAC in small, localized, and node-negative HER2-positive BC should be carefully assessed based on the presence of a larger tumor size, postoperative pathological evaluation of tumor size, and lymph vessel invasion.

Mini-probe endoscopic ultrasound for the diagnosis of congenital esophageal or duodenal stenosis.

PURPOSE: The usefulness of endoscopic ultrasound (EUS) in pediatric populations has been recently appreciated; however, published studies on mini-probe EUS in the diagnosis of congenital esophageal stenosis (CES) or congenital duodenal stenosis (CDS) in pre-school patients remain scarce. This study aimed to report the utility of mini-probe EUS for the diagnosis of CES or CDS in pre-school patients based on the etiology. METHODS: We retrospectively reviewed the medical records of pediatric patients with CES or CDS who underwent mini-probe EUS through the stenotic segments at our hospital between December 2006 and December 2021. RESULTS: Five patients with CES and one with CDS were enrolled. The median age and body weight when EUS was performed were 12.5 months and 8.5 kg, respectively. Hypoechoic lesions were observed on EUS in three patients, which were assessed as cartilage; one patient had no hypoechoic lesion but had a focal thickness of the muscular layer. They were diagnosed with tracheobronchial remnants based on EUS. The full circumferential wall thickness of the esophagus was visualized in one patient with fibromuscular hypertrophy. The histopathological findings confirmed the diagnoses. In the patient with CDS, EUS findings revealed pancreatic parenchyma encircling the stenotic part of the duodenum. The preoperative diagnosis was annular pancreas. The patient underwent duodenoduodenostomy, and intraoperative findings confirmed the diagnosis. CONCLUSION: Mini-probe EUS can be recommended as a feasible and safe technique for infants and toddlers. It can effectively diagnose CES or CDS based on etiology and can inform treatment strategies for pre-school patients.

Expression of T-cell immunoreceptor with immunoglobulin and tyrosine-based inhibitory motif domains (TIGIT) in anaplastic thyroid carcinoma.

BACKGROUND: Immune checkpoint proteins have not been fully examined in follicular cell-derived thyroid carcinoma and medullary thyroid carcinoma (MTC). Anaplastic thyroid carcinoma (ATC) is one of the most aggressive carcinomas. Even multimodal treatment does not result in favorable clinical outcomes for patients with ATC. Anti-tumor immunity has therefore been highlighted as having therapeutic promise for ATC. METHODS: We examined a novel immune checkpoint receptor, T-cell immunoreceptor with immunoglobulin and tyrosine-based inhibitory motif domains (TIGIT), in variable thyroid lesions: adenomatous goiter, follicular adenoma, and thyroid carcinoma (TC) using immunohistochemistry (IHC). RESULTS: Our IHC results showed that TIGIT expression was detected in cancer cells of MTC and high-grade TC: poorly differentiated thyroid carcinoma (PDTC) and ATC. Neoplastic cells were positive for TIGIT in four of five MTCs (80.0%), 17 of 31 ATCs (54.8%) and in 3 of 12 PDTCs (25.0%). TIGIT was not detected in any adenomatous goiters, thyroid benign tumors, or differentiated thyroid carcinoma (DTCs). Intriguingly, ATC cells showing pleomorphic/giant cell features were positive for TIGIT, while ATC cells with other cell morphologies lacked the immunoreactivity. Intra-tumoral immune cell was inclined to be enriched in TIGI-positive ATC. Although coexisting papillary thyroid carcinoma (PTC) components demonstrated high-grade microscopic features, neither the PTC nor follicular thyroid carcinoma (FTC) components expressed TIGT in any composite ATCs. CONCLUSION: TIGIT was immunohistochemically found in MTC with high frequency and partially in high-grade TC. TIGIT expression in cancer cells may be beneficial for a potential utility in MTC and a subset of high-grade TC, especially ATC therapy.

Recurrent massive bleeding from a small intestinal arteriovenous malformation after surgery for biliary atresia in an infant: a case report and literature review.

