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BACKGROUND: Poly(ADP-ribose) polymerase (PARP) inhibitor maintenance therapy is the standard of care for some patients with advanced ovarian cancer. We evaluated the efficacy and safety of PARP inhibitor rechallenge. PATIENTS AND METHODS: This randomized, double-blind, multicenter trial (NCT03106987) enrolled patients with platinum-sensitive relapsed ovarian cancer who had received one prior PARP inhibitor therapy for ≥18 and ≥12 months in the BRCA-mutated and non-BRCA-mutated cohorts, respectively, following first-line chemotherapy or for ≥12 and ≥6 months, respectively, following a second or subsequent line of chemotherapy. Patients were in response following their last platinum-based chemotherapy regimen and were randomized 2 : 1 to maintenance olaparib tablets 300 mg twice daily or placebo. Investigator-assessed progression-free survival (PFS) was the primary endpoint. RESULTS: Seventy four patients in the BRCA-mutated cohort were randomized to olaparib and 38 to placebo, and 72 patients in the non-BRCA-mutated cohort were randomized to olaparib and 36 to placebo; >85% of patients in both cohorts had received ≥3 prior lines of chemotherapy. In the BRCA-mutated cohort, the median PFS was 4.3 months with olaparib versus 2.8 months with placebo [hazard ratio (HR) 0.57; 95% confidence interval (CI) 0.37-0.87; P = 0.022]; 1-year PFS rates were 19% versus 0% (Kaplan-Meier estimates). In the non-BRCA-mutated cohort, median PFS was 5.3 months for olaparib versus 2.8 months for placebo (HR 0.43; 95% CI 0.26-0.71; P = 0.0023); 1-year PFS rates were 14% versus 0% (Kaplan-Meier estimates). No new safety signals were identified with olaparib rechallenge. CONCLUSIONS: In ovarian cancer patients previously treated with one prior PARP inhibitor and at least two lines of platinum-based chemotherapy, maintenance olaparib rechallenge provided a statistically significant, albeit modest, PFS improvement over placebo in both the BRCA-mutated and non-BRCA-mutated cohorts, with a proportion of patients in the maintenance olaparib rechallenge arm of both cohorts remaining progression free at 1 year.
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Antineoplásicos , Carcinoma Epitelial de Ovario , Neoplasias Ováricas , Inhibidores de Poli(ADP-Ribosa) Polimerasas , Femenino , Humanos , Antineoplásicos/uso terapéutico , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Quimioterapia de Mantención , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/inducido químicamente , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Ftalazinas , Inhibidores de Poli(ADP-Ribosa) Polimerasas/uso terapéuticoRESUMEN
BACKGROUND: Homologous recombination repair (HRR) enables fault-free repair of double-stranded DNA breaks. HRR deficiency is predicted to occur in around half of high-grade serous ovarian carcinomas. Ovarian cancers harbouring HRR deficiency typically exhibit sensitivity to poly-ADP ribose polymerase inhibitors (PARPi). Current guidelines recommend a range of approaches for genetic testing to identify predictors of sensitivity to PARPi in ovarian cancer and to identify genetic predisposition. DESIGN: To establish a European-wide consensus for genetic testing (including the genetic care pathway), decision making and clinical management of patients with recently diagnosed advanced ovarian cancer, and the validity of biomarkers to predict the effectiveness of PARPi in the first-line setting. The collaborative European experts' consensus group consisted of a steering committee (n = 14) and contributors (n = 84). A (modified) Delphi process was used to establish consensus statements based on a systematic literature search, conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. RESULTS: A consensus was reached on 34 statements amongst 98 caregivers (including oncologists, pathologists, clinical geneticists, genetic researchers, and patient advocates). The statements concentrated on (i) the value of testing for BRCA1/2 mutations and HRR deficiency testing, including when and whom to test; (ii) the importance of developing new and better HRR deficiency tests; (iii) the importance of germline non-BRCA HRR and mismatch repair gene mutations for predicting familial risk, but not for predicting sensitivity to PARPi, in the first-line setting; (iv) who should be able to inform patients about genetic testing, and what training and education should these caregivers receive. CONCLUSION: These consensus recommendations, from a multidisciplinary panel of experts from across Europe, provide clear guidance on the use of BRCA and HRR deficiency testing for recently diagnosed patients with advanced ovarian cancer.
