Genomic progression for local invasion of cutaneous squamous cell carcinoma from the superficial to the deep portion.

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer. While many treatments exist, our understanding of its genomic progression, especially from the epidermis to the deep dermis, remains limited. This study aims to identify genetic mutations associated with the progression of cSCC into the deep dermis, providing insights into its aggressive behavior and high-risk features. We performed high-depth whole-exome sequencing on 12 cSCC tissues, along with paired normal tissues from six patients, using microdissection techniques. The mutational analysis focused on identifying alterations enriched during cSCC progression. Gene Ontology enrichment analysis, immunohistochemical assays, and external single-cell RNA data were utilized for validation. A total of 8863 non-synonymous somatic mutations were identified in 4092 genes across the superficial and deep portions of cSCCs. Analysis of deep portion mutations revealed a significant correlation with gene ontology biological processes, particularly cell junction organization, and cell-cell adhesion. Clonal mutations in these processes were more prevalent in the deep portions, indicating their impact on the cSCC mutation landscape. Genetic evolution analysis identified 29 causal genes associated with dermal invasion in cSCC. We highlight somatic mutations in cSCC, revealing heterogeneity between superficial and deep regions. Altered genes in cell junction organization and cell-cell adhesion emerged as pivotal in dermal invasion. We identified 29 causal genes primarily in deep tumor regions. Our findings emphasize analyzing multiple tumor regions to capture varied mutational landscapes. These insights advance our understanding of cSCC progression, emphasizing genetic and cellular changes during tumor evolution.

The Prognostic Value of Sex-Determining Region Y-Box 2 and CD8+ Tumor-Infiltrating Lymphocytes in Limited-Stage Small-Cell Lung Cancer.

BACKGROUND: Sex-determining region Y-box 2 (SOX2) is a transcriptional factor that drives embryonic stem cells to neuroendocrine cells in lung development and is highly expressed in small-cell lung cancer (SCLC). However, the prognostic role of SOX2 and its relationship with tumor-infiltrating lymphocytes (TILs) has not been determined in SCLC. Herein, we assessed the expression of SOX2 and CD8+ TILs to obtain insights into the prognostic role of SOX2 and CD8+ TILs in limited-stage (LS)-SCLC. METHODS: A total of 75 patients with LS-SCLC was enrolled. The SOX2 expression and CD8+ TILs were evaluated by immunohistochemistry. RESULTS: High SOX2 and CD8+ TIL levels were identified in 52 (69.3%) and 40 (53.3%) patients, respectively. High SOX2 expression was correlated with increased density of CD8+ TILs (p = 0.041). Unlike SOX2, high CD8+ TIL numbers were associated with significantly longer progression-free survival (PFS; 13.9 vs. 8.0 months, p = 0.014). Patients with both high SOX2 expression and CD8+ TIL numbers (n = 29, 38.7%) had significantly longer PFS and overall survival (OS) compared to those from the other groups (median PFS 19.3 vs. 8.4 months; p = 0.002 and median OS 35.7 vs. 17.4 months; p = 0.004, respectively). Multivariate Cox regression analysis showed that the combination of high SOX2 expression and CD8+ TIL levels was an independent good prognostic factor for OS (HR = 0.471, 95% CI, 0.250-0.887, p = 0.02) and PFS (HR = 0.447, 95% CI, 0.250-0.801, p = 0.007) in SCLC. CONCLUSIONS: Evaluation of the combination of SOX2 and CD8+ TIL levels may be of a prognostic value in LS-SCLC.

Prognostic value of noggin protein expression in patients with resected gastric cancer.

