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Publikacije (67)

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I. Gupta, Halema F Al Farsi, A. Jabeen, F. Skenderi, Hamda A. Al-Thawadi, Yaman M AlAhmad, A. Al Moustafa, S. Vranić

Colorectal cancer (CRC) is a common malignancy with a high mortality rate worldwide. It is a complex, multifactorial disease that is strongly impacted by both hereditary and environmental factors. The role of microbes (e.g., viruses) in the pathogenesis of CRC is poorly understood. In the current study, we explored the status of high-risk human papillomaviruses (HPV) and Epstein–Barr virus (EBV) in a well-defined CRC cohort using immunohistochemistry and polymerase chain reaction assays. Our data showed that high-risk HPVs were common (~80%) and EBV had a low presence (14–25%) in the CRC samples. The most common high-risk HPVs are HPV16, 31, 18, 51, 52 and 45 genotypes. The co-presence of high-risk HPV and EBV was observed in ~16% of the sample population without any significant association with the clinicopathological variables. We conclude that high-risk HPVs are very prevalent in CRC samples while EBV positivity is relatively low. The co-expression of the two viruses was observed in a minority of cases and without any correlation with the studied parameters. Further studies are necessary to confirm the clinical relevance and potential therapeutic (preventive) effects of the observations reported herein.

S. Bešlija, Z. Gojković, T. Cerić, Alma Mekić Abazović, I. Marijanović, S. Vranić, Jasminka Mustedanagić-Mujanović, F. Skenderi et al.

The HERe2Cure project, which involved a group of breast cancer experts, members of multidisciplinary tumor boards (MTB) from health-care institutions in Bosnia and Herzegovina, was initiated with the aim of defining an optimal approach to the diagnosis and treatment of HER2 positive breast cancer. After individual multidisciplinary consensus meetings were held in all oncology centers in Bosnia and Herzegovina, a final consensus meeting was held to reconcile the final conclusions discussed in individual meetings. Guidelines were adopted by consensus, based on the presentations and suggestions of experts, which were first discussed in a panel discussion and then agreed electronically between all the authors mentioned. The conclusions of the panel discussion represent the consensus of experts in the field of breast cancer diagnosis and treatment in Bosnia and Herzegovina. The objectives of the guidelines include the standardization, harmonization, and optimization of the procedures for the diagnosis, treatment, and monitoring of patients with HER2-positive breast cancer, all of which should lead to an improvement in the quality of health care of mentioned patients. The initial treatment plan for patients with HER2-positive breast cancer must be made by a MTB comprised of at least: A medical oncologist, a pathologist, a radiologist, a surgeon, and a radiation oncologist/radiotherapist.

F. Skenderi, J. Palazzo, J. Swensen, R. Feldman, E. Contreras, Elena Florento, Z. Gatalica, S. Vranić

We profiled nine pure clear cell carcinomas of the breast using massively parallel DNA and RNA sequencing (NGS), in situ hybridization (ISH), and immunohistochemistry (IHC). All cases were primary mammary clear cell carcinomas that were diagnosed in female patients (mean age: 53.4 years; range: 31‐69 years). Based on our findings, we conclude that the majority of clear cell carcinomas are ER/PR positive and consequently amenable to anti‐ER treatment modalities. A subset of clear cell carcinomas also harbored alterations in PIK3CA/PTEN/AKT pathway, particularly PTEN, indicating a potential benefit of PI3K/Akt/mTOR inhibitors. The status of I‐O biomarkers in clear cell carcinomas indicates a limited therapeutic benefit of immune checkpoint inhibitors (against PD‐1/PD‐L1).

