Hypoxia-inducible factor 1 alpha expression is an indicator of invasiveness in uterine cervical tumors

Background: Hypoxia is a common feature of cancers. Hypoxia-inducible factor 1A (HIF1A) is a causative agent that changes the transcriptional response of tumors under hypoxia. Some alterations lead to an increase in HIF1A activity and this supports other critical pathways leading to angiogenesis, metabolic adaptation and tumor progression. This retrospective study was designed to evaluate the differences of tissue expressions of HIF1A in a spectrum of cervical neoplasms.Methods: Tissue expression of HIF1A was studied in a total of 107 formalin-fixed, paraffin-embedded uterine cervical tumors specimens and its association with different clinicopathologic parameters was evaluated.Results: In this series, there were 30 low and 29 high grade cervical intraepithelial neoplasms (CINs), 27 squamous cell carcinomas, 15 adenosquamous carcinomas and 6 adenocarcinomas. Strong and diffuse nuclear staining was evaluated as positive HIF1A expression. Positive HIF-1 alpha expression was detected in 7 (25.9%) of squamous cell carcinomas, 1 of adenocarcinomas (16.7%) and only 1 of HGSILs (3.4%). Statistically it was determined that the positivity rate of strong nuclear HIF1A expression was significantly higher in invasive carcinomas when compared with in non-invasive squamous cell carcinomas (p=0.07). Contrary, there was no statistically significant difference according to the subtypes of carcinomas due to scarce number of cases with adenocarcinoma (p=0.188).Conclusions: Our findings were demonstrated to link of nuclear HIF1A expression and the invasive characters of uterine neoplasms. As a result, HIF-1 alpha expression may be important in foreseeing of the invasion and tumor progression

Can preoperative magnetic resonance imaging replace intraoperative frozen sectioning in the evaluation of myometrial invasion for early-stage endometrial carcinoma?

Objectives: To examine the performance of preoperative magnetic resonance imaging (MRI) and intraoperative frozen sectioning in the assessment of myometrial invasion during the early stages of endometrial cancer.  Material and methods: This retrospective study employed data from patients with endometrial cancer who were operated on between January 2013 and November 2018. Patients who underwent preoperative MRI and were of FIGO 2009 stage I were included in the study. Radiological staging and intraoperative staging by frozen sectioning were carried out. The data were analyzed to assess agreement of the overall results concerning myometrial invasion.  Results: In total, 222 patients were enrolled. Their mean age was 58.3 ± 8.5 years. The accuracy of MRI for the detection of myometrial invasion was 88.7% and its sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 91.6%, 82.1%, 92.2%, and 80.9%, respectively, with a kappa coefficient of 0.734 (95% confidence interval [CI], 0.684–0.784; p < 0.001). The accuracy of intraoperative frozen sectioning was 94.4%, and its sensitivity, specificity, PPV, and NPV were 97.7%, 85.7%, 94.7%, and 93.4%, respectively, with a kappa coefficient of 0.856 (95% CI, 0.812–0.900; p < 0.001). No significant difference in accuracy was observed between MRI and frozen sectioning (p = 0.057). MRI and frozen sectioning were sensitive for the detection of myometrial invasion, according to receiver operating curve analyses (areas under the curve, 0.869 and 0.917, respectively; p < 0.001).  Conclusions: The assessment of myometrial invasion by preoperative MRI and intraoperative frozen sectioning during the early stages of endometrial carcinoma was highly accurate.

A case of bladder endometriosis that became symptomatic during the third trimester

AbstractBackgroundThe urinary tract endometriosis is observed in 1–2% of the patients and in 90% of these cases, there are endometriotic nodules in the bladder. With respect to knowledge, it is generally believed that pregnancy cures endometriosis. However in this case, symptoms developed during the third trimester of pregnancy.Case reportWe report a case of 31year old, 30week pregnant woman with a vegetative mass with 33×33×21 mm dimensions and irregular borders on the posterior wall of the bladder. After the cesarean section, the vegetative and superiorly localized mass on the internal wall of the bladder was excised with partial bladder excision. The patient had no other apparent findings of pelvic endometriosis at operation but the pathology result indicated endometriosis.ConclusionAlthough this case shows that endometriosis may become symptomatic during pregnancy, it has to be underlined that it cannot be discerned whether it is consequent to progress of the disease or to pregnancy-mediated modifications of a pre-existing lesion

Četverogodišnja studija učinkovitosti i sigurnosti entekavira u bolesnika s kroničnim hepatitisom B pozitivnih na HBeAg bez prethodne nukleoz(t)idne terapije

