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OBJECTIVE: To evaluate the effectiveness of implementing the Enhanced Recovery After Surgery (ERAS) protocol in patients undergoing elective hysterectomy in a network of regional hospitals, supported by an intensive audit-and-feedback (A&F) approach. DESIGN: A multi-centre, stepped-wedge cluster randomised trial (ClinicalTrials.gov NCT04063072). SETTING: Gynaecological units in the Piemonte region, Italy. POPULATION: Patients undergoing elective hysterectomy, either for cancer or for benign conditions. METHODS: Twenty-three units (clusters), stratified by surgical volume, were randomised into four sequences. At baseline (first 3 months), standard care was continued in all units. Subsequently, the four sequences implemented the ERAS protocol successively every 3 months, after specific training. By the end of the study, each unit had a period in which standard care was maintained (control) and a period in which the protocol, supported by feedback, was applied (experimental). MAIN OUTCOME MEASURES: Length of hospital stay (LOS), without outliers (>98th percentile). RESULTS: Between September 2019 and May 2021, 2086 patients were included in the main analysis with an intention-to-treat approach: 1104 (53%) in the control period and 982 (47%) in the ERAS period. Compliance with the ERAS protocol increased from 60% in the control period to 76% in the experimental period, with an adjusted absolute difference of +13.3% (95% CI 11.6% to 15.0%). LOS, moving from 3.5 to 3.2 days, did not show a significant reduction (-0.12 days; 95% CI -0.30 to 0.07 days). No difference was observed in the occurrence of complications. CONCLUSIONS: Implementation of the ERAS protocol for hysterectomy at the regional level, supported by an A&F approach, resulted in a substantial improvement in compliance, but without meaningful effects on LOS and complications. This study confirms the effectiveness of A&F in promoting important innovations in an entire hospital network and suggests the need of a higher compliance with the ERAS protocol to obtain valuable improvements in clinical outcomes.
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Recuperação Pós-Cirúrgica Melhorada , Histerectomia , Tempo de Internação , Humanos , Feminino , Histerectomia/métodos , Pessoa de Meia-Idade , Tempo de Internação/estatística & dados numéricos , Itália , Procedimentos Cirúrgicos Eletivos , Adulto , Complicações Pós-Operatórias/prevenção & controle , Auditoria Médica , RetroalimentaçãoRESUMO
STUDY OBJECTIVE: To evaluate recurrence rate and pattern in apparently early-stage endometrial cancer (EC) treated with minimally invasive surgery (MIS) and compare it to the "historical" populations treated by laparotomy. Secondary outcomes were to establish if, among MIS recurrent patients, intermediate-high/high-risk patients presented the same recurrence pattern compared to those at low/intermediate-risk and to evaluate time to first recurrence (TTR) of the study population. DESIGN: Multicenter retrospective observational study. SETTING: Five Italian Gynecologic Oncology referral centers. PATIENTS: All patients with proven recurrence of apparently early-stage EC treated with MIS from January 2017 to June 2022 . The laparotomic historical cohort was obtained from Laparoscopy Compared With Laparotomy for Comprehensive Surgical Staging of Uterine Cancer: Gynecologic Oncology Group Study (LAP2) and Laparoscopic Approach to Cancer of the Endometrium trials. INTERVENTIONS: Evaluation of recurrence rate and pattern. MEASUREMENTS AND MAIN RESULTS: Seventy-seven recurrences occurred on the total of 1028 patients treated with MIS for apparently early-stage EC during a median follow-up time of 36 months. The rate of recurrence in our cohort did not differ significantly from the rate of the historical cohort (7.4% vs 7.9%, odds ratio 0.9395, 95% CI 0.6901-1.2792). No significant differences were noticed for local, abdominal, nodal, and multiple site recurrence patterns; distant site recurrence appeared more likely in patients from the historical cohort. Postoperative low/intermediate risk patients had a higher likelihood of local recurrence compared to intermediate-high/high risk patients. Mean TTR was 19 months. No significant difference of TTR was observed for each pattern of recurrence compared to others. CONCLUSION: MIS appears to be safe for the treatment of early-stage EC. We did not identify any recurrence pattern specifically associated with MIS in early-stage EC.
