Browsing by Author "Liepniece-Karele, Inta"

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    Aerobic vaginitis - underestimated risk factor for cervical intraepithelial neoplasia
    (2021-01-09) Plisko, Olga; Zodzika, Jana; Jermakova, Irina; Pcolkina, Kristine; Prusakevica, Amanda; Liepniece-Karele, Inta; Donders, Gilbert G.G.; Rezeberga, Dace; Department of Obstetrics and Gynaecology
    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.
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    Assessment of Serum Pepsinogens with and without Co-Testing with Gastrin-17 in Gastric Cancer Risk Assessment—Results from the GISTAR Pilot Study
    (2022-07) Robles, Claudia; Rudzite, Dace; Polaka, Inese; Sjomina, Olga; Tzivian, Lilian; Kikuste, Ilze; Tolmanis, Ivars; Vanags, Aigars; Isajevs, Sergejs; Liepniece-Karele, Inta; Razuka-Ebela, Danute; Parshutin, Sergej; Murillo, Raul; Herrero, Rolando; Young Park, Jin; Leja, Marcis
    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.
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    Benign Notochordal Cell Tumours : Case Report and Literature Review
    (2024-07) Grabovska, Dagnija; Štrumfa, Ilze; Ositis, Janis; Liepniece-Karele, Inta; Balodis, Arturs; Department of Pathology; Department of Radiology
    Background: Benign notochordal cell tumours (BNCTs) represent a rare entity within the spectrum of bone neoplasms, which typically arise in the axial skeleton. Although these tumours are often benign, their diagnosis and management pose significant challenges due to their histological similarity to more aggressive lesions, such as chordomas. Understanding of the clinical behaviour, diagnostic nuances, and optimal management strategies for BNCTs continues to evolve. Case Report: Benign notochordal cell tumours of the vertebra are usually asymptomatic and identified on imaging and should be distinguished from chordomas, which has a more aggressive clinical course. This report describes a 15-year-old girl with lumbosacral pain and a diagnosis of a benign notochordal cell tumour, which affects a large part of the S1 vertebra in the lumbar spine, highlighting the diagnostic challenges encountered, the role of radiological and histological investigations, and the ultimate determination of the benign nature of the tumour. Conclusions: This report highlights the approach taken for the diagnosis of a benign notochordal cell tumour of the vertebra and the importance of excluding differential diagnoses. By exploring the intricacies of this case, we contribute to the growing body of literature surrounding BNCTs, with the aim of improving clinical awareness and management strategies for this uncommon bone tumour.
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    Breath Volatile Organic Compounds in Surveillance of Gastric Cancer Patients following Radical Surgical Management
    (2023-05) Škapars, Roberts; Gašenko, Evita; Broza, Yoav Y.; Sīviņš, Armands; Poļaka, Inese; Bogdanova, Inga; Pčolkins, Andrejs; Veliks, Viktors; Folkmanis, Valdis; Lesčinska, Anna; Liepniece-Karele, Inta; Haick, Hossam; Rumba-Rozenfelde, Ingrīda; Leja, Mārcis
    As of today, there is a lack of a perfect non-invasive test for the surveillance of patients for potential relapse following curative treatment. Breath volatile organic compounds (VOCs) have been demonstrated to be an accurate diagnostic tool for gastric cancer (GC) detection; here, we aimed to prove the yield of the markers in surveillance, i.e., following curative surgical management. Patients were sampled in regular intervals before and within 3 years following curative surgery for GC; gas chromatography-mass spectrometry (GC-MS) and nanosensor technologies were used for the VOC assessment. GC-MS measurements revealed a single VOC (14b-Pregnane) that significantly decreased at 12 months, and three VOCs (Isochiapin B, Dotriacontane, Threitol, 2-O-octyl-) that decreased at 18 months following surgery. The nanomaterial-based sensors S9 and S14 revealed changes in the breath VOC content 9 months after surgery. Our study results confirm the cancer origin of the particular VOCs, as well as suggest the value of breath VOC testing for cancer patient surveillance, either during the treatment phase or thereafter, for potential relapse.
