The protective effects of hormonal suppression by a gonadotropin-releasing hormone agonist or an oral contraceptive on the decreased ovarian reserve in female rats exposed to isotretinoin.

OBJECTIVE: The objective of our study was to evaluate whether ovarian suppression by two different hormonal methods may spare the ovary the cytotoxic effects of isotretinoin in a rat model. MATERIALS AND METHODS: Four groups (n=8 Sprague-Dawley albino rats per group) were studied: control (Group I), 7.5 mg/kg/day isotretinoin (Group II), isotretinoin plus the combination of 0.030 mg ethinyl estradiol/0.15 mg levonorgestrel (combined oral contraceptive, COC), and isotretinoin plus 100 µg (microgram) leuprolide acetate (GnRHa) (Group III and IV, respectively). Four rats from each group were decapitated on the 30th day of treatment, and the remaining rats were decapitated on the 30th day of untreated follow-up. Serum anti-Mullerian hormone (AMH) concentrations, healthy and atretic follicle numbers, and apoptotic activity of follicles in oophorectomy specimens were compared between the groups. RESULTS: There were no significant differences in AMH levels among the study groups before, immediately after (first month), and one month after their last medication (second month) (p=0.08, 0.47, and 0.08, respectively). At the end of the first month, the control group had a higher median count of healthy primordial follicles compared to the study groups: 13.5 (8-22), 5.5 (3-11), 6 (2-13), and 1 (0-1) in control, isotretinoin, isotretinoin+COC, and isotretinoin+GnRHa groups, respectively (p=0.02). However, there was no statistically significant difference in the number of healthy primordial follicles between the groups one month after the last medication (p=0.33). The median atretic antral follicle counts in the first month were 2 (1-4), 3.5 (1-4), 0 (0-2), and 0 (0-0) in the control, isotretinoin, isotretinoin+COC, and isotretinoin+GnRHa groups, respectively (p=0.02). Otherwise, there were no significant differences in other types of follicles among the control and treated groups (p>0.05). There was also no statistical difference between the groups regarding immunostaining intensity for active caspase-3 evaluated in the first or second month of treatment (p=0.8 and 0.2, respectively). CONCLUSIONS: Our results show that GnRH agonists or COC have no protective effects on ovarian reserve when co-administered with isotretinoin in the rat model.

Hypomorphic RAG deficiency: impact of disease burden on survival and thymic recovery argues for early diagnosis and HSCT.

Patients with hypomorphic mutations in the RAG1 or RAG2 gene present with either Omenn syndrome or atypical combined immunodeficiency with a wide phenotypic range. Hematopoietic stem cell transplantation (HSCT) is potentially curative, but data are scarce. We report on a worldwide cohort of 60 patients with hypomorphic RAG variants who underwent HSCT, 78% of whom experienced infections (29% active at HSCT), 72% had autoimmunity, and 18% had granulomas pretransplant. These complications are frequently associated with organ damage. Eight individuals (13%) were diagnosed by newborn screening or family history. HSCT was performed at a median of 3.4 years (range 0.3-42.9 years) from matched unrelated donors, matched sibling or matched family donors, or mismatched donors in 48%, 22%, and 30% of the patients, respectively. Grafts were T-cell depleted in 15 cases (25%). Overall survival at 1 and 4 years was 77.5% and 67.5% (median follow-up of 39 months). Infection was the main cause of death. In univariable analysis, active infection, organ damage pre-HSCT, T-cell depletion of the graft, and transplant from a mismatched family donor were predictive of worse outcome, whereas organ damage and T-cell depletion remained significant in multivariable analysis (hazard ratio [HR] = 6.01, HR = 8.46, respectively). All patients diagnosed by newborn screening or family history survived. Cumulative incidences of acute and chronic graft-versus-host disease were 35% and 22%, respectively. Cumulative incidences of new-onset autoimmunity was 15%. Immune reconstitution, particularly recovery of naïve CD4+ T cells, was faster and more robust in patients transplanted before 3.5 years of age, and without organ damage. These findings support the indication for early transplantation.

Basic characteristics and safety of donation in related and unrelated haematopoietic progenitor cell donors - first 10 years of prospective donor follow-up of Swiss donors.