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Neoplasias do Endométrio , Laparoscopia , Humanos , Feminino , Neoplasias do Endométrio/cirurgia , Neoplasias do Endométrio/patologia , Estudos Retrospectivos , Histerectomia , Laparotomia/efeitos adversos , Laparoscopia/efeitos adversos , Procedimentos Cirúrgicos Minimamente Invasivos , Estadiamento de Neoplasias , Recidiva Local de Neoplasia/cirurgiaRESUMO
No prospective study has validated molecular classification to guide adjuvant treatment in endometrial cancer (EC), and not even retrospective data are present for patients with morphological low-risk EC. We conducted a retrospective, multicenter, observational study including 370 patients with low-risk endometrioid EC to evaluate the incidence and prognostic role of p53 abnormal expression (p53abn) in this specific subgroup. Among 370 patients, 18 had abnormal expressions of p53 (4.9%). In 13 out of 370 patients (3.6%), recurrences were observed and two were p53abn. When adjusting for median follow-up time, the odds ratio (OR) for recurrence among those with p53abn versus p53 wild type (p53wt) was 5.23-CI 95% 0.98-27.95, p = 0.053. The most common site of recurrence was the vaginal cuff (46.2%). One recurrence occurred within the first year of follow-up, and the patient exhibited p53abn. Both 1-year and 2-year DFS rates were 94.4% and 100% in the p53abn and p53wt groups, respectively. One patient died from the disease and comprised p53wt. No difference in OS was registered between the two groups; the median OS was 21.9 months (16.4-30.1). Larger multicenter studies are needed to tailor the treatment of low-risk EC patients with p53abn. Performing molecular classification on all EC patients might be cost-effective, and despite the limits of our relatively small sample, p53abn patients seem to be at greater risk of recurrence, especially locally and after two years since diagnosis.
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BACKGROUND: Endometriosis is characterized by ectopic implantation of endometrial cells, which show increased proliferation and migration. Somatostatin (SST) and its analogues inhibit normal and cancer cell growth and motility through the SST receptors, sst1-5. Cortistatin (CST), which displays high structural and functional homology with SST, binds all ssts, as well as MrgX2. Our objective was to investigate the gene expression of the SST/CST system and to determine the effect of SST and its analogues on platelet-derived growth factor (PDGF)-induced proliferation and motility in telomerase-immortalized human endometrial stromal cell (T HESC) line and in primary endometrial stromal cell (ESCs) isolated from human endometriotic tissues. METHODS: Ectopic endometrial tissues were collected from women (n= 23) undergoing laparoscopic surgery for endometriosis (Stage III/IV). Gene expression was evaluated by real-time PCR, cell motility by wound healing assay, protein expression and ß-actin rearrangement by immunofluorescence, cell proliferation by the Alamar blue assay and ERK1/2 and Akt phosphorylation by western blot. RESULTS: Human endometriotic tissues, primary ESCs and T HESCs expressed SST, CST and ssts. SST, its analogues SOM230 and octreotide, as well as CST, counteracted PDGF-induced proliferation and migration in both ESCs and T HESCs. SST also inhibited vascular endothelial growth factor and metalloprotease-2 mRNA expression, and reduced basal and PDGF-induced ERK1/2 phosphorylation. CONCLUSION: These results indicate that the SST/CST system is expressed in endometriotic tissues and cells. The inhibitory effects of SST and its analogues on PDGF-induced proliferation and motility suggest that these peptides may represent promising tools in the treatment of endometriosis.
