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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 Endometriales , Laparoscopía , Humanos , Femenino , Neoplasias Endometriales/cirugía , Neoplasias Endometriales/patología , Estudios Retrospectivos , Histerectomía , Laparotomía/efectos adversos , Laparoscopía/efectos adversos , Procedimientos Quirúrgicos Mínimamente Invasivos , Estadificación de Neoplasias , Recurrencia Local de Neoplasia/cirugíaRESUMEN
isomiRs, the sequence-variants of microRNA, are known to be tissue and cell type specific but their physiological role is largely unknown. In our study, we explored for the first time the expression of isomiRs across different Stage I epithelial ovarian cancer (EOC) histological subtypes, in order to shed new light on their biological role in tumor growth and progression. In a multicentric retrospective cohort of tumor biopsies (n = 215) we sequenced small RNAs finding 971 expressed miRNAs, 64% of which are isomiRs. Among them, 42 isomiRs showed a clear histotype specific pattern, confirming our previously identified miRNA markers (miR192/194 and miR30a-3p/5p for mucinous and clear cell subtypes, respectively) and uncovering new biomarkers for all the five subtypes. Using integrative models, we found that the 38% of these miRNA expression alterations is the result of copy number variations while the 17% of differential transcriptional activities. Our work represents the first attempt to characterize isomiRs expression in Stage I EOC within and across subtypes and to contextualize their alterations in the framework of the large genomic heterogeneity of this tumor.
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MicroARNs , Neoplasias Ováricas , Humanos , Femenino , MicroARNs/genética , MicroARNs/metabolismo , Carcinoma Epitelial de Ovario/genética , Variaciones en el Número de Copia de ADN , Estudios Retrospectivos , Perfilación de la Expresión Génica , Neoplasias Ováricas/patologíaRESUMEN
OBJECTIVE: The prognostic significance of isolated tumor cells (≤0.2 mm) in sentinel lymph nodes (SLNs) of endometrial cancer patients is still unclear. Our aim was to assess the prognostic value of isolated tumor cells in patients with low risk endometrial cancer who underwent SLN biopsy and did not receive adjuvant therapy. Outcomes were compared with node negative patients. METHODS: Patients with SLNs-isolated tumor cells between 2013 and 2019 were identified from 15 centers worldwide, while SLN negative patients were identified from Mayo Clinic, Rochester, between 2013 and 2018. Only low risk patients (stage IA, endometrioid histology, grade 1 or 2) who did not receive any adjuvant therapy were included. Primary outcomes were recurrence free, non-vaginal recurrence free, and overall survival, evaluated with Kaplan-Meier methods. RESULTS: 494 patients (42 isolated tumor cells and 452 node negative) were included. There were 21 (4.3%) recurrences (5 SLNs-isolated tumor cells, 16 node negative); recurrence was vaginal in six patients (1 isolated tumor cells, 5 node negative), and non-vaginal in 15 (4 isolated tumor cells, 11 node negative). Median follow-up among those without recurrence was 2.3 years (interquartile range (IQR) 1.1-3.0) and 2.6 years (IQR 0.6-4.2) in the SLN-isolated tumor cell and node negative patients, respectively. The presence of SLNs-isolated tumor cells, lymphovascular space invasion, and International Federation of Obstetrics and Gynecology (FIGO) grade 2 were significant risk factors for recurrence on univariate analysis. SLN-isolated tumor cell patients had worse recurrence free survival (p<0.01) and non-vaginal recurrence free survival (p<0.01) compared with node negative patients. Similar results were observed in the subgroup of patients without lymphovascular space invasion (n=480). There was no difference in overall survival between the two cohorts in the full sample and the subset excluding patients with lymphovascular space invasion. CONCLUSIONS: Patients with SLNs-isolated tumor cells and low risk profile, without adjuvant therapy, had a significantly worse recurrence free survival compared with node negative patients with similar risk factors, after adjusting for grade and excluding patients with lymphovascular space invasion. However, the presence of SLNs-isolated tumor cells was not associated with worse overall survival.
