RESUMO
BACKGROUND: Patients with metastatic castration-resistant prostate cancer (mCRPC) and BRCA alterations have poor outcomes. MAGNITUDE found patients with homologous recombination repair gene alterations (HRR+), particularly BRCA1/2, benefit from first-line therapy with niraparib plus abiraterone acetate and prednisone (AAP). Here we report longer follow-up from the second prespecified interim analysis (IA2). PATIENTS AND METHODS: Patients with mCRPC were prospectively identified as HRR+ with/without BRCA1/2 alterations and randomized 1 : 1 to niraparib (200 mg orally) plus AAP (1000 mg/10 mg orally) or placebo plus AAP. At IA2, secondary endpoints [time to symptomatic progression, time to initiation of cytotoxic chemotherapy, overall survival (OS)] were assessed. RESULTS: Overall, 212 HRR+ patients received niraparib plus AAP (BRCA1/2 subgroup, n = 113). At IA2 with 24.8 months of median follow-up in the BRCA1/2 subgroup, niraparib plus AAP significantly prolonged radiographic progression-free survival {rPFS; blinded independent central review; median rPFS 19.5 versus 10.9 months; hazard ratio (HR) = 0.55 [95% confidence interval (CI) 0.39-0.78]; nominal P = 0.0007} consistent with the first prespecified interim analysis. rPFS was also prolonged in the total HRR+ population [HR = 0.76 (95% CI 0.60-0.97); nominal P = 0.0280; median follow-up 26.8 months]. Improvements in time to symptomatic progression and time to initiation of cytotoxic chemotherapy were observed with niraparib plus AAP. In the BRCA1/2 subgroup, the analysis of OS with niraparib plus AAP demonstrated an HR of 0.88 (95% CI 0.58-1.34; nominal P = 0.5505); the prespecified inverse probability censoring weighting analysis of OS, accounting for imbalances in subsequent use of poly adenosine diphosphate-ribose polymerase inhibitors and other life-prolonging therapies, demonstrated an HR of 0.54 (95% CI 0.33-0.90; nominal P = 0.0181). No new safety signals were observed. CONCLUSIONS: MAGNITUDE, enrolling the largest BRCA1/2 cohort in first-line mCRPC to date, demonstrated improved rPFS and other clinically relevant outcomes with niraparib plus AAP in patients with BRCA1/2-altered mCRPC, emphasizing the importance of identifying this molecular subset of patients.
Assuntos
Acetato de Abiraterona , Neoplasias de Próstata Resistentes à Castração , Masculino , Humanos , Prednisona , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/genética , Proteína BRCA1/genética , Reparo de DNA por Recombinação , Resultado do Tratamento , Proteína BRCA2/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
BACKGROUND: Peritoneal metastasis (PM) is currently treated with the complex procedure of cytoreductive surgery and hyperthermic intra-peritoneal chemotherapy (CRS + HIPEC). This procedure presents high morbidity and mortality rates, but they have only been examined in the immediate post-operative period. The aim of our study is to present, describe and analyze the post-operative events, secondary to a cytoreductive surgery and HIPEC procedure that occurs after the patients' discharge from the hospital. PATIENTS AND METHODS: We examine retrospectively 219 patients who were discharged from our hospital from the initial 230 patients with PM, who were operated on from August 2005 to August 2015 and underwent CRS and HIPEC. Complications are investigated from the patient's discharge date until the 90th post-operative day, and are categorized with the Clavien-Dindo classification. RESULTS: We identified 17 patients (7.8%) who developed late complications. No major differences in patient characteristics were identified between this group of 17 patients and the rest, apart from a slightly higher PCI (23.5 vs. 22.3). Mean length of stay at the re-admission was 11.7 days. 5 of the patients (29.4%) had to be re-operated on, whereas we found a mortality of 11.8% (2/17 patients). The most common complications involved abdominal abscesses (17.6%), ureteral strictures (17.6%) and enterocutaneous fistulae (17.6%). CONCLUSION: Our study highlights the late complications following CRS plus HIPEC procedures, that occur after the patient's discharge from the hospital, an issue that has not been investigated thoroughly yet and may have serious impact on the post-operative quality of life. The role of adjuvant chemotherapy following CRS and HIPEC procedures in the onset of such complications appears to be important and needs further investigation.