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Regulação da Expressão Gênica , Fator de Crescimento Derivado de Plaquetas/metabolismo , Somatostatina/análogos & derivados , Somatostatina/fisiologia , Movimento Celular , Proliferação de Células , Endometriose/metabolismo , Endométrio/citologia , Endométrio/metabolismo , Feminino , Humanos , Modelos Biológicos , Proteínas do Tecido Nervoso/metabolismo , Neuropeptídeos/metabolismo , Fosforilação , Receptores Acoplados a Proteínas G/metabolismo , Receptores de Neuropeptídeos/metabolismo , Células-Tronco/citologia , Células Estromais/citologia , CicatrizaçãoRESUMO
Background: The Quality of Recovery questionnaire (QoR-15) is an English instrument for measuring quality of recovery in surgical patients, not yet translated and validated in Italian when the Enhanced Recovery After Surgery (ERAS) Piemonte studies were planned. Objective: To produce the Italian version of the QoR-15 questionnaire, to evaluate its factorial structure and to assess the invariance between two types of surgery. Methods: The Italian version (QoR-15I) was obtained translating and adapting the original version to the Italian context. The validation was performed suppling the QoR-15I to 3,784 patients enrolled in two parallel stepped wedge cluster randomised trials (ERAS Colon-rectum Piemonte; ERAS Gyneco Piemonte). The factor structure and its invariance between types of surgery was tested using confirmatory bifactor model and multi-group analysis. Comparative fit index (CFI), root mean square error of approximation (RMSEA), and standardized root mean square residual (SRMR) fit indices and their changes between nested models were used to assess the factor structure and the invariance. Results: The bifactor model showed good fit (RMSEA = 0.049, CFI =0.957, SRMR = 0.036) and provided a general recovery factor and two specific factors for physical and mental recovery. Eighty-four percent of the common variance is attributable to the general factor, and thus the QoR-15I is sufficiently 'one-dimensional' with an adequate reliability (ωh = 0.70). The ωs values for the physical and mental recovery factors were 0.01 and 0.13, respectively. Multigroup analysis supported configural (RMSEA = 0.053, CFI = 0.950, SRMR = 0.035) and metric invariance (ΔRMSEA = -0.004; ΔCFI = -0.002; ΔSRMR = 0.014), whereas the intercept constraint was removed from item 15 to obtain partial scalar invariance (ΔRMSEA = 0.002; ΔCFI = 0.007; ΔSRMR = 0.004). Construct validity was supported by a negative association of QoR-15I scores with all variables related to worse patient condition and more complex surgery. Conclusion: Our results support the use of the QoR-15I as a valid, reliable, and clinically feasible tool for measuring the quality of recovery after surgery. The results of the confirmatory factor analyses suggest that a unique recovery score can be calculated and support measurement invariance of the QOR-15I across the two type of surgery, suggesting that the questionnaire has the same meaning and the same measurement parameters in colorectal and gynaecologic patients.
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INTRODUCTION: ERAS (Enhanced Recovery After Surgery) is a perioperative program combining multiple evidence-based interventions designed to reduce the surgical stress response. Despite the publication of dedicated guidelines, ERAS application to gynecologic surgery outside clinical studies has been slow and fragmented. To promote the systematic adoption of the ERAS program in the entire regional hospital network in Piedmont an Audit-and-Feedback approach (A&F) has been adopted within a cluster randomized controlled trial, aiming to estimate the true impact of the protocol on a large, unselected population. METHODS: The study protocol provides for a multicenter stepped wedge cluster randomized trial, focused on women undergoing an hysterectomy, for comparison between standard perioperative management and perioperative management according to the ERAS protocol. The primary outcome is the length of hospital stay (LOS). Secondary outcomes are: post-operative complications, quality-of-recovery at 24-hours after surgery, 30-day readmissions, patients' satisfaction, healthcare costs. The compliance to all the ERAS items is monitored with an A&F approach. All the gynecologic units of Piedmont hospitals are involved and all the patients hospitalized for elective hysterectomy in the period of the study are included. Centers, stratified by surgical volume and randomly assigned to four groups, are randomly ordered to activate the ERAS protocol in four periods, every three months. The planned calendar and the total duration of the study have been extended for six months due to the COVID-19 pandemic. The expected sample size of about 2400 patients has a high statistical power (99%) to detect a reduction of LOS of 1 day (effect size 0.5) and to estimate clinically meaningful changes in the other study endpoints. The study protocol has been approved by the Ethical Committee of all participating centers. Study results will be timely circulated within the hospital network and published in peer-reviewed journals. CONCLUSION: Results are expected to demonstrate positive clinical outcomes of the ERAS protocol even when its implementation is directed towards an entire regional network of gynecologic units, and not only towards selected and highly motivated centers. TRIAL REGISTRATION: NCT04063072.
