Three-Year Patency Results following Endovascular Transvenous Femoropopliteal Bypass.

Background and Objectives: Peripheral artery disease is one of the most common vascular pathologies. There is an ongoing debate among specialists on whether open or endovascular revascularization is preferred in cases of complex superficial femoral artery (SFA) lesions. The purpose of this study was to assess patency results of a relatively new transvenous endovascular bypass device. This could add to existing evidence and aid in comparison between open and endovascular bypass. Materials and Methods: Patients with complex TASC-C and D SFA lesions who had indications for revascularization were identified. Prospective analysis of stent graft patency from 54 transvenous femoropopliteal bypass procedures was performed. Patency was assessed by Duplex ultrasound every six months. Kaplan-Meier analysis was performed to assess primary, primary-assisted, and secondary patency of transvenous bypass. Results: Following endovascular transvenous femoropopliteal bypass, 3-year graft primary, primary-assisted, and secondary patency was 43.8%, 66.3%, and 73.9%, respectively. Conclusions: Transvenous endovascular femoropopliteal bypass is a viable option for selected patients who lack adequate saphenous vein or have comorbidities that increase the risk of open femoropopliteal bypass. Strict post-operative follow-up is necessary to improve patency rates.

Pregnancy after breast cancer in BRCA1/2 mutation carriers.

BACKGROUND: Often young women affected with BRCA1/2 positive breast cancer have not finished or even not started their childbearing before the onset of the disease. The aim of our mini-review is to summarize state of art knowledge on pregnancy after breast cancer in BRCA1/2 carriers. METHODS: A broad review of the literature was conducted using MEDLINE (via PubMed) for relevant articles published. This review summarizes the impact of different cytotoxic agents on a fertility, fertility preservation, maternal and fetal prognosis after pregnancy in breast cancer survivors with BRCA1/2. CONCLUSION: According to the existing literature evidence pregnancy after therapy for breast cancer in BRCA carriers is safe for the mother and offspring, but patients' needs, oncofertility counseling and fertility-sparing strategy should be carefully planned before starting the cytotoxic treatment.

Ultrasound guided needle biopsy of axilla to evaluate nodal metastasis after preoperative systemic therapy in cohort of 106 breast cancers enriched with BRCA1/2 pathogenic variant carriers.

BACKGROUND: Aim of the study is to evaluate the role of ultrasound guided fine needle aspiration cytology (FNAC) in the restaging of node positive breast cancer after preoperative systemic therapy (PST). METHODS: From January 2016 - October 2020 106 node positive stage IIA-IIIC breast cancer cases undergoing PST were included in the study. 18 (17 %) were carriers of pathogenic variant in BRCA1/2. After PST restaging of axilla was performed with ultrasound and FNAC of the marked and/or the most suspicious axillary node. In 72/106 cases axilla conserving surgery and in 34/106 cases axillary lymph node dissection (ALND) was performed. RESULTS: False Positive Rate (FPR) of FNAC after PST in whole cohort and BRCA1/2 positive subgroup is 8 and 0 % and False Negative Rate (FNR) - 43 and 18 % respectively. Overall Sensitivity - 55 %, specificity- 93 %, accuracy 70 %. CONCLUSION: FNAC after PST has low FPR and is useful to predict residual axillary disease and to streamline surgical decision making regarding ALND both in BRCA1/2 positive and negative subgroups. FNR is high in overall cohort and FNAC alone are not able to predict ypCR and omission of further axillary surgery. However, FNAC performance in BRCA1/2 positive subgroup is more promising and further research with larger number of cases is necessary to confirm the results.

Stemness, Inflammation and Epithelial-Mesenchymal Transition in Colorectal Carcinoma: The Intricate Network.

In global cancer statistics, colorectal carcinoma (CRC) ranks third by incidence and second by mortality, causing 10.0% of new cancer cases and 9.4% of oncological deaths worldwide. Despite the development of screening programs and preventive measures, there are still high numbers of advanced cases. Multiple problems compromise the treatment of metastatic colorectal cancer, one of these being cancer stem cells-a minor fraction of pluripotent, self-renewing malignant cells capable of maintaining steady, low proliferation and exhibiting an intriguing arsenal of treatment resistance mechanisms. Currently, there is an increasing body of evidence for intricate associations between inflammation, epithelial-mesenchymal transition and cancer stem cells. In this review, we focus on inflammation and its role in CRC stemness development through epithelial-mesenchymal transition.