BACKGROUND: Small intestinal arteriovenous malformation (AVM) can cause bleeding. Most small intestinal AVMs occur during adulthood, rarely in infancy. We report a case of an infant with hemorrhage due to small intestinal AVM early and recurrently after Kasai portoenterostomy (PE) for biliary atresia (BA). CASE PRESENTATION: A 51-day-old male infant was admitted to our institution for obstructive jaundice. Laparotomic cholangiography revealed BA (IIIb1µ), and Kasai PE was performed at 60 days of age. On postoperative day 17, he developed massive melena and severe anemia. Contrast-enhanced computed tomography (CT) revealed that the jejunum around the PE site was strongly enhanced with enhancing nodules in the arterial phase, and a wide area of the Roux limb wall was slightly enhanced in the venous phase. As melena continued, emergency laparotomy was performed. There were no abnormal macroscopic findings at the PE site except for a clot in the Roux limb 5 cm away from the PE site, and the Roux limb was resected 5 cm. On further investigation, a red spot was detected on the jejunal serosa 30 cm away from the Roux-en-Y anastomosis site. PE and wedge resection for the red spot were performed. Histopathologically, both specimens indicated AVM. He was jaundice-free 65 days after the first surgery. However, at 7 months of age, he developed massive melena again. Contrast-enhanced CT and upper gastrointestinal endoscopy revealed no bleeding lesions. Hemorrhagic scintigraphy showed a slight accumulation at the hepatic hilum prompting an emergency surgery. Intraoperative endoscopy detected a bleeding lesion at the PE site, and the Roux limb was resected (approximately 6 cm). Intraoperative frozen section analysis of the stump of the resected jejunum revealed no abnormal vessels. PE was performed, and permanent section analysis revealed an AVM in the resected jejunum. The postoperative course was uneventful without re-bleeding. CONCLUSIONS: We experienced a case of recurrent massive bleeding from small intestinal AVM in an infant after surgery for BA. Intraoperative endoscopy and frozen section analysis helped identify the bleeding lesion and perform a complete resection of the small intestinal AVM, even after surgery, in the infant.

Non-target environmental analysis by liquid chromatography/high-resolution mass spectrometry with a product ion and neutral loss database.

Despite the increasing detection of emerging substances in the environment, the identity of most are left unknown due to the lack of efficient identification methods. We developed a non-target analysis method for identifying unknown substances in the environment by liquid chromatography/high-resolution mass spectrometry (LC/HRMS) with a product ion and neutral loss database (PNDB). The present analysis describes an elucidation method with elemental compositions of the molecules, product ions, and corresponding neutral losses of the unknown substance: (1) with the molecular formula, possible molecular structures are retrieved from two chemical structure databases (PubChem and ChemSpider); then (2) with the elemental compositions of product ions and neutral losses, possible partial structures are retrieved from the PNDB; and finally, (3) molecular structures that match the possible partial structures are listed in order of number of hits. A molecular structure with a higher number of hits is more similar to the structure of the analyzed substance. The performance of the non-target method was evaluated by simulated analysis of 150 LC/HRMS spectra registered in MassBank. First, all substances of the same mass data (41/41) and 68% (39/57) of the mass data of the same substances not registered in the PNDB were elucidated. It was demonstrated that 14% (7/52) and 31% (16/52) of the substances with no mass spectral data registered in the PNDB were obtained at the first and within the fifth place, respectively. Owing to the fact that 10 of the total hits occurred in product ions and neutral losses, almost 50% of the substances evaluated with this method were placed at the top 4 positions in the similarity ranking. Importantly, the proposed method is effective for analyzing mass spectral data that has not been registered in the PNDB and thus is expected to be used for a variety of non-target analyses.

Solution properties of gemini surfactant of decanediyl-1-10-bis (dimethyltetradecylammonium bromide) in aqueous medium.

The solution properties of a typical gemini surfactant of decanediyl-1-10-bis (dimethyltetradecylammonium bromide) (abbrev. 14-10-14,2Br(-)) were examined in an aqueous medium at temperatures of 288.2, 298.2, and 308.2 K. The characterization was performed by employing surface tension measurements, electrical conductivity measurements, steady-state fluorescence quenching (SSFQ), and dynamic light scattering (DLS). The surface tension was measured with the drop volume method, in which an improved tensiometer was used and the experimental operation was modified. The resultant data were well reproducible and the equilibrium adsorption time after producing the droplet onto the tip of the capillary was on the order of minutes. In addition, the critical micelle concentration obtained from the surface tension data is in good agreement with that obtained from the conductivity data. Using the conductivity variation as a function of surfactant concentration, the thermodynamic parameters of micellization were calculated. Furthermore, the SSFQ method suggests a small and constant aggregation number, irrespective of temperature. The formation of small-size micelles was also confirmed by DLS measurements.

Relationship between the rheological properties of thickener solutions and their velocity through the pharynx as measured by the ultrasonic pulse Doppler method.