Entecavir is a guanosine analogue with activity against hepatitis B virus. The aim of this 4-year trial was to evaluate entecavir treatment in nucleos(t)ide-naive HBeAg-positive chronic hepatitis B patients. Forty-nine patients received entecavir and nine of them withdrew from the trial at the end of week 96. The initial mean value of alanine aminotransferase was 79.4}41.5 IU /L, and at the end of the 4-year study period, 90% of patients had alanine aminotransferase values within the normal range. At week 96, 91.7% of patients had HBV DNA <300 copies; at month 48, 90% of patients had HBV DNA <50 IU /mL. HBeAg loss was recorded in 7.1% of patients at week 96 and in 12.5% at month 48. The rate of HBeAg seroconversion was 4.8% at week 96 and 7.5% at month 48. The rate of HBsAg seroconversion was 2.1% at week 96 and 2.5% at month 48. Entecavir as a potent and safe agent leading to continuous viral suppression proved to be safe and well tolerated therapy.Entekavir je analog gvanozina koji djeluje protiv virusa hepatitisa B. Cilj ove četverogodišnje studije bio je procijeniti liječenje entekavirom kod bolesnika s kroničnim hepatitisom B pozitivnih na HBeAg bez prethodne nukleoz(t)idne terapije. Ukupno je 49 bolesnika primalo entekavir, a devetoro ih se povuklo s terapije na kraju 96. tjedna. Početna srednja vrijednost alanin aminotransferaze bila 79,4}41,5 IU /L, dok je nakon 4 godine vrijednost alanin aminotransferaze bila u normalnim granicama kod 90% bolesnika. U 96. tjednu je <300 kopija HBV DNA zabilježeno u 91,7% bolesnika, a u 48. mjesecu je 48,90% bolesnika imalo <50 IJ/mL HBV DNA. Gubitak HBeAg zabilježen je u 7,1% bolesnika u 96. tjednu te u 12,5% bolesnika u 48. mjesecu. Stopa serokonverzije HBeAg iznosila je 4,8% u 96. tjednu i 7,5% u 48. mjesecu. Stopa serokonverzije HBsAg bila je 2,1% u 96. tjednu i 2,5% u 48. mjesecu. Sigurnost terapije bila je dobra. Bolesnici su dobro podnosili entekavir, snažan i siguran lijek koji dovodi do ustaljenog suzbijanja virusa

Ekspresja caveoliny-1 w tkance okołoguzowej jest związana ze stopniem zróżnicowania histopatologicznego w surowiczych guzach jajnika

Background: Previous studies have demonstrated that Caveolin-1 (Cav-1) can ambiguously behave as tumor suppressor or tumor promoter in different neoplasms, depending on cancer type. Some findings have also revealed that cell proliferation, migration and invasion were attenuated by the knockdown of Caveolin-1 expressions. However, the functional and prognostic significance of Caveolin-1 in most tumors remains to be fully elucidated. Objectives: The aim of the study was to investigate a possible association between tissue Caveolin-1 expression and the clinicopathologic features of ovarian serous tumors. Material and methods: Caveolin-1 expression was studied in a total of 82 formalin-fixed, paraffin-embedded specimens of ovarian serous tumors and its association with different clinicopathologic parameters was evaluated. Results: The study included 36 (43.9%) benign, 12 (14.6%) borderline and 34 (41.5%) malignant serous tumors. Mean patient age was 43.9±14.4 years (17-72 years). Statistical analysis revealed that if the tumor becomes more aggressive and invasive, it losses the stromal Caveolin-1 expression (p=0.001). Also, parallel changes between stromal and perivascular Caveolin-1 expressions were observed. Conclusions: Our findings demonstrated a link between Caveolin-1 expression and the aggressiveness of ovarian cancer. Therefore, it seems safe to suggest that Cav-1 may act as a differential diagnostic biomarker in ovarian serous tumors.Wstęp: Wcześniejsze badania wykazały, że Caveolina-1 (Cav-1) może zachowywać się niejednoznacznie w zależności od rodzaju nowotworu, jako jego supresor lub promotor. Niektóre badania pokazały, że proliferacja komórek, migracja i inwazja były osłabiane przez obniżoną ekspresję Caveoliny-1. Jakkolwiek czynnościowe i prognostyczne znaczenie Caveoliny-1 w wielu guzach pozostaje w pełni do wyjaśnienia. Cel pracy: Celem badania była ocena możliwych związków pomiędzy ekspresją Caveoliny-1 i cechami klinicznopatologicznymi surowiczych guzów jajnika. Materiał i metoda: Ekspresję Caveoliny-1 oceniono w 82 tkankach surowiczych guzów jajnika utrwalonych w formalinie i zatopionych w parafinie i skorelowano z różnymi cechami kliniczno-patologicznymi. Wyniki: Do badania włączono 36 (43,9%) niezłośliwych, 12 (14,6%) granicznych i 34 (41,5%) złośliwych guzów surowiczych. Średnia wieku wynosiła 43,9±14,4 lat (17-72 lata). Analiza statystyczna wykazała, że im bardziej agresywny i inwazyjny był guz, tym bardziej tracił ekspresje Caveoliny-1 (p=0,001). Równolegle obserwowano zmiany ekspresji Caveoliny-1 w tkance łącznej i okołonaczyniowej. Wnioski: Nasze badania pokazują związek pomiędzy ekspresją Caveoliny-1 i złośliwością raka jajnika. Wydaje się, że Caveolina-1 może pełnić rolę biomarkera w diagnostyce różnicowej surowiczych guzów jajnika

