Ovarian dysgerminomas are rare entity and account for only about 2% of all malignant ovarian neoplasm. The aim of this study was to evaluate the clinicopathologic characteristics, treatment, long-term survival, and fertility outcome of women diagnosed with ovarian dysgerminoma at our institution. Sixty-five women with histologically proven pure ovarian dysgerminoma were identified in this retrospective study. They were treated at King Faisal Specialist Hospital, Riyadh; Saudi Arabia between 1976 and 2010. The median age was 20 years. The most frequent symptoms at presentation were abdominal pain and abdominal/pelvic mass. Thirty-three patients (50.7%) presented with stage I, 2 (3.1%) had stage II, 22 (33.8%) had stage III, and 4 (6.2%) had stage IV (4 unknown stage). Unilateral oophorectomy was performed in 50 patients (76.9%) while bilateral oophorectomy±hysterectomy was done in 12 patients (18.4%). Three patients had biopsy only. Forty patients (61.5%) received only chemotherapy, and 4 patients (6.2%) received radiotherapy alone. Recurrence was observed in 6 patients (9.2%). With median follow-up of 54 months, the 5-year disease-free survival (DFS) and overall survival (OS) were 88 and 95%, respectively. On univariate analysis, adjuvant chemotherapy was independent better prognostic factor for DFS (HR, 0.09; 95% CI, 0.01-0.84; P=0.034). Of the 50 patients treated with fertility-sparing surgery, 16 patients (32%) achieved pregnancy with 14 live births. Patients with pure ovarian dysgerminoma have excellent long-term outcome. There is no difference at outcome between fertility-sparing and nonconservative surgeries. Adjuvant chemotherapy was associated with significant improvement in DFS. It is possible to maintain good reproductive function after conservative surgery followed by chemotherapy in our series.
The clinical spectrum of ciliopathies affecting motile cilia spans impaired mucociliary clearance in the respiratory system, laterality defects including heart malformations, infertility and hydrocephalus. Using linkage analysis and whole exome sequencing, we identified two recessive loss-of-function MNS1 mutations in five individuals from four consanguineous families: 1) a homozygous nonsense mutation p.Arg242* in four males with laterality defects and infertility and 2) a homozygous nonsense mutation p.Gln203* in one female with laterality defects and recurrent respiratory infections additionally carrying homozygous mutations in DNAH5. Consistent with the laterality defects observed in these individuals, we found Mns1 to be expressed in mouse embryonic ventral node. Immunofluorescence analysis further revealed that MNS1 localizes to the axonemes of respiratory cilia as well as sperm flagella in human. In-depth ultrastructural analyses confirmed a subtle outer dynein arm (ODA) defect in the axonemes of respiratory epithelial cells resembling findings reported in Mns1-deficient mice. Ultrastructural analyses in the female carrying combined mutations in MNS1 and DNAH5 indicated a role for MNS1 in the process of ODA docking (ODA-DC) in the distal respiratory axonemes. Furthermore, co-immunoprecipitation and yeast two hybrid analyses demonstrated that MNS1 dimerizes and interacts with the ODA docking complex component CCDC114. Overall, we demonstrate that MNS1 deficiency in humans causes laterality defects (situs inversus) and likely male infertility and that MNS1 plays a role in the ODA-DC assembly.
Hodgkin's lymphoma (HL) patients with positive 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) post salvage chemotherapy or before high-dose chemotherapy and auto-SCT (HDC ASCT) have inferior outcomes. We reviewed 21 prognostic factors before salvage chemotherapy (at relapse/progression) and integrated post salvage FDG-PET results to develop a prognostic model for post HDC ASCT outcome. We used Fine and Gray method for competing risk analysis and regression model for risks assessment and outcome. One hundred and forty-one patients had post salvage FDG-PET before HDC ASCT (median age 25.5 years); male/female 55%:45%, relapsed/refractory 43%:57%, median follow-up 33 months. Multivariate analysis identified HL International Prognostic Score X3 (P ¼ 0.001; hazard ratio (HR): 3.7 (1.6-8.3)) and post salvage positive FDG-PET (P ¼ 0.011; HR: 3.4 (1.3-8.9)) with higher hazard of disease-specific death (model P ¼ 0.0001). Cumulative incidence of disease-specific death with 0, 1, 2 risk factors was 7%:29%:52%, respectively (P ¼ 0.00003). For disease-specific event (persistent, progressive or relapsed disease), mediastinal involvement (P ¼ 0.024; HR: 2.7 (1.14-6.5)), B symptoms (P ¼ 0.027; HR: 2.1 (1.09-4.2)) and positive post salvage FDG-PET (P ¼ 0.001; HR: 3.3 (1.7-6.7)) were significant (model P ¼o0.00001). Cumulative incidence of disease-specific event with 0, 1, 2, 3 risk factors was 8%:31%:50%:75%, respectively (P ¼ 0.0000006). Patients with higher scores have higher risk of treatment failure. They are potential candidates for newer therapies along with HDC ASCT.