BACKGROUND: Noggin and RNA-binding protein for multiple splicing 2 (RBPMS2) are known to regulate the expression of smooth muscle cells, endothelial cells, and osteoblasts. However, the prognostic role of combined Noggin and RBPMS2 expression in resected gastric cancer (GC) is unclear. METHODS: A total of 163 patients with GC who underwent gastrectomy were included in this study. The expression of Noggin and RBPMS2 proteins in tumor cells at the tumor center and invasive front of resected GC was evaluated by immunohistochemistry, and in conjunction with clinicopathological parameters the patient survival was analyzed. RESULTS: RBPMS2 protein expression was high at the tumor center (n = 86, 52.8%) and low at the invasive front (n = 69, 42.3%), while Noggin protein expression was high in both tumor center (n = 91, 55.8%) and the invasive front (n = 90, 55.2%). Noggin expression at the invasive front and tumor center was significantly decreased in advanced T stage, non-intestinal-type (invasive front, P = 0.008 and P <  0.001; tumor center lesion, P = 0.013 and P = 0.001). RBPMS2 expression at the invasive front was significantly decreased in non-intestinal-type and positive lymphatic invasion (P <  0.001 and P = 0.013). Multivariate analysis revealed that high Noggin protein expression of the invasive front was an independent prognostic factor for overall survival (hazard ratio [HR], 0.58; 95% confidence interval [CI]; 0.35-0.97, P <  0.036), but not at the tumor center (HR, 1.35; 95% CI; 0.81-2.26, P = 0.251). CONCLUSIONS: Our study indicates that high Noggin expression is a crucial prognostic factor for favorable outcomes in patients with resected GC.

Recent glycemic control can predict the progressive motor deficits of acute subcortical infarction with diabetes or prediabetes.

BACKGROUND AND PURPOSE: The predictors of progressive motor deficits in acute subcortical infarctions are still controversial. It is not known whether glycemic control influences on stroke progression. METHODS: A total of 268 consecutive patients with diabetes or prediabetes who had acute (< 24 h) subcortical infarction were enrolled. (1) All patients were divided into 4 groups by quartile of glycated hemoglobin (HbA1c). (2) Only the patients with diabetes were divided by effective glycemic control. Progressive motor deficits were prospectively captured and defined as an increase of motor score ≥ 1 on the upper or lower limb items of the National Institute of Health Stroke Scale within 72 h from stroke onset. RESULTS: Progressive motor deficits occur in 8/78 (10.3%) for ≤ 5.9, 15/61 (24.6%) for 6.0-6.4, 16/62 (25.8%) for 6.5-7.4, and 30/67 (44.8%) for ≥ 7.5. In diabetic patients alone, those occur in 5/37 (13.5%) for ≤ 6.5, 10/42 (23.8%) for 6.6-7.0, 12/42 (28.6%) for 7.1-8.0, and 24/50 (48.0%) for ≥ 8.1. An adjusted OR of progressive motor deficits was 2.61 (95% confidence interval [CI] 0.98-7.00, P = .056) for 6.0-6.4, 3.42 (95% CI 1.27-9.18, P = .015) for 6.5-7.4, and 6.65 (95% CI 2.38-18.62, P < .001) for ≥ 7.5. In diabetic patients alone, those were 3.15 (95% CI 0.89-11.15, P = .075) for 6.6-7.0, 2.90 (95% CI 0.79-10.61, P = .107) for 7.1-8.0, and 4.17 (95% CI 1.07-16.25, P = .038) for ≥ 8.1. The optimal cutoff value of HbA1c was 6.65% in discriminating progressive motor deficits. CONCLUSION: Increased HbA1c was associated with higher incidence of progressive motor deficits in acute subcortical infarction with diabetes and prediabetes.

A nomogram to predict pathologic complete response (pCR) and the value of tumor-infiltrating lymphocytes (TILs) for prediction of response to neoadjuvant chemotherapy (NAC) in breast cancer patients.

PURPOSE: The value of tumor-infiltrating lymphocytes (TILs) for prediction of pathologic complete response (pCR) in breast cancer (BC) patients treated with neoadjuvant chemotherapy (NAC) has received increasing attention. In human epidermal growth factor receptor 2 (HER2)-positive BC, advances in HER2-targeted therapy have not yet clarified the clinical implications of pre-NAC TILs. Likewise, the prognostic role of TILs for long-term survival is not well established. METHODS: Pre- and post-NAC TIL levels were evaluated in 248 pair-matched pre-NAC biopsy and post-NAC resection samples, and analyzed for predictive and prognostic significance with other clinicopathologic parameters. Additional 60 pre-NAC biopsy samples of HER2-positive BC treated with a TCHP regimen (docetaxel, carboplatin, and a combination of trastuzumab and pertuzumab) were also assessed. RESULTS: High pre-NAC TILs, clinical nodal stage 0-1 (cN0-1), and negative ER expression were shown to be strong predictive markers for pCR. A nomogram based on these significant clinicopathologic predictors was developed, providing integrated probability of achieving pCR after NAC. The association between high pre-NAC TIL levels and significantly increased pCR rate was also confirmed in HER2-positive BC patients treated with a TCHP regimen. After chemotherapy, increased quantity of post-NAC TILs was shown to have extended BC-specific survival and disease-free survival in univariable and multivariable analyses. CONCLUSIONS: High pre-NAC TIL levels were significantly predictive of pCR in BC, and can act as a surrogate marker for predicting therapeutic effects of a TCHP regimen for HER2-positive BC. Post-NAC TILs in residual disease were a new prognostic marker of risk stratification for long-term survival.