Tissue expression of human epididymal secretory protein 4 may be useful in the differential diagnosis of uterine cervical tumors

Objectives: Human Epididymal Secretory Protein 4 was firstly described as an epididymis-specific protein but more recently it has been demonstrated to be a putative serum tumor marker for different malignancies, especially ovarian epithelial cancers. The aim of this study is to investigate the association between tissue Human Epididymal Secretory Protein 4 expression and the clinicopathological features of uterine cervical tumors. Material and methods: This retrospective study was designed to evaluate the differences of tissue expressions of Human Epididymal Secretory Protein 4 protein in a spectrum of cervical neoplasms. One hundred and seven patients recently diagnosed as having cervical intraepithelial neoplasm or invasive squamous cell carcinoma, adenosquamous carcinoma and adenocarcinoma based on pathology databases. Results: Decreased or negative Human Epididymal Secretory Protein 4 expressions were determined in both normal cervical epithelia and in intraepithelial carcinomas, while increased HE4 expression was observed in invasive tumors. Conclusions: This study demonstrated that altered expression of Human Epididymal Secretory Protein 4 may involve in tumorigenesis in the uterine cervix. Our findings also suggested the presence of a correlation between Human Epididymal Secretory Protein 4 expression and the invasive potential of uterine tumors. Therefore it may be thought that the tissue expression of HE4 can be used to differentiate high grade intraepithelial tumors from carcinomas

Četverogodišnja studija učinkovitosti i sigurnosti entekavira u bolesnika s kroničnim hepatitisom B pozitivnih na HBeAg bez prethodne nukleoz(t)idne terapije

Entecavir is a guanosine analogue with activity against hepatitis B virus. The aim of this 4-year trial was to evaluate entecavir treatment in nucleos(t)ide-naive HBeAg-positive chronic hepatitis B patients. Forty-nine patients received entecavir and nine of them withdrew from the trial at the end of week 96. The initial mean value of alanine aminotransferase was 79.4}41.5 IU /L, and at the end of the 4-year study period, 90% of patients had alanine aminotransferase values within the normal range. At week 96, 91.7% of patients had HBV DNA <300 copies; at month 48, 90% of patients had HBV DNA <50 IU /mL. HBeAg loss was recorded in 7.1% of patients at week 96 and in 12.5% at month 48. The rate of HBeAg seroconversion was 4.8% at week 96 and 7.5% at month 48. The rate of HBsAg seroconversion was 2.1% at week 96 and 2.5% at month 48. Entecavir as a potent and safe agent leading to continuous viral suppression proved to be safe and well tolerated therapy.Entekavir je analog gvanozina koji djeluje protiv virusa hepatitisa B. Cilj ove četverogodišnje studije bio je procijeniti liječenje entekavirom kod bolesnika s kroničnim hepatitisom B pozitivnih na HBeAg bez prethodne nukleoz(t)idne terapije. Ukupno je 49 bolesnika primalo entekavir, a devetoro ih se povuklo s terapije na kraju 96. tjedna. Početna srednja vrijednost alanin aminotransferaze bila 79,4}41,5 IU /L, dok je nakon 4 godine vrijednost alanin aminotransferaze bila u normalnim granicama kod 90% bolesnika. U 96. tjednu je <300 kopija HBV DNA zabilježeno u 91,7% bolesnika, a u 48. mjesecu je 48,90% bolesnika imalo <50 IJ/mL HBV DNA. Gubitak HBeAg zabilježen je u 7,1% bolesnika u 96. tjednu te u 12,5% bolesnika u 48. mjesecu. Stopa serokonverzije HBeAg iznosila je 4,8% u 96. tjednu i 7,5% u 48. mjesecu. Stopa serokonverzije HBsAg bila je 2,1% u 96. tjednu i 2,5% u 48. mjesecu. Sigurnost terapije bila je dobra. Bolesnici su dobro podnosili entekavir, snažan i siguran lijek koji dovodi do ustaljenog suzbijanja virusa

