Multiparametric MRI Features of Breast Cancer Molecular Subtypes.

Background and Objectives: Breast cancer (BC) molecular subtypes have unique incidence, survival and response to therapy. There are five BC subtypes described by immunohistochemistry: luminal A, luminal B HER2 positive and HER2 negative, triple negative (TNBC) and HER2-enriched. Multiparametric breast MRI (magnetic resonance imaging) provides morphological and functional characteristics of breast tumours and is nowadays recommended in the preoperative setting. Aim: To evaluate the multiparametric MRI features (T2-WI, ADC values and DCE) of breast tumours along with breast density and background parenchymal enhancement (BPE) features among different BC molecular subtypes. Materials and Methods: This was a retrospective study which included 344 patients. All underwent multiparametric breast MRI (T2WI, ADC and DCE sequences) and features were extracted according to the latest BIRADS lexicon. The inter-reader agreement was assessed using the intraclass coefficient (ICC) between the ROI of ADC obtained from the two breast imagers (experienced and moderately experienced). Results: The study population was divided as follows: 89 (26%) with luminal A, 39 (11.5%) luminal B HER2 positive, 168 (48.5%) luminal B HER2 negative, 41 (12%) triple negative (TNBC) and 7 (2%) with HER2 enriched. Luminal A tumours were associated with special histology type, smallest tumour size and persistent kinetic curve (all p-values < 0.05). Luminal B HER2 negative tumours were associated with lowest ADC value (0.77 × 10−3 mm2/s2), which predicts the BC molecular subtype with an accuracy of 0.583. TNBC were associated with asymmetric and moderate/marked BPE, round/oval masses with circumscribed margins and rim enhancement (all p-values < 0.05). HER2 enriched BC were associated with the largest tumour size (mean 37.28 mm, p-value = 0.02). Conclusions: BC molecular subtypes can be associated with T2WI, ADC and DCE MRI features. ADC can help predict the luminal B HER2 negative cases.

Analysis of hereditary cancer syndromes by using a panel of genes: novel and multiple pathogenic mutations.

BACKGROUND: Hereditary cancer predisposition syndromes are responsible for approximately 5-10% of all diagnosed cancer cases. In the past, single-gene analysis of specific high risk genes was used for the determination of the genetic cause of cancer heritability in certain families. The application of Next Generation Sequencing (NGS) technology has facilitated multigene panel analysis and is widely used in clinical practice, for the identification of individuals with cancer predisposing gene variants. The purpose of this study was to investigate the extent and nature of variants in genes implicated in hereditary cancer predisposition in individuals referred for testing in our laboratory. METHODS: In total, 1197 individuals from Greece, Romania and Turkey were referred to our laboratory for genetic testing in the past 4 years. The majority of referrals included individuals with personal of family history of breast and/or ovarian cancer. The analysis of genes involved in hereditary cancer predisposition was performed using a NGS approach. Genomic DNA was enriched for targeted regions of 36 genes and sequencing was carried out using the Illumina NGS technology. The presence of large genomic rearrangements (LGRs) was investigated by computational analysis and Multiplex Ligation-dependent Probe Amplification (MLPA). RESULTS: A pathogenic variant was identified in 264 of 1197 individuals (22.1%) analyzed while a variant of uncertain significance (VUS) was identified in 34.8% of cases. Clinically significant variants were identified in 29 of the 36 genes analyzed. Concerning the mutation distribution among individuals with positive findings, 43.6% were located in the BRCA1/2 genes whereas 21.6, 19.9, and 15.0% in other high, moderate and low risk genes respectively. Notably, 25 of the 264 positive individuals (9.5%) carried clinically significant variants in two different genes and 6.1% had a LGR. CONCLUSIONS: In our cohort, analysis of all the genes in the panel allowed the identification of 4.3 and 8.1% additional pathogenic variants in other high or moderate/low risk genes, respectively, enabling personalized management decisions for these individuals and supporting the clinical significance of multigene panel analysis in hereditary cancer predisposition.

The decrease of some serum free amino acids can predict breast cancer diagnosis and progression.