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PURPOSE OF REVIEW: Sex cord-stromal tumours (SCSTs) are rare ovarian cancers. As in the literature, only small case series or case reports are published, gathering solid evidence about their management is challenging. Surgery plays a pivotal role, and accurate staging is one of the most important prognostic factors. This review focuses on the current evidence for surgical staging in the management of SCSTs. RECENT FINDINGS: Staging procedures have been inferred by epithelial ovarian cancers; however, they are often only partially performed, and most SCSTs therefore end up incompletely staged, raising the issue of the need for restaging or further treatments. In addition, some parts of the staging procedure have been questioned over the years, and lymphadenectomy is now considered unnecessary for SCSTs.The generally favourable prognosis of SCSTs, the introduction of minimally invasive surgery and fertility-sparing approaches is empowering the question of which staging procedures are beneficial for these patients. We reviewed the role of each staging procedure proposed by the guidelines in light of new scientific updates. SUMMARY: Surgical staging should always be performed. It includes peritoneal samplings (peritoneal washing, multiple peritoneal biopsies, omental biopsy and biopsy of any suspicious area), whereas lymphadenectomy could be omitted. Laparoscopy may be considered a feasible approach.
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Neoplasias Ováricas , Tumores de los Cordones Sexuales y Estroma de las Gónadas , Carcinoma Epitelial de Ovario , Femenino , Humanos , Escisión del Ganglio Linfático , Estadificación de Neoplasias , Neoplasias Ováricas/patología , Neoplasias Ováricas/cirugía , Pronóstico , Tumores de los Cordones Sexuales y Estroma de las Gónadas/patología , Tumores de los Cordones Sexuales y Estroma de las Gónadas/cirugíaRESUMEN
OBJECTIVE: To evaluate recurrence-free survival (RFS) and cause-specific survival (CSS) after observation or vaginal brachytherapy (VB) alone in all subgroups of early-stage high-intermediate (HIR) and high-risk endometrial cancer (EC). METHODS: We identified patients with stage I HIR (GOG-249 criteria) and stage II endometrioid EC, and stage I and II non-endometrioid EC who underwent surgery at Mayo Clinic and Cleveland Clinic between 1999 and 2016. Three-year RFS and CSS after observation or VB only were estimated in 16 subgroups defined by risk factors. RESULTS: Among 4156 ECs, we identified 447 (10.8%) stage I endometrioid HIR, 52 (1.3%) stage II endometrioid, 350 (8.4%) stage I non-endometrioid, and 17 (0.4%) stage II non-endometrioid ECs; observation or VB alone was applied in 349 (78.1%), 24 (46.2%), 187 (53.4%), and 2 (11.8%) patients, respectively. After observation or VB, stage I HIR endometrioid EC subgroups with <2 factors among grade 3, LVSI, or stage IB had a 3-year CSS >95% (lower 95% confidence intervals limit: 89.8%), whereas subgroups with ≥2 factors had poorer outcomes. No EC-related deaths after 3 years were reported in 97 stage IA non-endometrioid ECs without myometrial invasion. Stage II ECs had poor outcomes regardless of histology. CONCLUSIONS: Observation or VB only may be sufficient in stage I endometrioid HIR ECs with <2 factors among grade 3, LVSI, or IB and in stage IA non-endometrioid ECs without myometrial invasion. Stratification of early-stage HIR and high-risk ECs into risk subgroups potentially alleviates the overtreatment and undertreatment risk and should be considered in future research.
