Expression of Nectin-4 protein in luminal B (HER2 negative) breast cancer

Cilj istraživanja: Istražiti povezanost ekspresije Nectin-4 proteina u populaciji pacijenata s luminalnim B HER2 negativnim podtipom karcinoma dojke a u korelaciji sa prognostičkim parmetrima kao što su intenzitet hormonskih receptora, Ki-67 proliferacijski indeks, dob, veličiina i histološki gradus tumora te zahvaćenost pazušnih limfnih čvorova. Materijal i metode: Ispitivana je skupina od 147 pacijenata operiranih u KBC Osijek sa unilateralnim karcinomom dojke bez dokazanih udaljenih metastaza, koji se prema najnovijoj St. Gallenskoj klasifikaciji svrstavaju u luminalnu B HER2 negativnu podskupinu. Korištenjem arhivskih parafinskih kocaka učinjeno je imunohistokemijsko bojanje antitijelom na Nektin-4 protein, a rezultati su korelirani sa kliničkim podatcima uz Kaplan-Meier krivulje te Cox-ovu regresijsku analizu. Rezultati: Dokazana je statistički značajna povezanost ekspresije Nektina-4 sa veličinom tumora (p<0.05; Chi-Square Test) te negativna povezanost ukupnim preživljenjem, prežvljenjem bez bolesti, te preživljenjem bez pojave udaljenih metastaza (p<0,001; Kaplan-Meier). U Cox-ovoj univarijantnoj i multivarijantnoj analizi pokazao se kao statistički značajan nezavisni faktor za sveukupno preživljenje i preživljenje bez povrata bolesti (p<0,001). Nije uočena statistički značajna povezanost ekspresije Nektina-4 sa dobi, ekspresijom estrogenskih i progesteronskih receptora, zahvaćenošću pazušnih limfnih čvorova, diferencijacijom tumora, histološkim tipom i Ki-67 proliferacijskim indeksom. Zaključak: Nectin-4 je važan prognostički pokazatelj te potencijalna meta za nove terapijske metode u liječenju luminalnih B HER2 negativnih karcinoma dojke.Objectives: The aim of this study was to evaluate an expression of Nectin-4 in luminal B (HER2 negative) breast cancer, in correlation with other prognostic parameters as hormone positivity, Ki-67 proliferation index, age, tumor size, histological grade and axillary lymph node status. Patients and methods: In this retrospective study clinical and pathological parameters of 147 luminal B (HER2 negative) breast cancers have been examined from the patients who had undergone a surgery at the University Hospital Osijek. These patients were presenting with primary unilateral breast cancer with no evidence of distant metastasis. Nectin-4 protein expression was assessed by immunohistochemistry and the results were correlated with the clinical data using Kaplan-Meier curves and univariante and multivariate stepwise proportional-hazard analysis (Cox model). Results: Nectin-4 overexpression was significantly correlated with tumor size (p<0.05; Chi- Square Test), also Nectin-4 expression was negatively associated with overall survival, disease free survival and distant relapse free survival with the same significance (p<0,001; Kaplan-Meier). Cox analysis has shown statistically significant correlation between Nectin-4 and overall and disease free survival (p<0,001). Statistically significant correlation between Nectin-4 and age, ER, PR, age, lymph node metastasis, tumor differentiation, histological subtype and Ki-67 proliferation index was not found. Conclusion: Nectin-4 is relevant prognostic factor and a therapeutic target in luminal B (HER2 negative) breast cancer

Pojavnost intramiokardijalnih masnih stanica u stijenci desne pretklijetke i desne klijetke – postmortalna humana analiza

