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Renal masses are commonly encountered on cross-sectional imaging examinations performed for nonrenal indications. Although most can be dismissed as benign cysts, a subset will be either indeterminate or suspicious; in many cases, imaging cannot be used to reliably differentiate between benign and malignant masses. On-going research in defining characteristics of common renal masses on advanced imaging shows promise in offering solutions to this issue. A recent update of the Bosniak classification (used to categorize cystic renal masses) was proposed with the goals of decreasing imaging follow-up in likely benign cystic masses, and therefore avoiding unnecessary surgical resection of such masses.

Objective To investigate the interpretation differences of germline-shared somatic variants. Methods A total of 123,302 COSMIC variants associated with hematologic malignant neoplasms were used. The pathogenicity and actionability of shared variants were analyzed based on the standardized guidelines. Results The overall frequency of variants shared in ClinVar/HGMD and COSMIC was 10%. The pathogenicity of 54 shared variants was pathogenic/likely pathogenic (P/LP; n = 30), variants of unknown significance (n = 3), and benign/likely benign (n = 21). In total, 30 P/LP variants were reclassified to tier I/tier II (83%) and tier III (17%) variants. Conclusions This is the first study about different clinical interpretations of shared variants based on the current standard guidelines. This study takes a meaningful step in bridging the interpretation gap between the somatic and germline variants.

BackgroundThis study aimed to identify and resolve discordant variant interpretations across clinical molecular genetic laboratories through the Canadian Open Genetics Repository (COGR), an online collaborative effort for variant sharing and interpretation.MethodsLaboratories uploaded variant data to the Franklin Genoox platform. Reports were issued to each laboratory, summarising variants where conflicting classifications with another laboratory were noted. Laboratories could then reassess variants to resolve discordances. Discordance was calculated using a five-tier model (pathogenic (P), likely pathogenic (LP), variant of uncertain significance (VUS), likely benign (LB), benign (B)), a three-tier model (LP/P are positive, VUS are inconclusive, LB/B are negative) and a two-tier model (LP/P are clinically actionable, VUS/LB/B are not). We compared the COGR classifications to automated classifications generated by Franklin.ResultsTwelve laboratories submitted classifications for 44 510 unique variants. 2419 variants (5.4%) were classified by two or more laboratories. From baseline to after reassessment, the number of discordant variants decreased from 833 (34.4% of variants reported by two or more laboratories) to 723 (29.9%) based on the five-tier model, 403 (16.7%) to 279 (11.5%) based on the three-tier model and 77 (3.2%) to 37 (1.5%) based on the two-tier model. Compared with the COGR classification, the automated Franklin classifications had 94.5% sensitivity and 96.6% specificity for identifying actionable (P or LP) variants.ConclusionsThe COGR provides a standardised mechanism for laboratories to identify discordant variant interpretations and reduce discordance in genetic test result delivery. Such quality assurance programmes are important as genetic testing is implemented more widely in clinical care.

Up to 80% of BRCA1 and BRCA2 genetic variants remain of uncertain clinical significance (VUSs). Only variants classified as pathogenic or likely pathogenic can guide breast and ovarian cancer prevention measures and treatment by PARP inhibitors. We report the first results of the ongoing French national COVAR (cosegregation variant) study, the aim of which is to classify BRCA1/2 VUSs. The classification method was a multifactorial model combining different associations between VUSs and cancer, including cosegregation data. At this time, among the 653 variants selected, 101 (15%) distinct variants shared by 1,624 families were classified as pathogenic/likely pathogenic or benign/likely benign by the COVAR study. Sixty-six of the 101 (65%) variants classified by COVAR would have remained VUSs without cosegregation data. Of note, among the 34 variants classified as pathogenic by COVAR, 16 remained VUSs or likely pathogenic when following the ACMG/AMP variant classification guidelines. Although the initiation and organization of cosegregation analyses require a considerable effort, the growing number of available genetic tests results in an increasing number of families sharing a particular variant, and thereby increases the power of such analyses. Here we demonstrate that variant cosegregation analyses are a powerful tool for the classification of variants in the BRCA1/2 breast-ovarian cancer predisposition genes.