Evaluation and Predictive Factors of Complete Response in Rectal Cancer after Neoadjuvant Chemoradiation Therapy.

The response to neoadjuvant chemoradiation therapy is an important prognostic factor for locally advanced rectal cancer. Although the majority of the patients after neoadjuvant therapy are referred to following surgery, the clinical data show that complete clinical or pathological response is found in a significant proportion of the patients. Diagnostic accuracy of confirming the complete response has a crucial role in further management of a rectal cancer patient. As the rate of clinical complete response, unfortunately, is not always consistent with pathological complete response, accurate diagnostic parameters and predictive markers of tumor response may help to guide more personalized treatment strategies and identify potential candidates for nonoperative management more safely. The management of complete response demands interdisciplinary collaboration including oncologists, radiotherapists, radiologists, pathologists, endoscopists and surgeons, because the absence of a multidisciplinary approach may compromise the oncological outcome. Prediction and improvement of rectal cancer response to neoadjuvant therapy is still an active and challenging field of further research. This literature review is summarizing the main, currently known clinical information about the complete response that could be useful in case if encountering such condition in rectal cancer patients after neoadjuvant chemoradiation therapy, using as a source PubMed publications from 2010-2021 matching the search terms "rectal cancer", "neoadjuvant therapy" and "response".

Can We Predict Differentiated Thyroid Cancer Behavior? Role of Genetic and Molecular Markers.

Thyroid cancer is ranked in ninth place among all the newly diagnosed cancer cases in 2020. Differentiated thyroid cancer behavior can vary from indolent to extremely aggressive. Currently, predictions of cancer prognosis are mainly based on clinicopathological features, which are direct consequences of cell and tissue microenvironment alterations. These alterations include genetic changes, cell cycle disorders, estrogen receptor expression abnormalities, enhanced epithelial-mesenchymal transition, extracellular matrix degradation, increased hypoxia, and consecutive neovascularization. All these processes are represented by specific genetic and molecular markers, which can further predict thyroid cancer development, progression, and prognosis. In conclusion, evaluation of cancer genetic and molecular patterns, in addition to clinicopathological features, can contribute to the identification of patients with a potentially worse prognosis. It is essential since it plays a crucial role in decision-making regarding initial surgery, postoperative treatment, and follow-up. To date, there is a large diversity in methodologies used in different studies, frequently leading to contradictory results. To evaluate the true significance of predictive markers, more comparable studies should be conducted.

Contrast-Enhanced Ultrasound Qualitative and Quantitative Characteristics of Parathyroid Gland Lesions.

Background and Objectives: preoperative differentiation of enlarged parathyroid glands may be challenging in conventional B-mode ultrasound. The aim of our study was to analyse qualitative and quantitative characteristics of parathyroid gland lesions, using multiparametric ultrasound protocol-B-mode, Colour Doppler (CD), and contrast-enhanced ultrasound (CEUS)-and to evaluate correlation with morphology in patients with hyperparathyroidism (HPT). Materials and Methods: consecutive 75 patients with 88 parathyroid lesions and biochemically confirmed HPT prior to parathyroidectomy were enrolled in the prospective study. B-mode ultrasound, CD, and CEUS were performed with the subsequent qualitative and quantitative evaluation of acquired data. We used 1 mL or 2 mL of intravenous ultrasound contrast agent during the CEUS examination. Correlation with post-surgical morphology was evaluated. Results: seventy parathyroid adenomas were hypoechoic and well contoured with increased central echogenicity (44.3%), peripheral-central vascularization (47%), and polar feeding vessel (100%). Twelve hyperplasias presented with similar ultrasound appearance and were smaller in volume (p = 0.036). Hyperplasias had a tendency for homogenous, marked intense enhancement vs. peripherally enhanced adenomas with central wash-out in CEUS after quantitative analysis. No significant difference was observed in contrasting dynamics, regardless of contrast media volume use (1 mL vs. 2 mL). We achieved 90.9% sensitivity and 72.7% specificity, 93% positive predictive value (PPV), 87.3% negative predictive value (NPV), and 87.3% accuracy in the differentiation of parathyroid lesions prior to post-processing. In a quantitative lesion analysis, our sensitivity increased up to 98%, specificity 80%, PPV 98%, and NPV 80% with an accuracy of 96.4%. Conclusions: CEUS of parathyroid lesions shows potential in the differentiation of adenoma from hyperplasia, regardless of the amount of contrast media injected. The quantitative analysis improved the sensitivity and specificity of differentiation between parathyroid lesions. Hyperplasia was characterized by homogeneous enhancement, fast uptake, and homogeneous wash-out appearance; adenoma-by peripheral uptake, central wash-out, and reduced hemodynamics. The use of CEUS quantification methods are advised to improve the ultrasound diagnostic role in suspected parathyroid lesions.