Assuntos
Quimioterapia do Câncer por Perfusão Regional/efeitos adversos , Procedimentos Cirúrgicos de Citorredução/efeitos adversos , Readmissão do Paciente/estatística & dados numéricos , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia do Câncer por Perfusão Regional/métodos , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução/métodos , Diagnóstico Tardio , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Alta do Paciente/estatística & dados numéricos , Neoplasias Peritoneais/mortalidade , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/terapia , Estudos Retrospectivos , Medição de Risco , Taxa de Sobrevida , Fatores de TempoRESUMO
The first St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) Expert Panel identified and reviewed the available evidence for the ten most important areas of controversy in advanced prostate cancer (APC) management. The successful registration of several drugs for castration-resistant prostate cancer and the recent studies of chemo-hormonal therapy in men with castration-naïve prostate cancer have led to considerable uncertainty as to the best treatment choices, sequence of treatment options and appropriate patient selection. Management recommendations based on expert opinion, and not based on a critical review of the available evidence, are presented. The various recommendations carried differing degrees of support, as reflected in the wording of the article text and in the detailed voting results recorded in supplementary Material, available at Annals of Oncology online. Detailed decisions on treatment as always will involve consideration of disease extent and location, prior treatments, host factors, patient preferences as well as logistical and economic constraints. Inclusion of men with APC in clinical trials should be encouraged.
Assuntos
Adenocarcinoma/terapia , Antagonistas de Androgênios/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Conservadores da Densidade Óssea/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/terapia , Neoplasias da Próstata/terapia , Taxoides/uso terapêutico , Adenocarcinoma/patologia , Antineoplásicos/uso terapêutico , Docetaxel , Humanos , Masculino , Orquiectomia , Guias de Prática Clínica como Assunto , Prostatectomia , Neoplasias da Próstata/patologia , Neoplasias de Próstata Resistentes à Castração/patologia , Radioterapia AdjuvanteRESUMO
BACKGROUND: The current treatment of ovarian cancer consists of cytoreductive surgery (CRS) and systemic chemotherapy. The aim of this study was to examine if hyperthermic intraperitoneal chemotherapy (HIPEC) is an alternative modality to treat this category of patients along with a second attempt of surgical resection and second- or third-line systemic chemotherapy afterward. METHODS: In an 8-year period (2006-2013), 120 women with advanced ovarian cancer (International Federation of Gynecology and Obstetrics [FIGO] IIIc and IV) who experienced disease recurrence after initial treatment with conservative or debulking surgery and systemic chemotherapy were randomized into two groups. Group A comprised 60 patients treated with CRS followed by HIPEC and then systemic chemotherapy. Group B comprised 60 patients treated with CRS only and systemic chemotherapy. RESULTS: The mean survival for group A was 26.7 versus 13.4 months in group B (p < 0.006). Three-year survival was 75 % for group A versus 18 % for group B (p < 0.01). In the HIPEC group, the mean survival was not different between patients with platinum-resistant disease versus platinum-sensitive disease (26.6 vs. 26.8 months). On the other hand, in the non-HIPEC group, there was a statistically significant difference between platinum-sensitive versus platinum-resistant disease (15.2 vs. 10.2 months, p < 0.002). Complete cytoreduction was associated with longer survival. Patients with a peritoneal cancer index score of <15 appeared also to have longer survival. CONCLUSIONS: The use of HIPEC along with the extent of the disease and the extent of cytoreduction play an important role in the survival of patients with recurrence in an initially advanced ovarian cancer.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Procedimentos Cirúrgicos de Citorredução/mortalidade , Hipertermia Induzida/mortalidade , Recidiva Local de Neoplasia/terapia , Neoplasias Epiteliais e Glandulares/terapia , Neoplasias Ovarianas/terapia , Neoplasias Peritoneais/terapia , Carcinoma Epitelial do Ovário , Terapia Combinada , Feminino , Seguimentos , Humanos , Injeções Intraperitoneais , Metástase Linfática , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Neoplasias Epiteliais e Glandulares/mortalidade , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/mortalidade , Neoplasias Peritoneais/secundário , Prognóstico , Estudos Prospectivos , Taxa de SobrevidaRESUMO