Objective We investigated the proportions of and reclassified BRCA1/2 variants of unknown significance (VUS) in Korean patients with epithelial ovarian, tubal, and primary peritoneal cancers. Methods Data from 805 patients who underwent genetic testing for BRCA1/2 from January 1, 2006 to August 31, 2018 were included. The VUS in BRCA1/2 were reclassified using the 2015 American College of Medical Genetics and Genomics and the Association for Molecular Pathology standards and guidelines. Results A BRCA1 pathogenic variant was found in 17.0% (137/805) of the patients, and BRCA1 VUS were found in 15.9% (128/805) of the patients. Further, 8.7% (69/805) of the patients possessed a BRCA2 pathogenic variant and 18.4% (148/805) of the patients possessed BRCA2 VUS. Fifty-three specific BRCA1 VUS were found and 20 were further reclassified as benign (n=11), likely benign (n=5), likely pathogenic (n=3), and pathogenic (n=1). The remaining 33 remained classified as VUS. For BRCA2, 55 specific VUS were detected; among these, 14 were reclassified as benign or likely benign, and 2 were reclassified as likely pathogenic. Among the 805 patients, 195 were found to have only VUS and no pathogenic variants (PV), and 41.5% (81/195) were reclassified as benign or likely benign, and 10.3% (20/195) as pathogenic or likely pathogenic variants. Conclusions Approximately 33.3% (36/108) of the specific BRCA1/2 variants analyzed in this study that were initially classified as VUS over a 13-year period were reclassified. Among these, 5.6% (6/108) were reclassified as pathogenic or likely pathogenic variants.

We have identified six patients harbouring distinct germline BAP1 mutations. In this study, we functionally characterise known BAP1 pathogenic and likely benign germline variants out of these six patients to aid in the evaluation and classification of unknown BAP1 germline variants. We found that pathogenic germline variants tend to encode truncated proteins, show diminished expression of epithelial-mesenchymal transition (EMT) markers, are localised in the cytosol and have reduced deubiquitinase capabilities. We show that these functional assays are useful for BAP1 variant curation and may be added in the American College of Medical Genetics and Genomics (ACMG) criteria for BAP1 variant classification. This will allow clinicians to distinguish between BAP1 pathogenic and likely benign variants reliably and may aid to quickly benchmark newly identified BAP1 germline variants. Classification of novel BAP1 germline variants allows clinicians to inform predisposed patients and relevant family members regarding potential cancer risks, with appropriate clinical interventions implemented if required. Ministry of Health (MOH) National Medical Research Council (NMRC) National Research Foundation (NRF) Published version We would like to thank the patients and research participants for their contribution to the study. This work was supported by the Khoo Postdoctoral Fellowship Award (Duke-NUS-KPFA/2019/0034 to J.H.H), the National Medical Research Council Open Fund—Young Individual Research Grant (MOH-000232 to J.H.H), the National Medical Research Council Open Fund—Individual Research Grant (MOH-000144 to B.T.T), the National Medical Research Council Singapore Translational Research Investigator Award (MOH-000248 to B.T.T.), the NRF-NSFC Joint Research Grant (Data Science) (NRF2016NRF-NSFC001–057 to B.T.T), the LKC Startup Grant (LKC MOE to J.N.), the National Research Foundation Singapore under its Clinical Scientist Award (NMRC/CSA-INV/0017/2017) and administered by the Singapore Ministry of Health’s National Medical Research Council (to J.N.). This work is also partially funded by NCC Research Fund, NCC Cancer Fund, Terry Fox and Lee Foundation supporting funds to J.N.

