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1.
Community Dent Health ; 33(1): 6-8, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27149766
3.
BJOG ; 122(6): 843-849, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25132394

RESUMO

OBJECTIVE: To assess site of disease on preoperative computed tomography (CT) to predict surgical debulking in patients with ovarian cancer. DESIGN: Two-phase retrospective cohort study. SETTING: West London Gynaecological Cancer Centre, UK. POPULATION: Women with stage 3 or 4, ovarian, fallopian or primary peritoneal cancer undergoing cytoreductive surgery. METHODS: Preoperative CT images were reviewed by experienced radiologists to assess the presence or absence of disease at predetermined sites. Multivariable stepwise logistic regression models determined sites of disease which were significantly associated with surgical outcomes in the test (n = 111) and validation (n = 70) sets. MAIN OUTCOME MEASURES: Sensitivity and specificity of CT in predicting surgical outcome. RESULTS: Stepwise logistic regression identified that the presence of lung metastasis, pleural effusion, deposits on the large-bowel mesentery and small-bowel mesentery, and infrarenal para-aortic nodes were associated with debulking status. Logistic regression determined a surgical predictive score which was able to significantly predict suboptimal debulking (n = 94, P = 0.0001) with an area under the curve (AUC) of 0.749 (95% confidence interval [95% CI]: 0.652, 0.846) and a sensitivity of 69.2%, specificity of 71.4%, positive predictive value of 75.0% and negative predictive value of 65.2%. These results remained significant in a recent validation set. There was a significant difference in residual disease volume in the test and validation sets (P < 0.001) in keeping with improved optimal debulking rates. CONCLUSIONS: The presence of disease at some sites on preoperative CT scan is significantly associated with suboptimal debulking and may be an indication for a change in surgical planning.


Assuntos
Adenocarcinoma/cirurgia , Procedimentos Cirúrgicos de Citorredução , Técnicas de Apoio para a Decisão , Neoplasias das Tubas Uterinas/cirurgia , Neoplasias Ovarianas/cirurgia , Neoplasias Peritoneais/cirurgia , Tomografia Computadorizada por Raios X , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Neoplasias das Tubas Uterinas/diagnóstico por imagem , Neoplasias das Tubas Uterinas/patologia , Feminino , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/diagnóstico por imagem , Neoplasias Peritoneais/patologia , Cuidados Pré-Operatórios , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Resultado do Tratamento
5.
Ultrasound Obstet Gynecol ; 41(6): 672-8, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23371440

RESUMO

OBJECTIVE: To develop a model to predict the success of a trial of vaginal birth after Cesarean section (VBAC) based on sonographic measurements of Cesarean section (CS) scar features, demographic variables and previous obstetric history. METHODS: We used transvaginal sonography (TVS) to examine the CS scar of 320 consecutive pregnant women. TVS was carried out at 11-13, 19-21 and 34-36 weeks' gestation and prospective measurements of the scar were recorded at each visit according to a defined protocol. A logistic regression model to predict success of VBAC was developed for those patients with a visible scar on ultrasound and only one previous CS. The model was evaluated using bootstrap validation. RESULTS: There were 131 women with one previous CS and a visible scar, of whom 10 underwent CS prior to labor and were excluded from analysis. Successful VBAC was achieved in 74/121 (61%) of the remaining cases. The prediction model developed was based on patient age, previous history of VBAC, residual myometrial thickness (RMT) and the change in RMT from the first to the second trimester (ΔRMT). The internally validated area under the receiver-operating characteristics curve was 0.62 when measurements of RMT and ΔRMT were excluded, but 0.94 when scar information was incorporated into the model. CONCLUSION: Ultrasound measurements of CS scar, namely RMT and the change in RMT from the first to the second trimester of pregnancy, when incorporated into a mathematical model, can predict accurately a successful trial of labor in patients with one previous CS.