BACKGROUND: Anti-thymocyte globulin (ATG) has been used to prevent graft failure/rejection in the setting of allogeneic stem cell transplantation (allo-SCT) for hemoglobinopathies; however, epidemiology data for transplant-related infections in this population are scarce. METHOD: We retrospectively analyzed the epidemiology of bacterial, fungal, viral, and parasitic infections in a cohort of 105 children and adolescents with ß-thalassemia (n = 100) or sickle cell disease (n = 5) who underwent allo-SCT using human leukocyte antigen (HLA)-identical sibling (n = 96) or HLA-compatible unrelated donors (n = 9) in a single institution. All patients received an ATG-based conditioning regimen. RESULTS: The cumulative incidence of cytomegalovirus (CMV) viremia was 45.7% (95% confidence interval [CI] 33-55%), developing at a median of 48 (range 12-142) days without evidence of overt CMV disease. Herpes zoster developed in 8 patients at a median of 12 months post transplant, while 10 patients presented with late onset hemorrhagic cystitis at a median of 35 days post transplant. The cumulative incidence of bacteremia was 17.1% (95% CI 10.6-25%), occurring at a median of 74 (range 24-110) days. No patient developed probable or definite invasive fungal infection. Four deaths were recorded; 2 of them were attributed to infections (toxoplasmosis and Pneumocystis jirovecii pneumonia, respectively). CONCLUSION: The rate of infections after allo-SCT, using an ATG-containing preparative regimen, in our population of pediatric patients with hemoglobinopathies is comparable to that reported elsewhere with the use of non-ATG containing regimens.
Assuntos
Anemia Falciforme/terapia , Soro Antilinfocitário/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Hospedeiro Imunocomprometido , Imunossupressores/efeitos adversos , Infecções/etiologia , Condicionamento Pré-Transplante/efeitos adversos , Talassemia beta/terapia , Adolescente , Bacteriemia/etiologia , Bacteriemia/imunologia , Criança , Estudos de Coortes , Ciclosporina/uso terapêutico , Cistite/etiologia , Cistite/imunologia , Infecções por Citomegalovirus/etiologia , Infecções por Citomegalovirus/imunologia , Feminino , Doença Enxerto-Hospedeiro/prevenção & controle , Herpes Zoster/etiologia , Herpes Zoster/imunologia , Humanos , Infecções/imunologia , Masculino , Pneumonia por Pneumocystis/etiologia , Pneumonia por Pneumocystis/imunologia , Estudos Retrospectivos , Toxoplasmose/etiologia , Toxoplasmose/imunologia , Viremia/etiologia , Viremia/imunologiaRESUMO
BACKGROUND: Understanding stakeholders' perception of cure in prostate cancer (PC) is essential to preparing for effective communication about emerging treatments with curative intent. This study used artificial intelligence (AI) for landscape review and linguistic analysis of definition, context and value of cure among stakeholders in PC. MATERIALS AND METHODS: Subject-matter experts (SMEs) selected cure-related key words using Elicit, a semantic literature search engine, and extracted hits containing the key words from Medline, Sermo and Overton, representing academic researchers, health care providers (HCPs) and policymakers, respectively. NetBase Quid, a social media analytics and natural language processing tool, was used to carry out key word searches in social media (representing the general public). NetBase Quid analysed linguistics of key word-specific hit sets for key word count, geolocation and sentiments. SMEs qualitatively summarised key word-specific insights. Contextual terms frequently occurring with key words were identified and quantified. RESULTS: SMEs identified seven key words applicable to PC (number of acquired hits) across four platforms: Cure (12429), Survivor (6063), Remission (1904), Survivorship (1179), Curative intent (432), No evidence of disease (381) and Complete remission (83). Most commonly used key words were Cure by the general public and HCPs (11815 and 224 hits), Survivorship by academic researchers and Survivor by policymakers (378 hits each). All stakeholders discussed Cure and cure-related key words primarily in early-stage PC and associated them with positive sentiments. All stakeholders defined cure differently but communicated about it in relation to disease measurements (e.g. prostate-specific antigen) or surgery. Stakeholders preferred different terms when discussing cure in PC: Cure (academic researchers), Cure rates (HCPs), Potential cure and Survivor/Survivorship (policymakers) and Cure and Survivor (general public). CONCLUSION: This human-led, AI-assisted large-scale qualitative language-based research revealed that cure was commonly discussed by academic researchers, HCPs, policymakers and the general public, especially in early-stage PC. Stakeholders defined and contextualised cure in their communications differently and associated it with positive value.