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COVID-19 , Recuperação Pós-Cirúrgica Melhorada , Retroalimentação , Feminino , Humanos , Histerectomia , Estudos Multicêntricos como Assunto , Pandemias , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
In order to estimate the impact of laparoscopic stripping of endometriomas on the ovarian follicular reserve, 43 normo-ovulatory women were studied by endocrine (anti-Müllerian hormone (AMH), FSH, LH, inhibin B, oestradiol) and ultrasonographic (antral follicle count (AFC)) methods before surgery, and 3 and 9 months after surgery. The operation was performed by experienced laparoscopists, particularly aware of the need to avoid damaging the healthy part of the ovary. Serum AMH concentrations significantly decreased after the operation (1.4±0.2 ng/ml after 3 months and 1.3±0.3 ng/ml after 9 months versus 3.0±0.4 ng/ml before surgery; P<0.0001), whereas basal FSH, LH, oestradiol and inhibin B concentrations remained unchanged. The volume of the operated ovary significantly diminished after surgery (P<0.0001), whereas the AFC was not significantly altered. Overall, the data show that laparoscopic stripping of endometriomas reduces ovarian reserve. The significant decrease of AMH after surgery confirms that part of the healthy ovarian pericapsular tissue, containing primordial and preantral follicles, is removed or damaged despite all the surgical efforts to be atraumatic. This must be carefully considered when laparoscopic cystectomy surgery is scheduled for patients with no relevant symptoms besides infertility or with already small ovarian reserve.
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Endometriose/cirurgia , Laparoscopia/efeitos adversos , Folículo Ovariano/diagnóstico por imagem , Ovário/fisiologia , Adolescente , Adulto , Hormônio Antimülleriano/sangue , Estradiol/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Humanos , Inibinas/sangue , Hormônio Luteinizante/sangue , Ovário/diagnóstico por imagem , UltrassonografiaRESUMO
OBJECTIVES: Adenomyosis is a disorder defined by the presence of ectopic endometrial glands and stroma within the myometrium. Transvaginal ultrasound (TVU) is currently the first-line examination for this condition and the aim of this paper is to relate a pilot experience that was conducted using TVU to evaluate adenomyosis and which started from the assumption that tissues with anatomopathological differences show different elasticity values. METHODS: Using standard B-mode analysis and elastosonography, we evaluated 30 consecutive women with suspected uterine adenomyosis. In 15 cases the diagnosis was confirmed by histology. RESULTS: The adenomyotic area presented more softness (red and green) compared with the surrounding uterine tissue (blue); the borders of the adenomyotic area corresponded to the borders of the green area. CONCLUSIONS: These preliminary results suggest that elastosonography could be considered a useful tool in the diagnosis of adenomyosis because it is non-invasive, easy to understand, easy to perform, and has a short learning curve towards becoming skilled at the procedure.
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Técnicas de Imagem por Elasticidade/métodos , Endometriose/diagnóstico por imagem , Adulto , Diagnóstico Diferencial , Feminino , Humanos , Ultrassonografia DopplerRESUMO
PURPOSE OF REVIEW: The surgical management of deeply infiltrating endometriosis involving the ureter is a complex procedure that requires an accurate balance between the need for complete excision of endometriotic foci and the need to avoid any morbidity associated with radical surgery. Owing to its rarity, a clear surgical strategy to deal with this condition (e.g. ureterolysis vs. ureteroneocystostomy) has not as yet been identified. RECENT FINDINGS: A few studies present data about the conservative management of ureteral endometriosis. We reported the experience of some surgical topics dealing with ureteral endometriosis and their strategies for the conservative treatment of this condition. SUMMARY: Ureterolysis could be used as the initial surgical step for patients with ureteral endometriosis. For patients displaying extended severe ureteral involvement, stenosis, or moderate or severe hydronephrosis with a high risk of having intrinsic ureteral disease, ureteroneocystostomy is likely to be a wiser surgical strategy. Moreover the crucial role of the primary surgeon in the treatment definition will hardly be replaced by objective reproducible referral pattern.