Assuntos
Cicatriz/diagnóstico por imagem , Ultrassonografia Pré-Natal/métodos , Nascimento Vaginal Após Cesárea , Adulto , Feminino , Humanos , Modelos Biológicos , Gravidez , Resultado da Gravidez , Primeiro Trimestre da Gravidez , Segundo Trimestre da Gravidez , Curva ROC , Sensibilidade e Especificidade
6.
Ultrasound Obstet Gynecol ; 41(5): 556-62, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23108803

RESUMO

OBJECTIVES: To describe changes in Cesarean section (CS) scars longitudinally throughout pregnancy, and to relate initial scar measurements, demographic variables and obstetric variables to subsequent changes in scar features and to final pregnancy outcome. METHODS: In this prospective observational study we used transvaginal sonography (TVS) to examine the CS scar of 320 consecutive pregnant women at 11-13, 19-21 and 32-34 weeks' gestation. For scars visible on TVS, the hypoechoic part was measured in three dimensions and the residual myometrial thickness (RMT) was also measured. Analyses were carried out using one-way repeated measures ANOVA and mixed modeling. The incidence of subsequent scar rupture was recorded. RESULTS: The CS scar was visible in 284/320 cases (89%). Concerning length and depth of the hypoechoic part of the scar and RMT, the larger the initial scar measurement, the larger the decrease observed during pregnancy. For the hypoechoic part of the scar, the width increased on average by 1.8 mm per trimester, while the depth and length decreased by 1.8 and 1.9 mm, respectively (false discovery rate P < 0.0001). Mean RMT in the first trimester was 5.2 mm and on average decreased by 1.1 mm per trimester. Two cases (0.62%) of uterine scar rupture were confirmed following a trial of vaginal delivery; these had a mean RMT of 0.5 mm at second scan and an average decrease of 2.6 mm over the course of pregnancy. CONCLUSION: This study establishes reference data and confirms that the dimensions of CS scars change throughout pregnancy. Scar rupture was associated with a smaller RMT and greater decrease in RMT during pregnancy. There is the potential to test absolute values and observed changes in CS scar measurements as predictors of uterine scar rupture and outcome in trials of vaginal birth after Cesarean section.


Assuntos
Cesárea/efeitos adversos , Cicatriz/patologia , Complicações na Gravidez/patologia , Adulto , Análise de Variância , Cicatriz/diagnóstico por imagem , Feminino , Humanos , Gravidez , Complicações na Gravidez/diagnóstico por imagem , Resultado da Gravidez , Trimestres da Gravidez , Estudos Prospectivos , Ultrassonografia Pré-Natal , Ruptura Uterina/etiologia , Ruptura Uterina/patologia
7.
Br J Anaesth ; 109(1): 16-20, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22696556

RESUMO

Anaesthetic training in the UK has recently experienced significant organizational and politically driven changes. This article examines the effects these changes may have had on the training of anaesthetists and concludes that despite the introduction of changed working patterns and reduced hours over the past decade, academic and professional standards appear to have been maintained, but at the expense of reduced confidence among some trainees. The UK system focuses heavily on achieving competence in different areas of training. While this is clearly important, it understates the added value of consolidation and experience based on repeated exposure. Trainer and trainee surveys suggest that due to perceived service pressures, and worries about patient safety or clinical governance, this important latter stage in professional development is increasingly being omitted from the training programme.


Assuntos
Anestesiologia/educação , Competência Clínica , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Reino Unido
8.
BJOG ; 119(6): 662-71, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22390753

RESUMO

OBJECTIVE: To compare guidelines from the Royal College of Obstetricians and Gynaecologists (RCOG) based on the Risk of Malignancy Index (RMI) with a protocol based on logistic regression model LR2 developed by the International Ovarian Tumour Analysis (IOTA) group for triaging women with an ovarian mass as low, moderate, or high risk of malignancy. DESIGN AND SETTING: Observational diagnostic study conducted between 2005 and 2007 at 21 oncology referral centres, referral centres for ultrasonography and general hospitals. SAMPLE: In all, 1938 women undergoing surgery for an ovarian mass. METHODS: RCOG guidelines use the RMI to triage women as low (RMI < 25), moderate (25-250), or high (above >250) risk. The IOTA protocol uses LR2s estimated probability of malignancy (<0.05 indicates low risk, ≥ 0.05 but <0.25 moderate risk, and ≥ 0.25 high risk). MAIN OUTCOME MEASURE: Percentages of benign, borderline and invasive tumours classified as low, moderate or high risk. RESULTS: The IOTA and RCOG protocols classified 71.1% and 62.1% of benign tumours as low risk, respectively (difference 9.0; 95% CI 6.2-11.9, P < 0.0001). Of invasive tumours, 88.6% and 73.6% were labelled high risk (difference 15.0; 10.6-19.4, P < 0.0001), and 3.0% and 5.2% were labelled low risk (difference -2.2; -4.6 to 0.2, P = 0.07) respectively by each protocol. Similar results were found after stratification for menopausal status. CONCLUSIONS: The IOTA protocol was more accurate for triage than the RCOG protocol. The IOTA protocol would avoid major surgery for more women with benign tumours while still appropriately referring more women with an invasive tumour to a gynaecological oncologist.