Assuntos
Inteligência Artificial , Neoplasias da Próstata , Mídias Sociais , Humanos , Masculino , Neoplasias da Próstata/terapia , Linguística/métodos , Política de Saúde , Percepção , Processamento de Linguagem NaturalRESUMO
BACKGROUND: RET germline mutations predispose to the development of inherited cancer syndrome multiple endocrine neoplasia type 2 (MEN2). Several variants of the RET proto-oncogene including G691S and S904S have been suggested to act as genetic modifiers at the age of onset ofMEN2. AIM: The aim of this study is to characterize clinically and molecularly 7 Cypriot patients with familial medullary thyroid carcinoma (FMTC) and 1 with MEN2A and also to determine the allelic frequencies of the RET variants G691S and S904S. SUBJECTS AND METHODS: Seven probands from FMTC families and 1 from MEN2A were screened for the presence of RET mutations and the G691S and S904S variants. Additionally, 226 healthy Cypriots, who served as controls were analysed in an attempt to compare the frequencies of G691S and S904S RET variants to those observed in the 8 patients. RESULTS: The clinical diagnosis of the probands was based on clinical presentation and supported with biochemical findings. The germline C618R mutation of exon 10 was identified in all 8 probands and in 15 relatives from 7 different families. No significant difference in the G691S/S904S variants allele frequencies between patients (4/16 or 25%) and controls (124/452 or 27.4%) was found. CONCLUSIONS: Mutational screening of the RET gene identified a common mutation (C618R) in all 8 (7 FMTC and 1 MEN2A) unrelated Cypriot patients which may be explained by a founder effect. Additionally, no association of the G691S/S904S variants was linked with the disease.
Assuntos
Neoplasia Endócrina Múltipla Tipo 2a/genética , Síndromes Neoplásicas Hereditárias/genética , Proteínas Proto-Oncogênicas c-ret/genética , Proto-Oncogenes/genética , Neoplasias da Glândula Tireoide/genética , Adulto , Carcinoma Medular/congênito , Criança , Chipre , Feminino , Frequência do Gene , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Neoplásicas Hereditárias/cirurgia , Proto-Oncogene Mas , Neoplasias da Glândula Tireoide/cirurgia , TireoidectomiaRESUMO
The aim of this article was to offer a review on the management of peritoneal carcinomatosis (PC) from cancers of different primary origins. Peritoneal surface malignancies have been traditionally regarded as end-stage conditions amenable to merely palliative options, treated with systemic chemotherapy alone with very poor response and a median survival of less than 6 months. The combination of aggressive cytoreductive surgery (CRS), involving peritonectomy procedures and multivisceral resections with hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) to treat microscopic residual disease is a new concept. This method was established with several phase III studies in well selected patients with PC in whom sufficient cytoreduction could be achieved. Despite the need for more high quality phase III studies, there is now a consensus among many surgical teams around the world about the use of this new combination strategy as a standard of care in pseudomyxoma peritonei, peritoneal mesothelioma and colorectal cancer patients. This review summarizes the current status and possible progress in the future.
