RESPONSE TO NEOADJUVANT THERAPY AND LONG-TERM OUTCOME IN PATIENTS WITH TRIPLE NEGATIVE BREAST CANCER

Background. Triple negative breast cancer (TNBC) is defined by thelack of estrogen receptors (ER), progesterone receptors (PR) and humanepidermal growth factor receptor 2 (HER-2) expression. In this study weinvestigated response to neoadjuvant chemotherapy in TNBC patients and itsimpact on disease free (DFS) and overall survival (OS).Patients and methods. We identified 134 patients with stage I-III TNBCtreated at Riga East University Hospital between 2009-2012. 48 patients withTNBC received neoadjuvant chemotherapy. Correlation of clinical andpathological parameters with pathologic complete response (pCR) rate,disease-free and overall survival measurements and organ specific relapserates were analysed.Results. 48 patients with stage IIB-IIIC TNBC were included, 17 patientsreceived anthracycline based, 31 patients anthracycline and taxane basedneoadjuvant chemotherapy. 8 patients (16%) had pCR, 38 patients hadincomplete response, 2 patients had disease progression during neoadjuvantchemotherapy. pCR correlates with primary tumor size, but not with otherclinical and pathological factors. At a median follow-up of 30 months, 100%patients who reached pCR were disease-free versus 55% in those withoutpCR (p=0.017). Overall survival was 100% in patients who had pCR versus50% in those without pCR (p=0.020). 2 patients are alive after diseaserecurrence, 20 patients died. The most common sites of disease recurrencewere brain, lung and liver.Conclusions. Patients with TNBC who have a pCR in the breast and axillarynodes have a significantly improved disease-free and overall survival ratecompared with patients with residual disease after neoadjuvantchemotherapy

Aerobic vaginitis - underestimated risk factor for cervical intraepithelial neoplasia

Funding Information: Funding: Grant for this project (RSU ZP 04/2013, code 035, Investigation of clinical and molecular features of cervical cancer to improve early diagnosis and treatment strategy) was provided by Riga Stradins university. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.The aim of this study is to analyse the association between vaginal microbiota and the histological finding of CIN. From July 2016 until June 2017, we included 110 consecutive patients with abnormal cervical cytology results referred for colposcopy to Riga East Clinical University Hospital Outpatient department in the study group. 118 women without cervical pathology were chosen as controls. Certified colposcopists performed interviews, gynaecological examinations and colposcopies for all participants. Material from the upper vaginal fornix was taken for pH measurement and wet-mount microscopy. Cervical biopsy samples were taken from all subjects in the study group and in case of a visual suspicion for CIN in the control group. Cervical pathology was more often associated with smoking (34.6% vs. 11.0%, p <0.0001), low education level (47.2% vs. 25.5%, p = 0.001), increased vaginal pH (48.2% vs. 25.4%, p < 0.0001), abnormal vaginal microbiota (50% vs. 31.4%, p = 0.004) and moderate to severe aerobic vaginitis (msAV) (13.6% vs. 5.9%, p = 0.049) compared to controls. The most important independent risk factors associated with CIN2+ were smoking (OR 3.04 (95% CI 1.37–6.76), p = 0.006) and msAV (OR 3.18 (95% CI 1.13–8.93), p = 0.028). Bacterial vaginosis (BV) was found more often in CIN1 patients (8/31, 25.8%, p = 0.009) compared with healthy controls (8/118, 6.8%), or CIN2+ cases (8/79, 10.1%). In the current study msAV and smoking were the most significant factors in the development of CIN in HPV-infected women, especially high grade CIN. We suggest that AV changes are probably more important than the presence of BV in the pathogenesis of CIN and progression to cervix cancer and should not be ignored during the evaluation of the vaginal microbiota.publishersversionPeer reviewe

Comprehensive characterization of RNA cargo of extracellular vesicles in breast cancer patients undergoing neoadjuvant chemotherapy