Assuntos
Neoplasias Ovarianas/diagnóstico , Guias de Prática Clínica como Assunto/normas , Triagem/normas , Adulto , Idoso , Antígeno Ca-125/sangue , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/cirurgia , Medição de Risco/normas
9.
Ultrasound Obstet Gynecol ; 40(5): 549-56, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22323065

RESUMO

OBJECTIVES: To evaluate the visibility of cesarean section (CS) scars by transvaginal sonography (TVS) in pregnant women, to apply a standardized approach for measuring CS scars and to test its reproducibility throughout the course of pregnancy. METHODS: In this observational cohort study, 320 consecutive pregnant women with a previous cesarean delivery were examined to assess scar visibility by two independent examiners. TVS was carried out at 11-13, 19-21 and 34-36 weeks' gestation. A scar was defined as visible when an area of hypoechogenicity representing myometrial discontinuity at the anterior wall of the lower uterine segment was identified. In a subset of patients (n = 111), visible scars were measured by two independent examiners in three dimensions: scar width, depth and length as well as the residual myometrial thickness (RMT). Descriptive analysis was used to assess scar visibility, and the intraclass correlation coefficient (ICC) was calculated to show the strength of absolute agreement between two examiners for scar measurements. For RMT, a cut-off of 2.4 mm was used and measurement agreement was assessed using Cohen's kappa coefficient. RESULTS: The scar was visible in 284/320 cases (88.8%). Visible scars were significantly associated with anteverted uteri (P < 0.0001). Both examiners had 100% agreement on scar visibility at 12 and 20 weeks' gestation, while agreement was 96% at 34 weeks. The intra- and interobserver agreements for scar measurements were generally good (ICC 0.86 and 0.89, respectively). The kappa coefficient for the RMT was 0.27 in the first trimester, compared with 0.51 and 0.72 in the second and third trimesters, respectively. CONCLUSION: CS scars remain visible in the majority of women throughout pregnancy. They can be reproducibly measured in three dimensions when assessed by TVS in all trimesters of pregnancy. The agreement between two observers for CS scar measurement can be considered good for the first trimester, compared with relatively moderate agreement for the second and third trimesters.


Assuntos
Cesárea , Cicatriz/diagnóstico por imagem , Adulto , Cicatriz/patologia , Estudos de Coortes , Feminino , Humanos , Londres , Gravidez , Reprodutibilidade dos Testes , Ultrassonografia
10.
Ultrasound Obstet Gynecol ; 39(3): 252-9, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21858885

RESUMO

Incomplete healing of the scar is a recognized sequel of Cesarean section (CS) and may be associated with complications in later pregnancies. These complications can include scar pregnancy, a morbidly adherent placenta, scar dehiscence or rupture. To date there is uncertainty relating to the factors that lead to poor scar healing and how to recognize it. In recent years, there has been an increase in studies using ultrasound that describe scars as deficient, or poorly, incompletely or inadequately healed with few data to associate the morphology of the scar with the functional integrity of the lower segment of the uterus. There have been multiple attempts to describe CS scars using ultrasonography. Different terminology, methods and results have been reported, yet there is still no consensus regarding the prevalence, clinical significance or most appropriate method to describe the appearances of these scars. Developing a test that can predict the likelihood of women having problems associated with a CS scar is becoming increasingly important. On the other hand, understanding whether the ultrasound appearances of the scar can tell us anything about its integrity is not well supported by the research evidence. In this article we present an overview of ultrasound-based definitions and methods used to describe CS scars. We also present information relating to the performance of alternative techniques used to evaluate CS scars. Having examined the current evidence we suggest a standardized approach to describe CS scars using ultrasound so that future studies can be meaningfully compared.


