Epidemiological profile and clinico-pathological features of pediatric gynecological cancers at Moi Teaching & Referral Hospital, Kenya

Background: The main pediatric (0–18 years) gynecologic cancers include stromal carcinomas (juvenile granulosa cell tumors and Sertoli-Leydig cell tumors), genital rhabdomyosarcomas and ovarian germ cell. Outcomes depend on time of diagnosis, stage, tumor type and treatment which can have long-term effects on the reproductive career of these patients. This study seeks to analyze the trends in clinical-pathologic presentation, treatment and outcomes in the cases seen at our facility. This is the first paper identifying these cancers published from sub-Saharan Africa. Method: Retrospective review of clinico-pathologic profiles and treatment outcomes of pediatric gynecologic oncology patients managed at MTRH between 2010 and 2020. Data was abstracted from gynecologic oncology database and medical charts. Results: Records of 40 patients were analyzed. Most, (92.5%, 37/40) of the patients were between 10 and 18 years. Ovarian germ cell tumors were the leading histological diagnosis in 72.5% (29/40) of the patients; with dysgerminomas being the commonest subtype seen in 12 of the 37 patients (32.4%). The patients received platinum-based chemotherapy in 70% of cases (28/40). There were 14 deaths among the 40 patients (35%) Conclusion: Surgery remains the main stay of treatment and fertility-sparing surgery with or without adjuvant platinum-based chemotherapy are the standard of care with excellent prognosis following early detection and treatment initiation. LMICs face several challenges in access to quality care and that affects survival of these patients. Due to its commonality, ovarian germ cell cancers warrant a high index of suspicion amongst primary care providers attending to adnexal masses in this age group

The potential therapeutic role of lymph node resection in epithelial ovarian cancer: a study of 13 918 patients

The aim of the study is to determine the role of lymphadenectomy in advanced epithelial ovarian cancer. The data were obtained from the Surveillance, Epidemiology and End Results (SEER) program reported between 1988 and 2001. Kaplan–Meier estimates and Cox proportional hazards regression models were used for analysis. Of 13 918 women with stage III–IV epithelial ovarian cancer (median age: 64 years), 87.9% were Caucasian, 5.6% African Americans, and 4.4% Asians. A total of 4260 (30.6%) underwent lymph node dissections with a median number of six nodes reported. For all patients, a more extensive lymph node dissection (0, 1, 2–5, 6–10, 11–20, and >20 nodes) was associated with an improved 5-year disease-specific survival of 26.1, 35.2, 42.6, 48.4, 47.5, and 47.8%, respectively (P<0.001). Of the stage IIIC patients with nodal metastases, the extent of nodal resection (1, 2–5, 6–10, 11–20, and >20 nodes) was associated with improved survivals of 36.9, 45.0, 47.8, 48.7, and 51.1%, respectively (P=0.023). On multivariate analysis, the extent of lymph node dissection and number of positive nodes were significant independent prognosticators after adjusting for age, year at diagnosis, stage, and grade of disease. The extent of lymphadenectomy is associated with an improved disease-specific survival of women with advanced epithelial ovarian cancer

Plasma cells are not restricted to the CD27+phenotype: characterization of CD27-CD43+antibody-secreting cells

Circulating antibody-secreting cells are present in the peripheral blood of healthy individuals reflecting the continued activity of the humoral immune system. Antibody-secreting cells typically express CD27. Here we describe and characterize a small population of antibody-secreting class switched CD19+CD43+ B cells that lack expression of CD27 in the peripheral blood of healthy subjects. In this study, we characterized CD27-CD43+ cells. We demonstrate that class-switched CD27-CD43+ B cells possess characteristics of conventional plasmablasts as they spontaneously secrete antibodies, are morphologically similar to antibody-secreting cells, show downregulation of B cell differentiation markers, and have a gene expression profile related to conventional plasmablasts. Despite these similarities, we observed differences in IgA and IgG subclass distribution, expression of homing markers, replication history, frequency of somatic hypermutation, immunoglobulin repertoire, gene expression related to Toll-like receptors, cytokines, and cytokine receptors, and antibody response to vaccination. Their frequency is altered in immune-mediated disorders. Conclusionwe characterized CD27-CD43+ cells as antibody-secreting cells with differences in function and homing potential as compared to conventional CD27+ antibody-secreting cells.Stemcel biology/Regenerative medicine (incl. bloodtransfusion