IGNITE4: Results of a Phase 3, Randomized, Multicenter, Prospective Trial of Eravacycline vs Meropenem in the Treatment of Complicated Intraabdominal Infections.

BACKGROUND: Increasing antimicrobial resistance among pathogens that cause complicated intraabdominal infections (cIAIs) supports the development of new antimicrobials. Eravacycline, a novel member of the fluorocycline family, is active against multidrug-resistant bacteria including extended-spectrum ß-lactamase (ESBL) and carbapenem-resistant Enterobacteriaceae. METHODS: IGNITE4 was a prospective, randomized, double-blind trial. Hospitalized patients with cIAI received either eravacycline 1 mg/kg every 12 hours or meropenem 1 g every 8 hours intravenously for 4-14 days. The primary objective was to demonstrate statistical noninferiority (NI) in clinical cure rates at the test-of-cure visit (25-31 days from start of therapy) in the microbiological intent-to-treat population using a NI margin of 12.5%. Microbiological outcomes and safety were also evaluated. RESULTS: Eravacycline was noninferior to meropenem in the primary endpoint (177/195 [90.8%] vs 187/205 [91.2%]; difference, -0.5%; 95% confidence interval [CI], -6.3 to 5.3), exceeding the prespecified margin. Secondary endpoints included clinical cure rates in the modified ITT population (231/250 [92.4%] vs 228/249 [91.6%]; difference, 0.8; 95% CI, -4.1, 5.8) and the clinically evaluable population (218/225 [96.9%] vs 222/231 [96.1%]; (difference, 0.8; 95% CI -2.9, 4.5). In patients with ESBL-producing Enterobacteriaceae, clinical cure rates were 87.5% (14/16) and 84.6% (11/13) in the eravacycline and meropenem groups, respectively. Eravacycline had relatively low rates of adverse events for a drug of this class, with less than 5%, 4%, and 3% of patients experiencing nausea, vomiting, and diarrhea, respectively. CONCLUSIONS: Treatment with eravacycline was noninferior to meropenem in adult patients with cIAI, including infections caused by resistant pathogens. CLINICAL TRIALS REGISTRATION: NCT01844856.

Allelic variants of breast cancer susceptibility genes PALB2 and RECQL in the Latvian population.

BACKGROUND: Large-scale case control studies revealed a number of moderate risk - low frequency breast cancer alleles of the PALB2 and RECQL genes. Some of these were reported as founder variants of Central and Eastern Europe. Based on highly similar founder variant spectra of the BRCA1 in Poland and Latvia, we decided to test the frequency of other common variants of moderate breast cancer risk - c.509_510delGA (rs515726124) and c.172_175delTTGT (rs180177143) of the PALB2 gene and c.1667_1667+3delAGTA variant of the RECQL gene in a breast cancer case-control series from Latvia to better understand the role of genes in susceptibility to breast cancer and their clinical significance. METHODS: The case-control study was performed based on an unselected breast cancer case group of 2480 women and a control group, including 1240 voluntary, to our knowledge unrelated, female donors without reported oncological disease. RESULTS: The calculated frequency for c.509_510delGA of the PALB2 gene in the case group is 0.35 and 0.00% in the control group, with respective relative risk (RR) 7.18 (CI 95% 0.37-138.75; p = 0.19). As for the PALB2 c.172_175delTTGT variant, the frequency in the case group of our study is 0.04%. In the control group of our study all individuals were homozygous for the wild-type allele, which lead to calculated RR = 1.50 (CI 95% 0.06-36.83; p-value = 0.80). There were no carriers of the RECQL variant c.1667_1667+3delAGTA identified in our case group and 2 heterozygotes were identified in the control group. The calculated RR = 0.26 (CI 95% 0.01-5.33; p-value = 0.38). CONCLUSION: Results obtained for the PALB2 gene variants are able to supplement evidence on the allele frequency in breast cancer patients from the region of Central and Eastern Europe. Based on our results we cannot confirm the contribution of the RECQL variant c.1667_1667+3delAGTA allele to breast cancer development.