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Endometriose/cirurgia , Laparoscopia/métodos , Doenças Ureterais/cirurgia , Feminino , Procedimentos Cirúrgicos em Ginecologia/métodos , Humanos , Procedimentos Cirúrgicos Urológicos/métodosRESUMO
BACKGROUND: this study aims to evaluate the effectiveness and safety of laparoscopic conservative management of ureteral endometriosis. METHODS: Eighty cases of histologically confirmed endometriosis affecting the ureter, 10 of which with bladder involvement were prospectively studied. In detail, patients were 13 women with ureteral stenosis (7 with hydronephrosis), 32 with circular lesions totally encasing the ureter, and 35 with endometriotic foci on the ureteral wall, but not completely encasing it. They were submitted to laparoscopic ureterolysis with or without partial cystectomy, ureteroneocistostomy. The rate of surgical complications, the recurrence rate, the patients' satisfaction rate was assessed during 22 months (median) follow-up. RESULTS: Laparoscopic ureterolysis was employed for all patients and set free the ureter from the disease in 95% of cases, whereas ureteroneocystostomy was necessary for 4 patients showing severe stenosis with hydronephrosis, among which 2 had intrinsic endometriosis of the ureteral muscularis. Three post-surgery ureteral fistulae occurred in cases with ureteral involvement longer than 4 cm: two cases were successfully treated placing double J catheter, the third needed ureteroneocistostomy. During follow-up, ureteral endometriosis recurred in 2 patients who consequently underwent ureteroneocystostomy. Most patients expressed high satisfaction rate throughout the whole follow-up period. CONCLUSION: laparoscopic ureterolysis is effective and well tolerated in most cases of ureteral endometriosis. Ureteroneocystostomy is a better strategy for patients with extended (more than 4 cm) ureteral involvement or with severe stenosis with or without hydronephrosis.
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Endometriose/cirurgia , Laparoscopia/métodos , Doenças Ureterais/cirurgia , Ureteroscopia/métodos , Constrição Patológica/epidemiologia , Constrição Patológica/etiologia , Coleta de Dados , Disuria/epidemiologia , Disuria/etiologia , Endometriose/epidemiologia , Feminino , Seguimentos , Humanos , Hidronefrose/epidemiologia , Hidronefrose/etiologia , Laparoscopia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Prevalência , Recidiva , Estudos Retrospectivos , Resultado do Tratamento , Doenças Ureterais/epidemiologia , Ureteroscopia/efeitos adversosRESUMO
OBJECTIVE: The aim of this study was to assess the feasibility and safety of vaginal removal of ovaries at the time of vaginal hysterectomy. MATERIALS AND METHODS: All patients candidate to hystero-salpingo-oophorectomy by transvaginal approach, between 1 March 2004 and 28 February 2007, were admitted in the study. RESULTS: Of the 472 women included in the study, 432 (91.5%) underwent hysterectomy and bilateral oophorectomy by vaginal approach. There was only one case of major vessel injury, but no patients required blood transfusion. All the operations were performed only by vaginal route and no conversion to the abdominal route was required. CONCLUSION: The need to perform oophorectomy should not be considered a contraindication to vaginal hysterectomy.
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Histerectomia Vaginal/métodos , Neoplasias Ovarianas/prevenção & controle , Ovariectomia/métodos , Doenças Uterinas/cirurgia , Idoso , Idoso de 80 Anos ou mais , Estudos de Viabilidade , Feminino , Humanos , Histerectomia Vaginal/instrumentação , Pessoa de Meia-Idade , Cuidados Pós-Operatórios , Estatísticas não ParamétricasRESUMO
OBJECTIVE: This study was undertaken to assess safety and efficacy of vaginal hysterectomy in case of large uterine size (> or = 250 g) using the LigaSure bipolar diathermy (Valleylab, Boulder, CO). STUDY DESIGN: In a retrospective study, medical records of 102 patients who underwent vaginal hysterectomy and who had uterine weight (evaluated after surgery) 250 g or greater were reviewed. All hysterectomies were performed by using the LigaSure vessel sealing system to secure vascular pedicles (uterosacral-cardinal, uterine and ovarian and round ligaments). RESULTS: Of the 102 vaginal hysterectomies, 99 were successfully performed (97.1%; 95% confidence interval, 91.6-99.4%), whereas a conversion from the vaginal to the abdominal route was required in 3 cases. The median uterine weight was 455 g (range, 241-1913 g). The weight of the largest uterus successfully removed vaginally was 1600 g, without intraoperative and postoperative complications. The median operative time was 50 minutes (range, 25-50 minutes). CONCLUSION: The current study confirms that very large uterine volume does not represent a real obstacle to perform vaginal hysterectomy and that results in a safe and effective technique in cases of uterine weight 250 g or greater.