Histologic and radiologic studies describe intramyocardial fat tissue as a normal finding or as part of cardiac pathology. The role of fat cells within the myocardium is not fully understood. The aim of this study was to assess fat tissue distribution in the myocardium of right atrium (RA) and right ventricle (RV) and age differences in subjects free from cardiac disease. The study included 10 males without cardiac disease divided into two groups according to age (below/above 50 years). Three cross sections were performed (RV free wall and apex and RA free wall) with histomorphological analysis on digital photographs. The shares of total myocardial fat (TMF), perivascular fat (PVF) and non-perivascular (nPVF) fat were calculated. Samples from the older group had larger amounts of fat in the epicardium and myocardium, without statistically significant difference (TMF p=0.847, PVF p=0.4 and nPVF p=0.4). The largest quantities of fat tissue were found in the RV apex samples (14.9%), followed by RV free wall (7.5%) and RA (4.5%), where total apical RV fat share was significantly larger than in RA sample (p=0.044). Intramyocardial fat cells were present within the non-diseased RA and RV in all samples, mostly in the apex. Further investigations on age difference, effect of visceral obesity and sex differences are needed.Dosadašnja histološka i radiološka istraživanja opisuju pojavnost intramiokardijalnog masnog tkiva kao dio normalnog nalaza ili kao dio patološkog nalaza srca. Uloga intramiokardijalnih masnih stanica nije još razjašnjena. Cilj ovoga istraživanja bio je utvrditi raspodjelu masnog tkiva u miokardu desne pretklijetke (DP) i desne klijetke (DK) ovisno o dobi i lokalizaciji kod ispitanika bez kardijalnog morbiditeta. Patohistološka postmortalna studija uključila je 10 muškaraca bez kardijalnih bolesti podijeljenih u dvije skupine prema dobi (ispod/iznad 50 godina). Uzorci su uzeti u tri presjeka (projekcija slobodnog zida DK, slobodni zid vrha DK te stijenka DP) s histomorfološkom analizom na digitalnim fotografijama. Izračunati su udjeli ukupnog masnog tkiva unutar srčanog mišića (UMT), perivaskularnog masnog tkiva (PMT) i ne-perivaskularnog masnog tkiva (nPMT). U uzorcima starijih ispitanika prisutna je veća količina masnog tkiva u epikardu i miokardu, bez statistički značajne razlike (UMT p=0,847, PMT p=0,4, nPMT p=0,4). Najveće količine masnog tkiva pronađene su u uzorcima vrha DK (14,9%), nakon čega slijedi stijenka slobodnog zida DK (7,5%) i DP (4,5%), gdje je ukupni udio masnog tkiva DK bio znatno veći nego kod uzorka DP (p=0,044). Intramiokardijalne masne stanice sastavni su dio histološkog nalaza DP i DK u svim uzorcima bez prisutnih kardijalnih bolesti, dominantno u vrhu DK. Neophodna su daljnja istraživanja utjecaja dobi, spola i visceralne pretilosti na pojavnost intramiokardijalnih masnih stanica unutar stijenke desnog srca

IMPACT OF METEOROLOGICAL FACTORS ON SUICIDE ATTEMPTS AND COMPLETED SUICIDES IN CROATIA, OSIJEK-BARANJA COUNTY

Backgraund: Significant changes in the values of temperature, pressure, humidity and cloud cover can participate in the human behaviour including the mood disorders (especially depression and bipolar disorders) which can trigger suicidal ideas or their realization. The aim of this study is to estimate the connection between the aforesaid weather changes and a committed suicide along with the suicide attempts. Subjects and methods: We conducted a retrospective study in Osijek Baranja County in the period from 2000 to 2011. Meteorological, demographic and epidemiological analysis was performed on 569 suicides and 478 suicide attempts (total of 1047 events). We analyzed the values of the above-mentioned meteorological parameters at the exact time when the event had happened, as well as three days before the event and one day after the event, comparing it with the monthly mean values. Results: The results showed that the changes of temperature and pressure were significantly related with the suicides i.e. suicide attempts in general, while by separating genders, a connection with all examined meteorological factors was found by woman whereas men expressed significance only in the matter of temperature changes. Conclusions: Despite the fact that suicidality is caused by numerous factors, this study confirms that a sudden change of weather in the days preceding the suicide can be a trigger to suicidal behaviour. The study also suggests that in the matter of suicidal behaviour, female population is more susceptible to sudden weather changes