Glycogen-rich clear cell carcinoma (GRCC) is a very rare form of primary breast cancer (<0.1% of all breast cancers). It is characterized by the presence of neoplastic cells with a glycogen-abundant clear cytoplasm (the Periodic Acid Schiff–positive, diastase-sensitive). The expression of steroid receptors (estrogen and progesterone receptors) has been variably reported (35% to 100% of the cases), whereas most studies reported low human epidermal growth factor receptor 2 positivity in GRCC. High androgen receptor positivity without androgen receptor splice variant-7 was reported in one recent study. Although sparse, the preliminary theranostic data on GRCC indicate the potential of targeted treatments in selected cases (antiandrogen, PIK3CA, and immune checkpoint inhibitors). Because of its rarity, the prognosis for GRCC patients remains controversial. Herein, we comprehensively appraise the epidemiological, morphologic, molecular, and clinical characteristics of this rare mammary malignancy.

C. Moran, K. Lindholm, H. Brunnström, G. Langman, S. Jang, D. Spagnolo, S. Chai, A. Laycock et al.

F. Skenderi, J. Palazzo, J. Swensen, E. Contreras, Elena Florento, Z. Gatalica, S. Vranić

Z. Zvizdic, A. Summers, Z. Moinuddin, D. van Dellen, Irmina Pasic-Sefic, F. Skenderi, S. Vranić, T. Augustine

Encapsulating peritoneal sclerosis (EPS) is a rare life-threatening complication associated with peritoneal dialysis (PD). EPS is characterized by progressive fibrosis and sclerosis of the peritoneum, with the formation of a membrane and tethering of loops of the small intestine resulting in intestinal obstruction. It is very rare in children. We present a case of a 16-year-old adolescent boy who developed EPS seven years after being placed on continuous ambulatory peritoneal dialysis (CAPD) complicated by several episodes of bacterial peritonitis. The diagnosis was based on clinical, radiological, intraoperative and histopathological findings. The patient was successfully treated with surgical enterolysis. During a 7-year follow-up, there have been no further episodes of small bowel obstruction documented. He still continues to be on regular hemodialysis and is awaiting a deceased donor kidney transplant. EPS is a long-term complication of peritoneal dialysis and is typically seen in adults. Rare cases may be seen in the pediatric population and require an appropriate surgical approach that is effective and lifesaving for these patients.

Valentina Karin-Kujundzic, V. Kardum, I. Šola, F. Paić, A. Škrtić, F. Skenderi, A. Šerman, Tamara Nikuševa‐Martić et al.

Dishevelled family proteins (DVL1, DVL2, and DVL3) are cytoplasmic mediators involved in canonical and non‐canonical Wnt signaling that are important for embryonic development. Since Wnt signaling promotes cell proliferation and invasion, its increased activation is associated with cancer development as well. To get deeper insight into the behavior of Dishevelled proteins in cancer, we studied their expression in serous ovarian carcinomas [both low‐ (LGSC) and high‐grade (HGSC)], and HGSC cell lines OVCAR5, OVCAR8, and OVSAHO. DVL protein expression in serous ovarian carcinomas tissues was analyzed using immunohistochemistry, while DVL protein and mRNA expressions in HGSC cell lines were analyzed using Western blot and quantitative real‐time PCR. DVL1 protein expression was significantly higher in LGSC compared with normal ovarian tissue, while DVL3 was overexpressed in both LGSC and HGSC. DVL2 and DVL3 protein expression was higher in HGSC cell lines when compared with normal control cell line FNE1, while DVL1, DVL2, and DVL3 mRNA expression was significantly increased only in OVSAHO cell line. Survival analysis revealed no significant impact of DVL proteins on patients’ outcome. Our data show an active involvement of Dishevelled family proteins in serous ovarian carcinomas. Further studies should confirm the clinical relevance of these observations.