Since July 2007 prospective life-long follow-up (FU) for unrelated (URD) and related donors (RD) is mandatory in Switzerland and data on every allogeneic haematopoietic progenitor cell (HPC) donation are collected prospectively. We report the real-world experience of HPC donation during a 10-year study period (01.07.2007-30.06.2017) with basic characteristics and FU data. 1105 donors underwent 1155 HPC donation procedures. Eighty percent of first donations performed by 802 (73%) RDs and 303 (27%) URDs were peripheral blood stem cells (PBSC), 20% bone marrow (BM). Male donors were over-represented as URD (60% male vs 40% female). Main differences between RDs and URDs concerned age and pre-existing health disorders. RDs were significantly older at first donation (median age 48 years) compared to URD (34 years, p < 0.0001) and had more pre-existing health problems: 25% vs 9% in URD (p < 0.0001). No fatal complications occurred, collection related severe adverse events (SAE) after first donation were not significantly different between groups (RD 1.2%, URD 0.99%), incidence rates for neoplastic and autoimmune diseases did not exceed the rates of the general population. RDs are a more heterogeneous and potentially more vulnerable group, but if donor evaluation is performed appropriately, HPC donation is still safe.

Clinical assessment of primary and secondary hypertension in children and adolescents.

The aim of this study was to compare the clinical features of patients with elevated blood pressure and to detect variables associated with the diagnosis of primary hypertension. We identified 383 (69%) hypertensive children (197 [51.5%] with primary hypertension, and 186 [48.5%] with secondary hypertension) out of 553 children referred to our clinic with a history of elevated blood pressure. The primary hypertension group was significantly older and had higher BMI, positive family history of hypertension, and lower prevalence of preterm birth compared with those with secondary hypertension. No difference was found between the two groups in terms of the frequency of target organ damage. Multiple regression analysis showed that a family history of hypertension, obesity, age over 10 years, elevated uric acid, and presence of higher systolic blood pressure values at admission were independent predictors of primary hypertension; therefore, these parameters can be considered important clues for diagnosing primary hypertension.

A Comparative Study: Flow Cytometry, Complement-dependent Cytotoxicity, and Luminex Methods.

AIM: The cell-based flow cytometric and bead-based Luminex crossmatch methods have been used alongside the standard complement-dependent cytotoxic crossmatch (CDCXM) test to detect donor specific anti-HLA antibodies. In this study, it was aimed to compare flow cytometric crossmatch (FCXM), CDCXM, and Luminex donor-specific crossmatch (LM-XM) tests for pre-transplant assessment of patients who applied to Tepecik Education and Research Hospital for kidney transplantation from related or deceased donors. METHOD: HLA tissue typing of 1120 patients were tested using the sequence specific oligonucleotide probe method with low resolution. FCXM and LM-XM were performed according to the manufacturer's instructions. The CDCXM test was performed according to the standard procedure. The results were analyzed using SPSS version 21.0 software (IBM, Armonk, NY, United States). P < .05 was accepted as statistically significant. RESULTS: FCXM, CDCXM, and LM-XM tests were performed on 58.2% (n = 652), 91% (n = 1019), and 55.4% (n = 620) of 1120 patients. There were statistically significant differences between FCXM/CDCXM, LM-XM/CDCXM, and FCXM/LM-XM (P < .0001), although there was also a moderate correlation between them (for class I, r = .599, r = .693, and r = .507; for class II, r = .546, r = .471, and r = .495, respectively). The results obtained according to donor type were compatible with the total study group. CONCLUSION: The utilization of FCXM and/or LM-XM tests together with the CDCXM method before kidney transplantations from related and/or deceased donor may facilitate the determination of target cells of donor-specific antibodies or their antibody class, which may increase the success of transplantation.

High-resolution HLA matching in unrelated donor transplantation in Switzerland: differential impact of class I and class II mismatches may reflect selection of nonimmunogenic or weakly immunogenic DRB1/DQB1 disparities.