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Braquiterapia , Carcinoma Endometrioide , Neoplasias Endometriales , Femenino , Humanos , Estudios Retrospectivos , Estadificación de Neoplasias , Neoplasias Endometriales/radioterapia , Neoplasias Endometriales/cirugía , Carcinoma Endometrioide/radioterapia , Carcinoma Endometrioide/cirugía , Braquiterapia/efectos adversos , Recurrencia Local de Neoplasia/patología , Radioterapia AdyuvanteRESUMEN
Total skin electron beam therapy (TSEBT) is one of the mainstays of treatment for mycosis fungoides. The most common modalities are standard dose (30-36 Gy) and low dose (10-12 Gy). To review the literature on the efficacy and safety profiles of standard dose and low dose TSEBT. We searched electronic databases for studies that enrolled patients with Mycosis Fungoides and treated with TSEBT. We estimated the event rates associated with low dose and standard dose TSEBT. The Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline was followed. Main outcomes were complete response rate, partial response rate, mild and severe adverse events rate low dose TSEBT had a Complete Response Rate of 28% [0.19, 0.37], an Overall Response Rate of 85% [0.76, 0.93], a mild adverse events rate of 93% [0.82, 1.04] and a severe adverse events rate of 5% [-0.04; 0.14] Standard dose TSEBT had a Complete Response Rate of 57% [0.41; 0.73], the Overall Response Rate was 99% [0.97; 1.02], the mild adverse events rate was 100%, the severe adverse events rate was 7% [-0.01; 0.16]. Comparing standard dose TSEBT in the early versus advanced stages, advanced stages patients had a Risk Ratio = 0.77 in obtaining a Complete Response [0.64, 0.92](p = 0.0158). TSEBT is an associated with an excellent short term safety profile. Both schedules show high ORR, with standard dose TSEBT demonstrating highest CRR. Advanced stage of disease negatively influence the CRR.
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Micosis Fungoide , Neoplasias Cutáneas , Humanos , Electrones , Neoplasias Cutáneas/radioterapia , Micosis Fungoide/tratamiento farmacológico , Inducción de RemisiónRESUMEN
OBJECTIVE: advanced stage clear cell ovarian cancer (CCOC) carries a higher risk of relapse and death compared to other histological subtypes. The prognosis of early-stage CCOC is controversial. METHODS: Early-stage high-grade OC patients from two Italian oncologic centers were included. Patients with early-stage CCOC were compared with those with high-grade endometrioid (HGE) and serous (HGS) OC in terms of relapse-free interval (RFI), cancer-specific survival (CSS) and post relapse cancer-specific survival (prCSS). The Cox proportional hazard model and the restricted mean survival time were used. RESULTS: Between 1981 and 2012, 134 patients with CC, 152 with HGE and 160 with HGS were treated at two referral centers. Median follow-up was 11.5 years. Ten years RFI rates were 80.6%, 72.1%, 60.6%, and CSS rates were 84.3%, 82.6%, 81.7% respectively. Adjuvant chemotherapy significantly improved RFI (aHR 0.61, 95%CI 0.40 to 0.91, P = 0.015). In the multivariable analysis HGS histotype was associated with a shorter RFI compared to CC, (Hazard Ratio [HR]: 1.81; 95%CI: 1.12-2.93; P = 0.016), whereas CSS was not statistically different. prCSS was longer in HGS compared to CCOC (HR, 0.36; 95% CI, 0.17-0.74; P = 0.006). According to the stage, IA/IB/IC1 HGSOC had a shorter RFI (HR, 2.13; 95% CI, 1.14-3.99; P = 0.018) compared to IA/IB/IC1 CCOC, but similar CSS. For prCSS, CC compared to HGS conferred a worse prognosis regardless of the initial stage. CONCLUSIONS: Early-stage CCOC is associated with a longer RFI, similar CSS and a shorter prCSS compared to HGSOC. No prognostic differences were observed between CC and HGE OC. The relapse risk was the lowest in IA/IB/IC1 CC compared to HGS, whereas CC displayed poor sensitivity to chemotherapy after relapse.