Udio turmoske strome kao loš prognostički čimbenik kod karcinoma debelog crijeva

High stroma proportion appears to be a very important prognostic factor in esophageal and breast cancer. Previous researches have shown that it might have a similar effect on colorectal cancer. The aim of this study was to determine whether tumor stroma proportion influenced patient survival. This retrospective study included 236 patients with colorectal cancer having undergone surgery in 2006 and 2007 at Osijek University Hospital Center. Location with the highest stroma proportion at the site of deepest tumor invasion was determined. Patients were divided into the groups with high stroma proportion (>50%) and low stroma proportion (≤50%). Stroma proportion showed a statistically significant correlation with tumor stage. Kaplan-Meier survival curves yielded a statistically significant difference in patient overall survival (Cox ph model p=0.016) and progressionfree survival (Cox ph model, p=0.0188) according to stroma proportion. Study results showed a statistically significantly shorter overall survival and progression-free survival in patients with high stroma proportion.Dokazano je da je visok udio strome značajan prognostički čimbenik kod karcinoma jednjaka i karcinoma dojke. Prethodna istraživanja su pokazala da bi isti utjecaj stroma mogla imati i kod kolorektalnog karcinoma. Cilj istraživanja je bio utvrditi je li udio tumorske strome povezan s preživljenjem bolesnika s kolorektalnim karcinomom. Provedeno je retrospektivno istraživanje u 236 bolesnika koji su operirani na Klinici za kirurgiju Kliničkoga bolničkog centra Osijek. Određeno je područje s najvećim udjelom strome u području najdubljeg prodora tumora. Bolesnici su podijeljeni u dvije skupine: onu s visokim udjelom strome (>50%) i onu s niskim udjelom strome (≤50%). Udio tumorske strome bio je statistički značajno povezan sa stadijem tumora. Kaplan-Meierova analiza je pokazala statistički značajnu razliku u ukupnom preživljenju (Cox ph model p=0,016) i preživljenju do progresije (Cox ph model, p=0,0188) bolesnika u odnosu na udio strome. Rezultati su pokazali statistički značajno kraće ukupno preživljenje i preživljenje do progresije bolesti kod bolesnika s visokim udjelom strome

Prognostički utjecaj niskog pozitiviteta estrogenih i progesteronskih receptora u luminalnim B (HER2 negativnim) karcinonima dojke

