An Old Enemy: Still Nephrotoxic.

Tubulointerstitial nephritis (TIN) presents histopathologically as tubulitis and oedema/inflammation and fibrosis, affecting the renal tubules and interstitium with relative sparing of the glomeruli and vasculature. It can be acute or chronic or acute on chronic and has a wide range of etiologies. In this article, we report a case of a 44-year male who presented with acute TIN, associated with the use of diclofenac at therapeutic doses, that resolved with treatment but later progressed to chronic TIN after the patient resumed diclofenac therapy. The case is discussed in the context of literature regarding the nephrotoxic effects of nonsteroidal anti-inflammatory drugs (NSAIDs). Key Words: Nonsteroidal anti-inflammatory drugs, Acute kidney injury, Tubulointerstitial nephritis.

Does ovarian preservation have an effect on recurrence of early stage low-grade endometrial stromal sarcoma?

Surgical treatment of low-grade endometrial stromal sarcoma consists of hysterectomy. The role of oophorectomy is yet to be established. We aimed to examine the effect of preserving the ovaries on the pattern of recurrences in patients with stage I disease. Thirty-four patients with stage I low-grade endometrial stromal sarcoma were retrospectively analysed. Based on ovarian preservation the whole cohort was divided into two groups. Recurrence (liver, lung, groin and bone) was detected in 4 (11.8%) cases. No significant differences in overall survival or disease-free survival (DFS) were observed between the ovarian preservation and bilateral salpingo-oophorectomy (BSO) groups. Subset analysis revealed no significant difference in DFS between the ovarian preservation and BSO groups in the premenopausal arm. And also, the performance of pelvic (n = 2) or para-aortic lymphadenectomy (n = 6) or adjuvant hormonal therapy did not alter DFS significantly. The 5-year DFS rate for the group which received adjuvant radiotherapy was 62.5 and 94.4% for those which did not (p = .014). Preserving the ovaries had no adverse effect on the recurrence of stage I disease.IMPACT STATEMENTWhat is already known on this subject? Due to the rarity of the disease and the common postoperative diagnosis, only retrospective studies have been reported on low-grade endometrial stromal sarcoma. This disease is commonly diagnosed in premenopausal patients during the early stage. There is no consensus on preserving the ovaries, particularly in young patients, due to the tumour's hormonal characteristics and the risk of late recurrences.What do the results of this study add? Ovarian preservation had no effect on the recurrence of stage I low-grade endometrial stromal sarcoma. Lymphadenectomy and adjuvant hormonal treatment had no effect on DFS, and adjuvant radiotherapy decreased DFS in the current study.What are the implications of these findings for clinical practice and/or further research? Ovarian preservation should be considered, to prevent the negative effects of surgical menopause, particularly in young patients.

The effect of lymph node metastasis on overall survival and disease-free survival in vulvar cancer patients.

OBJECTIVES: To examine the effect of lymphadenectomy on survival in patients with squamous cell vulvar carcinoma. MATERIAL AND METHODS: Patients with squamous cell vulvar cancer who underwent surgery were retrospectively analyzed. All procedures were performed according to current recommendations/standard of treatment. The clinical and pathological features were examined. Sixty-eight patients were studied. The mean age was 64.7 ± 10.9 years. Twenty-three (33.8%) patients had nodal metastasis. Most patients (60.3%) were in stage IB. Adjuvant radiotherapy and chemo-radiotherapy were administered to 33.8% and 25% of the patients, respectively. The median follow-up time was 28.5 (4-183) months. Recurrence occurred in 18 (26.5%) cases. RESULTS: There was no significant difference between node-positive and node-negative patients in terms of age, number of dissected lymph nodes and recurrence. Tumor diameter was significantly higher in the metastatic group. Age and surgical margin positivity were independent prognostic factors for overall survival (OS). Surgical margin positivity and lymph node metastasis had no effect on disease-free survival (DFS). CONCLUSIONS: Our results showed that age and surgical margin positivity were independent prognostic factors for OS. Although surgical margin positivity increased the risk of recurrence in univariate analysis, it was not a significant factor affecting DFS. OS was significantly lower in patients with lymph node metastasis.

Impact of Subclinical Rejection on Kidney Graft Function.