The rapid deployment of 5G spectrum by the telecommunication industry is intended to promote better connectivity and data integration among various industries. However, since exposures to radio frequency radiations (RFR) >2.4 GHz are still uncommon, concerns about their potential health impacts are ongoing. In this study, we used the embryonic zebrafish model to assess the impacts of a 3.5 GHz RFR on biology- a frequency typically used by 5G-enabled cell phones and lies within the 4G and 5G bandwidth. We established a plate-based exposure setup for RFRs, exposed developing zebrafish to 3.5 GHz RFR, specific absorption rate (SAR) ≈ 8.27 W/Kg from 6 h post fertilization (hpf) to 48 hpf, and measured a battery of morphological and behavioral endpoints at 120 hpf. Our results revealed no significant impacts on mortality, morphology or photomotor response and a modest inhibition of startle response suggesting some levels of sensorimotor disruptions. This suggests that the cell phone radiations at low GHz-level frequencies are likely benign, with subtle sensorimotor effects. Through this assessment, we have established a robust setup for zebrafish RFR exposures readily amenable to testing various powers and frequencies. Future developmental exposure studies in zebrafish will evaluate a wider portion of the radio frequency spectrum to discover the bioactive regions, the potential molecular targets of RFR and the potential long-term effects on adult behavior.

The ClinGen PTEN Expert Panel was organized by the ClinGen Hereditary Cancer Clinical Domain Working Group to assemble clinicians, researchers, and molecular diagnosticians with PTEN expertise to develop specifications to the 2015 ACMG/AMP Sequence Variant Interpretation Guidelines for PTEN variant interpretation. We describe finalized PTEN-specific variant classification criteria and outcomes from pilot testing of 42 variants with benign/likely benign (BEN/LBEN), pathogenic/likely pathogenic (PATH/LPATH), uncertain significance (VUS), and conflicting (CONF) ClinVar assertions. Utilizing these rules, classifications concordant with ClinVar assertions were achieved for 14/15 (93.3%) BEN/LBEN and 16/16 (100%) PATH/LPATH ClinVar consensus variants for an overall concordance of 96.8% (30/31). The variant where agreement was not reached was a synonymous variant near a splice donor with non-canonical sequence for which in silico models cannot predict the native site. Applying these rules to six VUS and five CONF variants, adding shared internal laboratory data enabled one VUS to be classified as LBEN and two CONF variants to be as classified as PATH and LPATH. This study highlights the benefit of gene-specific criteria and the value of sharing internal laboratory data for variant interpretation. Our PTEN-specific criteria and expertly reviewed assertions should prove helpful for laboratories and others curating PTEN variants.

PurposeEfforts have been made by the American College of Medical Genetics and Genomics and the Association for Molecular Pathology to make variant classification more uniform, but many limitations remain. Reclassification of a variant of uncertain significance (VUS) is expected, but other more certain calls, like pathogenic or benign, can also be reclassified once additional information is gathered. Variant reclassification can create difficult circumstances for both patients and clinicians.MethodsRetrospective review of all variant reclassifications in genes associated with hereditary cancer syndromes at one clinic between September 2013 and February 2017 was completed. All variant reclassifications were completed and reported by the original testing laboratory.ResultsA total of 1,103 hereditary cancer tests were ordered. Fewer than 5% (40/1,103) of the initial reports were updated during that time period. Most reclassifications (29/40) were downgrades of VUS to likely benign. Only three reclassifications could potentially alter medical management.ConclusionThe majority of variant reclassifications do not impact medical management. Upgrading a variant call to pathogenic could be important for a patient's care and shows the importance of open communication between laboratories and clinicians. A variant downgrade from pathogenic can be a significant reclassification as well, especially if prophylactic surgery has been completed.

We read with interest the recent publication by Weiss and colleagues, which addressed the pitfalls of using next-generation sequencing (NGS) to diagnose PRSS1 variants in chronic pancreatitis (CP).1 Specifically, having failed to authenticate an NGS-identified ‘ PRSS1 c.47C>T (p.Ala16Val) variant’ by Sanger sequencing the PRSS1 gene in the supposed carrier, they postulated that this artefact could have arisen from sequence reads emanating from one of PRSS1 ’ highly homologous and closely linked (7q34) pseudogenes, PRSS3P2 . Herein, we address another NGS-related pitfall that contributes to confusion in relation to the clinical interpretation of PRSS1 p.Ala16Val. p.Ala16Val is the third most commonly detected rare PRSS1 variant in CP; its putative pathological involvement is supported by its ability to increase trypsinogen autoactivation.2 ClinVar, however, ascribes to it conflicting interpretations of pathogenicity (ie, likely benign (1); pathogenic (3) and uncertain significance (2)).3 The main reason for this appears to be its relatively high allele frequency (ie, 0.006607) in all gnomAD V.2.1.1 …

