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1.
Ann Oncol ; 31(9): 1240-1250, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32473302

RESUMEN

BACKGROUND: Median overall survival (OS) for women with high-grade serous ovarian cancer (HGSOC) is ∼4 years, yet survival varies widely between patients. There are no well-established, gene expression signatures associated with prognosis. The aim of this study was to develop a robust prognostic signature for OS in patients with HGSOC. PATIENTS AND METHODS: Expression of 513 genes, selected from a meta-analysis of 1455 tumours and other candidates, was measured using NanoString technology from formalin-fixed paraffin-embedded tumour tissue collected from 3769 women with HGSOC from multiple studies. Elastic net regularization for survival analysis was applied to develop a prognostic model for 5-year OS, trained on 2702 tumours from 15 studies and evaluated on an independent set of 1067 tumours from six studies. RESULTS: Expression levels of 276 genes were associated with OS (false discovery rate < 0.05) in covariate-adjusted single-gene analyses. The top five genes were TAP1, ZFHX4, CXCL9, FBN1 and PTGER3 (P < 0.001). The best performing prognostic signature included 101 genes enriched in pathways with treatment implications. Each gain of one standard deviation in the gene expression score conferred a greater than twofold increase in risk of death [hazard ratio (HR) 2.35, 95% confidence interval (CI) 2.02-2.71; P < 0.001]. Median survival [HR (95% CI)] by gene expression score quintile was 9.5 (8.3 to -), 5.4 (4.6-7.0), 3.8 (3.3-4.6), 3.2 (2.9-3.7) and 2.3 (2.1-2.6) years. CONCLUSION: The OTTA-SPOT (Ovarian Tumor Tissue Analysis consortium - Stratified Prognosis of Ovarian Tumours) gene expression signature may improve risk stratification in clinical trials by identifying patients who are least likely to achieve 5-year survival. The identified novel genes associated with the outcome may also yield opportunities for the development of targeted therapeutic approaches.


Asunto(s)
Cistadenocarcinoma Seroso , Neoplasias Ováricas , Cistadenocarcinoma Seroso/genética , Femenino , Humanos , Neoplasias Ováricas/genética , Pronóstico , Modelos de Riesgos Proporcionales , Análisis de Supervivencia , Transcriptoma
2.
EClinicalMedicine ; 20: 100301, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32300746

RESUMEN

BACKGROUND: Faecal Microbiota Transplant (FMT) has improved outcomes for the treatment of Clostridioides difficile infection (CDI) compared to antibiotic therapy. FMT is classified as a medicinal product in the United Kingdom, similar to the USA and Canada, limiting supply via stool banks without appropriate licencing. In the largest UK cohort to date, we describe the clinical outcomes for 124 patients receiving FMT for recurrent or refractory CDI and present a framework to produce FMT as a licenced medicinal product. METHODS: Anonymous unrelated healthy donors, screened via health assessment and microbiological testing donated stool. In aerobic conditions FMT aliquots were prepared for immediate use or frozen storage, following a production framework developed to comply with Good Manufacturing Practice. Outcome measures were clinical response to FMT defined as resolution of diarrhoea within seven days and clinical cure defined as response without diarrhoea recurrence at 90 days. FINDINGS: Clinical response was 83·9% (95% CI 76·0%-90·0%) after one treatment. Clinical cure was 78·2% (95% CI 67·4%-89·0%) across the cohort. Refractory cases appeared to have a lower initial clinical response rate compared to recurrent cases, however at day 90 there were no differences observed between these groups. INTERPRETATION: The methodology developed here enabled successful licencing of FMT by The Medicines and Healthcare products Regulatory Agency as a medicinal product. This has widened the availability of FMT in the National Health Service via a stool bank and can be applied in other centres across the world to improve access to safe and quality assured treatments.