BACKGROUND: In kidney transplant recipients with borderline infiltration, protocol biopsy results demonstrated the relationship with chronic injury. The purpose of this study was to evaluate the effect of subclinical rejection (SCR) on 6-month protocol biopsy results in long-term renal function in renal transplant recipients with stable graft function. MATERIAL AND METHODS: Transplant protocol biopsies performed in 45 patients with stable renal function were included in this study at 6 months. Biopsy specimens were evaluated for SCR. Study groups were divided into patients with and without SCR. Renal functions were compared with pathologic evaluation. The effect of immunosuppressive regimens on renal function were evaluated in patients with SCR RESULT: The median age of patients was 32 years (range, 18-64 years). The median follow-up was 56 months (range, 24-84 months). According to the 6-month protocol biopsy results, 20 of 45 patients (44.4%) met SCR criteria based on Banff 07 parameters. There was not a statistically significant difference in renal function with SCR. CONCLUSION: The presence of SCR on the 6-month protocol biopsy results in renal transplant recipients with a stable graft function does not cause deterioration in the long-term graft function.

Utility of the "floating ball sign" in diagnosis of ovarian cystic teratoma.

OBJECTIVE: To evaluate the incidence of the "floating ball" sign in cross-sectional imaging modalities in patients with ovarian teratoma, and to investigate the relationship between the morphologic features of the teratoma and this sign. MATERIALS AND METHODS: Preoperative computed tomography and magnetic resonance imaging studies of 112 women with a pathologic diagnosis of ovarian mature cystic teratoma (MCT) were reviewed for the presence of the floating ball sign. Tumor size, tumor characteristics and the number, size, and characteristics of floating globules were evaluated. RESULTS: In 112 patients (mean age 35.5±16 years, range 5-84 years), 118 ovarian MCTs were diagnosed pathologically. The floating ball sign was demonstrated in cross-sectional imaging in 30 (25.4%) patients. Among 2 of them, MCT was associated with malignancy (squamous cell carcinoma). There was a significant relationship between the floating ball sign, tumor size, and the wall thickness of the tumor (p=0.003 and p=0.018, respectively). In linear regression analysis, a similarly significant relationship was found between the presence of this sign and tumor size and patient age (p=0.003 and p=0.035, respectively). CONCLUSION: The floating ball sign, as a pathognomonic sign for the diagnosis of ovarian teratomas, seems to be more common than is known. Although this sign is almost always seen in MCTs, it may rarely be seen in teratomas with malignant transformation. The relationship of this sign with the characteristics of the tumor can provide an insight into the occurrence of these balls.

Una nueva variante del gen COL4A4 (c.1856G> A). De un caso de glomeruloesclerosis focal y segmentaria a una familia con síndrome de Alport / A novel COL4A4 gene variant (c.1856G>A): from a focal segmental glomerulosclerosis case to a family with Alport syndrome

El síndrome de Alport (SA), también conocido como nefritis hereditaria, es una forma progresiva hereditaria de enfermedad glomerular que a menudo se asocia con pérdida auditiva neurosensorial y anomalías oculares. Es causada por mutaciones en los genes que codifican varios miembros de las proteínas de colágeno del tipo IV, que se hallan en las membranas basales principalmente. Los análisis genéticos de las familias afectadas han identificado cuatro modos diferentes de transmisión en pacientes con síndrome de Alport. La forma del síndrome ligada al X surge a partir de mutaciones de COL4A5 y COL4A6 en el cromosoma X, mientras que las formas autosómicas resutan de defectos genéticos tanto en el gen COL4A3 como en el COL4A4, en el cromosoma 2q35-37. Las formas digénicas incluyen pacientes con mutaciones coexistentes en COL4A3, COL4A4 y COL4A5. El resultado clínico a largo plazo en pacientes con SA con mutaciones heterocigotas de COL4A3/A4es generalmente impredecible. La glomeruloesclerosis focal y segmentaria suele desarrollarse en el SA clásico en etapas posteriores y se presenta predominantemente con proteinuria asociada con hematuria. En el caso índice presentado en este informe, a un hombre de 26 años se le realizó una biopsia de riñón debido a una proteinuria nefrótica y una hematuria microscópica acompañada de una función renal alterada. Se le diagnosticó glomeruloesclerosis focal y segmentaria. Debido a que tenía una pérdida auditiva progresiva desde el inicio del estudio, se le realizó un estudio genético de mutaciones en los genes COL4A3 y COL4A4. Se detectó una nueva mutación en el gen COL4A4 (c.1804-7T> C).Debido a que sus padres tenían un matrimonio consanguíneo, el resto de la familia fue sometida a estudio para la misma variante. Sus padres y su hermana fueron heterocigotos y homocigota para la misma variante, respectivamente. En este estudio, se demostró la existencia de una familia con síndrome de Alport con una nueva mutación en el gen COL4A4 (c.1856G> A) que, según sabemos, es el primer caso reportado.