Evaluation of Stress Response During Mesiodens Extraction Under General Anesthesia Using Heart Rate Variability.

PURPOSE: Stress related to dental treatment can be associated with negative outcomes. Heart rate variability (HRV) is an objective measurement of autonomic nervous system activity. Therefore, HRV was used to identify autonomic nervous system reactions during mesiodens extraction under general anesthesia in children. MATERIALS AND METHODS: Electrocardiography was performed with customized software during treatment. HRV parameters were analyzed according to time and frequency domains during each dental procedure (local anesthesia, incision, flap, bone removal, extraction of mesiodens, and suturing). The relations of HRV parameters to age also were determined. RESULTS: Total autonomic nervous system activity decreased markedly after local anesthesia injection. Depending on the responses of sympathetic nerve activity, patients were categorized in a stress group and a nonstress group. The ratio of low-frequency power (LF) to high-frequency power (HF), an indication of sympathetic and parasympathetic balance, increased in the stress group after incision and flap formation. Conversely, the LF/HF ratio decreased during treatment in the nonstress group. However, HR, widely used to evaluate stress responses, did not change statistically during mesiodens extraction in either group. HRV parameters did not differ statistically according to age. CONCLUSIONS: The internal stress related to mesiodens extraction can be evaluated more objectively with HRV parameters than with conventional methods. Sympathetic nerve activity in the stress group differed from that in the nonstress group during the treatment procedures.

Frequency of MED12 mutations in phyllodes tumors: Inverse correlation with histologic grade.

Phyllodes tumor (PT) is a rare breast biphasic tumor with a potential risk of recurrence and metastasis. In this study, the frequency of MED12 mutations in 176 PTs (49 benign, 49 borderline, and 78 malignant) was determined and the prognostic effect of these mutations in malignant type PT was evaluated. Analysis of MED12 mutations was performed by Sanger sequencing targeting the hotspot mutation region (exon 2) of MED12. Immunohistochemistry was also applied for evaluation of MED12 protein expression on tissue microarray blocks for 133 PTs including 50 benign, 50 borderline, and 33 malignant cases. A notable difference in the frequency of MED12 mutations was found according to histologic grade (71.4% of benign PTs, 51% of borderline PTs, 26.9% of malignant PTs; P < 0.001). MED12 protein expression was not correlated with MED12 mutation status. Patients with malignant PTs that harbored MED12 mutations demonstrated improved disease-free survival (DFS) compared with those without MED12 mutation (P = 0.07). MED12 mutation was a common molecular alteration in PT and the frequency of MED12 mutation decreased with increasing histologic grade. In malignant PT, MED12 exon 2 mutations showed improved DFS but without significance. © 2016 Wiley Periodicals, Inc.

Relationship between tetrahydrobiopterin and portal hypertension in patients with chronic liver disease.

Tetrahydrobiopterin (BH4) is an essential cofactor in NO synthesis by endothelial nitric oxide synthase (eNOS) enzymes. It has been previously suggested that reduced intrahepatic BH4 results in a decrease in intrahepatic NO and contributes to increased hepatic vascular resistance and portal pressure in animal models of cirrhosis. The main aim of the present study was to evaluate the relationship between BH4 and portal hypertension (PHT). One hundred ninety-three consecutive patients with chronic liver disease were included in the study. Liver biopsy, measurement of BH4 and hepatic venous pressure gradient (HVPG) were performed. Hepatic fibrosis was classified using the Laennec fibrosis scoring system. BH4 levels were determined in homogenized liver tissues of patients using a high performance liquid chromatography (HPLC) system. Statistical analysis was performed to evaluate the relationship between BH4 and HVPG, grade of hepatic fibrosis, clinical stage of cirrhosis, Child-Pugh class. A positive relationship between HVPG and hepatic fibrosis grade, clinical stage of cirrhosis and Child-Pugh class was observed. However, the BH4 level showed no significant correlation with HVPG or clinical features of cirrhosis. BH4 concentration in liver tissue has little relation to the severity of portal hypertension in patients with chronic liver disease.