Unrelated donor searches in Switzerland require high-resolution HLA typing for HLA-A/B/C/DRB1/DRB3,4/DQB1 loci. We evaluated this strategy accepting donors with ⩾9/10 match. Of 802 unrelated donor transplants in 2000-2013, 570 were 10/10 matched, 31 were DRB3/4 mismatched, 261 were single-allele mismatched and 13 had 2 allele mismatches. Of the 261 single-allele disparities, 60 concerned HLA-A/-B, 55 HLA-C and 73 HLA-DRB1/-DQB1 loci. Transplants were reduced intensity conditioning (289, 36%), marrow (187, 23%), EBMT risk score was low in 39, intermediate I in 331, intermediate II in 333 and high in 99 patients. Five-year survival was 48±4%. HLA affected survival in the multivariate model adjusted for risk score. HLA-A/-B and HLA-C mismatches had twice the mortality risks, whereas HLA-DRB1/-DQB1 mismatches were similar to matched transplants. HLA-DRB3/4 mismatches were associated with a nonsignificant increased mortality risk. HLA-DRB3/4 mismatches had higher graft-versus-host disease and transplant-related mortality risks and lower relapse rates compared with matched transplants. We show significant effects of HLA class I, but not HLA class II, mismatches. The lack of impact of DRB1 disparities may be related to the lower immunogenicity of the DRB1*11:01/11:04 and DRB1*14:01/14:54 mismatches, representing 46% of DRB1 incompatibilities. These results support a matching algorithm that prioritizes mismatches considered as more permissive.

Emergency peripartum hysterectomy: experience of a major referral hospital in Ankara, Turkey.

The objective of this study was to report and discuss the incidence, clinical characteristics and outcomes of emergency peripartum hysterectomies (EPH) performed at a tertiary referral hospital in Ankara, Turkey. The labour and delivery unit database was retrospectively analysed for emergency peripartum hysterectomies (EPH) performed between January 2008 and January 2013, at the Zekai Tahir Burak Women's Health Training and Research Hospital. A total of 92,887 deliveries were accomplished within the study period. EPH was performed in 48 cases, and the incidence was 0.51 in 1,000. Abnormal placentation was the most common indication for EPH. Most common complications were blood product transfusion and postoperative fever. None of the cases resulted in maternal mortality. Serious maternal complication rates were relatively low in our study. In cases that are unresponsive to initial conservative measures, EPH should be performed without delay and a multidisciplinary team approach should be conducted whenever possible.

Endometrial adenocarcinoma in young-aged women: a Turkish population study.

PURPOSE OF INVESTIGATION: The present study aims to investigate the incidence, clinicopathological features, and experience of treat- ment outcomes of patients with endometrial adenocarcinoma (EC) at ≤ 40 years of age in a gynecologic oncology reference center in Ankara, Turkey. MATERIALS AND METHODS: This retrospective study included 577 patients with EC, diagnosed and treated between 2007 and 2013. RESULTS: The incidence of EC ≤ 40 years of age was 5.1% (n: 30). The mean age at diagnosis was 35.5 (range: 27-40). Most of the patients with EC were overweight or obese. However, 23% had normal body mass index (BMI). Infertility was seen as a risk factor in 38.4%. The mean duration of postoperative follow-up was 38.3 months with rates of disease persistence and recurrence 14.2% and 28.5%, respectively. CONCLUSION: The disease is diagnosed usually in its early stage and has a good prognosis. Appropriately selected patients with fertility desire have the opportunity to conceive with conservative management.

Preoperative prediction of poor prognostic parameters and adjuvant treatment in women with pure endometrioid type endometrial cancer: what is the significance of tumor markers?

UNLABELLED: Summary PURPOSE OF THE STUDY: The study was conducted to determine whether preoperative serum levels of cancer antigen (CA) 125, CA15- 3, CA19-9, carcinoembryonic antigen (CEA), and alpha-fetoprotein (AFP) are associated clinicopathologically with poor prognostic parameters and adjuvant treatment requirements in women with pure endometrioid endometrial cancer (EEC). MATERIALS AND METHODS: The authors performed a retrospective review of EEC cases that were treated between January 2008 and January 2011. The association between preoperative tumor markers and prognostic parameters, recurrence risk, and adjuvant treatment requirements were investigated. Following univariate analyses, receiver-operating characteristic (ROC) curves were constructed for each marker to assess their capacity to predict prognostic parameters and need for adjuvant treatment. RESULTS: A total of 166 EEC cases were identified. Mean CA125, CA15-3, and CA19-9 levels were higher in cases that required adjuvant treatment (p < 0.05). CA125 had significant power for prediction of extrauterine disease, tumor size > two cm, lymphovascular space invasion (LVSI), deep myometrial invasion, cervical involvement, adnexal involvement, positive cytology, lymph node metastasis, and adjuvant treatment requirement. CA15-3 was a significant marker for adjuvant treatment prediction. CA19-9 could predict deep myometrial invasion, cervical involvement, and adjuvant treatment requirement. However, CEA and AFP did not have adequate capacity to predict any of the poor prognostic parameters and adjuvant treatment requirements. CONCLUSIONs: CA125 is currently one of the most important preoperative markers for identifying EEC cases that exhibit postoperatively poor prognostic pathologic findings and a consequent need for adjuvant treatment. CA15-3 and CA19- 9 were also significant markers with limited capacity in detecting prognostic parameters.