3.
Gynecol Oncol ; 151(1): 117-123, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-30100053

RESUMEN

OBJECTIVE: Enhanced recovery pathways have been shown to reduce length of stay without increasing readmission or complications in numerous areas of surgery. Uptake of gynecologic oncology ERAS guidelines has been limited. We describe the effect of ERAS guideline implementation in gynecologic oncology on length of stay, patient outcomes, and economic impact for a province-wide single-payer system. METHODS: We compared pre- and post-guideline implementation outcomes in consecutive staging and debulking patients at two centers that provide the majority of surgical gynecologic oncology care in Alberta, Canada between March 2016 and April 2017. Clinical outcomes and compliance were obtained using the ERAS Interactive Audit System. Patients were followed until 30 days after discharge. Negative binomial regression was employed to adjust for patient characteristics. RESULTS: We assessed 152 pre-ERAS and 367 post-ERAS implementation patients. Mean compliance with ERAS care elements increased from 56% to 77.0% after implementation (p < 0.0001). Median length of stay for all surgeries decreased from 4.0 days to 3.0 days post-ERAS (p < 0.0001), which translated to an adjusted LOS decrease of 31.4% (95% CI = [21.7% - 39.9%], p < 0.0001). In medium/high complexity surgery median LOS was reduced by 2.0 days (p = 0.0005). Complications prior to discharge decreased from 53.3% to 36.2% post-ERAS (p = 0.0003). There was no significant difference in readmission (p = 0.6159), complications up to 30 days (p = 0.6274), or mortality (p = 0.3618) between the cohorts. The net cost savings per patient was $956 (95%CI: $162 to $1636). CONCLUSIONS: Systematic implementation of ERAS gynecologic oncology guidelines across a healthcare system improves patient outcomes and saves resources.


Asunto(s)
Neoplasias de los Genitales Femeninos/cirugía , Adhesión a Directriz/estadística & datos numéricos , Procedimientos Quirúrgicos Ginecológicos/efectos adversos , Atención Perioperativa/normas , Complicaciones Posoperatorias/epidemiología , Anciano , Ahorro de Costo , Procedimientos Quirúrgicos de Citorreducción/efectos adversos , Procedimientos Quirúrgicos de Citorreducción/economía , Procedimientos Quirúrgicos de Citorreducción/métodos , Femenino , Neoplasias de los Genitales Femeninos/economía , Procedimientos Quirúrgicos Ginecológicos/economía , Procedimientos Quirúrgicos Ginecológicos/métodos , Humanos , Tiempo de Internación/economía , Tiempo de Internación/estadística & datos numéricos , Auditoría Médica , Persona de Mediana Edad , Alta del Paciente/estadística & datos numéricos , Readmisión del Paciente/economía , Readmisión del Paciente/estadística & datos numéricos , Atención Perioperativa/economía , Atención Perioperativa/métodos , Guías de Práctica Clínica como Asunto , Evaluación de Programas y Proyectos de Salud
4.
Br J Cancer ; 111(12): 2297-307, 2014 Dec 09.
Artículo en Inglés | MEDLINE | ID: mdl-25349970

RESUMEN

BACKGROUND: Folate receptor 1 (FOLR1) is expressed in the majority of ovarian carcinomas (OvCa), making it an attractive target for therapy. However, clinical trials testing anti-FOLR1 therapies in OvCa show mixed results and require better understanding of the prognostic relevance of FOLR1 expression. We conducted a large study evaluating FOLR1 expression with survival in different histological types of OvCa. METHODS: Tissue microarrays composed of tumour samples from 2801 patients in the Ovarian Tumour Tissue Analysis (OTTA) consortium were assessed for FOLR1 expression by centralised immunohistochemistry. We estimated associations for overall (OS) and progression-free (PFS) survival using adjusted Cox regression models. High-grade serous ovarian carcinomas (HGSC) from The Cancer Genome Atlas (TCGA) were evaluated independently for association between FOLR1 mRNA upregulation and survival. RESULTS: FOLR1 expression ranged from 76% in HGSC to 11% in mucinous carcinomas in OTTA. For HGSC, the association between FOLR1 expression and OS changed significantly during the years following diagnosis in OTTA (Pinteraction=0.01, N=1422) and TCGA (Pinteraction=0.01, N=485). In OTTA, particularly for FIGO stage I/II tumours, patients with FOLR1-positive HGSC showed increased OS during the first 2 years only (hazard ratio=0.44, 95% confidence interval=0.20-0.96) and patients with FOLR1-positive clear cell carcinomas (CCC) showed decreased PFS independent of follow-up time (HR=1.89, 95% CI=1.10-3.25, N=259). In TCGA, FOLR1 mRNA upregulation in HGSC was also associated with increased OS during the first 2 years following diagnosis irrespective of tumour stage (HR: 0.48, 95% CI: 0.25-0.94). CONCLUSIONS: FOLR1-positive HGSC tumours were associated with an increased OS in the first 2 years following diagnosis. Patients with FOLR1-negative, poor prognosis HGSC would be unlikely to benefit from anti-FOLR1 therapies. In contrast, a decreased PFS interval was observed for FOLR1-positive CCC. The clinical efficacy of FOLR1-targeted interventions should therefore be evaluated according to histology, stage and time following diagnosis.