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    Comprehensive characterization of RNA cargo of extracellular vesicles in breast cancer patients undergoing neoadjuvant chemotherapy
    (2022-10-26) Sadovska, Lilite; Zayakin, Pawel; Eglītis, Kristaps; Endzeliņš, Edgars; Radoviča-Spalviņa, Ilze; Avotiņa, Elīza; Auders, Jānis; Keiša, Laura; Liepniece-Karele, Inta; Leja, Mārcis; Eglītis, Jānis; Linē, Aija; Department of Pathology
    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.
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    The diagnostic value of anti-parietal cell and intrinsic factor antibodies, pepsinogens, and gastrin-17 in corpus-restricted atrophic gastritis
    (2022-11) Kriķe, Petra; Shums, Zakera; Polaka, Inese; Kikuste, Ilze; Vanags, Aigars; Tolmanis, Ivars; Isajevs, Sergejs; Liepniece-Karele, Inta; Santare, Daiga; Tzivian, Lilian; Rudzite, Dace; Song, Minkyo; Camargo, Maria Constanza; Norman, Gary; Leja, Mārcis; Department of Pathology
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    Extracellular Vesicles—A Source of RNA Biomarkers for the Detection of Breast Cancer in Liquid Biopsies
    (2023-09) Zayakin, Pawel; Sadovska, Lilite; Eglītis, Kristaps; Romanchikova, Nadezhda; Radoviča-Spalviņa, Ilze; Endzeliņš, Edgars; Liepniece-Karele, Inta; Eglītis, Jānis; Linē, Aija; Department of Pathology
    Over the past decade, extracellular vesicles (EVs) have emerged as a promising source of cancer-derived RNAs for liquid biopsies. However, blood contains a pool of heterogeneous EVs released by a variety of cell types, making the identification of cancer RNA biomarkers challenging. Here, we performed deep sequencing of plasma EV RNA cargo in 32 patients with locally advanced breast cancer (BC) at diagnosis and 7 days after breast surgery and in 30 cancer-free healthy controls (HCs). To identify BC-derived RNA biomarkers, we searched for RNAs that had higher levels in BC EVs at the time of diagnosis compared with HCs and decreased after surgery. Data analysis showed that the fractions of miRNAs, snRNAs, snoRNAs, and tRFs were increased, but the fraction of lncRNAs was decreased in BC EVs as compared to HCs. BC-derived biomarker candidates were identified across various RNA biotypes. Considered individually, they had very high specificity but moderate sensitivity for the detection of BC, whereas a biomarker model composed of eight RNAs: SNORD3H, SNORD1C, SNORA74D, miR-224-5p, piR-32949, lnc-IFT-122-2, lnc-C9orf50-4, and lnc-FAM122C-3 was able to distinguish BC from HC EVs with an AUC of 0.902 (95% CI = 0.872–0.931, p = 3.4 × 10−9) in leave-one-out cross-validation. Furthermore, a number of RNA biomarkers were correlated with the ER and HER2 expression and additional biomarker models were created to predict hormone receptor and HER2 status. Overall, this study demonstrated that the RNA composition of plasma EVs is altered in BC patients and that they contain cancer-derived RNA biomarkers that can be used for BC detection and monitoring using liquid biopsies.