This study was targeted on a metabolomic approach to compare the blood serum free amino acid profiles and concentration of confirmed breast cancer (stages I-III) patients to healthy controls in order to establish reliable biomarkers of early detection and prediction of breast cancer. The ultra-high-performance liquid chromatography coupled with mass spectrometry using positive ionization electrospray was applied for the picoline-derivatized serum free amino acids using the EZ:faastTM kit. Multivariate statistical analysis principal component analysis, partial least squares discrimination analysis and univariate analysis were applied in order to discriminate between patient groups and putative amino acid biomarkers for breast cancer. A significant decrease of amino acid concentrations between the breast cancer group and the control group was positively correlated with breast cancer progression. Arginine, Alanine, Isoleucine, Tyrosine and Tryptophan were identified as being good potential discriminants (AUROC ≥0.85) and suitable candidates to diagnose and predict the breast cancer progression.

Mind the Gap Between Scientific Literature Recommendations and Effective Implementation. Is There Still a Role for Surgery in the Treatment of Locally Advanced Cervical Carcinoma?

According to evidence accumulated in the last years, many cancer centers recommend a treatment plan based solely on chemo-radiotherapy and exclude surgery from the treatment options in locally advanced cervical cancer (LACC). In Romania, surgery was at the forefront of therapeutic options. Nevertheless, current data shows that in fact, a large number of patients are still referred to surgery in various stages of diagnosis and treatment. It was noted that recommendations may differ, in spite of the wide dissemination of the literature data.Works published so far, discussing the role of surgery in LACC treatment shows a lack of consensus. A group of experts in oncology (SURCECAN research group - Surgery of Cervical Cancer) met for a session of the Romanian Surgical Society (Bucharest) on April 18, 2018. They found that LACC therapeutic strategy in Romania may differ somewhat from the European recommendations.On top of that, late enrolement to RT and low acces to specialized centers are the problem. Performing surgery not only allows the evaluation of the pathological response to chemo-radiotherapy, but also achieves a better local control. In conclusion, there is still a place for surgery within locally advanced cervical cancer treatment options. More trials need to be carried out in order to confirm the findings and establish high levels of confidence for each piece of information provided.

[Histopathological diagnostic concordance in bone and soft tissue sarcomas between two comprehensive cancer centers from eastern and western Europe: a collaborative experience]. / La concordance du diagnostic histopathologique des sarcomes osseux et des tissus mous entre deux centres anticancéreux de l'Europe de l'Est et de l'Ouest : une expérience de collaboration.

INTRODUCTION: This study aims to assess the degree of concordance of histological diagnosis of bone and soft tissue sarcomas between a Comprehensive Cancer Center (CCC) of Eastern Europe - not specialized in this area of pathology - and an important CCC of Western Europe, which is one of the coordinators of a clinical reference network in sarcoma pathology. The goal is to have an overview of the sarcomatous pathology in a region of Eastern Europe and to discover diagnostic discrepancies between the two centers, while determining their cause. MATERIALS AND METHODS: The initial diagnosis was compared with the revised diagnosis on 110 specimens from 88 patients with bone or soft tissue sarcomas from East-European CCC, in a one-year period of time. RESULTS: Complete diagnostic agreement was observed in 55 cases (62.5%), a partial agreement in 23 cases (26.1%) and a major disagreement in 10 cases (11.4%). Major discrepancies of the histological type was observed in only 3 cases (3.4%): one case of discordance benign/malignant and 2 cases of discordance mesenchymal/non mesenchymal. Minor histological discrepancies - not affecting the management of the patient - were observed in 18 cases (20.4%). A major discordance in grading - potentially changing the management of the patient - was noted in 7 cases (7.9%), and a minor discrepancy in 5 cases (5.7%). DISCUSSIONS: Some histological types were clearly overdiagnosed, like "adult fibrosarcomas" and "malignant peripheral nerve sheet tumors" (MPNST), mostly converted after the audit into "undifferentiated spindle cell sarcomas" or other types of sarcomas. Some "unclassified" sarcomas and "undifferentiated pleomorphic sarcomas" could be re-classified with the aid of an extensive panel of antibodies. Overall, immunohistochemistry was responsible, but not in exclusivity, for half of the minor discrepancies, and for 2 out of 3 cases of major histological discrepancies. Otherwise, the main cause of discrepancies was the difficulties in the interpretation of the morphology. Molecular biology was decisive in one case. Most grading discrepancies resulted from the appreciation of the mitotic index. CONCLUSIONS: The profile of the sarcomatous pathology in the northwest region of Romania does not appear to differ significantly from other parts of Europe or the world, but a prospective epidemiological study would be necessary to confirm this assessment. The expansion of immunohistochemical antibody panel, the over-specialization of pathologists and, in the future, the establishment of a national network of referral centers in sarcoma pathology, are required for a high level of histological diagnosis in Eastern Europe. A periodic external audit, continuing this trans-European collaboration between the two centers, would be beneficial for monitoring progress.