Alport syndrome, also known as hereditary nephritis, is an inherited progressive form of glomerular disease that is often associated with sensorineural hearing loss and ocular abnormalities. It is caused by mutations in genes encoding several members of type IV colagen proteins primarily found in basement membranes. Genetic analyses of affected families have identified four different modes of transmission in patients with Alport syndrome. X-linked form of the syndrome arises from mutations of COL4A5 and COL4A6 on chromosome X, whereas autosomal forms result from genetic defects in either the COL4A3 or COL4A4 genes at chromosome 2q35-37. Digenic forms include patients with coexisting mutations in COL4A3, COL4A4, and COL4A5. The long-term clinical outcome in AS patients with heterozygous COL4A3/A4 mutations is generally unpredictable. Focal segmental glomerulosclerosis usually develops in classical AS at later stages and presents predominantly with proteinuria associated with hematuria. The index case presented in this report, a 26-year-old man, had kidney biopsy because of nephrotic proteinuria and microscopic hematuria accompanied by impaired renal function. He diagnosed focal segmental glomerulosclerosis. As he had progressive hearing loss since chidhood we conducted a genetic study for mutations in COL4A3 and COL4A4 genes. A novel mutation in COL4A4 gene (c.1804-7T>C) was detected. As his parents had consanguineous marriage we investigated the rest of the family for the same variant. His parents, and his sister were found to be heterozygote, and homozygote for the same variant, respectively. In this report we demonstrated an Alport syndrome family with a novel mutation in COL4A4 gene (c.1856G>A) that has been first reported to our best knowledge.

Does lymphadenectomy effect postoperative surgical morbidity and survival in patients with adult granulosa cell tumor of ovary?

AIM: To evaluate the effect of lymphadenectomy on surgical morbidity and survival in adult granulosa cell tumor (AGCT) of the ovary. METHODS: Patients who underwent surgical treatment for AGCT between January 1993 and January 2016 were identified. Data were collected for patient age, menopausal status, surgical staging, lymphadenectomy, postoperative complications (anemia, wound infection, incisional hernia), length of hospital stay, follow-up duration, site and time for recurrence, management of recurrence and vital status. Histopathological records were also evaluated for number of cellular mitosis. RESULTS: Lymphadenectomy (pelvic-paraaortic) was performed in 53 (53%) of 98 patients. Decrease in postoperative hemoglobin level and increased wound infection and longer hospital stay were significantly higher in lymphadenectomy group (P = 0.003, 0.043 and <0.001, respectively). Tumor stage (HR 95% CI 14.9 [2.43-92.8]) and number of mitoses >5 (HR 95% CI 14.9 [2.43-92.8]) were significantly associated with recurrence (P = <0.001 and 0.02, respectively). Tumor stage was the only prognostic factor for predicting overall survival (HR 95% CI 8.47 [2.17-33.2]). Lymphadenectomy showed no effect on disease-free survival and overall survival both in multivariate Cox regression analyses (P = 0.46 and 0.69, respectively). Disease-free survival and overall survival were similar in lymphadenectomy and no lymphadenectomy groups (Log Rank P = 0.382, 0.741, respectively). CONCLUSION: Lymphadenectomy had no improved effect on survival and had negative effect on surgical morbidity in patients with AGCT.

Rectosigmoidectomy and Douglas Peritonectomy in the Management of Serosal Implants in Advanced-Stage Ovarian Cancer Surgery: Survival and Surgical Outcomes.