Molecular classification of diffuse gliomas.

In this study we assessed whether gliomas could be subdivided into different molecular subtypes by immunohistochemistry (IHC) reminiscent of those first described by Verhaak et al. in 2010 (classical, proneural, mesenchymal and neural). We also evaluated the prognostic significance of single molecular factors and searched for significant correlations between markers. In this study, we included 146 patients with glioblastomas (GBMs) and 26 with diffuse astrocytomas (DAs). The glioma samples were tested for PDGFRA, IDH1 R132H, CD44, p53, Ki-67, p21 and p27 expression. We found that gliomas could be subdivided into molecular subtypes by IHC. Fifty per cent of GBMs were of the proneural subtype, 18.5% of mesenchymal subtype and 31.5% were not otherwise classified. However, most of the DAs (92.3%) belonged to the proneural subtype. No prognostic role was found for the molecular subtypes, but predictive roles were noted. Both proneural and mesenchymal molecular subtypes showed a benefit from the addition of chemotherapy and radiotherapy; however, the mesenchymal subtype showed a greater response. Interestingly, the mesenchymal subtype did not receive any benefit from the addition of radiotherapy compared with palliative management and surgery alone. Regarding single molecular markers, only IDH1 R132H was found to have a prognostic role for GBMs. There was a trend towards better survival in tumours with lower PDGFRA expression (p = 0.066). In DAs, PDGFRA and Ki-67 expression had prognostic roles. The following statistically significant correlations were found in GBMs: Ki-67/p53, Ki-67/p27 and p53/PDGFRA; in DAs: p53/PDGFRA, CD44/PDGFRA, and p21/PDGFRA.

Pathogenic APC Variants in Latvian Familial Adenomatous Polyposis Patients.

Background and objectives: Familial adenomatous polyposis is one of the APC-associated polyposis conditions described as genetically predetermined colorectal polyposis syndrome with a variety of symptoms. The purpose of this study was to determine sequence variants of the APC gene in patients with familial adenomatous polyposis (FAP) phenotype and positive or negative family history. Materials and Methods: Eight families with defined criteria of adenomatous polyposis underwent molecular genetic testing. Coding regions and flanking intron regions of the APC gene were analyzed by Sanger sequencing. Results: Eight allelic variants of the APC gene coding sequence were detected. All allelic variants of the APC gene were predicted to be pathogenic based on criteria according to the "Joint Consensus Recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology" (2015), four of them c.1586_1587insAT, c.2336delT, c.3066_3067insGA, and c.4303_4304insC, were considered novel. Conclusions: The timely molecular genetic analysis of APC germline variants and standardized interpretation of the pathogenicity of novel allelic variants has a high impact on choice for treatment, cancer prevention, and family genetic counseling.

Body mass index and nipple preservation are major contributors to satisfaction and aesthetic outcome rates after implant-based immediate breast reconstruction.

INTRODUCTION: Immediate breast reconstructions (IBR) have become an integral part of modern breast cancer management. However, in a small breast unit the spectrum of methods used for IBR could be limited, which could result in poorer results in some cases. The aim of the study is to evaluate the patient satisfaction and aesthetic outcome results in a breast unit where only implant-based IBR were performed. MATERIAL AND METHODS: During 2009-2016, 64 cases of implant-based IBR were performed in the university hospital. 55 patients completed the questionnaire and 38 underwent evaluation by a plastic surgeon. 33 skin-sparing and 22 nipple-sparing mastectomies were included. The study included 30 two-stage expander/implant and 25 direct-toimplant IBR cases. RESULTS: Overall satisfaction was reported by 89% of respondents. 93% were satisfied with appearance in clothes and 82% with appearance in a bra. There was a significant difference with satisfaction in nude appearance between groups with a removed (3%) and a spared nipple (46%). The plastic surgeon evaluated overall outcome as satisfactory in 61% and poor in 39%. Spearman coefficient showed a moderate negative correlation between body mass index (BMI) and aesthetic outcome (p = 0.02), as well as BMI and volume differences between breasts (p = 0.03). Patients evaluated their breast symmetry as satisfactory in 55%, and the plastic surgeon concluded the same in 55% of 38 cases. CONCLUSIONS: Most of the patients were satisfied with the aesthetic outcome of IBR. Nipple preservation considerably improved satisfaction rates. However, implant-based IBR revealed suboptimal cosmetic results in the subset of cases with increased BMI and other IBR methods should be considered in those cases.