Intracranial arterial calcification can predict early vascular events after acute ischemic stroke.

BACKGROUND: Intracranial arterial calcification (IAC) is an evidence of advanced atherosclerosis. This study was aimed to investigate whether IAC predicts early vascular events (EVEs) during acute period of ischemic stroke. METHODS: We prospectively enrolled consecutive patients with acute ischemic stroke and transient ischemic attack within 48 hours from January 2005 to October 2012. Three IAC categories were defined according to the total IAC score as follows: no IAC (0 point), mild IAC (1-2 points), and severe IAC (≥3 points). EVEs included early progression/recurrence of stroke, coronary events, and vascular deaths within 2 weeks from stroke onset. We used multivariable Cox regression analyses to determine the effect of IAC on EVE. RESULTS: In the trend analysis of 1017 total patients, there were significant trends of increased IAC toward higher total EVEs (10.5% versus 13.8% versus 21.2%, P < .001). Severe IAC was related to increased rate of early progression/recurrence (hazard ratio [HR] 2.00; 95% confidence interval [CI] 1.07-3.71, P = .029) and coronary events (HR 3.51; 95% CI 1.00-12.31, P = .050) but did not show an association for mortality (HR .54; 95% CI .19-1.53, P = .224). Increased IAC was also related to a poor functional outcome after 3 months (odds ratio 2.23; 95% CI 1.38-3.59). CONCLUSIONS: IAC was significantly associated with increased early progression/recurrence of stroke and coronary events during acute period of ischemic stroke. IAC on the initial brain computed tomography would be used as a predictor for recurrent vascular events after acute ischemic stroke before further angiographic evaluation.

The Quality of Life and Psychosocial Impact on Female Pattern Hair Loss.

BACKGROUND: Alopecia, a benign dermatologic condition affecting both genders, particularly harms female patients due to psychosocial effects. Female pattern hair loss (FPHL), the primary cause of hair loss in women, lacks sufficient Korean epidemiological studies examining its psychosocial aspects. OBJECTIVE: This study aimed to explore FPHL's psychosocial impacts, including quality of life (QoL), depression, anxiety, medical consumption, and hair loss factors in Korean women. METHODS: A total of 202 patients with FPHL were interviewed using a validated questionnaire to assess the QoL, psychological impact, and pattern of medical consumption. The severity of hair loss was evaluated using the "basic and specific (BASP) classification" by dermatologists. The Hair-Specific Skindex-29 (HSS29) was used to assess the QoL and Beck depression inventory (BDI), Beck anxiety inventory (BAI) to evaluate psychological aspects, and medical expenses and the number of clinic visits to determine medical consumption. RESULTS: The global HSS29 score of FPHL was 40.97±18.92, indicating a notable impact on QoL. The mean BDI and BAI scores were 14.47 and 10.06, respectively. In multivariable regression analysis, HSS29, BDI, and BAI scores were most affected by the severity of hair loss (p<0.001). CONCLUSION: FPHL damages the psychosocial aspects of patients, such as QoL, depression, and medical consumption, according to the severity of hair loss.

Low glomerular filtration rate increases hemorrhagic transformation in acute ischemic stroke.