Lung cancer remains one of the most common cancers worldwide. Temporal evaluation is a useful tool for analyzing the malignant behavior of a lesion during treatment or that of indeterminate lesions which may be benign. Thereby, this work proposes a methodology for analysis, quantification and visualization of unsupervised changes in lung lesions, through principal component analysis. From change regions, we extracted texture features for lesion classification as benign or malignant. To reach this purpose, two databases with distinct behavior were used, one of which concerning malign under treatment and another indeterminate, but likely benign, lesions. The results have shown that the lesion’s density changes in a public database of malignant lesions under treatment were greater than the private database of benign lung nodules. From the texture analysis of the regions where the density changes occurred, we were able to discriminate lung lesions with an accuracy of 98.41 %, showing that these changes could point out the nature of the lesion. Other contribution was visualization of changes occurring in the lesions over time. Besides, we quantified these changes and analyzed the entire set through volumetry, the most commonly used technique to evaluate progression of lung lesions.

Objective To investigate the utility of a detailed medical history in the interpretation of chromosomal microarray results for pediatric patients with a constitutional disease. Study design A retrospective review and reinterpretation of test results from chromosomal microarrays performed from 2011 to 2013. Previously reported genetic variants were reanalyzed after review of the patient's complete electronic medical record (cEMR). A 3-tier system was used for reclassification of variants: pathogenic or likely pathogenic (P/LP); variant of uncertain significance (VUS); or benign or likely benign (B/LB). Results Over an 18-month period, 998 patients with chromosomal microarray results were identified. The most common reasons for chromosomal microarray testing were developmental delay (n = 336), autism spectrum disorder (n = 241), and seizures (n = 143). Chromosomal microarray testing identified 1 or more variants in 48% (482 of 998) of patients; 516 patients had a negative report. For the 482 patients with variants, the original interpretations were composed of 19.3% P/LP (93 of 482), 44.8% VUS (216 of 482), and 35.9% B/LB (173 of 482) variants. After review of the cEMR, 34% of patient results (164 of 482) were changed in interpretation. One case changed from B/LB to VUS, 7 VUS were upgraded to P/LP, and 156 VUS were downgraded to B/LB. No P/LP variants had a change in interpretation. Conclusions Overall, 16.4% (164 of 998) of patients with chromosomal microarray testing had a change in interpretation. Access to the patient's cEMR improves the interpretation of chromosomal microarrays by decreasing the number of uncertain (VUS) interpretations.

The clinical utility of BRCA1/2 genotyping was recently extended from the selection of subjects at high risk for hereditary breast and ovary cancer to the identification of candidates for poly (ADP-ribose) polymerase (PARP) inhibitor treatment. This underscores the importance of accurate interpretation of BRCA1/2 genetic variants and of reducing the number of variants of uncertain significance (VUSs). Two recent studies by Findlay et al. and Starita et al. introduced high-throughput functional assays, and proactively analyzed variants in specific regions regardless of whether they had been previously observed. We retrospectively reviewed all BRCA1 and BRCA2 germline genetic test reports from patients with breast or ovarian cancer examined at Asan Medical Center (Seoul, Korea) between September 2011 and December 2018. Variants were assigned pathogenic or benign strong evidence codes according to the functional classification and were reclassified according to the ACMG/AMP 2015 guidelines. Among 3684 patients with available BRCA1 and BRCA2 germline genetic test reports, 429 unique variants (181 from BRCA1) were identified. Of 34 BRCA1 variants intersecting with the data reported by Findlay et al., three missense single-nucleotide variants from four patients (0.11%, 4/3684) were reclassified from VUSs to likely pathogenic variants. Four variants scored as functional were reclassified into benign or likely benign variants. Three variants that overlapped with the data reported by Starita et al. could not be reclassified. In conclusion, proactive high-throughput functional study data are useful for the reclassification of clinically observed VUSs. Integrating additional evidence, including functional assay results, may help reduce the number of VUSs.