Funding Information: This work was funded by the ERDF project No. 1.1.1.1/18/A/084. Publisher Copyright: Copyright © 2022 Sadovska, Zayakin, Eglītis, Endzeliņš, Radoviča-Spalviņa, Avotiņa, Auders, Keiša, Liepniece-Karele, Leja, Eglītis and Linē.Extracellular vesicles (EVs) are g7aining increased attention as carriers of cancer-derived molecules for liquid biopsies. Here, we studied the dynamics of EV levels in the plasma of breast cancer (BC) patients undergoing neoadjuvant chemotherapy (NAC) and explored the relevance of their RNA cargo for the prediction of patients’ response to the therapy. EVs were isolated from serial blood samples collected at the time of diagnosis, at the end of NAC, and 7 days, 6, and 12 months after the surgery from 32 patients with locally advanced BC, and 30 cancer-free healthy controls (HCs) and quantified by nanoparticle tracking analysis. The pre-treatment levels of EVs in BC patients were higher than in HCs, significantly increased during the NAC and surgery, and decreased to the levels found in HCs 6 months after surgery, thus showing that a substantial fraction of plasma EVs in BC patients are produced due to the disease processes and treatment. RNA sequencing analysis revealed that the changes in the EV levels were associated with the alterations in the proportions of various RNA biotypes in EVs. To search for RNA biomarkers that predict response to the NAC, patients were dichotomized as responders and non-responders based on Miller-Payne grades and differential expression analyses were carried out between responders and non-responders, and HCs. This resulted in the identification of 6 miRNAs, 4 lncRNAs, and 1 snoRNA that had significantly higher levels in EVs from non-responders than responders at the time of diagnosis and throughout the NAC, and significantly lower levels in HCs, thus representing biomarkers for the prediction of response to NAC at the time of diagnosis. In addition, we found 14 RNAs representing piRNA, miRNA, lncRNA, snoRNA, and snRNA biotypes that were induced by NAC in non-responders and 2 snoRNAs and 1 piRNA that were induced by NAC in patients with early disease progression, thus warranting further functional studies on their role in chemoresistance and metastasis.publishersversionPeer reviewe

The diagnostic value of anti-parietal cell and intrinsic factor antibodies, pepsinogens, and gastrin-17 in corpus-restricted atrophic gastritis

Raksta tekstā kļuda: afilācijai "Digestive Diseases Centre GASTRO Ltd", norādīta atrašanas vieta: Hong Kong, ChinapublishersversionPeer reviewe

Assessment of Serum Pepsinogens with and without Co-Testing with Gastrin-17 in Gastric Cancer Risk Assessment—Results from the GISTAR Pilot Study

Introduction-Serum pepsinogen tests for gastric cancer screening have been debated for decades. We assessed the performance of two pepsinogen assays with or without gastrin-17 for the detection of different precancerous lesions alone or as a composite endpoint in a Latvian cohort. Methods-Within the intervention arm of the GISTAR population-based study, participants with abnormal pepsinogen values by ELISA or latex-agglutination tests, or abnormal gastrin-17 by ELISA and a subset of subjects with all normal biomarker values were referred for upper endoscopy with biopsies. Performance of biomarkers, corrected by verification bias, to detect five composite outcomes based on atrophy, intestinal metaplasia, dysplasia or cancer was explored. Results-Data from 1045 subjects were analysed, of those 273 with normal biomarker results. Both pepsinogen assays showed high specificity (>93%) but poor sensitivity (range: 18.4-31.1%) that slightly improved when lesions were restricted to corpus location (40.5%) but decreased when dysplasia and prevalent cancer cases were included (23.8%). Adding gastrin-17 detection, sensitivity reached 33-45% while specificity decreased (range: 61.1-62%) and referral rate for upper endoscopy increased to 38.6%. Conclusions-Low sensitivity of pepsinogen assays is a limiting factor for their use in population-based primary gastric cancer screening, however their high specificity could be useful for triage

Who Could Be Blamed in the Case of Discrepant Histology and Serology Results for Helicobacter pylori Detection?