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Neoplasias Ováricas , Carcinoma Epitelial de Ovario/genética , Femenino , Humanos , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Inhibidores de Poli(ADP-Ribosa) Polimerasas/uso terapéutico , Reparación del ADN por RecombinaciónRESUMEN
OBJECTIVE: The phase IIIb OPINION trial (NCT03402841) investigated olaparib maintenance monotherapy in patients without a deleterious or suspected deleterious germline BRCA1/BRCA2 mutation (gBRCAm) who had platinum-sensitive relapsed ovarian cancer (PSROC) and had received ≥2 previous lines of platinum-based chemotherapy. METHODS: In this single-arm, open-label, international study, patients who had responded to platinum-based chemotherapy received maintenance olaparib tablets (300â¯mg twice daily) until disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed progression-free survival (PFS) (modified RECIST version 1.1). A key secondary endpoint was PFS by homologous recombination deficiency (HRD) and somatic BRCAm (sBRCAm) status. The primary analysis of PFS was planned for 18â¯months after the last patient received their first dose. RESULTS: Two hundred and seventy-nine patients were enrolled and received olaparib. At data cutoff (October 2, 2020), 210 PFS events had occurred (75.3% maturity) and median PFS was 9.2â¯months (95% confidence interval [CI], 7.6-10.9) in the overall population. At 12 and 18â¯months, 38.5% and 24.3% of patients were progression-free, respectively. In the predefined biomarker subgroups, median PFS was 16.4, 11.1, 9.7, and 7.3â¯months in sBRCAm, HRD-positive including sBRCAm, HRD-positive excluding sBRCAm, and HRD-negative patients, respectively. The most common treatment-emergent adverse events (TEAEs) were nausea (48.4%) and fatigue/asthenia (44.1%). TEAEs led to dose interruption, dose reduction, and treatment discontinuation in 47.0%, 22.6%, and 7.5% of patients, respectively. CONCLUSION: Maintenance olaparib demonstrated clinical benefit in patients without a gBRCAm, and across all subgroups, compared with historical placebo controls. There were no new safety signals.
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Recurrencia Local de Neoplasia , Neoplasias Ováricas , Ftalazinas , Piperazinas , Proteína BRCA1/genética , Proteína BRCA2/genética , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Carcinoma Epitelial de Ovario/genética , Femenino , Células Germinativas , Mutación de Línea Germinal , Humanos , Quimioterapia de Mantención , Mutación , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/genética , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Ftalazinas/efectos adversos , Piperazinas/efectos adversos , Platino (Metal)/uso terapéuticoRESUMEN
AIMS: To assess the number of people with diabetes in Poland using combined national sources and to evaluate the usefulness of data from an insurance system for epidemiological purposes. METHODS: The data were collected from four sources: 1) 2013 all-billing records of the national insurance system comprising people of all age groups undergoing procedures or receiving services in primary healthcare, specialist practices and hospitals and also those receiving drugs; 2) an epidemiological study, NATPOL, that involved the assessment of people with undiagnosed diabetes; 3) the RECEPTOmetr Sequence study on prescriptions; and 4) regional child diabetes registries. RESULTS: In 2013, 1.76 million people (0.98 million women and 0.79 million men) had medical consultations (coded E10-E14) and 2.13 million people (1.19 million women and 0.94 million men) purchased drugs or strip tests for diabetes. A total of 0.04 million people who used medical services did not buy drugs. In total, the number of people with diabetes in the insurance system was 2.16 million (1.21 million women and 0.95 million men), which corresponds to 6.1% (95% CI 6.11-6.14) of women and 5.1% (95% CI 5.12-5.14) of men. Including undiagnosed cases, the total number of people with diabetes in Poland was 2.68 million in 2013. CONCLUSION: The estimated prevalence of diabetes (diagnosed and undiagnosed cases) in Poland is 6.97%. Data from the national insurance system with full coverage of the population can be treated as a reliable source of information on diseases with well-defined diagnosis and treatment methods, combined with an assessment of the number of undiagnosed individuals.