Background The sources and variants types of the copy number variations (CNVs) in prenatal fetal, and the critical role of parental origin on the interpretation of fetal CNVs are unclear. Methods One hundred and forty‐one prenatal core families with abnormal CNVs were selected and performed by low‐coverage massively parallel CNV sequencing (CNV‐seq). Results The data showed that 72.3% of fetal CNVs were derived from parents, and 27.7% were new variations. Sixty‐three cases were heterozygous deletion, 70 cases were threefold duplication, six cases were complex deletion and duplication, and two cases were fourfold repeats. That means the rate of heterozygous deletion and duplication was approximate one. In addition, in parental‐derived fetal abnormal CNVs reports, before validating parental origin, 62 CNVs were variants of uncertain significance (VUS), 15 CNVs were likely benign, 20 CNVs were likely pathogenic, and 5 CNVs were pathogenic. However, after validating parental origin, the total clinical significance changed into 12 VUS, 89 likely benign, 1 likely pathogenic, and 0 pathogenic. The clinical interpretation of 78.4% fetal CNVs was changed and tended to be benign after parental CNVs were detected. Besides, we followed up all families. 93.3% parental‐derived fetal and 30.3% fetus in new mutation group were born healthy. Conclusion Parental origin verification has an important significance for interpretation on the clinical significance of fetal CNVs.

This study aimed to obtain a quantitative assessment of the occurrence of contradictory evidence in functional classification of genetic variation, according to the American College of Medical Genetics and Genomics (ACMG) guidelines. We analyzed 140,883 genetic variation in the Human Gene Mutation Database (HGMD). The 2014 release of the HGMD dataset before the publication of the ACMG guidelines was used for its independence from the ACMG guidelines. Evidence for benign classification, BS2 (0.37%), was identified among variants classified as pathogenic. For likely pathogenic variation, BP1 (2.99%) and BS2 (0.37%) were identified. PM1 is commonly observed among variants classified as benign (28.45%), while PM2 and PM1 are commonly identified among variants classified as likely benign (48.91% and 42.95%, respectively). Taken together, these observations will inform better approaches to apply the ACMG guidelines.

Trisomy 9p is one of the most common chromosomal partial trisomies in newborns. However, reports on prenatal 9p microduplications are rare in the clinic. This study aimed to examine the genotype–phenotype correlation and assess the clinical significance of 9p24.3 microduplication encompassing the DOCK8 gene. Eight pregnant women underwent amniocentesis for cytogenetic and genetic testing for various indications for prenatal diagnosis from January 2019 to January 2020. Chromosomal karyotypic analysis was performed on G-band metaphases that were prepared from cultured amniotic fluid cells. Chromosomal microarray analysis was carried out to detect chromosomal copy number variations. We also performed a literature review on clinical data on similar 9p24.3 microduplications to determine the genotype–phenotype correlation. We detected 123–248-kb microduplications in the region of 9p24.3 (chr9: 208454–469022), involving part of or the entire DOCK8 gene. The indications for prenatal diagnosis mainly focused on the risk of maternal serum screening for trisomy 21/18, advanced maternal age, and increased nuchal translucency. No evident structural abnormalities were observed for all fetuses, except for case 5 who presented with increased nuchal translucency in prenatal ultrasound findings. Follow-up of postnatal health was performed and showed no apparent abnormalities for cases 1 to 6 after birth. The parents of case 7 chose to terminate the pregnancy while the parents of case 8 chose to continue the pregnancy. We propose that 9p24.3 microduplications that encompass part of or the entire DOCK8 gene are variants that might be benign. However, further large-scale studies are necessary to evaluate the clinical pathogenicity. For prenatal cases with 9p24.3 microduplication, postnatal health and growth should be followed up and assessed regularly from childhood to adulthood.