Rare ovarian tumors: a single center experience of 15 years.

OBJECTIVE: The present study aims to review cases of extremely rare primary ovarian tumors and thus, to evaluate the distribution of rare primary ovarian pathologies. Various aspects of the presentation, diagnosis, and treatment of these tumors are discussed. MATERIALS AND METHODS: A retrospective review of women with final pathology of rare primary ovarian tumors, which were managed at the Gynecologic Oncology Department of Zekai Tahir Burak Women's Health Education and Research Hospital, from 1995 to 2010 was undertaken. RESULTS: Among the 2,210 women treated during the study period, extremely rare ovarian tumors accounted for 1.62% (36/2210) of all cases. CONCLUSION: It is important to be aware of these rare entities in the pathological diagnosis of ovarian tumors. Intraoperative frozen examination should be performed because rare benign conditions that mimic malignancy may not require radical surgery. The rarity of these tumors renders basic scientific advances more challenging.

The impact of T-cell depletion techniques on the outcome after haploidentical hematopoietic SCT.

Several T-cell depletion (TCD) techniques are used for haploidentical hematopoietic SCT (HSCT), but direct comparisons are rare. We therefore studied the effect of in vitro TCD with graft engineering (CD34 selection or CD3/CD19 depletion, 74%) or in vivo TCD using alemtuzumab (26%) on outcome, immune reconstitution and infections after haploidentical HSCT. We performed a retrospective multicenter analysis of 72 haploidentical HSCT in Switzerland. Sixty-seven patients (93%) had neutrophil engraftment. The 1-year OS, TRM and relapse incidence were 48 (36-60)%, 20 (11-33)% and 42 (31-57)%, respectively, without differences among the TCD groups. In vivo TCD caused more profound lymphocyte suppression early after HSCT, whereas immune recovery beyond the second month was comparable between the two groups. Despite anti-infective prophylaxis, most patients experienced post-transplant infectious complications (94%). Patients with in vivo TCD had a higher incidence of CMV reactivations (54% vs 28%, P=0.015), but this did not result in a higher TRM. In conclusion, TCD by graft engineering or alemtuzumab are equally effective for haploidentical HSCT.

Apical extrusion of debris: a literature review of an inherent occurrence during root canal treatment.

Extrusion of intracanal debris as well as irrigants is a common occurrence during root canal treatment, and no instrument or technique has thoroughly solved this problem. Because flare-ups may arise with any irritation directed towards periapical tissues, a shaping or irrigation technique should minimize the risk of apical extrusion, even though it may not be prevented. There has been a rapid evolution of root canal instruments and irrigation systems through the last decade, and many have been assessed for their debris extrusion potential. The purpose of this review was to identify publications regarding the evaluation of debris, bacteria and irrigant extrusion during root canal treatment. A PubMed, Ovid and MEDLINE search was conducted using the keywords "apical extrusion", "debris extrusion" and "endodontic treatment". The literature search extended over a period of more than 30 years up to 2012. Content of the review was limited to apical extrusion of debris and irrigants, extrusion of liquid by irrigation methods and bacterial extrusion. Issues relevant to apical extrusion were obtained by further search in the reference sections of the retrieved articles. The review provides an update on the current status of apical extrusion.

Role of omentectomy and appendectomy in surgical staging of endometrioid endometrial cancer.