Platinum-based neoadjuvant chemotherapy in BRCA1-positive breast cancer: a retrospective cohort analysis and literature review.

BACKGROUND: There is increasing evidence of high platinum sensitivity in BRCA-associated breast cancer. However, evidence from randomized trials is lacking. The aim of this study was to analyze the results of platinum-based chemotherapy for BRCA1-positive breast cancer in a neoadjuvant setting. METHODS: A retrospective study was performed by obtaining information from patient files. The results were compared with the available data from a literature review. RESULTS: Twelve female patients with BRCA1 gene mutations who had stage I to III breast cancers were eligible for evaluation. They received platinum-based neoadjuvant chemotherapy between 2011 and 2016. Eleven patients received a combination of cisplatin and doxorubicin, and one patient received carboplatin and docetaxel. All patients underwent mastectomy after chemotherapy. Ten patients (83%) achieved pathological complete remission (pCR). The observed pCR rate was comparable to existing results found in similar studies. CONCLUSION: The results of the study confirm the high pCR rate in BRCA1-positive breast cancer after platinum-based neoadjuvant chemotherapy. Larger randomized studies and longer follow-up times are necessary to evaluate the role of platinum-based therapies in BRCA1-positive breast cancer.

An Effect of Culture Media on Epithelial Differentiation Markers in Breast Cancer Cell Lines MCF7, MDA-MB-436 and SkBr3.

Background and objectives: Cell culture is one of the mainstays in the research of breast cancer biology, although the extent to which this approach allows to preserve the original characteristics of originating tumor and implications of cell culture findings to real life situations have been widely debated in the literature. The aim of this study was to determine the role of three cell culture media on transcriptional expression of breast cancer markers in three breast cancer reference cell lines (MCF7, SkBr3 and MDA-MB-436). Materials and methods: Cell lines were conditioned in three studied media (all containing 5% fetal bovine serum (FBS) + hormones/growth factors; different composition of basal media) for four passages. Population growth was characterized by cumulative population doubling levels, average generation time, cell yield and viability at the fourth passage. Transcriptional expression of breast cancer differentiation markers and regulatory transcriptional programs was measured by qPCR. Results: Differences in the composition of growth media significantly influenced the growth of studied cell lines and the expression of mammary lineage governing transcriptional programs and luminal/basal markers. Effects of media on transcriptional expression were more pronounced in luminal cell lines (MCF7, SkBr3), than in the basal cell line (MDA-MB-436). Changes in growth media in terms of supplementation and basal medium delayed growth of cells, but improved cell yields. Conclusions: The expression of breast cancer cell differentiation phenotypic markers depends on the composition of cell growth medium, therefore cell culture as a tool in phenotypic studies should be used considering this effect. The findings of such studies should always be interpreted with caution. The formulation of cell growth media has greater effect on the expression of phenotypic markers in luminal, rather than basal cell lines. Media containing mitogens and higher vitamin content improved efficacy of cell culture in terms of cell yields, although greatly increased growth times.

Evaluation of malignant parathyroid tumours in two European cohorts of patients with sporadic primary hyperparathyroidism.