Luminal B (HER2 negative) subtype is the most diversiform type of breast cancers, with a high Ki-67 proliferation index (>20%) or/and low progesterone (PR; <20%) with various intensity and distribution of hormone receptors. Considerable difference has also been noticed in disease outcome, wherefore there is the need for a more detailed classification of this tumor subtype. The clinical and pathologic parameters of 147 luminal B (HER2 negative) breast cancers were examined. The expression of hormone receptors in correlation with other prognostic factors and disease outcome was analyzed by Kaplan-Meier curves and multivariate Cox regression analysis. The Kaplan-Mayer analysis showed that low positivity of estrogen (ER) and PR receptors in tumors was associated with a significantly worse disease outcome (overall survival (ER), p=0.020; disease free survival (ER), p=0.019; overall survival (PR), p=0.026; disease free survival (PR), p=0.038)), unlike Ki-67, which did not show a statistically significant connection (overall survival, p=0.343; disease free survival, p=0.322). The intensity of receptor staining and Ki-67 relative to other histopathologic prognostic factors showed a statistically significant correlation solely with histologic grade of tumor. By using the Cox regression model, PR proved to be an independent prognostic factor for overall survival (p=0.004) and disease free survival (p=0.029). The luminal B (HER2 negative) breast cancer with low expression of hormone receptors, independent of the Ki-67 proliferation index, and in correlation with a higher histologic grade, could be a unique subtype of cancer.Luminalni B (HER 2 negativni) karcinomi dojke najheterogenija su podskupina s velikim rasponom proliferacijskog indeksa Ki-67 kao i intenziteta te raspodjele hormonskih receptora unuatar tumorskih stanica. Također je zamjetna različitost u kliničkom ishodu bolesti, zbog čega se ukazuje potreba za detaljnijom subtipizacijom ove skupine tumora. Izdvojeno je 147 luminalnih B HER2 negativih karcinoma, a ispitani su kliničko-patološki parametri u korelaciji s intenzitetom hormonskih receptora (estrogen (ER) i progesteron (PR)) kao i Ki-67 u odnosu na sveukupno preživljenje te preživljenje bez povrata bolesti. Unutar ispitivanih kliničko patoloških parametara slabiji intenzitet hormonskih receptora kao i viši Ki-67 bili su statistički značajno povezani samo s gradusom tumora. Kaplan-Meierovom analizom ustanovljena je statistički značajna povezanost slabog intenziteta ER i PR s preživljenjem (sveukupno preživljenje (ER), p=0,020; preživljenje bez povrata bolesti (ER), p=0,019; sveukupno preživljenje (PR), p=0,026; preživljenje bez povrata bolesti (PR), p=0,038)), za razliku od Ki-67 vrijednosti kojega nisu bile statistički značajno povezane s preživljenjem (sveukupno preživljenje, p=0,343; preživljenje bez povrata bolesti, p=0,322). Coxovom regresijskom analizom PR se pokazao kao statistički značajan neovisni parametar povezan sa sveukupnim preživljenjem (p=0,004) i preživljenjem bez povrata bolesti (p=0,029). Ovi rezultati pokazuju da bi podskupina luminalnih B HER2 negativnih karcinoma dojke s niskim intenzitetom hormonskih receptora, neovisno o proliferacijskom indeksu Ki-67, a u korelaciji s histološkim gradusom tumora mogla biti zaseban podtip karcinoma dojke

Angiosarcoma of the Hypopharynx: Case Report

Angiosarcomas are malignant neoplasias of rapid growth that emerge from endothelial cells. They are rarely found in the area of the head and neck and account less than 0.1% of all head and neck malignancies. In some cases it has been linked to trauma, radiation and angiectasia but the etiology mainly remains unknown. Here we report a case of angiosarcoma of pyriform sinus manifested by dysphagia and dysphonia. The patient underwent endoscopic hypopharyngeal excision followed by radiation therapy with a good result. Our patient remains tumor free after two years. The purpose of this article is to add another case of primary angiosarcoma of a rare site, the hypopharynx

Neoadjuvant Chemotherapy Affects TFF3 Peptide Expression in Luminal B Subtype of Breast Cancer – A Pilot Study

Aim: Trefoil factor family 3 (TFF3) peptide is normally expressed by epithelial cells in breast ducts, but it is also associated with different pathological conditions, including breast cancer. It is considered a marker of poor prognosis and associated with increased resistance to chemotherapy. Data on the effect of chemotherapy on TFF3 peptide expression are scarce. The aim of this pilot study was to assess suitability of research on this topic for large-scale studies. Methods: Formalin-fixed, paraffin-embedded samples of core biopsies and of surgically removed tumors from patients with luminal B subtype of breast cancer were used for immunohistochemical analysis. Changes in TFF3 peptide and Ki-67 expression and microvessel density (MVD) values before and after chemotherapy were analyzed, as well as the association between TFF3 peptide expression and Ki-67 expression and MVD values. Results: Significant reduction in TFF3 and Ki 67 expression was observed after chemotherapy, while MVD values did not differ significantly before and after chemotherapy. The association of TFF3 peptide expression and Ki-67 expression and TFF3 peptide expression and MVD values was not significant before or after chemotherapy. Conclusion: The data obtained in this pilot study suggest that a large-scale study is justified, and it other breast cancer subtypes should be included. (Bijelić N, Abramović M, Rajc J, Rođak E, Marušić Z, Tolušić Levak M, Pauzar B, Belovari T. Neoadjuvant Chemotherapy Affects TFF3 Peptide Expression in Luminal B Subtype of Breast Cancer – A Pilot Study. SEEMEDJ 2020; 4(2); 20-27