OBJECTIVE: This study aimed to evaluate the outcomes of rectosigmoid resection (RR) and Douglas peritonectomy (DP) on postoperative complications and survival in advanced-stage ovarian cancer surgery. METHODS/MATERIALS: Patients who underwent optimal cytoreductive surgery including RR and DP between January 2007 and January 2013 were included. Patients with deeper invasion into the muscularis and mucosal layer reported in pathology results and colon wall injury necessitating suturing or resection suggesting invasion of implants into the colon wall were excluded. The decision for RR or DP was made according to the surgical team and patients' preference. Resections were performed with the suspicion of colon wall invasion. The collected data were age, previous operations, preoperative cancer antigen 125 and albumin levels, surgical procedures, duration of surgery, tumor histology, recurrence, hyperthermic intraperitoneal chemotherapy, and length of hospital stay. Kaplan-Meir survival estimates were calculated and compared between the groups using the log-rank test. Cox proportional models were built to evaluate factors that affected disease-free and overall survival. RESULTS: Age, body mass index, preoperative cancer antigen 125 levels, albumin levels, and amount of ascites were similar between the groups. Neoadjuvant chemotherapy followed by interval debulking surgery was performed in 15% of both groups. End colostomy was performed in 23.7% of the RR group, and only 5.08% of the patients underwent diverting ileostomy procedures. There was no significant difference in terms of surgical complications between the groups. Recurrence occurred in the RR and DP groups at rates of 42% and 47%, respectively. Only primary debulking surgery had an effect on overall survival (odds ratio, 0.5; 95% confidence interval, 0.31-0.88). Overall survival and disease-free survival were similar in the RR and DP groups. CONCLUSIONS: Douglas peritonectomy showed similar survival and surgical outcomes to RR and provided shorter hospital stay and earlier admission to chemotherapy in the management of serosal implants during advanced-stage ovarian cancer surgery.

Preoperative Magnetic Resonance Volumetry in Predicting Myometrial Invasion, Lymphovascular Space Invasion, and Tumor Grade: Is It Valuable in International Federation of Gynecology and Obstetrics Stage I Endometrial Cancer?

OBJECTIVE: The aim of this retrospective single-center study was to evaluate the relationship between maximum tumor size, tumor volume, tumor volume ratio (TVR) based on preoperative magnetic resonance (MR) volumetry, and negative histological prognostic parameters (deep myometrial invasion [MI], lymphovascular space invasion, tumor histological grade, and subtype) in International Federation of Gynecology and Obstetrics stage I endometrial cancer. METHODS/MATERIALS: Preoperative pelvic MR imaging studies of 68 women with surgical-pathologic diagnosis of International Federation of Gynecology and Obstetrics stage I endometrial cancer were reviewed for assessment of MR volumetry and qualitative assessment of MI. Volume of the tumor and uterus was measured with manual tracing of each section on sagittal T2-weighted images. Tumor volume ratio was calculated according to the following formula: TVR = (total tumor volume/total uterine volume) × 100. Receiver operating characteristics curve was performed to investigate a threshold for TVR associated with MI. The Mann-Whitney U test, Kruskal-Wallis test, and linear regression analysis were applied to evaluate possible differences between tumor size, tumor volume, TVR, and negative prognostic parameters. RESULTS: Receiver operating characteristics curve analysis of TVR for prediction of deep MI was statistically significant (P = 0.013). An optimal TVR threshold of 7.3% predicted deep myometrial invasion with 85.7% sensitivity, 46.8% specificity, 41.9% positive predictive value, and 88.0% negative predictive value. Receiver operating characteristics curve analyses of TVR, tumor size, and tumor volume for prediction of tumor histological grade or lymphovascular space invasion were not significant. The concordance between radiologic and pathologic assessment for MI was almost excellent (κ value, 0.799; P < 0.001). Addition of TVR to standard radiologic assessment of deep MI increased the sensitivity from 90.5% to 95.2%. CONCLUSIONS: Tumor volume ratio, based on preoperative MR volumetry, seems to predict deep MI independently in stage I endometrial cancer with insufficient sensitivity and specificity. Its value in clinical practice for risk stratification models in endometrial cancer has to be studied in larger cohort of patients.