BACKGROUND: Decreased glomerular filtration rate (GFR) can increase the risk of bleeding tendency and hemorrhagic stroke. However, the relationship between the levels of GFR and hemorrhagic transformation (HT) after acute ischemic stroke is largely unknown. The aim of this study was to assess whether GFR level is associated with HT in acute ischemic stroke. METHODS: We reviewed 770 consecutive patients with acute ischemic stroke within 7 days from September 2007 to February 2012 in a prospective stroke registry database. We calculated the patient's GFR using the Cockcroft-Gault equation, and divided them into 3 groups: ≥60, 30-59 and <30 ml/min/1.73 m(2). HTs were identified by follow-up computed tomography (CT) or magnetic resonance imaging, and were defined as (1) any degree of high density within the area of low attenuation of vascular territory on noncontrast brain CT, or (2) low-signal intensity area in gradient echo within high-signal intensity meaning acute infarct on diffusion-weighted imaging. Multivariable logistic regression analyses were used to estimate the risk of GFR for HT. Stratification analyses were done according to the presence of HT high risk factors: atrial fibrillation (AF), thrombolysis and large size infarction. Additional logistic regression model for symptomatic HTs was established with the same variables. RESULTS: HTs were noted in 131 patients (17.0%) and symptomatic HTs in 63 patients (8.2%). In univariate analysis, HTs were more frequent in patients with AF (51.9 vs. 16.7%, p < 0.001) and large-size infarction (42.0 vs. 5.3%, p < 0.001). The risk of HT was associated with decreased GFR among 3 subgroups classified according to the value of estimated GFR: 49/394 (12.4%) in the GFR ≥60 group, 66/312 (21.2%) in the 30≤ GFR <59 group and 16/64 (25.0%) in the GFR <30 group (p = 0.002). We found a significant association between the GFR <30 group and HTs in acute ischemic stroke (OR 2.90; 95% CI 1.26-6.68, p = 0.012) after adjusting for other risk factors. Moreover, the incidence of HTs was higher in the subgroups without thrombolysis (OR 3.49; 95% CI 1.44-8.46) and without AF (OR 3.44; 95% CI 1.10-10.76). Decreased GFR also had a tendency of increasing symptomatic HTs (OR 2.39; 95% CI 0.72-7.94, p = 0.154). CONCLUSIONS: Low levels of GFR are associated with a high risk of HT after acute ischemic stroke. Further studies are needed to elucidate whether HT in the patients with renal insufficiency are related to a worse outcome after acute ischemic stroke.

A Case of Perineal Hemangioma, External Genitalia Malformations, Lipomyelomeningocele, Vesicorenal Abnormalities, Imperforate Anus, and Skin Tag (PELVIS) Syndrome with Extensive Perineal Infantile Hemangioma.

PELVIS syndrome describes the constellation of perineal hemangioma, external genitalia malformations, lipomyelomeningocele, vesicorenal abnormalities, imperforate anus, and skin tag. A 2-month-old girl presented with infantile hemangioma on her perineum and genitalia with imperforate anus, rectovaginal fistula and perineal skin tag at birth. Under the impression of PELVIS syndrome, consequential spinal sonography was conducted and revealed an intrasacral meningocele without clinical neurologic deficit. The anorectal malformation was surgically corrected, she was taking oral propranolol for the cutaneous lesion, and she showed improvement and no complications.

Valorization of leftover green tea residues through conversion to bioactive peptides using probiotics-aided anaerobic digestion.

Bioactive peptides (BPs) are protein fragments that benefit human health. To assess whether leftover green tea residues (GTRs) can serve as a resource for new BPs, we performed in silico proteolysis of GTRs using the BIOPEP database, revealing a wide range of BPs embedded in GTRs. Comparative genomics and the percentage of conserved protein analyses enabled us to select a few probiotic strains for GTR hydrolysis. The selected probiotics digested GTRs anaerobically to yield GTR-derived peptide fractions. To examine whether green tea (GT) peptide fractions could be potential mediators of host-microbe interactions, we comprehensively screened agonistic and antagonistic activities of 168 human G protein-coupled receptors (GPCRs). NanoLC-MS/MS analysis and thin-layer chromatography allowed the identification of peptide sequences and the composition of glycan moieties in the GTRs. Remarkably, GT peptide fractions produced by Lactiplantibacillus plantarum APsulloc 331261, a strain isolated from GT, showed a potent-binding activity for P2RY6, a GPCR involved in intestinal homeostasis. Therefore, this study suggests the potential use of probiotics-aided GTR hydrolysates as postbiotic BPs, providing a biological process for recycling GTRs from agro-waste into renewable resources as health-promoting BPs.

A Genomics-Based Semirational Approach for Expanding the Postbiotic Potential of Collagen Peptides Using Lactobacillaceae.