Asunto(s)
Biomarcadores de Tumor/biosíntesis , Receptor 1 de Folato/biosíntesis , Neoplasias Glandulares y Epiteliales/metabolismo , Neoplasias Ováricas/metabolismo , Carcinoma Epitelial de Ovario , Supervivencia sin Enfermedad , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Análisis de Supervivencia , Análisis de Matrices Tisulares
6.
Frontline Gastroenterol ; 5(3): 161-166, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-28839765

RESUMEN

OBJECTIVE: To examine the outcome of endoscopic retrograde cholangiopancreatography (ERCP) in the management of common bile duct (CBD) stones. DESIGN: A retrospective review of 100 consecutive ERCPs performed for CBD stones. RESULTS: 100 ERCPs were performed on 84 patients with a median cohort age of 77. Completion in this cohort, as defined by duct clearance, was achieved in 65% of cases. Completion rates fell rapidly after two ERCPs. 33% of the cohort had small stones <10 mm, and 67% had stones >10 mm. Size, but not number of stones, affected the completion rate and frequency of complications (16%). Presence of periampullary diverticulum did not affect completion or complication rates. MR cholangiopancreatography (MRCP) had a 90% sensitivity for detecting CBD stones compared with 56% for CT. DISCUSSION AND CONCLUSIONS: ERCP remains a high-risk procedure with a significant complication rate when performed to deal with CBD stones. MRCP should be the second choice of investigation for CBD stones. This cohort had an unusually high number of larger stones at ERCP of 67% compared with other published UK cohorts of 8%, and this was reflected in the completion and complication rate.

7.
Aliment Pharmacol Ther ; 37(11): 1084-92, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23600758

RESUMEN

SUMMARY: Barrett's oesophagus (BO) and gastro-oesophageal reflux disease (GERD) are precursors of oesophageal adenocarcinoma (OAC). There is an oesophageal biofilm, which changes in disease, but its role in aetiopathogenesis remains unclear. AIM: To define the oesophageal microbiota of patients with GERD, BO and OAC compared with controls and to investigate mucosal responses related to the microbiota. METHODS: Cultural analysis identified the dominant bacterial species from a subset of each disease group. Based on this, molecular techniques were used to define the cohort. Host responses were analysed in tissues and co-culture experiments. RESULTS: A total of 111 species belonging to 26 genera were isolated. There was a significant decrease in bacterial counts in the GERD and BO groups for all genera except Campylobacter, which colonised GERD and Barrett's patients in increasing numbers. Campylobacter concisus was the dominant species. This relationship was not seen in the cancer group. Significant increases in IL-18 were seen in GERD and BO colonised by Campylobacter. CONCLUSIONS: This study defines differences in the oesophageal biofilm in disease states, revealing the emergence of C. concisus as the dominant new colonist in the refluxed oesophagus. We also associate the presence of these bacteria with increased expression of cytokines related to carcinogenesis.


Asunto(s)
Adenocarcinoma/microbiología , Esófago de Barrett/microbiología , Biopelículas/crecimiento & desarrollo , Neoplasias Esofágicas/microbiología , Reflujo Gastroesofágico/microbiología , Metagenoma , Adulto , Anciano , Anciano de 80 o más Años , Fenómenos Fisiológicos Bacterianos , Estudios de Casos y Controles , Técnicas de Cocultivo , Estudios de Cohortes , Recuento de Colonia Microbiana , Citocinas/genética , Esófago/microbiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , ARN Mensajero/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Adulto Joven
8.
Alcohol Alcohol ; 47(1): 75-8, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22085525

RESUMEN

AIMS: To assess perceptions on alcohol misuse and addiction among medical students prior to in-depth training in order to determine areas of the curriculum that need to be reshaped or focused on. METHODS: A questionnaire assessment of first- and second-year medical students' perceptions of alcohol misuse. RESULTS: Students had some misconceptions about current alcohol misuse rates, including a perception that addiction is common among health professionals, that the under-25s had the fastest increasing rate of alcohol addiction and that British women had a more rapidly increasing rate of alcohol addiction than British men. CONCLUSION: Encouragingly, students overwhelmingly felt that alcohol addiction was something to which they could make a difference. It highlights that early education about alcohol misuse is important in terms of teaching students how to recognize hazardous and harmful drinkers and how to manage them.