Radiotherapy Versus Inguinofemoral Lymphadenectomy as Treatment for Vulvar Cancer Patients With Micrometastases in the Sentinel Node: Results of GROINSS-V II

PURPOSE: The Groningen International Study on Sentinel nodes in Vulvar cancer (GROINSS-V)-II investigated whether inguinofemoral radiotherapy is a safe alternative to inguinofemoral lymphadenectomy (IFL) in vulvar cancer patients with a metastatic sentinel node (SN). METHODS: GROINSS-V-II was a prospective multicenter phase-II single-arm treatment trial, including patients with early-stage vulvar cancer (diameter < 4 cm) without signs of lymph node involvement at imaging, who had primary surgical treatment (local excision with SN biopsy). Where the SN was involved (metastasis of any size), inguinofemoral radiotherapy was given (50 Gy). The primary end point was isolated groin recurrence rate at 24 months. Stopping rules were defined for the occurrence of groin recurrences. RESULTS: From December 2005 until October 2016, 1,535 eligible patients were registered. The SN showed metastasis in 322 (21.0%) patients. In June 2010, with 91 SN-positive patients included, the stopping rule was activated because the isolated groin recurrence rate in this group went above our predefined threshold. Among 10 patients with an isolated groin recurrence, nine had SN metastases > 2 mm and/or extracapsular spread. The protocol was amended so that those with SN macrometastases (> 2 mm) underwent standard of care (IFL), whereas patients with SN micrometastases (≤ 2 mm) continued to receive inguinofemoral radiotherapy. Among 160 patients with SN micrometastases, 126 received inguinofemoral radiotherapy, with an ipsilateral isolated groin recurrence rate at 2 years of 1.6%. Among 162 patients with SN macrometastases, the isolated groin recurrence rate at 2 years was 22% in those who underwent radiotherapy, and 6.9% in those who underwent IFL (P = .011). Treatment-related morbidity after radiotherapy was less frequent compared with IFL. CONCLUSION: Inguinofemoral radiotherapy is a safe alternative for IFL in patients with SN micrometastases, with minimal morbidity. For patients with SN macrometastasis, radiotherapy with a total dose of 50 Gy resulted in more isolated groin recurrences compared with IFL

Unilateral inguinofemoral lymphadenectomy in patients with early-stage vulvar squamous cell carcinoma and a unilateral metastatic sentinel lymph node is safe.

OBJECTIVE: Optimal management of the contralateral groin in patients with early-stage vulvar squamous cell carcinoma (VSCC) and a metastatic unilateral inguinal sentinel lymph node (SN) is unclear. We analyzed patients who participated in GROINSS-V I or II to determine whether treatment of the contralateral groin can safely be omitted in patients with a unilateral metastatic SN. METHODS: We selected the patients with a unilateral metastatic SN from the GROINSS-V I and II databases. We determined the incidence of contralateral additional non-SN metastases in patients with unilateral SN-metastasis who underwent bilateral inguinofemoral lymphadenectomy (IFL). In those who underwent only ipsilateral groin treatment or no further treatment, we determined the incidence of contralateral groin recurrences during follow-up. RESULTS: Of 1912 patients with early-stage VSCC, 366 had a unilateral metastatic SN. Subsequently, 244 had an IFL or no treatment of the contralateral groin. In seven patients (7/244; 2.9% [95% CI: 1.4%-5.8%]) disease was diagnosed in the contralateral groin: five had contralateral non-SN metastasis at IFL and two developed an isolated contralateral groin recurrence after no further treatment. Five of them had a primary tumor ≥30 mm. Bilateral radiotherapy was administered in 122 patients, of whom one (1/122; 0.8% [95% CI: 0.1%-4.5%]) had a contralateral groin recurrence. CONCLUSION: The risk of contralateral lymph node metastases in patients with early-stage VSCC and a unilateral metastatic SN is low. It appears safe to limit groin treatment to unilateral IFL or inguinofemoral radiotherapy in these cases

HIV-1 protease mutation 82M contributes to phenotypic resistance to protease inhibitors in subtype G.