Yaman M AlAhmad, I. Abdelhafez, F. Cyprian, S. Akhtar, F. Skenderi, S. Vranić

Predatory journals refer to journals that recruit articles through aggressive marketing and spam emails, promising a quick, but not robust, review and fast open-access (OA) publication, thus compromising scholarly publishing standards.1–5 Their key motive is a financial benefit via article processing charges (APCs) and other additional fees.1 3 4 The number of OA journals has dramatically risen over the past 15 years,6 reaching 11 376 journals, indexed in the Directory of Open Access Journals (DOAJ) in 2018 (available at https://doaj.org). This expansion was parallel to the increase in the number of predatory publishers.7 8 Predatory journals have become more prevalent than ever due to massive internet expansion and extensive spam email soliciting.2 4 9 Since 2011, when Jeffrey Beall launched his first list of potential predatory OA publishers and journals, predatory journals have come into focus.3 4 Recent studies have highlighted the significant burden of potentially predatory journals in several biomedical specialties, including neuroscience/neurology, urology, emergency medicine, physical medicine, orthopaedics, rehabilitation, as well as anaesthesiology.7 8 10–13 No study on predatory journals in pathology has been conducted so far. As previously suggested, we explored Beall’s list of predatory journals as an initial database of suspected journals related to pathology.2 8 The term predatory was only applied after assessing each journal separately. The assessment was based on the recommended …

B. Krušlin, Z. Gatalica, O. Hes, F. Skenderi, M. Miettinen, E. Contreras, J. Xiu, Michelle Ellis et al.

S. Bešlija, T. Cerić, Berisa Hasanbegović, F. Skenderi, J. Alidžanović, Dijana Koprić, I. Marjanović, A. Mekić-Abazović et al.

Abstract Background An optimal adjuvant treatment of HER2 positive breast cancer includes the initiation of trastuzumab within 6 months after the surgery. However, due to limited resources and waiting lists, this timeframe is often exceeded in developing countries. We previously reported short-term outcomes of a time-optimal versus delayed postoperative initiation of trastuzumab in women with HER2 positive, non-metastatic, neoadjuvant naive breast cancer. Here, we report an extended follow-up, summarizing outcomes of our cohorts. Methods We included 223 consecutive women with surgically treated, non-metastatic, neoadjuvant naive, HER2 positive breast cancer from 2009 to 2011, from four institutions in Bosnia and Herzegovina. Patients were assigned to a time-optimal group (TOG), or a delayed group 1 (DG1), or a delayed group 2 (DG2), depending on whether their adjuvant trastuzumab was initiated 6 months, or 6-12 months, or more than 12 months after the surgery, respectively. A cut-off point for the follow-up was January 2019. We compared clinical outcomes between the groups, taking into account lymph node status. Results The patient’s median age was 55 (range 27-80) years. Mean follow-up period was 67 (range 4-109) months. Node-negative disease was found in 38.6% patients overall. 37% (TOG) patients received trastuzumab within 6 months, while 41% (DG1) received it within 6-12, and 22% (DG2) more than 12 months after their surgery. A higher number of node negative patients was found in the DG2 group compared to the TOG and DG1 groups (48%, 35%, and 36% respectively). 5-year DFS rate was 70.73% (TOG), 67.03% (DG1), and 62.00% (DG2). The OS rate was 78.05% (TOG), 75.82% (DG1), and 74.00% (DG2). Conclusions From the above, a conclusion can be made that patients with time-optimal initiation of adjuvant trastuzumab therapy had a higher 5-year DFS and OS rate compared to the delayed treatment initiation groups. Results of the DG1 and the DG2 group indicate that trastuzumab therapy shows a persistent benefit even if administered with a delay. Higher DFS and OS rates in the DG2 group could be explained by a higher number of node-negative low-risk, patients in this group. Legal entity responsible for the study The authors. Funding Roche. Disclosure S. Beslija: Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy: Novartis; Advisory / Consultancy: MSD; Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer. T. Ceric: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy: MSD; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Novartis. B. Hasanbegovic: Advisory / Consultancy: Roche. A. Pasic: Advisory / Consultancy: Merck; Advisory / Consultancy: Sanofi. All other authors have declared no conflicts of interest.

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