Asunto(s)
Alcoholismo/epidemiología , Alcoholismo/prevención & control , Actitud del Personal de Salud , Percepción Social , Estudiantes de Medicina/psicología , Consumo de Bebidas Alcohólicas/epidemiología , Consumo de Bebidas Alcohólicas/prevención & control , Alcoholismo/diagnóstico , Curriculum/tendencias , Femenino , Humanos , Masculino , Informe de Investigación , Escocia/epidemiología , Encuestas y Cuestionarios
9.
J R Coll Physicians Edinb ; 41(3): 206-10, 2011 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-21949914

RESUMEN

Anaemia is common in a wide range of malignancies and individual studies have demonstrated it to be an independent prognostic marker for survival in certain cancer types. The study population consisted of 171 patients: 77 anaemic and 94 non-anaemic. Sixty per cent of the study population had adenocarcinoma with 37% having squamous cell carcinoma. Late-stage disease occurred in 80% of individuals. There was no significant difference in survival times between the two groups (p=0.1), and after adjusting for confounding factors including age, sex, stage and physical status (p=0.8). Anaemic individuals with adenocarcinoma suffered a poorer survival probability compared to those with normal haemoglobon level (p=0.02). Anaemia is common at diagnosis in oesophageal cancer and was found to be a significant prognostic indicator of survival in adenocarcinoma, but not squamous cell carcinoma.


Asunto(s)
Adenocarcinoma/mortalidad , Anemia , Carcinoma de Células Escamosas/mortalidad , Neoplasias Esofágicas/mortalidad , Hemoglobinas/metabolismo , Adenocarcinoma/sangre , Adulto , Anciano , Anciano de 80 o más Años , Anemia/sangre , Anemia/etiología , Carcinoma de Células Escamosas/sangre , Progresión de la Enfermedad , Neoplasias Esofágicas/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico
10.
Aliment Pharmacol Ther ; 32(7): 872-83, 2010 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-20735782

RESUMEN

BACKGROUND: Crohn's disease is an inflammatory illness in which the immune response against gut microorganisms is believed to drive an abnormal immune response. Consequently, modification of mucosal bacterial communities, and the immune effects they elicit, might be used to modify the disease state. AIM: To investigate the effects of synbiotic consumption on disease processes in patients with Crohn's disease. METHODS: A randomized, double-blind placebo-controlled trial was conducted involving 35 patients with active Crohn's disease, using a synbiotic comprising Bifidobacterium longum and Synergy 1. Clinical status was scored and rectal biopsies were collected at the start, and at 3- and 6-month intervals. Transcription levels of immune markers and mucosal bacterial 16S rRNA gene copy numbers were quantified using real-time PCR. RESULTS: Significant improvements in clinical outcomes occurred with synbiotic consumption, with reductions in both Crohn's disease activity indices (P = 0.020) and histological scores (P = 0.018). The synbiotic had little effect on mucosal IL-18, INF-gamma and IL-1beta; however, significant reductions occurred in TNF-alpha expression in synbiotic patients at 3 months (P = 0.041), although not at 6 months. Mucosal bifidobacteria proliferated in synbiotic patients. CONCLUSION: Synbiotic consumption was effective in improving clinical symptoms in patients with active Crohn's disease.


Asunto(s)
Bifidobacterium/metabolismo , Enfermedad de Crohn/tratamiento farmacológico , Mucosa Intestinal/microbiología , Lactobacillus acidophilus/metabolismo , Oligosacáridos/uso terapéutico , Probióticos/uso terapéutico , Adulto , Anciano , Recuento de Colonia Microbiana , Enfermedad de Crohn/inmunología , Método Doble Ciego , Femenino , Humanos , Mucosa Intestinal/inmunología , Masculino , Persona de Mediana Edad , Prebióticos , Probióticos/farmacología , Resultado del Tratamiento
11.
Scott Med J ; 55(3): 22-5, 2010 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-20795513

RESUMEN

BACKGROUND & AIMS: The incidence of Crohn's disease (CD) in northeastern Scotland was last reported as rising in the 1980's, while in the rest of Europe it had reached steady state. This study reviewed the incidence of CD in NHS Tayside. METHODS: Data was collected retrospectively and analysed using age and sex standardization, socioeconomic factors and urban and rural postcodes. RESULTS: A point prevalence of 157 per 100,000 population in the Tayside region was found. The average incidence of CD was 9.56 per 100,000 per year between 2003 and 2007 and 7.16 per 100,000 per year between 1998 and 2001. There was no link to urbanization and no difference in incidence between the sexes. Incidence was not related to affluence in this population and peak age of onset occurred in the third decade of life only. 12.7% of patients had a family history of inflammatory bowel disease and 25% of patients were current smokers. CONCLUSIONS: The incidence of CD appears to have arrived at a steady state in Tayside, while recent evidence suggests that it is on the rise in Scandinavia again. The results of the genetic studies to come from the east of Scotland are eagerly awaited to help shed light on the aetiology of this complex disorder.