Highlights • An 84-year-old Japanese woman with a history of multiple primary meningiomas (PPMs) we first reported. • Histologically confirmed for a right-sided slowly growing lung nodule for 20 years. • Long-term follow-up CT scans reveal multiple lung nodules. • Multiple PPMs are most effectively treated with surgical resection and follow-up examinations. • The tumors prove to be benign by morphology with a relatively long, asymptomatic clinical course., Introduction Primary pulmonary meningiomas (PPMs) are very rare neoplasms, and we reported the first multiple case of PPMs in 1998. Usually, PPMs are slow-growing tumors with a good prognosis. Herein, we reported a rare multiple case of PPMs with an extremely long clinical course. Presentation of the case An 84-year-old Japanese woman with a history of multiple PPMs histologically confirmed as having a right-sided slowly growing lung nodule for 20 years. In 2010, we also reported the additional clinical course in the initial case 10 years after surgery implying a benign biological nature. Subsequent to that report, new lesions appeared in the bilateral lung fields with quite a slow growth rate. She was asymptomatic, and no tumor was observed in the cranial cavity during the course of her disease. Discussion and conclusion This case illustrates rare multiple PPMs and highlights their biological behavior with very slow progression from a most likely benign tumor over a 20-year period.

Based on a homozygous missense variant p.Pro311Ala found in three siblings of a consanguineous family, mutations in the STYXL1 gene were suggested to cause moderate intellectual disability, epilepsy and complex behavioural abnormalities. We have detected this variant via whole exome sequencing in a homozygous state in two families. Segregation analyses in our families and thorough validation in international genetic databases provides evidence that this variant is most likely benign. This is important information for genetic counselling. The role of STYXL1 variants in human disease needs to be established.

Family studies are an important but underreported source of information for reclassification of variants of uncertain significance (VUS). We evaluated outcomes of a patient-driven framework that offered familial VUS reclassification analysis to any adult with any clinically ascertained VUS from any laboratory in the United States. With guidance from FindMyVariant.org, participants recruited their own relatives for study participation. We genotyped relatives, calculated quantitative cosegregation likelihood ratios, and evaluated variant classifications using Tavtigian’s unified framework for Bayesian analysis with American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) criteria. We report participation and VUS reclassification rates from the 50 families enrolled for at least one year and reclassification results for 112 variants from the larger 92-family cohort. For the 50-family cohort, 6.7 relatives per family were invited to participate and 67% of relatives returned samples for genotyping. Sixty-one percent of VUS were reclassified, 84% of which were classified as benign or likely benign. Genotyping relatives identified a de novo variant, phase variants, and relatives with phenotypes highly specific for or incompatible with specific classifications. Motivated families can contribute to successful VUS reclassification at substantially higher rates than those previously published. Clinical laboratories could consider offering family studies to all patients with VUS.

Background Significant numbers of variants detected in cancer patients are often left labeled only as variants of unknown significance (VUS). In order to expand precision medicine to a wider population, we need to extend our knowledge of pathogenicity and drug response in the context of VUS’s. Methods In this study, we analyzed variants from AACR Project GENIE Consortium APG (Cancer Discov 7:818-831, 2017) and compared them to the COSMIC database Forbes et al. (Nucleic Acids Res 43:D805-811, 2015) to identify recurrent variants that would merit further study. We filtered out known hotspot variants, inactivating variants in tumor suppressors, and likely benign variants by comparing with COSMIC and ExAC Lee et al. (Science 337:967-971, 2012). Results We have identified 45,933 novel variants with unknown significance unique to GENIE. In our analysis, we found on average six variants per patient where two could be considered as pathogenic or likely pathogenic and the majority are VUS’s. More importantly, we have discovered 730 recurrent variants that appear more than 3 times in GENIE but less than 3 in COSMIC. If we combine the recurrences of GENIE and COSMIC for all variants, 2586 are newly identified as occurring more than 3 times than when using COSMIC alone. Conclusions Although it would be inappropriate to blindly accept these recurrent variants as pathogenic, they may warrant higher priority than other observed VUS’s. These newly identified recurrent variants might affect the molecular profiles of approximately 1 in 6 patients. Further analysis and characterization of these variants in both research and clinical contexts will improve patient treatments and the development of new therapeutics. Electronic supplementary material The online version of this article (10.1186/s12885-019-5313-1) contains supplementary material, which is available to authorized users.