Assuntos
Cesárea/efeitos adversos , Cicatriz/diagnóstico por imagem , Deiscência da Ferida Operatória/diagnóstico por imagem , Cicatriz/etiologia , Cicatriz/patologia , Feminino , Humanos , Imageamento Tridimensional , Gravidez , Prevalência , Padrões de Referência , Deiscência da Ferida Operatória/complicações , Deiscência da Ferida Operatória/patologia , Ultrassonografia , Cicatrização
11.
BJOG ; 119(3): 369-74; discussion 374, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22168173

RESUMO

The standard management of placental site trophoblastic tumours (PSTTs) is a radical hysterectomy with pelvic lymph node sampling. We present five cases to demonstrate a modified Strassman procedure (MSP), which is an alternative fertility-sparing technique. Each had a presumed solitary uterine PSTT. Following surgery, one patient remained in remission with her fertility intact. The other four underwent a completion hysterectomy because of incomplete excision of the disease. No residual disease was later found in two of these four uteri. This treatment should only be offered after extensive counselling. We intend to investigate the use of intraoperative frozen section analysis with cold-knife dissection in future.


Assuntos
Preservação da Fertilidade , Procedimentos Cirúrgicos em Ginecologia/métodos , Tumor Trofoblástico de Localização Placentária/cirurgia , Neoplasias Uterinas/cirurgia , Adulto , Feminino , Humanos , Histerectomia , Gravidez , Estudos Retrospectivos , Resultado do Tratamento
12.
BJOG ; 119(2): 187-93, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22168762

RESUMO

OBJECTIVE: Traditionally, the surgical management of invasive cervical carcinoma that has progressed beyond microinvasion has been a radical abdominal hysterectomy. However, this results in the loss of fertility, with significant consequences for the young patient. This report describes abdominal radical trachelectomy (ART) as a potential replacement for radical hysterectomy in patients with stage IA2-IIA cervical cancer who desire a fertility-sparing procedure without decreasing the curative rates. DESIGN: Observational, retrospective study. SETTING: Teaching hospital and regional cancer centre in London, UK. POPULATION: Patients undergoing ART. METHODS: Patients presenting during the period 2000-2009 with cervical cancer stage IA2-IIA were offered a trachelectomy, if they expressed a desire to preserve fertility. The type of trachelectomy (vaginal/abdominal) was chosen based on patient anatomy and neoplastic and magnetic resonance imaging characteristics. Each patient was counselled as to the experimental nature of the procedure. MAIN OUTCOME MEASURES: Survival, recurrence and fertility issues among ART patients. RESULTS: A total of 30 patients underwent ART (open and laparoscopic) between 2001 and 2009. Three patients presented with a recurrence, two of which have died (median follow-up: 24 months). Only three patients required further surgical re-intervention because of operative complications. Ten patients attempted to conceive, resulting in three conceptions (30%) and two live children. CONCLUSIONS: Abdominal radical trachelectomy provides a feasible, cost-effective and safe treatment option for young women who have been diagnosed with early-stage cervical cancer and wish to preserve their fertility.


Assuntos
Colo do Útero/cirurgia , Neoplasias do Colo do Útero/cirurgia , Adulto , Criopreservação , Estudos de Viabilidade , Feminino , Humanos , Infertilidade Feminina/prevenção & controle , Londres/epidemiologia , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/cirurgia , Recuperação de Oócitos , Gravidez , Complicações Neoplásicas na Gravidez/cirurgia , Resultado da Gravidez , Taxa de Gravidez , Reoperação , Estudos Retrospectivos , Neoplasias do Colo do Útero/mortalidade
15.
Br J Anaesth ; 103(4): 518-23, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19700443

RESUMO

BACKGROUND: We wished to ascertain in what way recent changes such as Modernising Medical Careers (MMC) and the implementation of the Working Time Directive (WTD) have affected clinical training and experience for anaesthetists in a teaching centre, in particular the provision of training in specialized fields of anaesthesia provided in the teaching hospital. METHODS: Data were extracted from the computerized system for every operating theatre in this Trust. This provided a continuous record of all operations undertaken, and has previously been validated as an accurate record against individual anaesthetists' personal logbooks. We compared recent data with that of 10 yr ago. RESULTS: Comparing data for 1997 and 2008 showed that registrars and post-fellowship senior registrars (SRs) in anaesthesia continue to be well supervised directly by consultants (49% and 39%) and subspeciality training has been protected in our department. Average case numbers for SRs increased from 442 to 623 yr(-1), including an increase in emergency workload and theatre cases undertaken during the evening and at night. Although average case numbers for both SRs and consultants increased, we detected a small decrease in average case numbers from 394 to 353 yr(-1) for pre-fellowship registrars. CONCLUSIONS: In spite of many pressures on training in the clinical setting, the number of cases and senior supervision in specialist modules for trainee anaesthetists in our teaching hospital has been maintained. Continuous monitoring of in-theatre supervision is one way of confirming that training is not compromised as changes occur in hospital workload.