OBJECTIVES: The purpose of this study was the qualitative and quantitative assessment of the in vitro effect of HIV-1 protease (PR) mutation 82M on replication capacity and susceptibility to the eight clinically available PR inhibitors (PIs).¦METHODS: The 82M substitution was introduced by site-directed mutagenesis in wild-type subtype B and G strains, as well as reverted back to wild-type in a therapy-failing strain. The recombinant viruses were evaluated for their replication capacity and susceptibility to PIs.¦RESULTS: The single 82M mutation within a wild-type subtype B or G background did not result in drug resistance. However, the in vitro effect of single PR mutations on PI susceptibility is not always distinguishable from wild-type virus, and particular background mutations and polymorphisms are required to detect significant differences in the drug susceptibility profile. Consequently, reverting the 82M mutation back to wild-type (82I) in a subtype G isolate from a patient that failed therapy with multiple other PR mutations did result in significant increases in susceptibility towards indinavir and lopinavir and minor increases in susceptibility towards amprenavir and atazanavir. The presence of the 82M mutation also slightly decreased viral replication, whether it was in the genetic background of subtype B or subtype G.¦CONCLUSIONS: Our results suggest that 82M has an impact on PI susceptibility and that this effect is not due to a compensatory effect on the replication capacity. Because 82M is not observed as a polymorphism in any subtype, these observations support the inclusion of 82M in drug resistance interpretation systems and PI mutation lists

Defining the surgical management of suspected early-stage ovarian cancer by estimating patient numbers through alternative management strategies

En el contexto de mejoramiento de la calidad de la educación en Chile, este estudio tiene como objetivo establecer si existe relación entre la creatividad,  las inteligencias múltiples y el rendimiento académico. Las pruebas de creatividad e inteligencias múltiples fueron aplicadas a 73 alumnos de 3º año de enseñanza media de la especialidad gráfica. Los estudiantes presentan una alta creatividad y un nivel medio en cuanto al desarrollo de las inteligencias múltiples. Existe una relación positiva entre la mayoría de las inteligencias múltiples con la creatividad, no obstante, es inexistente  la relación entre el rendimiento académico con la creatividad y también con las inteligencias múltiples. Se observa necesario incorporar, dentro del currículo escolar, metodologías que desarrollen la capacidad creativa y las inteligencias múltiples de los alumnos, instaurando en la práctica docente algunas estrategias innovadoras que permitan el máximo desarrollo de las capacidades de los alumnos y avanzar hacia una educación de alta calidad, considerando los aportes de la neuropsicología y de las Tecnologías de la Información y Comunicación (TIC)

EURADOS intercomparison on compartmental model for ₁₈F-FDG developed by Hays and Segall.

This report was originated from the analysis of the results of a joint EURADOS-EANM project about the assessment of the external radiation dose rate to comforters and caregivers exposed to patients undergoing nuclear medical diagnostics and therapy. The compartmental model for 18F-FDG developed by Hays and Segall in 1999 was applied by EURADOS members for predicting the time activity curves (TAC) in the source organs and tissues, and the urinary excretion. Inconsistencies have been found between the TAC and the time integrated activity coefficients (TIAC) calculated by EURADOS and those published by Hays and Segall and the Committee on Medical Internal Radiation Dose (MIRD). A quality assurance in form of an intercomparison on the implemented Hays and Segall compartmental model for 18F-FDG was carried out between four institutions of EURADOS voting members to validate the model predictions. The differences in calculated TIAC between EURADOS and MIRD results reach up to a factor of 3.2 by using arithmetic mean model parameters and 3.8 by using geometric mean parameters. The inconsistencies are under investigation in contact with MIRD Committee. A suggestion of updating the compartmental model for 18F-FDG with new available data is made