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Diabetes Mellitus/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Glucemia/análisis , Niño , Preescolar , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/terapia , Diabetes Mellitus Tipo 1/epidemiología , Femenino , Humanos , Lactante , Recién Nacido , Reembolso de Seguro de Salud/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Programas Nacionales de Salud/estadística & datos numéricos , Polonia/epidemiología , Prevalencia , Adulto JovenRESUMEN
Background: Niraparib is a poly(ADP-ribose) polymerase inhibitor approved in the USA and Europe for maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy. In the pivotal ENGOT-OV16/NOVA trial, the dose reduction rate due to treatment-emergent adverse event (TEAE) was 68.9%, and the discontinuation rate due to TEAE was 14.7%, including 3.3% due to thrombocytopenia. A retrospective analysis was carried out to identify clinical parameters that predict dose reductions. Patients and methods: All analyses were carried out on the safety population, comprising all patients who received at least one dose of study drug. Patients were analyzed according to the study drug consumed (i.e., as treated). A predictive modeling method (decision trees) was used to identify important variables for predicting the likelihood of developing grade ≥3 thrombocytopenia within 30 days after the first dose of niraparib and determine cut-off points for chosen variables. Results: Following dose modification, 200 mg was the most commonly administered dose in the ENGOT-OV16/NOVA trial. Baseline platelet count and baseline body weight were identified as risk factors for increased incidence of grade ≥3 thrombocytopenia. Patients with a baseline body weight <77 kg or a baseline platelet count <150 000/µl in effect received an average daily dose â¼200 mg (median = 207 mg) due to dose interruption and reduction. Progression-free survival in patients who were dose reduced to either 200 or 100 mg was consistent with that of patients who remained at the 300 mg starting dose. Conclusions: The analysis presented suggests that patients with baseline body weight of <77 kg or baseline platelets of <150 000/µl may benefit from a starting dose of 200 mg/day. ClinicalTrials.gov ID: NCT01847274.
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Indazoles/administración & dosificación , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Piperidinas/administración & dosificación , Inhibidores de Poli(ADP-Ribosa) Polimerasas/administración & dosificación , Trombocitopenia/epidemiología , Administración Oral , Adulto , Peso Corporal , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Incidencia , Indazoles/efectos adversos , Quimioterapia de Mantención/efectos adversos , Quimioterapia de Mantención/métodos , Recurrencia Local de Neoplasia/sangre , Recurrencia Local de Neoplasia/mortalidad , Neoplasias Ováricas/sangre , Neoplasias Ováricas/mortalidad , Piperidinas/efectos adversos , Recuento de Plaquetas , Inhibidores de Poli(ADP-Ribosa) Polimerasas/efectos adversos , Supervivencia sin Progresión , Estudios Retrospectivos , Factores de Riesgo , Trombocitopenia/sangre , Trombocitopenia/inducido químicamenteRESUMEN
An increasing number of patients with diagnosed synchronous or metachronous neoplasms that arc gene as well as non-gene dependent which are associated with the development of new oncological treatment, and environmental factors, prompted the authors of this study to conduct an analysis in a narrow group of patients with multiple cancers and simultaneous BRCA1I mutations (confirmed by genetic analysis). BRCA1 mutation, as well as multiple cancers were found in seven patients treated between 2007 and 2013. The patients diagnosed with a second cancer shared a uniquely common trait - a 5382insC mutation. The study describes four patients that did not carry a BRCA 1/2 mutation, yet were diagnosed with multiple cancers. A brief review of literature was performed concerning multiple cancers in women.
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Genes BRCA1 , Genes BRCA2 , Mutación , Neoplasias Primarias Múltiples/genética , Femenino , HumanosRESUMEN
The authors present two cases of benign tumors one located on the outer surface of the vulva, and the second extending beyond the vagina. The first, originating from the right pudendal lip, a lipoma measuring 23 cm in greatest diameter, weighing 6.6 kg, and the second a pedunculated, uterine smooth muscle myoma with a pedicle of 6.5 cm, maximum diameter 18 cm, weight 700 grams, which caused significant metroptosis. Operative procedures in each case were free of complications.