Funding Information: Acknowledgments: The study was funded in part by the Fundamental and Applied Research Project Program in Latvia, project No. lzp-2018/1-0135 “Research on implementation of a set of measures for prevention of gastric cancer mortality by eradication H. pylori and timely recognition of precancerous lesions”. We acknowledge the entire GISTAR study team as well as the infrastructure provided by the Digestive Diseases Centre GASTRO for endoscopy and the Academic Histology Laboratory for pathology infrastructures. Our acknowledgements also to Biohit Oyj, Finland, for their support with laboratory reagents. Funding Information: Funding: The work is funded by ERDF (European Regional Development Fund) within the frame-work of 2nd part of measure 1.1.1.1. ‘Practical Studies’, project ID Nr. 1.1.1.1/18/A/184. Funding Information: The work is funded by ERDF (European Regional Development Fund) within the framework of 2nd part of measure 1.1.1.1. ?Practical Studies?, project ID Nr. 1.1.1.1/18/A/184. Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.Background. Discrepancies between histology and serology results for Helicobacter pylori detection could be caused by a variety of factors, including a biopsy sampling error, expertise of the pathologist, natural loss of infection due to advanced atrophy, or a false-positive serology in the case of a previous infection, since antibodies may be present in blood following recovery from the infection. Aims. To identify true H. pylori-positive individuals in discrepant cases by serology and histology using real time polymerase chain reaction (RT-PCR) as a gold standard. Methods. Study subjects with discrepant histology and serology results were selected from the GISTAR pilot study data base in Latvia. Subjects having received previous H. pylori eradication therapy or reporting use of proton pump inhibitors, antibacterial medications, or bismuth containing drugs one month prior to upper endoscopy were excluded. We compared the discrepant cases to the corresponding results of RT-PCR performed on gastric biopsies. Results. In total, 97 individuals with discrepant results were identified: 81 subjects were serology-positive/histology-negative, while 16 were serologynegative/histology-positive. Among the serology-positive/histology-negative cases, 64/81 (79.0%) were false-positives by serology and, for the majority, inflammation was absent in all biopsies, while, in the serology-negative/histology-positive group, only 6.2% were proven false-positives by histology. Conclusions. Among this high H. pylori prevalent, middle-aged population, the majority of discrepant cases between serology and histology were due to false positive-serology, rather than false-negative histology. This confirms the available evidence that the choice of treatment should not be based solely on the serological results, but also after excluding previous, self-reported eradication therapy.publishersversionPeer reviewe

Reproducibility and predictive value of scoring stromal tumour infiltrating lymphocytes in triple-negative breast cancer : a multi-institutional study

Several studies have demonstrated a prognostic role for stromal tumour infiltrating lymphocytes (sTILs) in triple-negative breast cancer (TNBC). The reproducibility of scoring sTILs is variable with potentially excellent concordance being achievable using a software tool. We examined agreement between breast pathologists across Europe scoring sTILs on H&E-stained sections without software, an approach that is easily applied in clinical practice. The association between sTILs and response to anthracycline-taxane NACT was also examined. Pathologists from the European Working Group for Breast Screening Pathology scored sTILs in 84 slides from 75 TNBCs using the immune-oncology biomarker working group guidance in two circulations. There were 16 participants in the first and 19 in the second circulation. Moderate agreement was achieved for absolute sTILs scores (intraclass correlation coefficient (ICC) = 0.683, 95% CI 0.601-0.767, p-value = 25% (kappa = 0.53) and for LPBC (kappa = 0.49), but poor for sTILs as 10% increments (kappa = 0.24). Increasing sTILs was significantly associated with an increased likelihood of a pathological complete response (pCR) on multivariable analysis. Increasing sTILs in TNBCs improves the likelihood of a pCR. However, inter-observer agreement is such that H&E-based assessment is not sufficiently reproducible for clinical application. Other methodologies should be explored, but may be at the cost of ease of application.Non peer reviewe