Unselective Measurement of Tumor-to-Stroma Proportion in Colon Cancer at the Invasion Front-An Elusive Prognostic Factor: Original Patient Data and Review of the Literature.

The tumor-to-stroma ratio is a highly debated prognostic factor in the management of several solid tumors and there is no universal agreement on its practicality. In our study, we proposed confirming or dismissing the hypothesis that a simple measurement of stroma quantity is an easy-to-use and strong prognostic tool. We have included 74 consecutive patients with colorectal cancer who underwent primary curative abdominal surgery. The tumors have been grouped into stroma-poor (stroma < 10%), medium-stroma (between 10 and 50%) and stroma-rich (over 50%). The proportion of tumor stroma ranged from 5% to 70% with a median of 25%. Very few, only 6.8% of patients, had stroma-rich tumors, 4% had stroma-poor tumors and 89.2% had tumors with a medium quantity of stroma. The proportion of stroma, at any cut-off, had no statistically significant influence on the disease-specific survival. This can be explained by the low proportion of stroma-rich tumors in our patient group and the inverse correlation between stroma proportion and tumor grade. The real-life proportion of stroma-rich tumors and the complex nature of the stroma-tumor interaction has to be further elucidated.

Structure-Activity Relationship Studies Based on Quinazoline Derivatives as EGFR Kinase Inhibitors (2017-Present).

The epidermal growth factor receptor (EGFR) plays a critical role in the tumorigenesis of various forms of cancer. Targeting the mutant forms of EGFR has been identified as an attractive therapeutic approach and led to the approval of three generations of inhibitors. The quinazoline core has emerged as a favorable scaffold for the development of novel EGFR inhibitors due to increased affinity for the active site of EGFR kinase. Currently, there are five first-generation (gefitinib, erlotinib, lapatinib, vandetanib, and icotinib) and two second-generation (afatinib and dacomitinib) quinazoline-based EGFR inhibitors approved for the treatment of various types of cancers. The aim of this review is to outline the structural modulations favorable for the inhibitory activity toward both common mutant (del19 and L858R) and resistance-conferring mutant (T790M and C797S) EGFR forms, and provide an overview of the newly synthesized quinazoline derivatives as potentially competitive, covalent or allosteric inhibitors of EGFR.

Prevalence of MMTV-like sequences in breast cancer samples in Romanian patients-there is a geographic difference compared to the Western world.

BACKGROUND: Breast cancer, although the most frequently diagnosed malignant tumor in humans, has a less clear etiology compared to other frequent cancer types. Mouse-mammary tumor virus (MMTV) is involved in breast cancer in mice and dogs and might play a role in the etiology of some breast cancers in humans, since an MMTV-like sequence was identified in 20-40% of breast cancer samples in Western Europe, USA, Australia and some other parts of the world. The purpose of our study was to identify MMTV-like DNA sequences in breast tissue samples from breast cancer patients who underwent curative surgery in our regional academic center in Romania, EU. METHODS: We selected 75 patients with non-metastatic breast cancer treated surgically with curative intent, who did not undergo any neoadjuvant treatment. Out of these patients, 50 underwent radical lumpectomy and 25 modified radical mastectomy. Based on previous reports in the literature we searched using PCR the MMTV-like DNA env sequence in the breast cancer tissue and normal breast tissue obtained from the same patients. RESULTS: None of the examined samples was positive for MMTV-like target sequences on PCR. CONCLUSIONS: We could not prove that MMTV plays a role in the etiology of breast cancer in our patient group. This finding is similar to those from publications of other geographically related research groups.