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Lipoma/patología , Mioma/patología , Neoplasias de la Vulva/patología , Femenino , Humanos , Lipoma/cirugía , Persona de Mediana Edad , Mioma/cirugía , Carga Tumoral , Neoplasias de la Vulva/cirugíaRESUMEN
A case report of a 50-cm diameter and 20-kg mass of benign ovarian tumor. Total abdominal hysterectomy with a bilateral salpingooophorectomy was performed with full patient recovery. Fibrothecomas can remain long asymptomatic and can grow to giant sizes.
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Síndrome de Meigs , Neoplasias Ováricas , Ovariectomía/métodos , Neoplasia Tecoma , Femenino , Humanos , Síndrome de Meigs/diagnóstico , Síndrome de Meigs/fisiopatología , Síndrome de Meigs/cirugía , Persona de Mediana Edad , Neoplasias Ováricas/patología , Neoplasias Ováricas/cirugía , Neoplasia Tecoma/patología , Neoplasia Tecoma/cirugía , Resultado del Tratamiento , Carga TumoralRESUMEN
INTRODUCTION: High mortality rate, absence of reliable methods for early diagnosis and poor prognosis of advanced ovarian cancer prompted to investigate the role of prophylactic oophorectomy in BRCA1 mutation carriers as well as evaluate the expression of BRCA1, p53, Nm23, and KAI1 proteins in ovarian tissue from these patients. MATERIALS AND METHODS: Ovaries from BRCA1 mutation carriers underwent prophylactic adnexectomy and control group of patients were operated from other than cancer reasons. The expression of selected proteins was studied using immunohistochemical staining. The intensity of immunostaining and the number of tumor cells showing the reaction for selected proteins were analyzed. RESULTS: We have analyzed ovarian tissues from 18 BRCA1 mutation carriers and 11 women included in control group. Positive expression of BRCA1 protein was presented in 83.3 % cases in BRCA1 mutation carriers and in 72.7 % in the control group (p > 0.05). Positive expression of p53 protein was observed, respectively, in 27.8 vs. 36.4 % (p > 0.05), Nm23 protein 77.7 vs. 90.9 % (p > 0.05), and KAI1 in 72.2 vs. 72.7 % (p > 0.05). Mean percent of tumor cells that showed the reaction for selected proteins as well as the intensity of immunostaining for all analyzed proteins seems to be lower in BRCA1 mutation carriers. CONCLUSIONS: However, any significant differences between study group and control group have not been found; there were similar trends showing reduced expression of studied proteins in BRCA1 mutation carriers.
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Biomarcadores de Tumor/metabolismo , Síndrome de Cáncer de Mama y Ovario Hereditario/prevención & control , Ovariectomía , Ovario/metabolismo , Salpingectomía , Adulto , Proteína BRCA1/metabolismo , Estudios de Casos y Controles , Femenino , Genes BRCA1 , Predisposición Genética a la Enfermedad , Síndrome de Cáncer de Mama y Ovario Hereditario/genética , Síndrome de Cáncer de Mama y Ovario Hereditario/metabolismo , Humanos , Inmunohistoquímica , Proteína Kangai-1/metabolismo , Persona de Mediana Edad , Mutación , Nucleósido Difosfato Quinasas NM23/metabolismo , Ovario/cirugía , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
Angiogenesis is a dynamic process which leads to a development of cancer and metastases. The most recognized and dominant prognostic factor is vascular endothelial growth factor (VEGF) and its receptors. VEGF was identyfied in 1989. There are three receptors for VEGF: VEGFR1 (VEGF receptor 1) and VEGFR2 that play the role in angiogenesis and development of ascites, and VEGFR3 is critical for lymphangiogenesis. There is bevacizumab--a new drug, monoclonal antibody that can block connection VEGF to its receptors. The first notification of activity of bevacizumab in ovarian cancer was in 2005. The aim of the article is to show some clinical trials in ovarian cancer and their results. The bevacizumab was registered in November 2011 in first line with standard chemotherapy in ovarian cancer. There is a new weapon against this disease.