The prognostic significance of pdl1 and foxp3 expressions in tumor cells and the tumor microenvironment of ovarian epithelial tumors.

BACKGROUND: The aim of this study is to determine the prognostic values of PDL1 expression in ovarian epithelial tumors and to detect the presence of FOXP3-positive T reg cells in the tumor microenvironment. METHODS: This study included patients with benign, borderline or malignant ovarian serous tumors (n=82), mucinous cancer (n=17) and endometrioid cancer (n=36). FOXP3 and PDL1 were immunohistochemically evaluated and compared with histopathological and clinical prognostic parameters. RESULTS: There was no expression of PDL1 in any tumor cell. However, PDL1-positive inflammatory cells were seen in 10 cases (7.3%) with mucinous carcinoma (n=6), endometrioid carcinoma (n=2), borderline (n=1), and benign (n=1) serous tumors. It was also determined that there was a significant positive correlation between PD-L1 expression in tumor infiltrating cells and survival (P<0.01). In 47 (34.3%) cases, there were FOXP3-positive cells. The number of FOXP3-positive cells was significantly higher in ovarian cancer, especially in serous and endometrioid carcinomas, rather than benign and borderline tumors (P=0.007). But there was no statistically significant association between the survival times and the presence of T regs (P=0.241). CONCLUSIONS: This study demonstrated that the presence of FOXP3 and PDL1-positive regulatory T cells in TILs was associated with mainly malignant tumors. We also found that the presence of PD-L1-positive inflammatory cells has a positive effect on survival.

MELF Pattern for Predicting Lymph Node Involvement and Survival in Grade I-II Endometrioid-type Endometrial Cancer.

The aim of this study was to examine the associations between microcystic, elongated, and fragmented (MELF) pattern and other prognostic factors and lymph node involvement, disease-free survival, and overall survival (OS) using a case-control group consisting of grade I-II endometrioid endometrial carcinoma (EEC) patients with/without lymph node involvement. The files of the patients were searched electronically for all hysterectomy specimens with a diagnosis of grade I-II EEC of the uterine body from January 1, 2008 to July 31, 2014. Lymph node involvement was detected in 27 patients who were histologically diagnosed with grade I-II EEC, and these patients made up the case group. Using a dependent random sampling method, 28 grade I-II EEC patients without lymph node involvement were selected. According to multivariate regression analysis, lymphovascular space invasion [odds ratio, 23.5; 95% confidence interval (CI), 2.4-223.5] and MELF pattern (odds ratio, 13.3; 95% CI, 1.4-121.8) were significant predictors of lymph node involvement. There was recurrence in 15.8% of cases that showed a MELF pattern and in 19.4% of those that did not (P=0.738). According to Kaplan-Meier analysis, the MELF pattern revealed no significant differences in disease-free survival (hazard ratio, 1.0; 95% CI, 0.1-36.5), whereas the effect on OS was significant (hazard ratio, 2.2; 95% CI, 1.3-4.2). The presence of MELF pattern was a substantial risk factor for detecting lymph node involvement in patients with grade I-II EEC. The MELF pattern may be important for identifying which patients need staging surgery, in addition to its effect on the OS.

The Effect of Adenomyosis in Myometrial Invasion and Overall Survival in Endometrial Cancer.