The dependence of the dynamic viscoelastic parameters of carboxymethylcellulose (CMC), xanthan gum, and guar gum solutions on the angular frequency (omega) was compared with that of their viscosity (mu) on the shear rate (gamma). In addition, the effect of these rheological properties on the maximum velocity through the pharynx, V(max), as measured by the ultrasonic pulse Doppler method, was investigated. The CMC and guar gum solutions examined were taken as a dilute solution and a true polymer solution, respectively. The xanthan gum solution was taken as a weak gel above 0.5% and a true polymer solution below 0.2%. The maximum velocity, V(max), of the thickener solutions correlated well with mu, the dynamic viscosity eta', and the complex viscosity eta(*), especially those measured at gamma or omega of 20-30 s(-1) (or rad/s) and above, suggesting that mu, eta', and eta(*) are suitable indexes for care foods of the liquid type for dysphagic patients.

Caspase inhibitors increase the rate of recovery of neural stem/progenitor cells from post-mortem rat brains stored at room temperature.

To match the demand of regenerative medicine for nerve system, collection of stem cells from the post-mortem body is one of the most practical ways. In this study, the storage condition of the post-mortem body was examined. We prepared neural stem/progenitor cells (NSPCs) from post-mortem rat brains stored at different temperatures. When brains were stored at 4 degrees C, for one week, we were able to obtain neurospheres (a spheroid body containing NSPCs) by stimulation of cells with epidermal growth factor (EGF). Incremental increases in storage temperature decreased the rate of appearance of neurospheres. Within 48 h at 15 degrees C, 24 h at 25 degrees C, in both condition, we were able to recover NSPCs from post-mortem rat brains. At 15 degrees C, 90% of neurosphere-forming activity was lost within 24 h. However, even after 24 h at 25 degrees C, 2% neurosphere-forming activity remained. After 6 h of death, there was very little difference between the rates of NSPC recovery at 4 degrees C and 25 degrees C. Addition of caspase inhibitors to both the rat brain storage solution and the NSPC culture medium increased the rate of neurosphere-forming activity. In particular, an inhibitor of caspase-8 activity increased the NSPC recovery rate approximately three-fold, with no accompanying detrimental effects on neural differentiation in vitro.

Engineering of Pseudomonas aeruginosa lipase by directed evolution for enhanced amidase activity: mechanistic implication for amide hydrolysis by serine hydrolases.

A lipase from Pseudomonas aeruginosa was subjected to directed evolution for increased amidase activity to probe the catalytic mechanism of serine hydrolases for the hydrolysis of amides. Random mutagenesis combined with saturation mutagenesis for all the amino acid residues at the substrate-binding site successfully identified the mutation at the residue 252 next to the catalytic H251 as a hot spot for selectively increasing the amidase activity of the lipase. The saturation mutagenesis targeted for the oxyanion hole (M16 and H83) gave no positive results. The substitutions of Met or Phe for Leu252 significantly increased the amidase activity toward N-(2-naphthyl)oleamide (2), whereas the esterase activity toward structurally similar 2-naphthyl oleate (1) was not affected by the substitution. The triple mutant F207S/A213D/M252F (Sat252) exhibited amidase activity (k(cat)/K(m)) 28-fold higher than that of the wild-type lipase. Kinetic analysis of Sat252 and its parental clone 10F12 revealed that the amidase activity was increased by the increase in the catalytic efficiency (k(cat)). The increase in k(cat) suggested the importance of the leaving group protonation by the catalytic His during the break down of the tetrahedral intermediate in the hydrolysis of amides.

Determination of hexabromocyclododecane diastereoisomers and tetrabromobisphenol A in water and sediment by liquid chromatography/mass spectrometry.

A method to determine alpha-, beta- and gamma-hexabromocyclododecane (HBCD) and tetrabromobisphenol A (TBBPA) in water and sediments was presented using solid phase extraction (SPE) and/or solvent extraction. Recoveries from sediments were approximately 100% for all the chemicals, while recoveries of alpha-, beta- and gamma-HBCDs from water were dependent on the extraction method. In the case of dichloromethane (CH2Cl2) extraction, recoveries of alpha-, beta- and gamma-HBCD from landfill leachates were 77%, 88% and 92%, respectively. Technical difficulties in HBCD measurement are discussed in terms of the physico-chemical properties of HBCD isomers. The method was applied to landfill samples and marine sediment.

Synthetic studies of psilocin analogs having either a formyl group or bromine atom at the 5- or 7-position.

Psilocin analogs having either a formyl group (9-12) or a bromine atom (13-18) at the 5- or 7-position have been prepared for the first time. Syntheses of 5- and 7-bromo derivatives of 4-hydroxy- (23, 24, 28) and 4-benzyloxyindole-3-carbaldehyde (19, 25, 29, 30), 4-benzyloxyindole-3-acetonitriles (20, 31), and 4-benzyloxy-N,N-dimethyltryptamine (32, 34, 35) have also been established.