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Inhibidores de la Angiogénesis/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Neoplasias Ováricas/tratamiento farmacológico , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Bevacizumab , Ensayos Clínicos como Asunto , Femenino , Humanos , Neoplasias Ováricas/mortalidadRESUMEN
The unfolding pandemic necessitated optimalization of treatment methods and assurance of the highest precautionary standards to prevent transmission of COVID-19 to burn patients. One of them included an expanded access treatment with the minimally invasive method - enzymatic burn wound debridement using Nexobrid concentrate. The study assessed the effectiveness and usefulness of the expanded treatment project using enzymatic burn wound debridement with Nexobrid concentrate in patients (n=11) during the pandemic (2020) when compared with the results of the same method in a corresponding period of 2019. The concentrate was applied to the wound on the third day following injury at the latest. All patients were treated with the same accepted standards, including initial debridement of the wound, application of Nexobrid concentrate, and removal of devitalized tissue and dressing. Clinical visual assessment of the wound sites confirmed successful debridement of dead tissue following the application of the concentrate. No allergic or adverse reaction, nor significant deterioration of CBC parameters were observed in any patient. Although surgical excision of necrosis is recognized as the method of choice, enzymatic wound debridement using Nexobrid concentrate may contribute to a reduction in epidemiological risk when treating burn patients for several reasons; the procedure can be performed at the patient's bedside, it limits the number of required surgeries, helps to improve medical equipment and supplies management, and saves human resources.
La pandémie incontrôlée a nécessité une optimisation du traitement et des précautions d'hygiène maximales vis à vis des brûlés. Une d'entre elles consistait en l'utilisation de méthodes peu invasives dont l'excision enzymatique au Nexobrid . Cette étude compare l'efficacité et l'utilité l'utilisation larga manu de Nexobrid chez 11 patients pendant la période COVID (2020), comparée à son utilisation habituelle dans la période précédente. Ils bénéficiaient tout du même protocole à savoir nettoyage des plaies, application du Nexobrid au plus tard à J3 puis dépose du tissu nécrotique avec le pansement, confirmé par l'examen de la plaie. Nous n'avons observé ni allergie ni anomalie hématologique. Bien que la technique chirurgicale reste le traitement de référence, l'excision enzymatique peut limiter le risque épidémique qui y est lié car elle peut être réalisée au lit du patient, car elle diminue le nombre d'interventions chirurgicales, car elle permet d'améliorer les équipements, car elle diminue le nombre d'intervenants.
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OBJECTIVE: Olaparib is the poly-[Adenosine diphosphate ribose (ADP-ribose)] polymerase inhibitor (PARPI) used in maintenance therapy of patients with platinum-sensitive ovarian cancer with mutations in breast cancer genes 1/2 (BRCA1/2). Oncologists still do not have recommendations of treatment depending on efficient plasma concentrations of the PARP inhibitor. The aim of the study was the assessment of plasma trough concentrations of olaparib at steady state (Ctrough) in ovarian cancer patients. The severity of olaparib adverse effects (AEs) was noted. PATIENTS AND METHODS: The retrospective study involved 33 patients [mean standard deviation (SD)]; age 57.0 (8.4) years; weight 68.7 (13.7) kg; and body mass index (BMI) 26.4 (4.9) kg/m2, with ovarian cancer treated with olaparib (tablets in dose 300 mg/12 h, 250 mg/12 h, 200 mg/12 h or capsules 400 mg/12 h, 200 mg/12 h, 100 mg/12 h). Plasma drug levels were measured by HPLC-UV method (λ = 254 nm; Symmetry C8 column; gradient flow). The severity of olaparib AEs was assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5.0 scale. Drug interactions were analyzed. RESULTS: In total, 130 measurements (n) of Ctrough were determined in 33 patients (median sample frequency per patient was 4). The olaparib Ctrough in patients with AEs was 87.840-7,213.262 ng/mL [coefficient of variation (CV) = 91%], in patients without AEs 48.021-7,073.350 ng/mL (CV = 88%). AEs were the following: fatigue (modest, n = 4, severe, n = 2), anemia (grade G1 n = 66, G2 n = 6, G3 n = 3), neutropenia (grade G1 n = 15, G2 n = 4), prediabetes (n = 1). There was a correlation between Ctrough and olaparib-induced fatigue (p = 0.0015). The lower values of dose-adjusted olaparib concentrations (p = 0.0121) and dose/kg-adjusted olaparib concentrations (p = 0.0389) were correlated with higher grade of neutropenia. CONCLUSIONS: There was a correlation between Ctrough, expressed as ng/ml, ng/ml/mg or ng/ml/mg/kg, and fatigue degree, but not anemia. Patients with neutropenia had statistically significant lower plasma concentrations of olaparib.