Assuntos
Carcinoma/terapia , Neoplasias Peritoneais/terapia , Neoplasias Colorretais/terapia , Terapia Combinada , Feminino , Humanos , Hipertermia Induzida , Neoplasias Ovarianas/terapia , Seleção de Pacientes , Neoplasias Gástricas/terapiaRESUMO
BACKGROUND: 5α steroid reductase deficiency (5αSRD) is an autosomal recessive enzymatic deficiency and mutations in the 5α steroid reductase type 2 gene (SRD5A2) result in male pseudohermaphrodism caused by decreased dihydrotestosterone (DHT) synthesis. AIM: To identify the specific mutations of the SRD5A2 gene in Cypriot patients with 5αSRD. SUBJECTS AND METHODS: Five unrelated patients with 46,XY karyotype were examined. Four of them were born with ambiguous genitalia and 1 patient, who was raised as girl, presented with primary amenorrhea. The hCG test was informative (elevated testosterone/DHT) of 5αSRD in 3 out of 4 subjects. Sequencing of the SRD5A2 gene was completed for all patients. Genomic DNA was also isolated from a total of 204 healthy unrelated Cypriot subjects. Screening for the IVS1-2A>G mutation was performed by using direct sequencing and restriction enzyme analysis. RESULTS: The IVS1-2A>G was identified in homozygosity in 3 patients and in a compound heterozygote state in the other 2 patients, in combination with p.P181L and p.R171S in exon 3, respectively. The carrier frequency in the Cypriot population for the IVS1-2A>G mutation was estimated to be 0.98% or 2 in 204. CONCLUSIONS: The same IVS1-2A>G mutation in the SRD5A2 gene seems to characterize all Cypriot patients with 5αSRD diagnosed so far. Furthermore this relatively rare genetic defect, which has only been reported previously in a single case in the Eastern Mediterranean region, is very likely to be the result of a founder effect.
Assuntos
3-Oxo-5-alfa-Esteroide 4-Desidrogenase/deficiência , Proteínas de Membrana/genética , 3-Oxo-5-alfa-Esteroide 4-Desidrogenase/genética , Adolescente , Adulto , Sequência de Bases , Pré-Escolar , Gonadotropina Coriônica , Chipre , Transtornos do Desenvolvimento Sexual/genética , Feminino , Efeito Fundador , Humanos , Lactente , Recém-Nascido , Masculino , MutaçãoRESUMO
BACKGROUND: The median age of prostate cancer diagnosis is 66 years, and the median age of men who die of the disease is eighty years. The public health impact of prostate cancer is already substantial and, given the rapidly ageing world population, can only increase. In this context, the International Society of Geriatric Oncology (SIOG) Task Forces have, since 2010, been developing guidelines for the management of senior adults with prostate cancer. MATERIAL AND METHODS: Since prostate cancer and geriatric oncology are both rapidly evolving fields, a new multidisciplinary Task Force was formed in 2018 to update SIOG recommendations, principally on health status screening tools and treatment. The task force reviewed pertinent articles published between June 2016 and June 2018 and abstracts from European Association of Urology (EAU), European Society for Medical Oncology (ESMO), American Society of Clinical Oncology (ASCO) and American Society of Clinical Oncology Genito-urinary (ASCO GU) meetings over the same period, using search terms relevant to prostate cancer, the elderly, geriatric evaluation, local treatments and advanced disease. Each member of the group proposed modifications to the previous guidelines. These were collated and circulated. The final manuscript reflects the expert consensus. RESULTS: The 2019 consensus is that men aged 75 years and older with prostate cancer should be managed according to their individual health status, and not according to age. Based on available rapid health screening tools, geriatric evaluation and geriatric interventions, the Task Force recommends that patients are classified according to health status into three groups: (1) 'healthy' or 'fit' patients should have the same treatment options as younger patients; (2) 'vulnerable' patients are candidates for geriatric interventions which-if successful-may make it appropriate for them to receive standard treatment and (3) 'frail' patients with major impairments who should receive adapted or palliative treatment. The 2019 SIOG Task Force recommendations also discuss prospects and unmet needs for health status evaluation in everyday practice in older patients with prostate cancer.