PURPOSE: Parathyroid carcinoma (PC) is remarkable for its rare occurrence and challenging diagnostics. PC accounts for 0.1-5 % cases of primary hyperparathyroidism (PHPT). The differentiation from benign tumours is difficult even by morphological criteria. To address these issues, we assessed the PC frequency in two separate European PHPT cohorts and evaluated the demographic, clinical, morphological and molecular background. METHODS: A retrospective study was carried out, using continuously maintained database (2005-2014) of PHPT patients from two tertiary referral university hospitals in Europe. The demographic, clinical data and frequency of PC among surgically treated PHPT was detected. Immunohistochemistry (IHC) was performed to detect parafibromin, representing protein product of HRPT2 gene and proliferation marker Ki-67. RESULTS: Both PHPT cohorts were characterised by close mean age values (58.6 and 58.0 years) and female predominance. The frequency of PC differed significantly between the cohorts: 2.1 vs. 0.3 %; p = 0.004. PC was characterised by invariable complete loss of parafibromin contrasting with parathyroid adenomas. The proliferation fraction was similar in both PC cohorts (10.6 and 11.0 %). PC showed significantly higher proliferation fraction than typical parathyroid adenomas (1.6 %), atypical adenomas (1.6 %) or adenomas featuring focal loss of parafibromin (2.2 %). CONCLUSIONS: PC frequency can range significantly between the two European cohorts. The differences can be attributable to selection bias of patients referred for surgery and are not caused by discordant definition of malignant parathyroid histology. Diffuse loss of parafibromin and increased proliferation fraction by Ki-67 are valuable adjuncts in PC diagnostics due to significant differences with various clinical and morphological subtypes of adenoma.

High expression of miR-214 is associated with a worse disease-specific survival of the triple-negative breast cancer patients.

BACKGROUND: Hereditary triple-negative breast cancer patients have better recurrence-free survival than triple-negative sporadic ones. High expression of some of the miRNAs is related to worse overall and disease-free survival of triple-negative breast cancer patients. The attempt to associate expression level of some miRNA in triple-negative hereditary and sporadic breast cancers to disease specific survival was performed in this study. MATERIAL AND METHODS: Study group was made of 18 triple-negative breast cancer patients harboring the BRCA1 gene mutations and 32 triple-negative sporadic breast cancer patients. Quantitative amount of mir-10b, mir-21, mir-29a, mir-31, and mir-214 by real-time PCR was assessed. The disease-specific survival in relation of high and low levels of some of the miRNAs was analyzed using Log-rank (Mantel-Cox) test. RESULTS: MiR-214 showed significantly higher expression level in sporadic tissues than in hereditary ones (p = 0.0005). Triple-negative breast cancer patients with high level of miR-214 showed significantly worse disease-specific survival than patients with low level (p = 0.0314). CONCLUSIONS: Our finding suggests that miR-214 possibly could be used as a potential prognostic biomarker for triple-negative breast cancer patients.

Morphological and immunohistochemical profile of pancreatic neuroendocrine neoplasms.

The study represents a comprehensive retrospective morphological and immunohistochemical profiling of pancreatic neuroendocrine neoplasms (PNENs) in order to reveal the associations between morphological and molecular parameters. The local tumour spread (T), presence of metastases in regional lymph nodes (N) and distant organs (M), tumour grade (G) and resection line status (R) by pathology findings (pTNMGR), mitotic activity, perineural, vascular and lymphatic invasion were assessed in 16 surgically resected PNENs. By immunohistochemistry, expression of Ki-67, p53, p27, p21, cyclin D1, Bcl-2, E-cadherin, CD44, vimentin, cyclooxygenase 2 (COX-2), microvascular density, and cytokeratin (CK) spectrum, along with neuroendocrine, intestinal and squamous markers were detected. Descriptive statistics, Chi-square test, Spearman's rank correlation, Mann-Whitney and Kruskal-Wallis methods were applied; p<0.05 was considered significant. Ki-67, CK19, p63, vimentin and COX-2 were significantly up-regulated in PNENs in comparison to benign pancreatic islets. A complex network of morphological and molecular associations was identified. Ki-67 correlated with PNEN size (p=0.022), the World Health Organization 2004 and 2010 classification grades (p=0.021 and p=0.002), stage (p=0.028) and mitotic count (p=0.007) but among molecular markers--with CK19 (p=0.033) and vimentin (p=0.045). CK19 was significantly up-regulated in PNENs, having higher pT (p=0.018), pR (p=0.025), vascular (p=0.020), perineural (p=0.026) and lymphatic invasion (p=0.043). In conclusion, proliferation activity (by Ki-67), E-cadherin, vimentin and CK19 are important molecular characteristics of PNENs due to significant associations with morphological tumour characteristics, pTNMGR and invasive growth.

Epidemiological analysis of hereditary endometrial cancer in a large study population.