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Neutropenia , Neoplasias Ováricas , Humanos , Femenino , Persona de Mediana Edad , Monitoreo de Drogas , Estudios Retrospectivos , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Ftalazinas/efectos adversos , Fatiga , Neutropenia/inducido químicamente , Neutropenia/tratamiento farmacológicoRESUMEN
Stevens-Johnson's Syndrome (SJS) and Toxic Epidermal Necrolysis are rare, life-threatening dermatologic conditions with acute onset and not clearly established treatment protocol. A plethora of observational studies are present with lack of up-to-date consensus based on evaluation of objective endpoints, among others mortality. Thorough analysis of available databases (Pubmed, EMBASE, Cinahl, Web of Science, Clinical Trials) was conducted according to PRISMA guidelines. Authors initially identified 700 papers, with 82 of them potentially eligible according to adopted criteria. A total of 42 studies were included into pooled synthesis. For continuous outcomes we analyzed the pooled means for endpoint scores using observed cases data. Categorical outcomes were analyzed by calculating the pooled event rates. We conducted subgroup and exploratory maximum likelihood random effects meta-regression analyses regarding SCORTEN of all outcomes. Using random-effects model, the overall pooled Mortality Rate was 0.191 (95%CI, 0.132-0.269). The lowest mortality rate was found to be linked with Etanercept and highest in Total Plasma Exchange (TPE) and Intravenous Immunoglobulin (IVIG). Overall reepithelization was 13.278 days (95%CI, 8.773-17.784),The highest was found in cyclosporine treatment; 14.739 whilst the lowest for steroids. Length of hospital stay in overall analysis was 19.99 days (95%CI, 16.53-23.44),the highest was linked with TPE/TPE+IvIg treatment, the lowest with steroids. Risk of bias of assessed studies was estimated to be high (for observational studies mean STROBE score 12.44). High quality TEN and SJS studies are lacking. Almost all papers report observational data without randomization and double-blind control. Therefore, the pooled analysis cannot be presented with initial bias. In our meta-analysis the most successful regimen was Etanercept treatment. It was linked with the lowest mortality. The most negative treatment outcome was observed in studies reporting TPE and IVIG. Randomized trials of high quality are needed in SJS and TEN.
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Quemaduras , Síndrome de Stevens-Johnson , Quemaduras/tratamiento farmacológico , Etanercept/uso terapéutico , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Tiempo de Internación , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Retrospectivos , Esteroides/uso terapéuticoRESUMEN
Procedures aimed at the treatment of precancerous lesions and ectopia on the uterine cervix are frequently linked to lesions of anatomical structures. The application of hyaluronic acid (Cicatridine vaginal ovules) promotes accelerated healing of the uterine cervix and acquisition of a normal shape in the uterine cervix canal. Local application of hyaluronic acid in the vagina following radiotherapy due to cancer in the uterine cervix or endometrium favourably affects the healing of post-irradiation lesions in the vagina and improves quality of life. Over 90% of patients responded positively to the application of hyaluronic acid in the form of a cream on dystrophic lesions in the vulva. Hyaluronic acid aids the healing process of post-procedural wounds in the uterine cervix, following radiotherapy applied due to cancer of the uterine cervix, endometrium and in vulvar dystrophy.