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Adenocarcinoma de Células Claras/patología , Neoplasias Ováricas/patología , Adenocarcinoma de Células Claras/tratamiento farmacológico , Adenocarcinoma de Células Claras/mortalidad , Adenocarcinoma de Células Claras/cirugía , Adulto , Carcinoma Endometrioide/tratamiento farmacológico , Carcinoma Endometrioide/mortalidad , Carcinoma Endometrioide/patología , Carcinoma Endometrioide/cirugía , Quimioterapia Adyuvante , Cistadenocarcinoma Seroso/tratamiento farmacológico , Cistadenocarcinoma Seroso/mortalidad , Cistadenocarcinoma Seroso/patología , Cistadenocarcinoma Seroso/cirugía , Supervivencia sin Enfermedad , Femenino , Humanos , Italia/epidemiología , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/cirugía , Pronóstico , Resultado del TratamientoRESUMEN
OBJECTIVE: To evaluate trends in outpatient versus inpatient hysterectomy for endometrial cancer and assess enabling factors, cost and safety. METHODS: In this retrospective cohort study, patients aged 18 years or older who underwent hysterectomy for endometrial cancer between January 2008 and September 2015 were identified in the Premier Healthcare Database. The surgical approach for hysterectomy was classified as open/abdominal, vaginal, laparoscopic or robotic assisted. We described trends in surgical setting, perioperative costs and safety. The impact of patient, provider and hospital characteristics on outpatient migration was assessed using multivariate logistic regression. RESULTS: We identified 41 246 patients who met inclusion criteria. During the time period studied, we observed a 41.3% shift from inpatient to outpatient hysterectomy (p<0.0001), an increase in robotic hysterectomy, and a decrease in abdominal hysterectomy. The robotic hysterectomy approach, more recent procedure (year), and mid-sized hospital were factors that enabled outpatient hysterectomies; while abdominal hysterectomy, older age, Medicare insurance, black ethnicity, higher number of comorbidities, and concomitant procedures were associated with an inpatient setting. The shift towards outpatient hysterectomy led to a $2500 savings per case during the study period, in parallel to the increased robotic hysterectomy rates (p<0.001). The post-discharge 30-day readmission and complications rate after outpatient hysterectomy remained stable at around 2%. CONCLUSIONS: A significant shift from inpatient to outpatient setting was observed for hysterectomies performed for endometrial cancer over time. Minimally invasive surgery, particularly the robotic approach, facilitated this migration, preserving clinical outcomes and leading to reduction in costs.
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Procedimientos Quirúrgicos Ambulatorios/estadística & datos numéricos , Neoplasias Endometriales/cirugía , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Adulto , Anciano , Comorbilidad , Neoplasias Endometriales/epidemiología , Femenino , Humanos , Histerectomía/métodos , Histerectomía/estadística & datos numéricos , Persona de Mediana Edad , Procedimientos Quirúrgicos Mínimamente Invasivos/estadística & datos numéricos , Estudios Retrospectivos , Procedimientos Quirúrgicos Robotizados/estadística & datos numéricosRESUMEN
High-grade serous ovarian cancer (HGS-EOCs) is generally sensitive to front-line platinum (Pt)-based chemotherapy although most patients at an advanced stage relapse with progressive resistant disease. Clinical or molecular data to identify primary resistant cases at diagnosis are not yet available. HGS-EOC biopsies from 105 Pt-sensitive (Pt-s) and 89 Pt-resistant (Pt-r) patients were retrospectively selected from two independent tumor tissue collections. Pathway analysis was done integrating miRNA and mRNA expression profiles. Signatures were further validated in silico on a cohort of 838 HGS-EOC cases from a published dataset. In all, 131 mRNAs and 5 miRNAs belonging to different functionally related molecular pathways distinguish Pt-s from Pt-r cases. Then, 17 out of 23 selected elements were validated by orthogonal approaches (SI signature). As resistance to Pt is associated with a short progression-free survival (PFS) and overall survival (OS), the prognostic role of the SI signature was assessed, and 14 genes associated with PFS and OS, in multivariate analyses (SII signature). The prognostic value of the SII signature was validated in a third extensive cohort. The expression profiles of SDF2L1, PPP1R12A and PRKG1 genes (SIII signature) served as independent prognostic biomarkers of Pt-response and survival. The study identified a prognostic molecular signature based on the combined expression profile of three genes which had never been associated with the clinical outcome of HGS-EOC. This may lead to early identification, at the time of diagnosis, of patients who would not greatly benefit from standard chemotherapy and are thus eligible for novel investigational approaches.