AIM: The aim of this study was to evaluate whether adenomyosis had an effect on myometrial tumor invasion, stage of the disease, and survival in endometrial cancer. METHODS: Endometrial cancer patients encountered between 2007 and 2016 were identified from pathology records. Patients who underwent suboptimal surgical or medical treatment or with insufficient clinical or surgical data were excluded. Patients diagnosed as having concurrent adenomyosis constituted the study group. Control group patients were randomly selected in a paired design according to the tumor grades in the study group, and for each tumor grade, 4 times as many as patients were included. Tumor stage, histologic type and grade, myometrial invasion, lymphovascular space invasion, presence and location of the adenomyosis in myometrial wall, distance from endometrial line, tumor in adenomyosis, adjuvant treatment, and relapse were primary outcomes.Age, body mass index, medical comorbidities, and type of operation were also recorded. Univariate and multivariate Cox proportional hazards regression models were performed for overall survival. RESULTS: Of those 1242 endometrial cancer patients, 80 with concurrent adenomyosis were identified and compared with 320 patients without adenomyosis following a paired selection based on tumor grade. Higher rates of myometrial invasion, lymphovascular space invasion, tumor diameter, and adjuvant treatments were found in the nonadenomyosis group compared with adenomyosis group (P ≤ 0.001). In patients with adenomyosis, rates of early-stage disease and overall survival were significantly higher compared with the control group (P = 0.001 and 0.01, respectively). CONCLUSIONS: Our results showed that adenomyosis is significantly associated with lower stage in endometrial cancer that may suggest a possible limiting effect on endometrial cancer spread. In addition, despite similar rates in disease-free survival and endometrial cancer-related death, overall survival rate was significantly higher in the presence of adenomyosis and might be considered as a good prognostic factor for endometrial cancer.

Analysis of endometrial carcinoma in young women at a high-volume cancer center.

OBJECTIVE: To investigate the clinicopathological characteristics, treatment, survival, and prognosis of endometrial cancer in women aged ≤40 years. METHODS: Women who underwent surgery for endometrial cancer at a single high-volume cancer center between January 1995 and December 2014 were retrospectively reviewed. Women aged >40, patients with missing data, and those who did not undergo surgical staging were excluded. Univariate and multivariate regression models were used to identify the risk factors for overall survival and progression-free survival. RESULTS: A total of 40 patients with endometrial cancer were assessed. The median age at diagnosis was 38 (range, 21-40) years, and most of the uterine tumors found were early-stage (85%), low-grade (67.5%), and endometrioid carcinomas (97.5%). The median serum cancer antigen 125 level was 10.9 IU/mL (range, 3-1284 IU/mL). Optimal cytoreductive surgery was achieved in 35 patients (87.5%). All patients underwent total abdominal hysterectomy, and 97.5% of the patients underwent hysterectomy plus bilateral salpingo-oophorectomy. Among the total group of 40 patients, 21 (52.5%) underwent pelvic and para-aortic lymph node dissection, and 15 (37.5%) underwent only pelvic lymph node dissection. Multivariate analysis confirmed that a cancer antigen 125 level ≥35 was the only independent prognostic factor for both progression-free survival (hazard ratio, 22.997; 95% confidence interval, 1.783-296.536; p = 0.016) and overall survival (hazard ratio, 22.541; 95% confidence interval, 1.75-290.364; p = 0,017). CONCLUSIONS: Our study demonstrated that a cancer antigen 125 level ≥ 35 is the only independent prognostic factor for both progression-free survival and overall survival in patients aged ≤40 years with endometrial cancer.

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.

The evaluation of the caveolin-1 and AT-rich interactive domain 1 alpha expressions in uterine smooth muscle tumors.

OBJECTIVES: This retrospective study was designed to evaluate the importance of tissue expressions of caveolin-1 (Cav-1) and AT-rich interactive domain 1 alpha (ARID-1A) which are known as signal regulator and tumor suppressor in differential diagnosis of uterine smooth muscle tumors (SMTs). MATERIALS AND METHODS: Thirty patients recently diagnosed as uterine SMTs at the Tepecik Training and Research Hospital were identified using pathology databases. Immunohistochemical stains for Cav-1 and ARID-1A were performed. RESULTS: In this series, there were 10 leiomyosarcomas (LMSs), 10 uterine smooth muscle tumors of uncertain malignant potentials (STUMPs), and 10 leiomyomas (LMs). Cav-1 expression located cytoplasmic or perivascular area. Cytoplasmic Cav-1 expression was determined in 5 LMSs and 2 STUMPs while perivascular Cav-1 expression was determined in 9 LMSs and 2 STUMPs. Statistically, it was determined that if the tumor becomes malignant and more invasive, it gains the perivascular Cav-1 expression (P = 0.029). On the other hand, the mean nuclear staining rate for ARID-1A in LMSs (63 ± 23.4%) was higher than both STUMPs (60 ± 18.5%) and LMs (34.5 ± 16.5%). Statistically, it was determined that the expression of ARID-1A was significantly downregulated in LMs when compared with STUMPs and LMSs (P = 0.004). CONCLUSIONS: Our findings were demonstrated that perivascular Cav-1 expression was seen to be a marker for malignancy of uterine SMTs. Similarly, we found to link of ARID-1A expression and the aggressiveness of SMTs. Therefore, it may be suggested that Cav-1 and ARID-1A may act as predictive biomarkers in uterine SMTs.