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Cuello del Útero/patología , Ácido Hialurónico/uso terapéutico , Neoplasias del Cuello Uterino/radioterapia , Neoplasias del Cuello Uterino/cirugía , Enfermedades Vaginales/tratamiento farmacológico , Enfermedades de la Vulva/tratamiento farmacológico , Cicatrización de Heridas , Femenino , Humanos , Regeneración , Vagina/patología , Vulva/patologíaRESUMEN
Both ghrelin and obestatin are derived from preproghrelin by post-translational processing. The two peptides are secreted into the blood but circulating levels of these peptides have not been assessed in women with ovarian tumours. Therefore, the purpose of this study was to evaluate peripheral blood concentrations of active and total ghrelin and obestatin in patients with benign ovarian tumours and those with ovarian cancer. The studies were conducted on 22 patients operated due to benign ovarian tumours, and 31 patients operated due to ovarian cancer. A control group consisted of 32 women, 24 to 65 years of age. Both in women with benign ovarian tumours and those with ovarian cancer blood concentrations of active ghrelin and obestatin were higher than in the control group (active ghrelin: 90 +/- 4, 84 +/- 4 and 56 +/- 9 pg/ml, respectively, obestatin: 660 +/- 36; 630 +/- 30 and 538 +/- 31 ng/ml (x +/- SE), respectively). In contrast, total ghrelin concentrations in blood were similar in the studied groups. The alterations resulted in increased values of active to total ghrelin concentration ratio in the peripheral blood of patients with benign ovarian tumours or with ovarian cancer (0.79 +/- 0.02 and 0.93 +/- 0.05, respectively vs 0.58 +/- 0.02 in the control group). Due to the absence of any convincing proof for the presence of a functional GHS-R-1a receptor for ghrelin in human ovaries it did not seem probable that the observed elevated levels of active ghrelin and obestatin were directly linked to development of ovarian tumours.
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Ghrelina/sangre , Neoplasias Ováricas/sangre , Neoplasias Ováricas/patología , Hormonas Peptídicas/sangre , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Humanos , Persona de Mediana Edad , Adulto JovenRESUMEN
OBJECTIVE: Epithelial ovarian cancer is a highly fatal gynecologic malignancy with a poor prognosis. Therefore, identification of new modifiable prognostic factors is important. Due to the fact that the effect of body weight changes during chemotherapy for EOC is still not very well known we aimed to describe, considering evidence, role of body weight changes in relation to survival. MATERIALS AND METHODS: Between October 2014 and August 2015 we systematically searched the following databases: Medline, Scopus, Web of Science and EMBASE to identify the studies describing the influence of body weight changes on survival in patients undergoing chemotherapy for EOC. RESULTS: We identified 601 potentially relevant publications, however finally only one article was included for data extraction and analysis. The overall survival in the selected paper was significantly associated with body weight changes during the first-line chemotherapy. Nevertheless, no influence on progression free survival was found. CONCLUSIONS: The analyzed data provides initial evidence, showing poorer overall survival associated with body weight loss and improved overall survival associated with body weight gain during primary chemotherapy for epithelial ovarian cancer. Prospective and retrospective trials are an urgent calling to confirm this conclusion.
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Peso Corporal , Neoplasias Glandulares y Epiteliales , Neoplasias Ováricas , Carcinoma Epitelial de Ovario , Femenino , Humanos , Neoplasias Glandulares y Epiteliales/tratamiento farmacológico , Neoplasias Glandulares y Epiteliales/mortalidad , Neoplasias Glandulares y Epiteliales/fisiopatología , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/fisiopatología , Estudios Retrospectivos , Análisis de SupervivenciaRESUMEN
BACKGROUND/OBJECTIVES: Coffee consumption has been hypothesized to be associated with blood pressure (BP), but previous findings are not homogeneous. The aim of this study was to evaluate the association between coffee consumption and the risk of developing hypertension. SUBJECTS/METHODS: Data on coffee consumption, BP and use of anti-hypertensive medicament were derived from 2725 participants of the Polish arm of the HAPIEE project (Health, Alcohol and Psychosocial factors In Eastern Europe) who were free of hypertension at baseline and followed up for an average of 5 years. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by multivariate logistic regression analyses and stratified for potential confounding factors. RESULTS: Coffee consumption was related to decreased age, smoking status and total energy intake. Compared with persons who drink <1 cup coffee per day, systolic BP was significantly associated with coffee consumption and the risk of hypertension was lower for individuals consuming 3-4 cups per day. Despite the analysis stratified by gender showed that the protective effect of coffee consumption on hypertension was significant only in women, the analysis after stratification by smoking status revealed a decreased risk of hypertension in non-smokers drinking 3-4 cups of coffee per day in both sexes (OR 0.41, 95% CI: 0.21, 0.79 for men and OR 0.54, 95% CI: 0.29, 0.99 for women). Upper category coffee consumption (>4 cups per day) was not related to significant increased risk of hypertension. CONCLUSIONS: Relation between coffee consumption and incidence of hypertension was related to smoking status. Consumption of 3-4 cups of coffee per day decreased the risk of hypertension in non-smoking men and women only.