Prognostic impact of BCL2, BCL6 and MYC status in de novo diffuse large B-cell lymphoma: a regional study of 43 patients

Background: Diffuse large B-cell lymphoma (DLBCL) is an aggressive non-Hodgkin lymphoma with marked biologic heterogeneity. We aimed to evaluate the status of MYC, BCL2, BCL6 in patients with DLBCL.Methods: Herein, we have investigated the prognostic relevance of MYC, BCL2 and BCL6 from 43 de novo DLBCL patients.Results: In this study, protein overexpression of BCL2 and BCL6 was encountered in 46.5% (n=20) and 27.9% (n=12) of the tumors, respectively.  Rearrangements in MYC, BCL6, and BCL2 were detected in 9.3% (n=4), 25.6% (n=11), and 4.7% (n=2) of the cases, respectively. Any statistically significant difference could not be found between Bcl-2, Bcl-6 expression, C-MYC rearrangement and the survival.Conclusions: We concluded that C-MYC and BCL2 may contribute to aggressive transformation, so more mechanism-based therapy should be explored. A larger study is warranted to better understand the immunophenotypic and molecular features of DLBCL and their respective impact on patient survival

Evaluation of the Relationship of PD-L1 and FOXP3 Expressions With Clinicopathological Parameters in Gastric Carcinomas

Objective: At the time of diagnosis, gastric cancers are generally at an advanced stage and the survival rates are very low. The aim of this study is to determine the prognostic values of PD-L1 expression in gastric carcinomas and to detect the presence of FOXP3- positive Treg cells in tumor microenviroment. Method: In this study, PD-L1 and FOXP3 expressions were evaluated in 125 patients with gastric carcinoma who had undergone gastrectomy between 2011, and 2015. Results: The mean age of the patients was 64.18+-12.3 years and the patients were followed up for a mean period of 29.6+-26.4 months. In only 2 (1.6%) cases there were weak membranous expressions of PD-L1 in tumor cells. PD-L1- positive inflammatory cells were also seen in tumors of 2 (1.6%) cases. There was no significant relationship between PD-L1 expression and survival times (p= 0.690). In 57(45.6%) cases, FOXP3- positive lymphocytes were detected. The number of FOXP3-positive cells ranged between 1 and 55/HPF. There was no statistically significant correlation between the survival times and presence of Tregs (p=0.793). Twenty-two cases (17.6%) were evaluated as HER2-positive. There was a statistical relationship between HER2-positivity and perineural invasion (p=0.006). Statistical significance between survival and some prognostic factors such as nodal metastasis (p=0.004), pT stage (p&lt;0.01) and presence of perineural invasion (p=0.010) was determined. Conclusion: This study has demonstrated that the PD-L1 positivity was not effective on gastric tumorigenesis. We have found a positive correlation between the presence of Treg inflammatory cells and PD-L1 expression. But this relationship could not be proved by statistical analyses. However since PD-L1 expression was detected in only 4 cases, these findings should be confirmed in larger series

Intraarticular Giant Size Angiolipoma of the Knee Causing Lateral Patellar Dislocation

Background: Angiolipomas are benign tumors usually seen in patients during their 2nd and 3rd decades. The subcutaneous region of the trunk, neck and extremities are the places where they generally settle. There is only one case report on angiolipoma in the knee joint that was resected by arthroscopic procedure in the English literature. Case Report: We present a case of a giant-size multilobular non-infiltrating angiolipoma, extending outside of the right knee joint and causing lateral patellar dislocation in a thirteen-year-old boy. A large encapsulated mass with fatty and soft-tissue components on magnetic resonance imaging was suggestive of a liposarcoma. However, the diagnosis after the tru-cut biopsy was angiolipoma. The Quadriceps angle was 25°. Complete resection of the tumoral mass and repair of the medial retinaculum were performed with open surgery. Patellofemoral alignment was provided by transferring the tibial tuberosity medially. One year after the surgery, there was no evidence of recurrence. Conclusion: Intra-articular angiolipomas are rarely seen masses in the knee joint. To our knowledge, this case report is the first to demonstrate that angiolipoma causes patellar dislocation