18F-fluorodeoxyglucose positron emission tomography (FDG-PET) documented response after salvage chemotherapy has been reported to impact survival in patients with aggressive non-Hodgkin's lymphoma, especially diffuse large B cell lymphoma (DLBCL) undergoing high dose chemotherapy and autologous SCT (HDC auto-SCT). We reviewed the impact of 19 different prognostic/ predictive factors before salvage chemotherapy and post-salvage chemotherapy FDG-PET results in patients with aggressive lymphoma and developed an FDG-PET integrated model for post-HDC auto-SCT outcome. The Fine and Gray method for competing risk analysis and a regression model was used to assess the risk associated with different factors on outcome. Fifty-five patients had FDG-PET after salvage chemotherapy; male 65%, female 45%, relapsed 55%, refractory 45%, DLBCL 82%, T cell lymphoma 18%, median age at auto-SCT 40 years, median follow-up 42.4 months. Multivariate analysis identified only positive FDG-PET (P ¼ 0.04) and mediastinal involvement (P ¼ 0.05) with higher hazard rate of disease-specific death (model P ¼ 0.008) but only positive FDG-PET (P ¼ 0.01) for disease-specific events (persistent, progressive or relapsed disease). Cumulative incidence of disease-specific death for patients with 0, 1 and 2 risk factors was 5, 30 and 62%, respectively (P ¼ 0.01). Our model is significant and showed an increasing risk of failure with mediastinal involvement and post-salvage positive FDG-PET.
Our results demonstrate that changes in tumor metabolic activity after neoadjuvant chemotherapy predicts PFS and OS in esophageal SCC patients.
BACKGROUND AND OBJECTIVEUterine papillary serous cancer (UPSC) represents only 10% of all uterine cancers and is associated with a significantly worse prognosis compared with other histological types of endometrial cancers. It closely resembles the behavior of ovarian carcinoma.DESIGN AND SETTINGRetrospective study in a referral center covering period from February 1989 to January 2009.PATIENTS AND METHODSEighteen patients who underwent definitive surgery followed by adjuvant therapy—platinum-based chemotherapy, radiotherapy, or both—were reviewed. Median age was 62 years (range, 52–76 years). All patients underwent total abdominal hysterectomy and salpingo-oophorectomy. Positive lymph nodes were found in 4 of 7 patients who underwent lymph node sampling/dissection. Seven patients had stage I/II disease, whereas 11 patients had stage III disease. Six patients received chemotherapy, 5 patients received radiation therapy, while 7 patients received both chemotherapy and radiation therapy.RESULTMedian follow-up was 27 months. The median survival and relapse-free survival were 33 and 23 months, respectively. Eight patients were alive and free of disease, of whom 5 patients were stage I/II and 4 patients were stage III. Distant metastasis was the most common site of relapse. Early stage (I/II) was associated with significant improvement in relapse-free survival (RFS) and overall survival (OS) (P=.004 and P=.05, respectively). The combined-modality treatment including chemotherapy-radiotherapy showed statistically significant improvement in RFS (P=.012), while the improvement in OS did not reach statistical significance (P=.12).CONCLUSIONThis study indicates that postoperative combined treatment with chemotherapy and radiation therapy plays a role in the management of UPSC by improving RFS. Distant metastasis remains the major site of relapse. Future studies using combined-modality therapy are needed to improve the outcome in patients with UPSC.
Producing accurate and comprehensible language requires grammatical and syntactic knowledge; however, language accuracy does not ensure avoiding miscommunication which arises from the inappropriate use of speech acts. Thus, speech acts are among the prominent areas that have been investigated in the field of Inter-language pragmatics (ILP). Hence, the current study examines the realizations of the speech act of refusal by young adult Egyptian students in their L1 (Egyptian Arabic) and L2 (English). The study also explores the socio-pragmatic features of Egyptian refusals in terms of power and distance. 2270 cases of refusals were collected by means of a Discourse Completion Task (DCT) and field notes. The sample consists of 200 DCTs and 60 instances of refusals extracted from field notes collected by the researcher from natural observations. The data are analyzed according to an adaptation of the taxonomy of refusal strategies (RS) by Beebe et al. (1990). The findings reflect a great amount of positive pragmatic transfer as most of the participants' refusals are indirect refusals. The main strategies that are used include statements of explanations, statements of alternatives, and statements of regret. In addition, adjuncts to refusals such as gratitude and positive opinion are used in refusals to interlocutors of equal and higher power. Furthermore, the results reveal an amount of negative pragmatic transfer in the participants' L2 refusals. Finally, practical implications and future recommendations are suggested based on the given results.
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