Spectrum of High-Risk Mutations among Breast Cancer Patients Referred for Multigene Panel Testing in a Romanian Population.

(1) Background: Multigene panel testing for Hereditary Breast and Ovarian Cancer (HBOC) using next generation sequencing (NGS) is becoming a standard in medical care. There are insufficient genetic studies reported on breast cancer (BC) patients from Romania and most of them are focused only on BRCA 1/2 genes (Breast cancer 1/2). (2) Methods: NGS was performed in 255 consecutive cases of BC referred for management in our clinic between 2015-2019. (3) Results: From the 171 mutations identified, 85 were in the high-penetrance BC susceptibility genes category, 72 were pathogenic genes, and 13 genes were in the (variants of uncertain significance) VUS genes category. Almost half of the mutations were in the BRCA 1 gene. The most frequent BRCA1 variant was c.3607C>T (14 cases), followed by c.5266dupC (11 cases). Regarding BRCA-2 mutations we identified c.9371A>T (nine cases), followed by c.8755-1G>A in three cases, and we diagnosed VUS mutations in three cases. We also identified six pathogenic variants in the PALB2 gene and two pathogenic variants in (tumor protein P 53) TP53. (4) Conclusions: The majority of pathogenic mutations in the Romanian population with BC were in the BRCA 1/ 2 genes, followed by PALB2 (partner and localizer of BRCA2) and TP53, while in the CDH1 (cadherin 1) and STK11 (Serine/Threonine-Protein Kinase) genes we only identified VUS mutations.

Whole-Tumor ADC Texture Analysis Is Able to Predict Breast Cancer Receptor Status.

There are different breast cancer molecular subtypes with differences in incidence, treatment response and outcome. They are roughly divided into estrogen and progesterone receptor (ER and PR) negative and positive cancers. In this retrospective study, we included 185 patients augmented with 25 SMOTE patients and divided them into two groups: the training group consisted of 150 patients and the validation cohort consisted of 60 patients. Tumors were manually delineated and whole-volume tumor segmentation was used to extract first-order radiomic features. The ADC-based radiomics model reached an AUC of 0.81 in the training cohort and was confirmed in the validation set, which yielded an AUC of 0.93, in differentiating ER/PR positive from ER/PR negative status. We also tested a combined model using radiomics data together with ki67% proliferation index and histological grade, and obtained a higher AUC of 0.93, which was also confirmed in the validation group. In conclusion, whole-volume ADC texture analysis is able to predict hormonal status in breast cancer masses.

Copy Number Variations (CNVs) Account for 10.8% of Pathogenic Variants in Patients Referred for Hereditary Cancer Testing.

BACKGROUND/AIM: Germline copy number variation (CNV) is a type of genetic variant that predisposes significantly to inherited cancers. Today, next-generation sequencing (NGS) technologies have contributed to multi gene panel analysis in clinical practice. MATERIALS AND METHODS: A total of 2,163 patients were screened for cancer susceptibility, using a solution-based capture method. A panel of 52 genes was used for targeted NGS. The capture-based approach enables computational analysis of CNVs from NGS data. We studied the performance of the CNV module of the commercial software suite SeqPilot (JSI Medical Systems) and of the non-commercial tool panelcn.MOPS. Additionally, we tested the performance of digital multiplex ligation-dependent probe amplification (digitalMLPA). RESULTS: Pathogenic/likely pathogenic variants (P/LP) were identified in 464 samples (21.5%). CNV accounts for 10.8% (50/464) of pathogenic variants, referring to deletion/duplication of one or more exons of a gene. In patients with breast and ovarian cancer, CNVs accounted for 10.2% and 6.8% of pathogenic variants, respectively. In colorectal cancer patients, CNV accounted for 28.6% of pathogenic/likely pathogenic variants. CONCLUSION: In silico CNV detection tools provide a viable and cost-effective method to identify CNVs from NGS experiments. CNVs constitute a substantial percentage of P/LP variants, since they represent up to one of every ten P/LP findings identified by NGS multigene analysis; therefore, their evaluation is highly recommended to improve the diagnostic yield of hereditary cancer analysis.