Utjecaj neurotropnih virusa na preživljenje pacijenata operiranih od glioblastoma

Introduction: Glioblastoma represents the most aggressive tumor of the brain with an estimated survival rate of twelve to fifteen months after the primary diagnosis. The role of neurotropic viruses in pathogenesis of the tumor has remained unclear to date. During the last two decades, many studies were conducted with the aim of confirming viral influence in the development of glioblastoma. Methods: We conducted a retrospective study in a time period of five years using formalin-fixed paraffin-embedded tissues of glioblastoma. Immunohistochemistry was performed for three viruses: CMV, EBV and HSV-1, using an automated staining system. Results: Mean age of patients in our group was 66.7±8.5 years. A slight male dominance was noted. Negative immunohistochemistry results were obtained for CMV and EBV, which were excluded from further investigation. Based on IRS score, we confirmed six HSV-1 samples which were rated as IRS score 2. Five more samples of HSV-1 were rated as IRS score 1 and were excluded from the study. Conclusion: According to our retrospective study and its results, we found no impact of neurotropic viruses in the survival rate of glioblastoma. Further studies should be conducted including a wider range of viral detection methods.Uvod: Glioblastom predstavlja najagresivniji tumor mozga s procijenjenom stopom preživljenja od dvanaest do petnaest mjeseci nakon primarne dijagnoze. Uloga neurotropnih virusa u patogenezi tumora do danas je nejasna. Tijekom posljednja dva desetljeća provedena su mnoga istraživanja s ciljem potvrde utjecaja virusa na razvoj glioblastoma. Metode: Provedena je retrospektivna studija u vremenskom razdoblju od pet godina. Korištena su arhivska tkiva glioblastoma uklopljena u parafin. Imunohistokemija je rađena za tri virusa: CMV, EBV i HSV-1 pomoću automatiziranog sustava bojenja. Rezultati: Prosječna dob bolesnika u našoj skupini bila je 66,7 ± 8,5 godina. Zabilježena je blaža predominacija oboljelih muškaraca. Dobiveni su negativni imunohistokemijski rezultati za CMV i EBV koji su isključeni iz daljnjeg ispitivanja. Prema IRS procjeni potvrdili smo šest uzoraka HSV-1 koji su ocijenjeni kao IRS 2. Još pet uzoraka HSV-1 ocijenjeno je kao IRS 1 i izuzeti su iz studije. Zaključak: Prema našoj retrospektivnoj studiji i posljedičnim rezultatima, nismo pronašli utjecaj neurotropnih virusa na stopu preživljenja u oboljelih od glioblastoma, no potrebna su daljnja istraživanja koja uključuju širi spektar metoda dokazivanja virusa

Angiosarcoma of the Hypopharynx: Case Report

Angiosarcomas are malignant neoplasias of rapid growth that emerge from endothelial cells. They are rarely found in the area of the head and neck and account less than 0.1% of all head and neck malignancies. In some cases it has been linked to trauma, radiation and angiectasia but the etiology mainly remains unknown. Here we report a case of angiosarcoma of pyriform sinus manifested by dysphagia and dysphonia. The patient underwent endoscopic hypopharyngeal excision followed by radiation therapy with a good result. Our patient remains tumor free after two years. The purpose of this article is to add another case of primary angiosarcoma of a rare site, the hypopharynx