The widespread use of abdominal imaging techniques has increased the detection of solid renal masses over the past years. Imaging plays a crucial role in the management and surveillance and in determining which lesions need treatment. The "classical angiomyolipoma" is the only benign solid renal mass that can be characterized with confidence by imaging through the detection of a fat-containing lesion without calcifications. There is a large overlap of imaging features between benign and malignant renal masses that often makes difficult a correct characterization of these lesions. In this review, we discuss the imaging features of the main solid renal masses that may suggest a likely benign diagnosis.

Key Clinical Message BRCA1, c.4096+3A>G was identified in a consanguineous Danish family with several cases of breast/ovarian cancer. In silico analysis and splicing assays indicated that the variant caused aberrant splicing. However, based on segregation data and the finding of a healthy homozygous carrier, we classify the BRCA1 c.4096+3A>G variant as likely benign.

Among the detected small nodules sized from 3 to 30mm in CT images, a significant portion is undetermined in terms of malignancy which needs biopsy or other follow-up means, resulting in excessive risk and cost. Therefore, predicting the malignancy of the nodules becomes a clinically desirable task. Based on the previous study of texture features extracted from gray-tone spatial-dependence matrices, this study aims to find more efficient texture features or image texture markers in discriminating the nodule malignancy. Two new image texture markers (median and variance) are proposed to classify the small nodules into different malignant levels, thus the risk prediction could be performed through image analysis. These two new image texture markers can minimize the effect of outliers in the feature series, thus can reduce the noise influence to the feature classification. Total 1,353 nodule samples selected from the Lung Image Database Consortium were used to evaluate the efficiency of the proposed new features. All the classification results are shown in the ROC curves and tabulated by the AUC values. The classification outcomes from (1) the most likely and likely benign nodules vs. the most likely and likely malignant nodules, (2) the most likely vs. likely benign nodules, and (3) the most likely vs. likely malignant nodules, are 0.9125±0.0096, 0.9239±0.0147, and 0.8888±0.0197, respectively, in terms of the largest AUC values. From the experimental outcomes on different malignant levels, the two new image texture markers from nodule volumetric CT image data have shown encouraging performance for the risk prediction.

The 2010 consensus statement on diagnostic chromosomal microarray (CMA) testing recommended an array resolution ≥400 kb throughout the genome as a balance of analytical and clinical sensitivity. In spite of the clear evidence for pathogenicity of large copy-number variants (CNVs) in neurodevelopmental disorders and/or congenital anomalies, the significance of small, nonrecurrent CNVs (

Enucleation is the preferred surgical management of small, likely benign, insulinomas. Sparing pancreatic parenchyma and minimizing morbidity are of greater importance in these patients due to their anticipated long survival time. Although a laparoscopic approach is ideal, it can be particularly challenging when the insulinoma is retropancreatic or adjacent to critical vascular structures [i.e., superior mesenteric vein-portal vein confluence (SMV-PV)].A 35-year-old woman with neuroglycopenic symptoms and hypoglycemia was diagnosed with hyperinsulinemia. Preoperative CT and EUS-FNA confirmed a 6- × 9-mm neuroendocrine tumor in the parenchyma of the posterior pancreatic neck along the left lateral aspect of the SMV-PV.With the patient in stirrups and arms tucked (French Position), the lesser sac was opened to expose the pancreatic body. A retropancreatic tunnel was created anterior to the SMV-PV and the pancreatic neck encircled with umbilical tape to allow for retraction while minimizing pancreatic manipulation. The insulinoma was definitively identified using intraoperative ultrasound (IOUS). IOUS-guided clip placement facilitated direct identification and permitted safe image-guided enucleation. The enucleation was performed at the parenchymal interface, minimizing the risk of main pancreatic duct injury.Complete pancreatic neck mobilization and view through the laparoscope along the axis of the PV can facilitate exposure at the challenging location of the retropancreatic neck. Transpancreatic IOUS guidance is crucial to identify and safely enucleate small insulinomas in this location. This totally minimally invasive approach can reduce the morbidity of pancreatic surgery for these patients and permit organ-sparing despite the challenging anatomic location.