Assuntos
Geriatria/normas , Oncologia/normas , Neoplasias da Próstata/terapia , Idoso , Idoso de 80 Anos ou mais , Humanos , MasculinoRESUMO
The role of high-dose chemotherapy (HDCT) in epithelial ovarian cancer (EOC) remains controversial. This study was initiated to compare the efficacy and tolerability of HDCT as a consolidation approach in women with chemosensitive advanced EOC (FIGO stages IIC-IV). Patients who had achieved their first clinical complete remission after six cycles of conventional paclitaxel and carboplatin combination chemotherapy were randomly assigned to receive or not high-dose melphalan. The primary objective was to compare time to disease progression (TTP). A total of 80 patients were enrolled onto the trial. Patients who were randomized to receive HDCT were initially treated with cyclophosphamide 4 g/m(2) for PBPC mobilization. HDCT consisted of melphalan 200 mg/m(2). Of the 37 patients who were allocated to HDCT, 11 (29.7%) did not receive melphalan either due to patient refusal (n=5) or due to failure of PBPC mobilization (n=6). In an intent-to-treat analysis, there were no significant differences between the two arms in TTP (P=0.059) as well as in overall survival (OS) (P=0.38).
Assuntos
Antineoplásicos Alquilantes/administração & dosagem , Transplante de Células-Tronco Hematopoéticas , Melfalan/administração & dosagem , Neoplasias Ovarianas/terapia , Adjuvantes Imunológicos/administração & dosagem , Adulto , Idoso , Antineoplásicos Alquilantes/efeitos adversos , Transfusão de Sangue Autóloga , Terapia Combinada , Ciclofosfamida/administração & dosagem , Progressão da Doença , Feminino , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Humanos , Lenograstim , Melfalan/efeitos adversos , Pessoa de Meia-Idade , Neoplasias Ovarianas/mortalidade , Proteínas Recombinantes/administração & dosagem , Análise de Sobrevida , Fatores de TempoRESUMO
BACKGROUND: Non-small cell lung cancer (NSCLC) in young patients is uncommon and is thought to constitute a distinct oncological entity with characteristic clinicopathological patterns. Since the reported data are scant and discordant, the presentation, management and outcome data of NSCLC patients aged under 45 years of age were analyzed and compared with those of patients over 45 years old. Prognostic factors for risk classification were also evaluated. MATERIALS AND METHODS: The data were abstracted from the Hellenic Cooperative Oncology Group (HeCOG) cancer registry database. The presentation, management and outcome data of patients with histologically confirmed NSCLC, managed from 1989 until 2004 in HeCOG participating centers, were retrospectively analyzed. The clinicopathological characteristics of patients aged < and > than 45 years old were compared and evaluated for prognostic significance regarding outcome. RESULTS: The data for NSCLC patients (1906), of whom 115 were aged <45, were retrieved. In comparative analysis, the young patients were more frequently asymptomatic at diagnosis, while older patients presented significantly higher rates of thoracic pain, cough and fatigue (p<0.01). The young patients were more commonly diagnosed with adenocarcinoma and less frequently with squamous cancer than patients aged over 45. Although the stage distribution was distinct, with older patients presenting higher rates of stage IV disease (21.9% vs. 12.2%), the rates of early lung cancer (stages I-IIIa) were similar. The overall survival (OS) was not significantly different (median OS 12 vs. 11.5 months, p=0.277). Among patients who underwent first-line palliative chemotherapy, young individuals had a significantly shorter time to progression: 4.3 vs. 5.8 months (p=0.0049). Univariate and multivariate regression analyses established the prognostic usefulness of the performance status, disease stage and disease-free interval for the risk of death, both in the total number of patients (1906) and in young patients (115). CONCLUSION: This large retrospective series failed to present strong evidence that NSCLC among young individuals constitutes a distinct clinicopathological entity with differing biological behavior, since the same clinicopathological prognostic factors were valid in both age groups. Molecular phenotypic studies are needed to shed light on this controversial subject.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Adulto , Fatores Etários , Ensaios Clínicos como Assunto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do TratamentoRESUMO