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Coffea/efectos adversos , Café/efectos adversos , Dieta/efectos adversos , Conducta Alimentaria , Hipertensión/etiología , Fumar/efectos adversos , Estudios de Cohortes , Femenino , Humanos , Hipertensión/epidemiología , Incidencia , Modelos Logísticos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Polonia/epidemiología , Factores de RiesgoRESUMEN
BACKGROUND: Psychosocial factors at work are thought to influence health partly through health behaviours. AIMS: To examine the association between effort-reward imbalance and job control and several alcohol related measures in three eastern European populations. METHODS: A cross-sectional study was conducted in Novosibirsk (Russia), Krakow (Poland), and Karvina (Czech Republic). The participants completed a questionnaire that included effort-reward at work, job control, and a number of sociodemographic variables. Annual alcohol intake, annual number of drinking sessions, the mean dose of alcohol per drinking session, and binge drinking (> or =80 g of ethanol in one session at least once a week) were based on graduated frequencies in the questionnaire. Data were also available on problem drinking (> or =2 positive answers on CAGE questionnaire) and negative social consequences of drinking. All male participants in full employment (n = 694) were included in the present analyses. RESULTS: After controlling for age and centre, all indices of alcohol consumption and problem drinking were associated with the effort-reward ratio. Adjustment for material deprivation did not change the results but adjustment for depressive symptoms reduced the estimated effects. Job control was not associated with any of the alcohol related outcomes. CONCLUSIONS: The imbalance of effort-reward at work is associated with increased alcohol intake and problem drinking. The association appears to be partly mediated by depressive symptoms, which might be either an antecedent or a consequence of men's drinking behaviour.
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Consumo de Bebidas Alcohólicas/psicología , Empleo/psicología , Factores de Edad , Consumo de Bebidas Alcohólicas/epidemiología , Intoxicación Alcohólica , Estudios Transversales , República Checa/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Polonia/epidemiología , Recompensa , Federación de Rusia/epidemiología , Factores Socioeconómicos , Lugar de TrabajoRESUMEN
Thrombosis plays a major role in the development of atherosclerosis and its acute vascular complications. Epidemiological studies have shown that elevated levels of plasma fibrinogen are associated with an increased risk of coronary heart disease (CHD). It is not clear whether this association is linked to hemostatic functions of fibrinogen which serves as a substrate for thrombin. Generation of thrombin in vivo can be evaluated by measurement of its specific markers in plasma, i.e. thrombin-antithrombin III complex (TAT) and prothrombin fragment 1 + 2 (F1 + 2). We determined plasma levels of TAT and F1 + 2 in a population sample of southeastern Poland and evaluated relations of these markers with plasma fibrinogen, factor VII coagulant activity (FVIIc), and other known CHD risk factors. The population studied consisted of 215 men and 251 women, aged 43-75 years. Final analysis was performed on 195 men and 222 women. The distribution of plasma TAT and F1 + 2 concentrations were highly skewed with the higher median values for women than for men. Log values of TAT correlated with log values of F1 + 2 in men (r = 0.27, p < 0.01) and in women (r = 0.15, p < 0.05). In the regression analysis both markers were positively related to age in women but not in men. After adjustment to age there was a positive relation between TAT and fibrinogen in both sexes. In women, but not in men, F1 + 2 showed a positive association with FVIIc. Total plasma cholesterol was negatively related to TAT in women only. There was no association between thrombin generation markers and plasma triglycerides, HDL-cholesterol, LDL-cholesterol, blood pressure, cigarette smoking and body mass index (BMI). The association of plasma fibrinogen and FVIIc with thrombin generation markers points to an important role of the hemostatic system in the pathogenesis of atherosclerosis and coronary heart disease in humans.