Food-derived bioactive peptides (BPs) have received considerable attention as postbiotics for human gut health. Here we used a genomics-based semirational approach to expand the postbiotic potential of collagen peptides (CPs) produced from probiotic fermentation. In silico digestion revealed distinct BPs embedded in fish collagen in a protease-dependent manner. Anaerobic digestion of collagen by representative Lactobacillaceae species revealed differential substrate utilization and collagen degradation patterns. Nanoliquid chromatography-mass spectrometry analysis of CPs showed that each species exhibited different cleavage patterns and unique peptide profiles. Remarkably, the 1-10 kDa CPs produced by Lacticaseibacillus paracasei showed agonistic activities toward G protein-coupled receptor 35 (GPR35). These CPs could repair intestinal epithelium through the GPR35-mediated extracellular signal-regulated protein kinase (ERK) 1/2 signaling pathway, suggesting that probiotic-aided collagen hydrolysates can serve as postbiotics for host-microbe interactions. Therefore, this study provides an effective strategy for the rapid screening of CPs for gut health in the gastrointestinal tract.

Evaluation of an automated superimposition method based on multiple landmarks for growing patients.

OBJECTIVES: To determine if an automated superimposition method using six landmarks (Sella, Nasion, Porion, Orbitale, Basion, and Pterygoid) would be more suitable than the traditional Sella-Nasion (SN) method to evaluate growth changes. MATERIALS AND METHODS: Serial lateral cephalograms at an average interval of 2.7 years were taken on 268 growing children who had not undergone orthodontic treatment. The T1 and T2 lateral images were manually traced. Three different superimposition methods: Björk's structural method, conventional SN, and the multiple landmark (ML) superimposition methods were applied. Bjork's structural method was used as the gold standard. Comparisons among the superimposition methods were carried out by measuring the linear distances between Anterior Nasal Spine, point A, point B, and Pogonion using each superimposition method. Multiple linear regression analysis was performed to identify factors that could affect the accuracy of the superimpositions. RESULTS: The ML superimposition method demonstrated smaller differences from Björk's method than the conventional SN method did. Greater differences among the cephalometric landmarks tested resulted when: the designated point was farther from the cranial base, the T1 age was older, and the more time elapsed between T1 and T2. CONCLUSIONS: From the results of this study in growing patients, the ML superimposition method seems to be more similar to Björk's structural method than the SN superimposition method. A major advantage of the ML method is likely to be that it can be applied automatically and may be just as reliable as manual superimposition methods.

Evaluation of an individualized facial growth prediction model based on the multivariate partial least squares method.

OBJECTIVES: To develop a facial growth prediction model incorporating individual skeletal and soft tissue characteristics. MATERIALS AND METHODS: Serial longitudinal lateral cephalograms were collected from 303 children (166 girls and 137 boys), who had never undergone orthodontic treatment. A growth prediction model was devised by applying the multivariate partial least squares (PLS) algorithm, with 161 predictor variables. Response variables comprised 78 lateral cephalogram landmarks. Multiple linear regression analysis was performed to investigate factors influencing growth prediction errors. RESULTS: Using the leave-one-out cross-validation method, a PLS model with 30 components was developed. Younger age at prediction resulted in greater prediction error (0.03 mm/y). Further, prediction error increased in proportion to the growth prediction interval (0.24 mm/y). Girls, subjects with Class II malocclusion, growth in the vertical direction, skeletal landmarks, and landmarks on the maxilla were associated with more accurate prediction results than boys, subjects with Class I or III malocclusion, growth in the anteroposterior direction, soft tissue landmarks, and landmarks on the mandible, respectively. CONCLUSIONS: The prediction error of the prediction model was proportional to the remaining growth potential. PLS growth prediction seems to be a versatile approach that can incorporate large numbers of predictor variables to predict numerous landmarks for an individual subject.

Histologic analysis according to HER2 gene status in HER2 2 + invasive breast cancer: a study of 280 cases comparing ASCO/CAP 2013 and 2018 guideline recommendations.

The American Society of Clinical Oncology and College of American Pathologists guidelines for HER2 testing in breast cancer (BC) have been updated with more stringent criteria regarding immunohistochemistry (IHC) 2 + interpretation. The aim of our study was to determine HER2 status in IHC 2 + cases based on 2013 and 2018 guidelines and to investigate specific histologic characteristics that might predict HER2 status in tumors with equivocal IHC staining. Two hundred eighty BC cases reported as IHC 2 + and 24 cases reported as non-IHC 2 + were reviewed with 12 histologic characteristics. Of the IHC 2 + cases based on 2013 guideline, 21% were reclassified to IHC 1 + when applying the 2018 guidelines. Consequently, it led to an 8% increase of HER2 amplification rate in 2018 IHC 2 + group. Seven characteristics were significantly associated with prediction of HER2 amplification in IHC 2 + BCs, including high tumor-infiltrating lymphocytes (TILs), distinct cellular membrane, no apical snout, large nuclear size, nuclear size variation, high nuclear grade, and tubule formation < 10%. Using these criteria, the presence of four or more characteristics significantly indicates HER2 amplification. Moreover, four characteristics among them, including high TILs, distinct cellular membrane, nuclear size variation, and high nuclear grade, were also associated with HER2 amplification in non-IHC 2 + cases, demonstrating their predictive value as complements to IHC. In conclusion, we provide specific morphologic features that will improve pathologist performance in identifying more HER2-positive BCs. We further suggest an algorithm for trastuzumab therapy decisions using a combination of histomorphologic evaluation and the updated 2018 guidelines.