PURPOSE: An experimental study was undertaken in order to estimate the angiogenic activity in different free grafts and pedicle flap in urethral reconstruction in an animal model. METHODS: Twenty-eight white New Zealand rabbits were randomly divided into five groups (O, A, B, C and D). A ventral urethral defect was created in all groups. In the group O, (n = 4), a simple closure of the defect was performed. Free penile skin graft (group A, n = 6), buccal mucosal graft (group B, n = 6), bladder mucosal graft (group C, n = 6), and pedicle penile skin graft (group D, n = 6) were used to bridge the urethral defect as an onlay patch. The animals were euthanized on the 21st postoperative day. The angiogenic activity was assessed with immunohistochemistry, using the anti-CD31 MoAb and the alkaline phosphatase antialkaline phosphatase procedure. The native vascularity of penile skin as well as buccal and bladder mucosa was assessed in rabbits from group O (n = 3). Statistical analysis was performed using one-way ANOVA. RESULTS: The angiogenesis seen with a magnification of x 200 in groups O, A, B, C, and D was 34.1 +/- 4.1 (mean +/- SD), 61.7 +/- 6.4, 94.3 +/- 6.4, 91.5 +/- 7.2, and 30.8 +/- 5.2 vessels per optical field, respectively. There were statistically significant differences (p < 0.001) between group O and groups A, B, C and between group A and groups B, C, D, but not (p > 0.5) between groups B and C and groups O and D. The native vascularity of penile skin, buccal mucosa and bladder mucosa was 23.3 +/- 3.0, 24.6 +/- 3.7 and 17.0 +/- 2.6 vessels per optical field, respectively. CONCLUSION: Buccal and bladder mucosal grafts exhibit a higher angiogenic activity than free and pedicle penile skin flap when transplanted in urethral defects. As the buccal mucosal graft showed the higher angiogenic activity and its harvesting is easier than bladder mucosa, we propose that in urethral reconstruction surgery the use of this graft might offer more reliable results.
Assuntos
Neovascularização Fisiológica , Retalhos Cirúrgicos/irrigação sanguínea , Uretra/cirurgia , Animais , Imuno-Histoquímica , Masculino , Modelos Animais , Coelhos , Uretra/lesõesRESUMO
Carboplatin-related hypersensitivity reactions, frequently encountered in the heavily pretreated subpopulation of patients with gynecologic malignancies, can be severe and even potentially lethal-precluding these patients from an effective salvage treatment. We describe our experience in the management of such reactions and the application of a pretreatment protocol with corticosteroids, antihistamines and a slow infusion rate in order to safely re-administer carboplatin to the above patients. From 1998 to 2004, twenty patients developed an allergic reaction to carboplatin. Sixteen of them (80%) suffered from ovarian cancer. Upon resolution of the acute reaction, thirteen patients were pretreated according to our protocol and were re-exposed to carboplatin. Fifteen patients experienced the reaction during second-line carboplatin-based treatment and 5 patients after 3 or more regimens. Fifteen of the reactions (75%) were severe. Thirteen patients were re-treated with carboplatin after the application of our protocol, all of them successfully, even though 10 patients (77%) experienced minor symptoms during subsequent courses. On the contrary, only one of the 6 patients who were re-treated without the application of the protocol was able to receive further platinum-based treatment. In conclusion, pretreatment with corticosteroids, antihistamines and a slower infusion rate may make re-treatment possible in patients having experienced hypersensitivity to carboplatin.