Expression of caveolin-1 in peritumoral stroma is associated with histological grade in ovarian serous tumors.

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.

Differences in the ARID-1 alpha expressions in squamous and adenosquamous carcinomas of uterine cervix.

AT-rich interactive domain 1A (ARID1A) is a tumor suppressor gene involved in chromatin remodeling which encodes ARID1A (BAF250a) protein. Recent studies have shown the loss of ARID1A expression in several types of tumors. This retrospective study was designed to evaluate the differences in tissue expressions of ARID1A in a spectrum of cervical neoplasms. Cervical intraepithelial neoplasms, invasive squamous or adenosquamous carcinomas were identified in 100 patients recently diagnosed as cervical neoplasms based on pathology databases. In this series, there were 29 low- and 29 high-grade cervical intraepithelial neoplasms, 27 squamous cell carcinomas, and 15 adenosquamous carcinomas. Mean age of the patients was 47.8 ± 13 years (20-80 years). It was determined that the expression of ARID1A was statistically significantly down-regulated in adenosquamous carcinomas when compared with non-invasive or invasive squamous cell carcinomas (p = 0.015). Lower levels of the ARID1A expression were detected in cases with adenosquamous carcinomas (60%), low- or high-grade squamous intraepithelial lesion (SIL) (31%), and squamous cell carcinomas (18.5%). Our findings have demonstrated the presence of a correlation between ARID1A expression and adenomatous differentiation of uterine squamous cell carcinomas. Therefore, ARID1A gene may suggestively have a role in the pathogenesis of cervical adenosquamous carcinomas.

Experimental comparison of protective characteristics of enalapril and trimetazidine in diabetic nephropathy.

Abstract Hyperglycemia, hypertension, dyslipidemia, and inflammation have been proposed to account for the development of nephropathy in diabetic subjects. The beneficial effects of enalapril on diabetic nephropathy are known. However, the effects of trimetazidine (TMZ) are still unknown. We aimed at comparing the effects of the enalapril and TMZ treatment on fibronectin expression, inducible nitric oxide synthase expression, urine proteinuria, blood glucose and glomerular, and mesangial structures of kidney in rats that take streptozotocin (STZ). In this study, 32 male Sprague-Dawley albino mature rats of 8 weeks, weighing 200-220 g were used. Diabetes was induced by intraperitoneal injection of STZ (60 mg/kg) for 24 rats. We made four groups (Group 1: control, non-diabetic rats (n = 8), Group 2: diabetes, without treatment (n = 8), Group 3: diabetes treatment with enalapril (n = 8), Group 4: diabetes treatment with TMZ (n = 8). The positive effects of renal tissue and tubules in the mesangium immunohistochemical were shown in TMZ receiving rat groups. These positive effects were in parallel with the reduction in fibronectin and I-NOS expression and reduction in the proteinuria. TMZ and enalapril treatment of diabetic rats and renal parenchyma in this study are shown to have positive effects on the different levels.

A pitfall in transrectal prostate biopsy: malakoplakia evaluation of two cases based on the literature review.

Malakoplakia is a rarely seen inflammatory condition that is considered to develop secondary to a chronic Escherichia coli infection. Although malakoplakia usually affects the genitourinary tract, it may also be observed in the colon, stomach, lungs, liver, bones, uterus, and skin. Malakoplakia of the genitourinary system usually involves the bladder, whereas it may also affect the prostate along with the bladder. Malakoplakia of the prostate is very rare, and it may be clinically mistaken for prostatic malignancies. Definitive diagnosis is only possible through histopathological examination. This study elaborates on two patients who presented to our hospital in 2013 with high PSA levels. The primary clinical consideration was prostate carcinoma. However, these two cases were diagnosed as malakoplakia based on the results of histopathological analysis of the transrectal prostate biopsy specimen.