Asunto(s)
Enfermedad de Crohn/epidemiología , Humanos , Incidencia , Escocia/epidemiología , Fumar/epidemiología
12.
Alcohol Alcohol ; 45(4): 395-7, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-20501550

RESUMEN

AIMS: This study was aimed to review and rewrite the undergraduate curriculum on alcohol use disorders, implement the changes and assess for any early evidence of an improvement in knowledge. METHODS: A three-stage process was used to review the old curriculum and a new one was designed around the five undergraduate years. Students' opinions were sought about the acceptability of the new curriculum using a questionnaire, to which 93 responded and 70 volunteers were objectively assessed using an examination based on questions from the text of the Medical Students' Handbook on Alcohol and Health. RESULTS: There was no evidence of any improvement in the students' knowledge using the old curriculum. After teaching with the new curriculum, examination scores significantly increased (P < 0.0001). There was no difference between the sexes. The new curriculum was assessed as acceptable to the students. CONCLUSION: This new curriculum reflects the need for a new teaching method and not only offers improved teaching, but also produces a generation of doctors equipped to identify alcohol-related problems and to deliver brief interventions, helping to reduce the projected consequences of alcohol abuse and the associated burden on the health service.


Asunto(s)
Trastornos Relacionados con Alcohol , Curriculum , Educación de Pregrado en Medicina/métodos , Femenino , Humanos , Masculino , Encuestas y Cuestionarios , Enseñanza
13.
Curr Pharm Des ; 15(13): 1528-36, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19442170

RESUMEN

Crohn's disease and ulcerative colitis are the two principal forms of inflammatory bowel disease (IBD). The root causes of these chronic and acute immunological disorders are unclear, but intestinal microorganisms are known to play a key role in the initiation and maintenance of disease. However, at present, there is no clear evidence for a single transmissible agent being involved in IBD aetiology. Although marked alterations occur in faecal and mucosal bacterial communities in IBD, it is unclear whether they are responsible for causing disease, or are due to changes in the gut environment that result from inflammatory reactions and extensive tissue destruction. Despite the involvement of microorganisms in inflammatory processes, antibiotic therapy has generally been unsuccessful in IBD. However, recent studies involving the use of probiotics, prebiotics and synbiotics suggest that there is potential for controlling these diseases through manipulation of the composition of the gut microbiota, and direct interactions with the gut immune system.


Asunto(s)
Colitis Ulcerosa/microbiología , Enfermedad de Crohn/microbiología , Tracto Gastrointestinal/microbiología , Animales , Antibacterianos/uso terapéutico , Ensayos Clínicos como Asunto , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/etiología , Enfermedad de Crohn/tratamiento farmacológico , Enfermedad de Crohn/etiología , Tracto Gastrointestinal/inmunología , Tracto Gastrointestinal/fisiopatología , Humanos , Probióticos/uso terapéutico
14.
J Appl Microbiol ; 104(2): 305-44, 2008 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-18215222

RESUMEN

Most studies involving prebiotic oligosaccharides have been carried out using inulin and its fructo-oligosaccharide (FOS) derivatives, together with various forms of galacto-oligosaccharides (GOS). Although many intestinal bacteria are able to grow on these carbohydrates, most investigations have demonstrated that the growth of bifidobacteria, and to a lesser degree lactobacilli, is particularly favoured. Because of their safety, stability, organoleptic properties, resistance to digestion in the upper bowel and fermentability in the colon, as well as their abilities to promote the growth of beneficial bacteria in the gut, these prebiotics are being increasingly incorporated into the Western diet. Inulin-derived oligosaccharides and GOS are mildly laxative, but can result in flatulence and osmotic diarrhoea if taken in large amounts. However, their effects on large bowel habit are relatively minor. Although the literature dealing with the health significance of prebiotics is not as extensive as that concerning probiotics, considerable evidence has accrued showing that consumption of GOS and FOS can have significant health benefits, particularly in relation to their putative anti-cancer properties, influence on mineral absorption, lipid metabolism, and anti-inflammatory and other immune effects such as atopic disease. In many instances, prebiotics seem to be more effective when used as part of a synbiotic combination.