Assuntos
Antineoplásicos/efeitos adversos , Carboplatina/efeitos adversos , Hipersensibilidade a Drogas/etiologia , Recidiva Local de Neoplasia/tratamento farmacológico , Terapia de Salvação , Adulto , Idoso , Anti-Inflamatórios/uso terapêutico , Dexametasona/uso terapêutico , Hipersensibilidade a Drogas/tratamento farmacológico , Neoplasias do Endométrio/complicações , Neoplasias do Endométrio/tratamento farmacológico , Feminino , Antagonistas dos Receptores Histamínicos H1/uso terapêutico , Humanos , Masculino , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Neoplasias Ovarianas/complicações , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Peritoneais/complicações , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias da Bexiga Urinária/complicações , Neoplasias da Bexiga Urinária/tratamento farmacológicoRESUMO
PURPOSE OF INVESTIGATION: Late relapses are infrequent in ovarian cancer. We present the characteristics and outcome of patients who relapsed at least five years after first-line chemotherapy. METHODS: Six cases were retrieved from 203 patients treated from 1994 to 1998. RESULTS: Time to recurrence ranged from five to nine years. The initial stage was I or II in all cases, while histology was: endometrioid (4 cases), clear cell (1 case) and unspecified adenocarcinoma (1 case). Only two of five assessable patients responded to chemotherapy. Compared to earlier relapses, late relapses were characterized by earlier stages (p < 0.001), non serous histology (p = 0.010) and absence of symptoms (0% vs 46.5%, p = 0.025) at baseline. Five of 16 relapses (31%) among patients with Stage I or II were late relapses. CONCLUSION: Late relapses of ovarian cancer occur in early stages, where they are relatively frequent, while the chemosensitivity of the disease may be less than expected.
Assuntos
Adenocarcinoma/terapia , Recidiva Local de Neoplasia/terapia , Neoplasias Ovarianas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Feminino , Procedimentos Cirúrgicos em Ginecologia , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de TempoRESUMO
We report a case of delayed perforation of the large bowel because of thermal injury during a laparoscopic cholecystectomy. A 78-year-old male with symptomatic cholelithiasis underwent a difficult laparoscopic cholecystectomy because of multiple adhesions resulting from two previous cholecystitis episodes. The patient recovered well after surgery and was discharged on post-operative day 2. On postoperative day 10, the patient returned to the hospital with peritonitis. An exploratory laparotomy revealed perforation of the wall of the hepatic flexure of the large bowel, which was centred in a necrotic area 1 cm in diameter. The perforation was sutured and a temporary ileostomy performed, which was closed at a later date. The patient was doing well at a 10-month follow-up review. A delayed rupture of any part of the bowel after laparoscopic surgery can be potentially fatal if not treated during an emergency exploratory laparotomy, even if the clinical signs are not severe.
Assuntos
Colecistectomia Laparoscópica/efeitos adversos , Intestino Grosso/lesões , Intestino Grosso/patologia , Idoso , Temperatura Alta , Humanos , Ileostomia , Complicações Intraoperatórias , Laparotomia/efeitos adversos , Masculino , Necrose , Fatores de TempoRESUMO
BACKGROUND: Peritoneal carcinomatosis (PC) is associated with a poor prognosis. Cytoreductive surgery (CRS) and HIPEC play an important role in well-selected patients with PC. The aim of the study is to present the differences in the intraoperative parameters in patients who received HIPEC in two different manners, open versus closed abdomen. PATIENTS AND METHODS: The population includes 105 patients with peritoneal carcinomatosis from colorectal, gastric, and ovarian cancer, sarcoma, mesothelioma, and pseudomyxoma peritonei. Group A (n = 60) received HIPEC using the open technique and Group B (n = 45) received HIPEC with the closed technique. The main end points were morbidity, mortality, and overall hospital stay. RESULTS: There were two postoperative deaths (3.3%) in the open group versus no deaths in the closed group. Twenty-two patients in the open group (55%) had grade III-IV complications versus 18 patients in the closed group (40%). There are more stable intraoperative conditions in the closed abdomen HIPEC in CVP, pulse rate, and systolic pressure parameters. CONCLUSIONS: Both methods are equal in the HIPEC procedures. Perhaps the closed method is the method of choice for frail patients due to more stable hemodynamic parameters.