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Diatermia/métodos , Histerectomia/métodos , Útero/anatomia & histologia , Adulto , Idoso , Feminino , Técnicas Hemostáticas , Humanos , Ligamentos/cirurgia , Pessoa de Meia-Idade , Tamanho do Órgão , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Women with newly diagnosed breast cancer may have lesions undetected by conventional imaging. Recently contrast-enhanced magnetic resonance mammography (CE-MRM) showed higher sensitivity in breast lesions detection. The present analysis was aimed at evaluating the benefit of preoperative CE-MRM in the surgical planning. From 2005 to 2009, 525 consecutive women (25-75 years) with breast cancer, newly diagnosed by mammography, ultrasound, and needle-biopsy, underwent CE-MRM. The median invasive tumour size was 19 mm. In 144 patients, CE-MRM identified additional lesions. After secondlook, 119 patients underwent additional biopsy. CE-MRM altered surgery in 118 patients: 57 received double lumpectomy or wider excision (41 beneficial), 41 required mastectomy (40 beneficial), and 20 underwent contra lateral surgery (18 beneficial). The overall false-positive rate was 27.1% (39/144). CE-MRM contributed significantly to the management of breast cancer, suggesting more extensive disease in 144/525 (27.4%) patients and changing the surgical plan in 118/525 (22.5%) patients (99/525, 18.8% beneficial).
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STUDY OBJECTIVE: To compare feasibility and surgical outcome of laparoscopic gynecologic surgery between obese, overweight, normal-weight, and underweight women. DESIGN: Retrospective case control study (Canadian Task Force classification II-3). SETTING: Surgery Unit of Minimally Invasive Gynaecology. PATIENTS: A total of 503 women who underwent laparoscopic procedures for both benign disease and malignancies. INTERVENTIONS: Four main categories of gynecologic disease were identified: uterine fibroids, benign adnexal masses, endometriosis, and endometrial cancer (stage I). For each category patients were divided into 4 groups: underweight (BMI <18.5 kg/m(2)), normal-weight (BMI 18.5-24.9 kg/m(2)), overweight (BMI 25-29.9 kg/m(2)), and obese (BMI ≥30 kg/m(2)). MEASUREMENTS AND MAIN RESULTS: Selected outcomes were duration of surgery, rate of laparotomy conversion, intraoperative and postoperative complications, and duration of hospital stay. No statistical difference regarding demographic data, surgical and medical history, and intraoperative findings was present between groups. No laparotomy conversion occurred. Regarding duration of surgery, we found no statistical difference among the BMI groups with regard to benign diseases, whereas pelvic lymphadenectomy in obese patients with endometrial cancer had a statistically significant longer duration than in the control group (122 +/- 47 min vs 65 +/- 21 min, p <.001). The postoperative complication rate was 0.01%: 3 cases of blood transfusion and 1 case of hemoperitoneum among myomectomies; 1 ureteral fistula in surgery for pelvic endometriosis; and 1 case of postoperative lymphocele in endometrial cancer group. No statistically significant difference was found in duration of hospital stay among the BMI groups in any of the categories of disease. For each category we conducted an analysis to identify any possible risk factors other than BMI in the surgical outcomes. CONCLUSION: Laparoscopic approach in the various applications of gynecologic surgery does not appear to be significantly influenced by BMI in terms of surgical outcomes, laparotomy conversion rate, intraoperative and postoperative complications rate, and duration of hospital stay. The technical difficulties can be solved if skilled surgeons and anesthetists are available.