Assuntos
Anestesiologia/educação , Educação de Pós-Graduação em Medicina/tendências , Hospitais de Ensino/tendências , Salas Cirúrgicas/tendências , Educação de Pós-Graduação em Medicina/métodos , Educação de Pós-Graduação em Medicina/organização & administração , Emergências , Inglaterra , Pesquisa sobre Serviços de Saúde/métodos , Hospitais de Ensino/organização & administração , Humanos , Corpo Clínico Hospitalar/educação , Medicina/organização & administração , Medicina/tendências , Mentores/estatística & dados numéricos , Salas Cirúrgicas/organização & administração , Admissão e Escalonamento de Pessoal/organização & administração , Admissão e Escalonamento de Pessoal/tendências , Especialização , Carga de Trabalho/estatística & dados numéricos
16.
Anaesthesia ; 62(8): 838-41, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17635436

RESUMO

An anaesthetised 48-year-old woman became haemodynamically unstable following biopsy of a thoracic mass suggesting a diagnosis of a thoracic phaeochromocytoma. Surgery was postponed to allow confirmatory investigations and pre-operative adrenoceptor blockade with phenoxybenzamine and labetalol. Nine days later, following resection of her phaeochromocytoma, she suffered an intra-operative asystolic cardiac arrest which was unresponsive to standard resuscitation protocols and required external cardiac pacing. We discuss the issues involved and suggest that the competitive alpha(1) adrenoceptor antagonist doxazosin may be preferable to the covalently bound mixed alpha adrenoceptor antagonist phenoxybenzamine in the pre-operative preparation of patients with phaeochromocytoma.


Assuntos
Neoplasias das Glândulas Suprarrenais/complicações , Estimulação Cardíaca Artificial/métodos , Parada Cardíaca/etiologia , Complicações Intraoperatórias , Feocromocitoma/complicações , Neoplasias das Glândulas Suprarrenais/cirurgia , Antagonistas Adrenérgicos alfa/uso terapêutico , Doxazossina/uso terapêutico , Feminino , Parada Cardíaca/terapia , Humanos , Pessoa de Meia-Idade , Fenoxibenzamina/uso terapêutico , Feocromocitoma/cirurgia , Medicação Pré-Anestésica
17.
Eur J Anaesthesiol ; 23(2): 165-8, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16426472

RESUMO

BACKGROUND AND OBJECTIVES: The potential for increased drug administration errors during the transition to the International Colour Coding syringe labelling system has been highlighted. The purpose of this study was to assess the potential effects before their introduction into our department. METHODS: Thirty-one anaesthetists, 19 with no previous practical experience of the new labelling system (Group 1), and 12 with previous experience (Group 2), volunteered to induce general anaesthesia for a standardized simulated patient in a designated theatre. They were presented with a scenario designed to suggest the need for a rapid sequence induction and provided with drug syringes labelled with the International Colour Coding system. All drug administrations were recorded. Active error was defined as the injection of the wrong drug. Latent error was defined as the selection of a syringe in error but stopping short of administering the drug. RESULTS: In Group 1 a total of 107 drug injections were recorded of which 1 (0.9%) was an active error and 16 (15%) involved latent errors. Eleven anaesthetists (58%) performed at least one latent error. Group 2 had an error rate of 3%, a 6.9 (1.3-26.7) fold reduction in the rate of error (P = 0.023). CONCLUSIONS: Although only one drug was given in active error, latent errors occurred in 15% of drug administrations. The only factor conferring protection against error was prior experience of the new labelling system. The period of transition to the International Colour Coding syringe labelling system represents a time of increased risk of drug administration error.


Assuntos
Anestesia Geral , Erros de Medicação , Rotulagem de Produtos , Seringas , Adulto , Anestesiologia , Cor , Emergências , Humanos , Masculino
18.
Br J Anaesth ; 95(5): 616-21, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16169892

RESUMO

BACKGROUND: We aimed to assess the influence of reduced working hours on training in a UK teaching hospital as the specialist registrar grade was introduced in 1996, the New Deal was implemented in 2001 and the Working Time Directive (WTD) took effect for doctors in training in 2004. METHODS: We analysed data from operating theatres in our hospital looking at grade of anaesthetist, time of day, emergency category, and specialty for more than 50,000 cases. RESULTS: Although direct supervision of trainees increased from 32 to 37 to 47%, senior house officer (SHO) and specialist registrar (SpR) caseload reduced by 20 and 21%, respectively, while that of the consultants rose. CONCLUSIONS: The reduction in total operating theatre cases for our trainees was evident across the epochs analysed, case numbers fell after introduction of the New Deal as well as more recently following the WTD, particularly for SHOs who are now doing a larger proportion of their work at night. SHOs and SpRs are doing more obstetric cases than in previous times but these are regional and not general anaesthetics.