PURPOSE: The purpose of this study was to determine whether it was necessary to add omentectomy and appendectomy to the surgical staging of endometrioid endometrial cancer. MATERIALS AND METHODS: Records were reviewed from June 2005 to June 2009 for endometrioid endometrial cancer patients who underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, pelvic and para-aortic lymphadenectomy, infracolic omentectomy and appendectomy. RESULTS: In total, 186 patients were included in the analysis. Disease was limited to uterus in 93% of patients and 87% of patients had Stage I disease. There was only one omental metastasis and no appendix metastasis in all stages. CONCLUSION: Routine omentectomy and appendectomy are unnecessary in surgical staging of endometrioid endometrial cancer unless there is suspicion of gross metastases during intraoperative examination.

The impact of ultrasonographic lesion size and initial human chorionic gonadotropin values on treatment success in cases with complete hydatidiform mole.

OBJECTIVE: Our aim to assess the impact of sonographically measured lesion size and initial human chorionic gonadotropin levels on treatment success in cases of complete hydatidiform mole (CHM). PATIENTS AND METHODS: Patients with CHM diagnosed between January 2007 and January 2012 were included in the study. Clinical parameters such as patient age, fertility history, smoking, alcohol consumption, presenting symptom, pregnancy duration, ultrasonographic mean lesion size, beta-hCG level on admission, primary treatment method, beta-hCG normalization time (NT) and adjuvant treatments were recorded and analyzed. RESULTS: One hundred-twelve cases of CHM were identified in the study period. Mean patient age was 27.3 ± 8.2 years. Suction curettage was employed as the primary treatment in all of the study cases. No perioperative complications were encountered. None of the patients were treated with prophylactic adjuvant chemotherapy. Twelve patients (10.7%) required adjuvant chemotherapy. Beta-hCG NT did not have an association with patient age and initial beta-hCG levels (p > 0.05). Also, patient age, gravidity, parity, smoking, initial beta-hCG and ultrasonographic mean lesion size did not predict adjuvant chemotherapy requirement (p > 0.05). CONCLUSIONS: Early detection and treatment of CHM is associated with a favorable clinical outcome.

The use of a prostacyclin analog, iloprost, as an adjunct to uterus preservation with histidine-tryptophan-ketoglutarate solution.

INTRODUCTION: Although assisted reproductive techniques have made most causes of both male and female infertility treatable, uterine factor infertility is not able to therapy. Therefore, transplantation of the uterus has been suggested as a future possible cure. Organ preservation solutions seek to reduce reperfusion injury. Since iloprost is an antioxidant with cytoprotective properties, we investigated its potential positive effects in histidine-tryptophan-ketoglutarate (HTK) solution after 4 or 24 h cold storage period of the rat uterus. METHODS: We divided 24 female Wistar-albino rats into four groups: Group 1 had the uterus tissue stored in HTK solution at 4 °C for 4h. Group 2, the tissue was stored in HTK solution combined with iloprost (10(-8) M) for 4h at 4 °C. The same procedures were repeated for 24 h for Groups 3 and 4 respectively. Tissue levels of malondialdehyde (MDA) and nitric oxide (NO), as indicators of oxidative stress were determined with histopathological evaluations. RESULTS: MDA and NO levels were compared between the group 1 vs 3; and 2 vs 4. No significant difference was observed between the groups. Cold storage for 24 h produced alterations in histological appearances that were mitigated by the addition of iloprost to HTK solution. CONCLUSION: In conclusion, addition of iloprost to HTK solution reversed the histological alterations after 24h-cold storage of the rat uterus.

Vertical rectus abdominis myocutaneous flap for vaginal reconstruction after radical pelvic surgery for Stage II vaginal carcinoma.

Primary carcinomas of the vagina are uncommon, occurring only 2-3% of all gynecological malignancies. In women with early stage of disease, primary surgery, consisting of radical vaginectomy (plus hysterectomy in patients with tumors involving the upper vagina) and systematic dissection of lymphatic drainage of tumor, is a valid option. In these patients, a rectus abdominis myocutaneous (RAM) flap may be favorably used for vaginal reconstruction during radical pelvic surgery. Here we describe a case of Stage II vaginal carcinoma treated with radical pelvic surgery and vertical-RAM (V-RAM) flap reconstruction.