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Índice de Massa Corporal , Doenças dos Genitais Femininos/complicações , Doenças dos Genitais Femininos/cirurgia , Laparoscopia , Obesidade/complicações , Magreza/complicações , Adulto , Idoso , Estudos de Viabilidade , Feminino , Humanos , Complicações Intraoperatórias , Tempo de Internação , Pessoa de Meia-Idade , Obesidade/cirurgia , Complicações Pós-Operatórias , Estudos Retrospectivos , Magreza/cirurgiaRESUMO
OBJECTIVE: To determine the effect of the GHRH antagonist JV-1-36 on proliferation and survival of primary ectopic human endometriotic stromal cells (ESCs) and the T HESC cell line. DESIGN: Prospective laboratory study. SETTING: University hospital. PATIENT(S): 22 women with endometriosis (aged 34.8+/-5.7 years) undergoing therapeutic laparoscopy. INTERVENTION(S): Eutopic (n=10) and ectopic (n=22) endometrial tissues were collected from women who underwent therapeutic laparoscopic surgery for endometriosis (stage III/IV). MAIN OUTCOME MEASURE(S): Expression of GHRH, GHRH receptor (GHRH-R) and GHRH-R splice variant (SV) 1 mRNA was determined by reverse-transcription polymerase chain reaction (RT-PCR). The ESC proliferation was assessed by 5-bromo-2-deoxyuridine incorporation, cell survival by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) and Trypan blue assay. The T HESC survival was evaluated by MTT, cyclic adenosine monophosphate (cAMP) levels by ELISA, extracellular signal-regulated kinases 1 and 2 (ERK1/2) phosphorylation by Western blot, and insulin-like growth factor (IGF)-2 mRNA by real-time PCR. RESULT(S): The ESCs and T HESCs, but not normal endometrial tissues, expressed GHRH-R mRNA; SV1 mRNA was determined in normal endometrial tissues, ESCs, and T HESCs; GHRH mRNAwas found in T HESCs; JV-1-36 inhibited ESC proliferation and ESC and T HESC survival. In T HESCs, JV-1-36 reduced cAMP production and ERK1/2 phosphorylation but had no effect on IGF-2 mRNA expression. CONCLUSION(S): The GHRH antagonist JV-1-36 inhibits endometriotic cell proliferation and survival, suggesting that GHRH antagonist may represent promising tools for treatment of endometriosis.
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Proliferação de Células/efeitos dos fármacos , Coristoma/patologia , Endometriose/patologia , Hormônio Liberador de Hormônio do Crescimento/análogos & derivados , Células Estromais/efeitos dos fármacos , Doenças Uterinas/patologia , Adulto , Linhagem Celular Transformada , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Coristoma/genética , Coristoma/metabolismo , Avaliação Pré-Clínica de Medicamentos , Endometriose/genética , Endometriose/metabolismo , Endométrio , Feminino , Hormônio Liberador de Hormônio do Crescimento/antagonistas & inibidores , Hormônio Liberador de Hormônio do Crescimento/genética , Hormônio Liberador de Hormônio do Crescimento/metabolismo , Hormônio Liberador de Hormônio do Crescimento/farmacologia , Antagonistas de Hormônios/farmacologia , Humanos , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Receptores de Neuropeptídeos/genética , Receptores de Neuropeptídeos/metabolismo , Receptores de Hormônios Reguladores de Hormônio Hipofisário/genética , Receptores de Hormônios Reguladores de Hormônio Hipofisário/metabolismo , Células Estromais/metabolismo , Células Estromais/patologia , Células Estromais/fisiologia , Doenças Uterinas/genética , Doenças Uterinas/metabolismoRESUMO
We evaluated the effectiveness and the cost of axillary staging in breast cancer patients by ultrasound-guided fine-needle aspiration cytology (US-FNAC), sentinel node biopsy (SNB), and frozen sections of the sentinel node to achieve the target of the highest number of immediate axillary dissections. From January 2003 through October 2005, a total of 404 consecutive eligible breast cancer patients underwent US-FNAC of suspicious axillary lymph nodes. If tumor cells were found, immediate axillary dissection was proposed (33% of node-positive cases). If US or cytology was negative, SNB was performed. Frozen sections of the sentinel node allowed immediate axillary dissection in 31% of node-positive cases. The remaining 36% underwent delayed axillary dissection. We compared our policy with clinical evaluation of the axilla, showing better specificity of US-FNAC, the cost balanced by a 12% reduction of SNBs, and a marked reduction of unnecessary axillary dissections resulting from false-positive clinical staging. Moreover, the comparison between our policy and permanent histology of the sentinel node showed an 8% cost saving, mainly associated with the immediate axillary dissections. US-FNAC of axillary lymph nodes in breast cancer patients reliably predicts the presence of metastases and therefore refers a significant number of patients to the appropriate surgical treatment, avoiding an SNB. As cost saving to the health care system in our study is mainly related to one-step axillary surgery, US-FNAC of axillary lymph nodes and frozen section of the sentinel node generate significant cost saving for patients who have metastatic nodes.