Asunto(s)
Bacterias/metabolismo , Alimentos Formulados , Intestino Grueso/microbiología , Oligosacáridos/administración & dosificación , Anciano , Anciano de 80 o más Años , Bifidobacterium/metabolismo , Terapia Combinada , Fermentación , Fructanos/administración & dosificación , Humanos , Lactante , Recién Nacido , Enfermedades Intestinales/dietoterapia , Enfermedades Intestinales/inmunología , Intestino Grueso/inmunología , Inulina/administración & dosificación , Lactobacillus/metabolismo , Probióticos
15.
Gynecol Oncol ; 103(1): 53-7, 2006 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-16516279

RESUMEN

OBJECTIVE: To determine the incidence of parametrial involvement in clinical stage IA and IB1 cervical cancer and whether pelvic lymph node status is a predictor of parametrial status. METHODS: Retrospective review of 120 patients with FIGO stage IA/IB1 cervical carcinoma treated by class II radical abdominal hysterectomy between January 1997 and December 2001 was performed. The parametria were examined for microscopic involvement of parametrial lymph nodes and/or tissue. Continuous variables were compared using Wilcoxon rank sum test, and Fisher's exact test was used to categorical variables. Kaplan-Meier curves were constructed for overall survival (OS) and recurrence-free survival (RFS). Cox proportional hazards model was used to investigate prognostic factors. RESULTS: One hundred ten patients were eligible. Five patients (5%) had positive parametria and 13 patients (12%) had positive pelvic lymph nodes. Four (80%) patients with positive parametria had positive pelvic lymph nodes. The groups did not differ significantly in terms of age (P = 0.92), histology (P = 0.15), or LVSI (P = 0.20). Positive parametria was associated with larger tumor size (3.0 vs. 2.0 cm, P < 0.05), greater depth of invasion (16 mm vs. 5 mm, P = 0.03), and pelvic lymph node metastases (80% vs. 10%, P = 0.001). The only variable that was significant in the proportional hazards model was lymph node status (P = 0.02). After median follow-up of 48 months, there was a significant difference in recurrence (40% vs. 4%, P = 0.03) and RFS (0.0003). CONCLUSIONS: Acknowledging small sample size and retrospective study, positive parametrial involvement in stage IA and IB1 cervical cancer is infrequent. There is a significant association with lymph node status. Thus, there may be a role for less radical surgery combined with pelvic lymphadenectomy in this patient population.


Asunto(s)
Neoplasias del Cuello Uterino/patología , Adulto , Anciano , Femenino , Estudios de Seguimiento , Humanos , Histerectomía , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Neoplasias del Cuello Uterino/cirugía
16.
Int J Gynecol Cancer ; 16 Suppl 1: 47-53, 2006.
Artículo en Inglés | MEDLINE | ID: mdl-16515567

RESUMEN

The objective of this study is to compare progression-free survival (PFS) and overall survival (OS) of ovarian cancer patients treated with neoadjuvant chemotherapy and surgery to primary surgery and postoperative chemotherapy. Retrospective analysis from 1998 to 2003 of 116 patients with ovarian cancer was performed. Fifty women diagnosed by positive cytology received three cycles of carboplatin and paclitaxel. Thirty-six patients subsequently underwent cytoreductive surgery and completed three further cycles postoperatively. The OS and PFS were compared in 66 women treated with primary surgery and postoperative chemotherapy. A statistically significant difference was observed for OS (P= 0.03, HR = 1.85, CI = 1.06-3.23) and PFS (P= 0.04, HR = 1.61, CI = 1.03-2.53) favoring the primary surgery group. Due to the small numbers, age, grade, stage, pleural effusions, and histologic cell type were controlled for separately in the bivariate analyses. Controlling for stage made the results weaker. A matched subgroup survival analysis was performed on patients who had surgery following neoadjuvant chemotherapy. After matching for stage and grade and controlling age and pleural effusions (N= 28 matched pairs), there was no statistical difference for OS (P= 0.95, HR = 1.04, CI = 0.33-3.30) or PFS (P= 0.79, HR = 1.11, CI = 0.98-1.04). It is concluded that primary surgery should be considered in all patients. Neoadjuvant chemotherapy may be an alternative in a subset of women with the intent to also perform interval debulking.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/cirugía , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/cirugía , Adenocarcinoma/patología , Anciano , Anciano de 80 o más Años , Carboplatino/administración & dosificación , Quimioterapia Adyuvante , Supervivencia sin Enfermedad , Femenino , Procedimientos Quirúrgicos Ginecológicos , Humanos , Persona de Mediana Edad , Terapia Neoadyuvante , Estadificación de Neoplasias , Neoplasias Ováricas/patología , Paclitaxel/administración & dosificación , Estudios Retrospectivos , Análisis de Supervivencia
17.
Int J Gynecol Cancer ; 16 Suppl 1: 278-85, 2006.
Artículo en Inglés | MEDLINE | ID: mdl-16515604