Krukenberg tumor in pregnancy: a rare case and review of the literature.

Krukenberg's tumor diagnosed in pregnancy is an uncommon situation that raises both diagnosis and medical management issues. We performed a review of the existing literature regarding this pathology, diagnostic means and therapeutic approaches, motivated by a case in our own practice. A 35-year-old primigravida was diagnosed with an adnexal mass during the first trimester prenatal ultrasound. Ultrasound revealed a 10 cm right adnexal mass with multiple septae, richly vascularized, whose presence and characteristics were confirmed by magnetic resonance imaging. Due to the progressively increasing tumor size, laparoscopy was performed with right adnexectomy and peritoneal biopsies. Histopathology diagnosed a metastatic ovarian tumor from a mucinous colorectal adenocarcinoma. After delivery the patient was further investigated and diagnosed with sigmoid cancer. Even though ovarian cancer in pregnancy is rare, adnexal ultrasound is mandatory when scanning during the first trimester to rule out the presence of associated fallopian or ovarian masses.

Are Mutation Carrier Patients Different from Non-Carrier Patients? Genetic, Pathology, and US Features of Patients with Breast Cancer.

The purpose of this study is to evaluate the relationship between the pathogenic/likely pathogenic mutations, US features, and histopathologic findings of breast cancer in mutation carriers compared to non-carrier patients. Methods: In this retrospective study, we identified 264 patients with breast cancer and multigene panel testing admitted to our clinic from January 2018 to December 2020. Patient data US findings, US assessment of the axilla, multigene panel tests, histopathology, and immunochemistry reports were reviewed according to the BI-RADS lexicon. Results: The study population was comprised of 40% pathogenic mutation carriers (BRCA1, BRCA2, CHEK2, ATM, PALB, TP 53, NBN, MSH, BRIP 1 genes) and 60% mutation-negative patients. The mean patient age was 43.5 years in the carrier group and 44 years in the negative group. Carrier patients developed breast cancer with benign morphology (acoustic enhancement, soft elastography appearance) compared to non-carriers (p < 0.05). A tendency towards specific US features was observed for each mutation. BRCA1 carriers were associated with BC with microlobulated margins, hyperechoic rim, and soft elastography appearance (p < 0.05). Estrogen receptor (ER)-negative tumors were associated with BRCA1, TP53, and RAD mutations, while BRCA2 and CHEK2 were associated with ER-positive tumors. Conclusions: Patients with pathogenic mutations may exhibit BC with benign US features compared to negative, non-carrier patients. BRCA1, TP53, and RAD carriers account for up to one third of the ER tumors from the carrier group. Axillary US performed worse in depicting involved lymph nodes in carrier patients, compared to negative patients.

SERS liquid biopsy in breast cancer. What can we learn from SERS on serum and urine?

SERS analysis of biofluids, coupled with classification algorithms, has recently emerged as a candidate for point-of-care medical diagnosis. Nonetheless, despite the impressive results reported in the literature, there are still gaps in our knowledge of the biochemical information provided by the SERS analysis of biofluids. Therefore, by a critical assignment of the SERS bands, our work aims to provide a systematic analysis of the molecular information that can be achieved from the SERS analysis of serum and urine obtained from breast cancer patients and controls. Further, we compared the relative performance of five different machine learning algorithms for breast cancer and control samples classification based on the serum and urine SERS datasets, and found comparable classification accuracies in the range of 61-89%. This result is not surprising since both biofluids show striking similarities in their SERS spectra providing similar metabolic information, related to purine metabolites. Lastly, by carefully comparing the two datasets (i.e., serum and urine) we show that it is possible to link the misclassified samples to specific metabolic imbalances, such as carotenoid levels, or variations in the creatinine concentration.