AIMS: To determine the prevalence of hereditary endometrial cancer and the clinical and molecular characteristics of hereditary endometrial cancer patients. METHODS: Standardized oncological family histories were collected from 704 consecutive patients with endometrial cancer from January 2006 to April 2012 and analyzed using internationally approved and modified diagnostic criteria based on the Amsterdam I and II criteria. Blood samples were collected from 648 patients. Paraffin embedded tissues for immunohistochemical examination were gathered from 109 patients. All patients were split into two main groups corresponding to hereditary and sporadic endometrial cancer. RESULTS: The prevalence of hereditary endometrial cancer was established as 2.7 % (95 % CI 1.7-4.2 %) or 19/704 patients. 15/19 (78.9 %; 95 % CI 56.7-91.5 %) patients were diagnosed in stage I. Grade 2 tumors were the most common ones with 11/19 (57.9 %; 95 % CI 36.3-76.9 %) patients. In the MLH1 gene, two patients were carrying the missense mutations P640S (rs63749792) and I219V (rs1799977) each. In the MSH2 gene, one had the splice site mutation IV5+3A>T while another had the missense mutation G322D (rs4987188). In the MSH6 gene, two were carrying the frameshift mutations 2150TCAG (rs63750159) and 1050delC each. No clinically putative significant mutations were found in two patients. CONCLUSIONS: No significant survival, stage and grade of differentiation differences were observed between the hereditary group and the sporadic group. Clinical and molecular investigations promote an earlier diagnosis of endometrial cancer in families where at least three first-degree relatives have endometrial cancer.

Prostate cancer trends in Latvia during 1990-2012: incidence, prevalence, mortality, and survival rates.

BACKGROUND AND OBJECTIVE: Prostate cancer (PCa) is one of the most common form of cancer in males worldwide. One of the highest PCa-related mortality rates in the world is observed in Latvia. MATERIALS AND METHODS: Our study included male patients diagnosed with PCa between 1990 and 2012. We analyzed incidence, prevalence and mortality trends using joinpoint analysis. Kaplan-Meier analysis was performed for 5-, 10-, 15- and 20-year overall survival and cancer-specific survival rates. RESULTS: A total of 14,083PCa patients with a mean age of initial PCa diagnosis being 70.1 (SD 8.6) was registered. The standardized incidence rates (per 100,000) increased from 18.9 in 1990 to 74.7 in 2012, while the standardized prevalence rates (per 100,000) increased from 69.9 in 1990 to 437.6 in 2012. Standardized PCa mortality rates (per 100,000) also rose from 13.2 in 1990 to 27.2 in 2006 followed by statistically insignificant decrease continuing up to 2012. The mean 5-year cancer-specific survival rates increased from 43.6% in 1990 to 70.7% in 2007, and the mean 10-year cancer-specific survival rates from 32.9% in 1990 to 40.5% in 2001. CONCLUSIONS: This study revealed that the incidence, prevalence and mortality rates increased between 1990 and 2012, and although the 5- and 10-year overall and cancer-specific survival rates improved over the reviewed period they still needed to get better.

BRCA1/2 mutation screening in high-risk breast/ovarian cancer families and sporadic cancer patient surveilling for hidden high-risk families.

BACKGROUND: The estimated ratio of hereditary breast/ovarian cancer (HBOC) based on family history is 1.5% in Latvia. This is significantly lower than the European average of 5-10%. Molecular markers like mutations and SNPs can help distinguish HBOC patients in the sporadic breast and ovarian cancer group. METHODS: 50 patients diagnosed with HBOC in the Latvian Cancer Registry from January 2005 to December 2008 were screened for BRCA1 founder mutation-negatives and subjected to targeted resequencing of BRCA1 and BRCA2 genes. The newly found mutations were screened for in the breast and ovarian cancer group of 1075 patients by Real Time-PCR/HRM analysis and RFLP. RESULTS: Four BRCA2 mutations including three novel BRCA2 frameshift mutations and one previously known BRCA2 frameshift mutation and one BRCA1 splicing mutation were identified. Two of the BRCA2 mutations were found in a group of consecutive breast cancer patients with a frequency of 0.51% and 0.38%. CONCLUSIONS: Molecular screening of sequential cancer patients is an important tool to identify HBOC families.