RESUMEN

The aim of this study was to compare overall survival (OS), progression-free survival (PFS), and relapse patterns between different modalities of treatment for uterine papillary serous carcinoma (UPSC). A retrospective review of 124 patients with pathologically confirmed UPSC was performed, of whom, 97 patients were eligible for study. Postoperative treatment groups included adjuvant radiotherapy consisting of whole abdomen and a pelvic boost (abdominopelvic radiotherapy [APRT]) (55 patients), paclitaxel and carboplatin chemotherapy (CT) for six cycles followed by APRT (18 patients), CT only (5 patients), and 19 patients were observed without postoperative adjuvant therapy. Three-year OS was 81% and 63% for the CT followed by APRT and APRT alone, respectively (P= 0.11). After controlling for stage, the group treated with APRT alone had significantly decreased OS and PFS compared to the CT/APRT group (HR 3.6; 1.3-9.8; P= 0.01) and (HR 2.9; 95% CI 1.1-7.3; P= 0.03), respectively. Within the limitations of a retrospective study, the results of this study indicate that multimodality postoperative treatment with paclitaxel and a platinum-based CT followed by APRT may increase the survival of patients with UPSC. However, further prospective studies using these combined modalities are needed to confirm these findings.


Asunto(s)
Adenocarcinoma Papilar/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias Uterinas/terapia , Adulto , Anciano , Anciano de 80 o más Años , Carboplatino/administración & dosificación , Terapia Combinada , Femenino , Procedimientos Quirúrgicos Ginecológicos , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Paclitaxel/administración & dosificación , Radioterapia , Estudios Retrospectivos , Análisis de Supervivencia
18.
Int J Gynecol Cancer ; 14(3): 546-50, 2004.
Artículo en Inglés | MEDLINE | ID: mdl-15228432

RESUMEN

Female adnexal tumors of probable wolffian origin (FATWOs) are rare tumors arising in the broad ligament from the remnants of the mesonephric duct. We report a case of recurrent disease. A 15-year-old girl who presented with a painful pelvic mass underwent a laparotomy with tumor resection. Pathology findings confirmed a FATWO. The tumor recurred within 2 years and was treated with multiple chemotherapy regimens, including a platinum-based drug, and surgery for progressive disease. The tumor was positive for c-kit oncogene (CD 117). Gleevac therapy, a tyrosine kinase inhibitor, was prescribed, and she developed severe persistent lower abdominal pain 2 months later. She underwent a hysterectomy and debulking of retroperitoneal masses. Pathology showed evidence of tumor necrosis, suggesting a possible beneficial effect, and she was recommenced on Gleevac in an effort to prevent recurrences. She is currently asymptomatic, without evidence of disease 10 months after surgery, continuing on Gleevac therapy. FATWOs are very rare tumors. Most cases are benign but have the potential to recur and metastasize. There is limited knowledge about the optimal treatment for this neoplasm. Our patient's favorable response to Gleevac therapy supports the concept of targeted molecular therapy in patients with c-kit-positive FATWO tumors.


Asunto(s)
Recurrencia Local de Neoplasia/diagnóstico , Neoplasias Peritoneales/diagnóstico , Conductos Mesonéfricos , Dolor Abdominal/etiología , Adolescente , Terapia Combinada , Diagnóstico Diferencial , Inhibidores Enzimáticos/uso terapéutico , Femenino , Humanos , Recurrencia Local de Neoplasia/complicaciones , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/terapia , Neoplasias Peritoneales/complicaciones , Neoplasias Peritoneales/patología , Neoplasias Peritoneales/terapia , Proteínas Tirosina Quinasas/antagonistas & inhibidores
19.
Gynecol Oncol ; 93(3): 588-93, 2004 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-15196849