Revisiting the Implications of Positive Germline Testing Results Using Multi-gene Panels in Breast Cancer Patients.

BACKGROUND/AIM: The use of multi-gene panels for germline testing in breast cancer enables the estimation of cancer risk and guides risk-reducing management options. The aim of this study was to present data that demonstrate the different levels of actionability for multi-gene panels used in genetic testing of breast cancer patients and their family members. MATERIALS AND METHODS: We performed an analysis in our clinical database to identify breast cancer patients undergoing genetic testing. We reviewed positive results in respect of risk estimation and management, cascade family testing, secondary findings and information for treatment decision-making. RESULTS: A total of 415 positive test reports were identified with 57.1%, 18.1%, 10.8% and 13.5% of individuals having pathogenic/likely pathogenic variants in high, moderate, low and with insufficient evidence for breast cancer risk genes, respectively. Six point seven percent of individuals were double heterozygotes. CONCLUSION: Germline findings in 92% of individuals are linked to evidence-based treatment information and risk estimates for predisposition to breast and/or other cancer types. The use of germline findings for treatment decision making expands the indication of genetic testing to include individuals that could benefit from targeted treatments.

The Role of US in Depicting Axillary Metastasis in High-Risk Breast Cancer Patients.

PURPOSE: The aim of this study is to evaluate the role of US in depicting axillary nodal disease in high-risk patients with and without pathogenic mutations. Methods: The retrospective study included consecutive high-risk breast cancer (BC) patients who underwent a multigene testing panel for hereditary cancers, pre-operative axillary US and breast/axillary surgery. The group was divided into patients with pathogenic mutations (PM group) and patients without PM. Statistical analyses were performed using GraphPad Prism by applying Chi-square and Fisher exact tests, with a reference p-value < 0.05 and a CI of 95%. Results: Out of 190 patients with BC, 96 (51%) were negative and 94 (49%) were positive for PM as follows: 28 (25.5%) BRCA1, 16 (17%) BRCA2, 15 (16%) CHECK2, 14 (14%) RAD Group, 7 (7%) PALB, 6 (6%) NBN, 3 (3%) TP53 and ATM and 2 (2%) BARD1. US was positive in 88 of the patients, 36 with PM and 52 without PM. US and surgery (≥N1 stage) were both positive in 31 (62%) of PM patients and 44 (88%) of patients without genetic changes. There were 19 (61%) false negative US examinations in the PM group and 6 (13%) in the group without genetic changes, respectively. If the US is positive, there is a 2.6 times greater risk of positive nodes in PM patients (p-value < 0.000, 95% CI = 4.2-37.9), and a 6.2 times greater risk of positive nodes in patients without genetic changes (p-value < 0.000, 95%CI = 8.4-37.4). In the PM group, US compared to surgery reached a sensitivity = 62, with PPV = 86 and NPV = 67. In the BRCA1/2 subgroup, there is 2.5 greater times risk of nodal disease if the US is positive (p-value = 0.001, 95%CI = 2.6-76). In patients without PM, US compared to surgery reached a sensitivity = 88, PPV = 84 and NPV = 86. Conclusion: US is more sensitive in depicting axillary nodal disease in high-risk patients without PM compared to PM patients. Furthermore, there are more false negative US examinations in PM patients, compared to surgery patients.

Lipidomic Signatures for Colorectal Cancer Diagnosis and Progression Using UPLC-QTOF-ESI+MS.

Metabolomics coupled with bioinformatics may identify relevant biomolecules such as putative biomarkers of specific metabolic pathways related to colorectal diagnosis, classification and prognosis. This study performed an integrated metabolomic profiling of blood serum from 25 colorectal cancer (CRC) cases previously classified (Stage I to IV) compared with 16 controls (disease-free, non-CRC patients), using high-performance liquid chromatography and mass spectrometry (UPLC-QTOF-ESI+ MS). More than 400 metabolites were separated and identified, then all data were processed by the advanced Metaboanalyst 5.0 online software, using multi- and univariate analysis, including specificity/sensitivity relationships (area under the curve (AUC) values), enrichment and pathway analysis, identifying the specific pathways affected by cancer progression in the different stages. Several sub-classes of lipids including phosphatidylglycerols (phosphatidylcholines (PCs), phosphatidylethanolamines (PEs) and PAs), fatty acids and sterol esters as well as ceramides confirmed the "lipogenic phenotype" specific to CRC development, namely the upregulated lipogenesis associated with tumor progression. Both multivariate and univariate bioinformatics confirmed the relevance of some putative lipid biomarkers to be responsible for the altered metabolic pathways in colorectal cancer.