A Fibroma of Tendon Sheath Causing Carpal Tunnel Syndrome: A Case Report of an Atypical Clinical Presentation.

Fibroma of the tendon sheath is a benign slow-growing fibrous tumor. Although rare, cases occurring in the upper extremities usually involve the fingers. It appears as a well-defined, roundor oval-shaped mass originating from the flexor tendon. Abundant fibrous stroma makes fibromas appear as a low intensity mass in all MRI sequences. Most of the fibromas manifest as painless soft tissue masses. Herein, we report a case of fibroma of the tendon sheath with an unusual clinical presentation, triggering carpal tunnel syndrome during wrist movement.

Evaluation of automated cephalometric analysis based on the latest deep learning method.

OBJECTIVES: To compare an automated cephalometric analysis based on the latest deep learning method of automatically identifying cephalometric landmarks (AI) with previously published AI according to the test style of the worldwide AI challenges at the International Symposium on Biomedical Imaging conferences held by the Institute of Electrical and Electronics Engineers (IEEE ISBI). MATERIALS AND METHODS: This latest AI was developed by using a total of 1983 cephalograms as training data. In the training procedures, a modification of a contemporary deep learning method, YOLO version 3 algorithm, was applied. Test data consisted of 200 cephalograms. To follow the same test style of the AI challenges at IEEE ISBI, a human examiner manually identified the IEEE ISBI-designated 19 cephalometric landmarks, both in training and test data sets, which were used as references for comparison. Then, the latest AI and another human examiner independently detected the same landmarks in the test data set. The test results were compared by the measures that appeared at IEEE ISBI: the success detection rate (SDR) and the success classification rates (SCR). RESULTS: SDR of the latest AI in the 2-mm range was 75.5% and SCR was 81.5%. These were greater than any other previous AIs. Compared to the human examiners, AI showed a superior success classification rate in some cephalometric analysis measures. CONCLUSIONS: This latest AI seems to have superior performance compared to previous AI methods. It also seems to demonstrate cephalometric analysis comparable to human examiners.

Heterotopic pancreas: the added value of endoscopic ultrasound with Computed Tomography for diagnosis.

AIMS: To investigate the added value of endoscopic ultrasound (EUS) with computed tomography (CT) in distinguishing heterotopic pancreas (HP) from other pathologies, when gastroduodenal subepithelial tumors (SETs) are suspected on an upper endoscopic examination. MATERIAL AND METHODS: We retrospectively included 54 consecutive patients with gastroduodenal SETs who had undergone both abdominal CT and EUS within a 3-month interval. All EUS, endoscopy, and CT images were reviewed and evaluated in a blinded manner by an endoscopist and a radiologist, respectively. Univariate and multivariate analyses were performed to identify EUS/CT findings related to HP. Diagnostic performance of CT only and CT combined with EUS was compared for distinguishing HP from other SETs. RESULTS: We included patients with HP (n=17; pathologically confirmed, n=6), gastrointestinal stromal tumor (GIST, n=24), and other pathologies (n=13). Multivariate logistic regression analyses revealed that irregular margin, origin from submucosal layer, internal microcystic-tubular structure, and oval shape were independent factors in diagnosing HP by EUS, whereas a micro-lobulating contour was the only significantly independent factor in CT. In assessments of diagnostic performance, CT combined with EUS showed significantly superior diagnostic performance in comparison with CT only (area under the curve, 0.961 vs. 0.833, p=0.028) in the consensus interpretation of an endoscopist and a radiologist. CONCLUSIONS: CT combined with EUS with a comprehensive and complementary interpretation showed significant added value compared to CT only in diagnosing gastroduodenal HP.