RESUMEN

OBJECTIVES: The aim of this study was to compare peri-operative morbidity and recurrence-free survival of early-stage cervical cancer patients treated by laparoscopic-assisted radical vaginal hysterectomy (LARVH) with time-matched radical abdominal hysterectomy (RAH) controls at our center. METHODS: Since July 1984, all patients with FIGO stage IA/IB cervical cancer undergoing radical surgery by members of our division have been entered into a prospective database. Since November 1996, one surgeon at our center has performed LARVH on all surgically appropriate patients. Non-parametric tests were used. Differences between medians were compared using Wilcoxon Rank Sum test. Statistical analysis used the Kaplan-Meier method to calculate disease-free survival. Differences between survival curves were compared with the log rank test. Statistical significance was defined as P < 0.05. RESULTS: Between November 1996 and December 2003, 71 and 205 patients have undergone LARVH and RAH, respectively, for FIGO stage IA/IB carcinoma of the cervix. Both groups were similar with respect to age and Quetelet index. There were no differences in tumor size, histology, grade, depth of invasion, lymph node metastases, or surgical margins. All laparoscopic procedures were completed successfully with no conversions to laparotomy. Intra-operative morbidity characteristics analyzed (LARVH vs. RAH) were blood loss 300 ml vs. 500 ml (P < 0.001), operative time 3.5 h vs. 2.5 h (P < 0.001), and intra-operative complications 13% vs. 4% (P < 0.03). Intra-operative complications in the LARVH group included: cystotomy (7), ureteric injury (1), and bowel injury (1). There was no difference in transfusion rates. There was no difference between post-operative infectious and non-infectious complications (LARVH vs. RAH), 9% vs. 5% and 5% vs. 2%, respectively. The median time to normal urine residual was 10 days vs. 5 days (P < 0.001), and the median length of hospital stay was 1 day vs. 5 days (P < 0.001). Twenty-two percent of patients received post-operative radiotherapy for high-risk features in both groups. After a median follow-up of 17 and 21 months, there have been 4 recurrences in the LARVH group and 13 in the RAH (P = NS). The overall 2-year recurrence-free survival was 94% and 94% in the LARVH and RAH groups, respectively (P = NS). CONCLUSION: Our data demonstrate that early cervical cancer can be treated successfully with LARVH with similar efficacy and recurrence rates to RAH. The major benefits are less intra-operative blood loss and shorter hospital stay. It is a safe procedure with low overall morbidity and complication rates. However, at present, LARVH is associated with an increase in intra-operative complications, and patients may have an increased time to return to normal bladder function.


Asunto(s)
Histerectomía Vaginal/métodos , Laparoscopía/métodos , Neoplasias del Cuello Uterino/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Femenino , Humanos , Histerectomía Vaginal/efectos adversos , Laparoscopía/efectos adversos , Escisión del Ganglio Linfático , Persona de Mediana Edad , Morbilidad , Estadificación de Neoplasias , Resultado del Tratamiento , Neoplasias del Cuello Uterino/patología
20.
Obstet Gynecol ; 100(5 Pt 2): 1105-8, 2002 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-12423823

RESUMEN

BACKGROUND: Squamous cell carcinoma of the vagina in pregnancy is rare. CASE: A 28-year-old primigravida with antepartum bleeding at 20 weeks' gestation was diagnosed with squamous cell carcinoma after biopsy of a vaginal mass. The histology revealed an invasive grade 3 squamous cell carcinoma of large-cell, nonkeratinizing type. The patient declined pregnancy termination and immediate radiation treatment. She continued to have episodes of vaginal bleeding and was admitted at 30 weeks' gestation. A decision was made in consultation with the neonatal unit to deliver her at 32 weeks' gestation. After corticosteroid treatment, she was delivered by cesarean delivery. Positive pelvic lymph nodes were noted at surgery. Postoperatively, she received external beam radiation and brachytherapy and concurrent cisplatin chemotherapy. She is disease free 3 years from her original diagnosis. CONCLUSION: This case emphasizes the importance of a thorough pelvic examination to assess the vaginal walls and cervix at the first prenatal visit and with any antepartum bleeding episode.


Asunto(s)
Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/terapia , Complicaciones Neoplásicas del Embarazo/patología , Complicaciones Neoplásicas del Embarazo/terapia , Neoplasias Vaginales/patología , Neoplasias Vaginales/terapia , Adulto , Braquiterapia , Carcinoma de Células Escamosas/metabolismo , Cisplatino/uso terapéutico , Terapia Combinada , Femenino , Humanos , Inmunohistoquímica , Metástasis Linfática , Embarazo , Complicaciones Neoplásicas del Embarazo/metabolismo , Dosificación Radioterapéutica , Neoplasias Vaginales/metabolismo
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