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    Intra-tumour heterogeneity is one of the main sources of inter-observer variation in scoring stromal tumour infiltrating lymphocytes in triple negative breast cancer
    (2021-08-31) Kilmartin, Darren; O’Loughlin, Mark; Andreu, Xavier; Bagó-Horváth, Zsuzsanna; Bianchi, Simonetta; Chmielik, Ewa; Cserni, Gábor; Figueiredo, Paulo; Floris, Giuseppe; Foschini, Maria Pia; Kovács, Anikó; Heikkilä, Päivi; Kulka, Janina; Laenkholm, Anne Vibeke; Liepniece-Karele, Inta; Marchiò, Caterina; Provenzano, Elena; Regitnig, Peter; Reiner, Angelika; Ryška, Aleš; Sapino, Anna; Stovgaard, Elisabeth Specht; Quinn, Cecily; Zolota, Vasiliki; Webber, Mark; Roshan, Davood; Glynn, Sharon A.; Callagy, Grace; Department of Pathology
    Stromal tumour infiltrating lymphocytes (sTILs) are a strong prognostic marker in triple negative breast cancer (TNBC). Consistency scoring sTILs is good and was excellent when an internet-based scoring aid developed by the TIL-WG was used to score cases in a reproducibility study. This study aimed to evaluate the reproducibility of sTILs assessment using this scoring aid in cases from routine practice and to explore the potential of the tool to overcome variability in scoring. Twenty-three breast pathologists scored sTILs in digitized slides of 49 TNBC biopsies using the scoring aid. Subsequently, fields of view (FOV) from each case were selected by one pathologist and scored by the group using the tool. Inter-observer agreement was good for absolute sTILs (ICC 0.634, 95% CI 0.539–0.735, p < 0.001) but was poor to fair using binary cutpoints. sTILs heterogeneity was the main contributor to disagreement. When pathologists scored the same FOV from each case, inter-observer agreement was excellent for absolute sTILs (ICC 0.798, 95% CI 0.727–0.864, p < 0.001) and good for the 20% (ICC 0.657, 95% CI 0.561–0.756, p < 0.001) and 40% (ICC 0.644, 95% CI 0.546–0.745, p < 0.001) cutpoints. However, there was a wide range of scores for many cases. Reproducibility scoring sTILs is good when the scoring aid is used. Heterogeneity is the main contributor to variance and will need to be overcome for analytic validity to be achieved.
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    Reproducibility and predictive value of scoring stromal tumour infiltrating lymphocytes in triple-negative breast cancer : a multi-institutional study
    (2018-08-01) O’Loughlin, Mark; Andreu, Xavier; Bianchi, Simonetta; Chemielik, Ewa; Cordoba, Alicia; Cserni, Gábor; Figueiredo, Paulo; Floris, Giuseppe; Foschini, Maria P.; Heikkilä, Päivi; Kulka, Janina; Liepniece-Karele, Inta; Regitnig, Peter; Reiner, Angelika; Ryska, Ales; Sapino, Anna; Shalaby, Aliaa; Stovgaard, Elisabeth Specht; Quinn, Cecily; Walsh, Elaine M.; Zolota, Vicky; Glynn, Sharon A.; Callagy, Grace
    Background: 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. Methodology: 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. Results: Moderate agreement was achieved for absolute sTILs scores (intraclass correlation coefficient (ICC) = 0.683, 95% CI 0.601–0.767, p-value < 0.001). Agreement was less when a 25% threshold was used (ICC 0.509, 95% CI 0.416–0.614, p-value < 0.001) and for lymphocyte predominant breast cancer (LPBC) (ICC 0.504, 95% CI 0.412–0.610, p-value < 0.001). Intra-observer agreement was strong for absolute sTIL values (Spearman ρ = 0.727); fair for sTILs ≥ 25% (κ = 0.53) and for LPBC (κ = 0.49), but poor for sTILs as 10% increments (κ = 0.24). Increasing sTILs was significantly associated with an increased likelihood of a pathological complete response (pCR) on multivariable analysis. Conclusion: 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.
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    Who Could Be Blamed in the Case of Discrepant Histology and Serology Results for Helicobacter pylori Detection?
    (2022-01) Skrebinska, Sabine; Megraud, Francis; Daugule, Ilva; Santare, Daiga; Isajevs, Sergejs; Liepniece-Karele, Inta; Bogdanova, Inga; Rudzite, Dace; Vangravs, Reinis; Kikuste, Ilze; Vanags, Aigars; Tolmanis, Ivars; Savcenko, Selga; Alix, Chloé; Herrero, Rolando; Park, Jin Young; Leja, Marcis
    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.