Assuntos
Anestesiologia/educação , Educação de Pós-Graduação em Medicina/tendências , Hospitais de Ensino/tendências , Corpo Clínico Hospitalar/educação , Anestesia Obstétrica/estatística & dados numéricos , Anestesia Obstétrica/tendências , Anestesiologia/organização & administração , Anestesiologia/tendências , Cesárea/estatística & dados numéricos , Educação de Pós-Graduação em Medicina/estatística & dados numéricos , Inglaterra , Feminino , Pesquisa sobre Serviços de Saúde , Hospitais de Ensino/estatística & dados numéricos , Humanos , Corpo Clínico Hospitalar/organização & administração , Mentores/estatística & dados numéricos , Admissão e Escalonamento de Pessoal/organização & administração , Admissão e Escalonamento de Pessoal/tendências , Gravidez , Carga de Trabalho/estatística & dados numéricos
20.
Cancer Immunol Immunother ; 53(9): 809-16, 2004 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15127236

RESUMO

INTRODUCTION: An extended phase I trial was conducted in a total of 26 patients with ovarian cancer. The objectives were to assess the safety and tolerability of idiotypic vaccination using the murine monoclonal antibody HMFG1 (anti-MUC1), and to develop robust assays to monitor humoral immune responses generated against either the antibody or MUC1. MATERIAL AND METHODS: All patients had undergone standard debulking surgery (where appropriate) and at least one regimen of platinum-based chemotherapy. Eligibility criteria included: (a) residual disease at the end of chemotherapy, (b) relapsed disease, and (c) pathologically confirmed second complete remission following salvage chemotherapy. Patients received a priming dose of 25 mg of HMFG1 either intravenously or intraperitoneally, followed by up to six intradermal doses of HMFG1 in 10% Alhydrogel at intervals of 1 month. The three dose levels were 0.5 mg, 1 mg and 5 mg. We devised modifications of published protocols for the measurement of anti-idiotypic and anti-MUC1 antibody responses and also extended the use of the IAsys resonant mirror biosensor to measure the kinetics of the idiotypic network response in these patients. RESULTS: There were no serious adverse events at any dose level. The trial confirmed that all doses could be administered safely with minimal toxicity. No clinical responses were seen in patients with evaluable disease. ELISA for anti-idiotypic antibodies (Ab2) showed significant levels in patients who completed the protocol. There were no significant differences in the levels of Ab2 generated by the different doses of antibody. These results were confirmed by biosensor assays for Ab2, which also showed affinity maturation of the Ab2 response as patients progressed through the vaccination protocol. Biosensor assays also demonstrated no difference in the affinity of Ab2 generated by different booster doses of HMFG1. ELISA for anti-MUC1 antibodies showed less consistent results, with very small but statistically significant rises in anti-MUC1 signals seen in 38% of patients who completed the vaccination regimen. DISCUSSION: The clinical endpoints of safety and tolerability were met. The assays developed for this project have shown reproducibility and may provide surrogate endpoints to assess vaccination for future trials. The use of similar biosensors may be of particular relevance for monitoring of humoral immune responses in other vaccine trials. The low levels of anti-MUC1 antibodies generated may correspond with the lack of clinical efficacy in the few patients with evaluable disease.


Assuntos
Anticorpos Anti-Idiotípicos/imunologia , Anticorpos Monoclonais/uso terapêutico , Imunoterapia , Mucina-1/imunologia , Recidiva Local de Neoplasia/terapia , Neoplasia Residual/terapia , Neoplasias Ovarianas/terapia , Vacinação , Antígeno Ca-125/imunologia , Vacinas Anticâncer/uso terapêutico , Estudos de Coortes , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Dose Máxima Tolerável , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/patologia , Neoplasia Residual/imunologia , Neoplasia Residual/patologia , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/patologia , Indução de Remissão , Segurança , Terapia de Salvação
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