T4 retroperitoneal liposarcoma. Challenges of big size sarcomas surgical treatment.

Our article presents some of the challenges of the surgical treatment of T4 (>15 cm) retroperitoneal liposarcomas (up to 65∕56∕30 cm, 25.5 kg) series of cases treated by the Department of Surgical Oncology, Prof. Dr. Ion Chiricuta Oncology Institute, Cluj-Napoca (IOCN), Romania, with illustrations, insisting on important blood vessels and nerves dissection and preservation and discussions of strategies with references to important articles from the last 10 years specialty literature. Challenges do not come only from intraoperative difficulties but also from establishing the right attitude from the extent of resection and oncological safety point of view, the role of the pathologist being very important because histological subtype and completeness of the resections are the most important prognostic factors for such tumors. Despite all today available aids in decision making, like nomograms or high-resolution imagery, sometimes this decision is to be taken intraoperative based on surgeon's expertise and skills. That is why is strongly advised that such cases to be treated in high-volume specialized tertiary centers of surgical oncology.

Endoscopic Ultrasound Elastography in the Assessment of Rectal Tumors: How Well Does It Work in Clinical Practice?

Endorectal ultrasound applications in the evaluation of rectal tumors could be a useful tool in achieving proper staging of rectal cancer. The purpose of this study was to compare the efficacy of rectal tumor staging by flexible endoscopic ultrasound (EUS) with real-time elastography (RTE) using the gold standard post-surgery histological analysis of the resected tissue as the control. The second aim of our research was to establish cutoff values for the EUS-RTE strain ratio corresponding to stages by independently comparing the stiffness values obtained with histology and EUS-RTE staging in order to minimize observation bias. We evaluated the records of 130 patients with a rectal tumor confirmed by biopsy. EUS was used in 70 patients, EUS-RTE-in the other 60. We found no statistically significant differences in staging accuracy when comparing EUS to EUS-RTE. Through a correspondence method between staging assessment and the EUS-RTE stain ratio, we identified cutoff intervals for T2, T3, and T4 staging that were nonoverlapping and proved to be statistically significant in terms of EUS-RTE values (significantly different ascending values from one interval to the other). We found that EUS-RTE offers slightly better, although not statistically significant sensitivity and specificity for T and N stage predictions compared to 2D EUS. Our results showed that EUS-RTE offers slightly higher sensitivity and specificity compared to EUS. Reliable cutoff intervals were found for strain rate elastography, previously available only for shear wave elastography (SWE) which is currently unavailable on any EUS system. Thus, these commonly available EUS-RTE systems can serve as a complementary tool in the staging of rectal tumors.

Clinical Utility of Functional RNA Analysis for the Reclassification of Splicing Gene Variants in Hereditary Cancer.

BACKGROUND: Classification of splicing variants (SVs) in genes associated with hereditary cancer is often challenging. The aim of this study was to investigate the occurrence of SVs in hereditary cancer genes and the clinical utility of RNA analysis. MATERIAL AND METHODS: 1518 individuals were tested for cancer predisposition, using a Next Generation Sequencing (NGS) panel of 36 genes. Splicing variant analysis was performed using RT-PCR and Sanger Sequencing. RESULTS: In total, 34 different SVs were identified, 53% of which were classified as pathogenic or likely pathogenic. The remaining 16 variants were initially classified as Variant of Uncertain Significance (VUS). RNA analysis was performed for 3 novel variants. CONCLUSION: The RNA analysis assisted in the reclassification of 20% of splicing variants from VUS to pathogenic. RNA analysis is essential in the case of uncharacterized splicing variants, for proper classification and personalized management of these patients.