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Proteína Quinasa Dependiente de GMP Cíclico Tipo I/genética , Cistadenocarcinoma Seroso/tratamiento farmacológico , Perfilación de la Expresión Génica/métodos , Proteínas de la Membrana/genética , Fosfatasa de Miosina de Cadena Ligera/genética , Neoplasias Ováricas/tratamiento farmacológico , Platino (Metal)/uso terapéutico , Adulto , Anciano , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/patología , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Persona de Mediana Edad , Clasificación del Tumor , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
OBJECTIVE: To date, there is no universal consensus on which is the optimal ultrastaging protocol for sentinel lymph node (SLN) evaluation in gynecologic malignancies. To estimate the impact of different ultrastaging methods of SLNs on the detection of patients with nodal metastases in early-stage cervical and endometrial cancers and to describe the incidence of low-volume metastases between two ultrastaging protocols. METHODS: We retrospectively compared two ultrastaging protocols (ultrastaging-A vs ultrastaging-B) in patients with clinical stage I endometrial cancer or FIGO stage IA-IB1 cervical cancer who underwent primary surgery including SLN biopsy from October 2010 to December 2017 in our institution. The histologic subtypes and grades of the tumors were evaluated according to WHO criteria. Only SLNs underwent ultrastaging, while other lymph nodes were sectioned and examined by routine hematoxylin and eosin (H&E). RESULTS: Overall 224 patients were reviewed (159 endometrial cancer and 65 cervical cancer). Lymph node involvement was noted in 15% of patients with endometrial cancer (24/159): 24% of patients (9/38) with the ultrastaging protocol A and 12% (15/121) with the ultrastaging protocol B (p=0.08); while for cervical cancer, SLN metastasis was detected in 14% of patients (9/65): 22% (4/18) in ultrastaging-A and 11% (5/47) in ultrastaging-B (p=0.20). Overall, macrometastasis and low-volume metastases were 50% and 50% for endometrial cancer and 78% and 22% for cervical cancer. Median size of nodal metastasis was 2 (range 0.9-8.5) mm for the ultrastaging-A and 1.2 (range 0.4-2.6) mm for the ultrastaging-B protocol in endometrial cancer (p=0.25); 4 (range 2.5-9.8) mm for ultrastaging-A and 4.4 (range 0.3-7.8) mm for ultrastaging-B protocol in cervical cancer (p=0.64). CONCLUSION: In endometrial or cervical cancer patients, the incidence of SLN metastasis was not different between the two different types of ultrastaging protocol.
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Neoplasias Endometriales/diagnóstico por imagen , Metástasis Linfática/diagnóstico por imagen , Neoplasias del Cuello Uterino/diagnóstico por imagen , Anciano , Femenino , Humanos , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
BACKGROUND: In the primary treatment of apparent uterine-confined endometrial carcinoma, pelvic ± para-aortic lymphadenectomy has been considered the standard of care. Although some retrospective data suggest that the sentinel lymph node algorithm without complete lymphadenectomy can be used without jeopardizing oncologic outcome, prospective data are lacking. PRIMARY OBJECTIVES: To assess the 36 month incidence of pelvic/non-vaginal recurrence in women with pathologically confirmed stage I intermediate-risk endometrioid endometrial carcinoma who have bilateral negative pelvic sentinel lymph nodes. STUDY HYPOTHESIS: We hypothesize that patients with stage I, intermediate-risk endometrioid endometrial carcinoma who have bilateral negative pelvic sentinel lymph nodes will demonstrate a pelvic/non-vaginal recurrence rate comparable to historical estimate of stage I, intermediate-risk endometrioid endometrial carcinoma patients (estimated 2.5%). TRIAL DESIGN: This prospective multicenter single-arm observational study will follow women with stage I, intermediate risk endometrioid endometrial adenocarcinoma who have undergone successful hysterectomy, bilateral salpingo-oophorectomy, and bilateral sentinel lymph node biopsies, for recurrence. All patients will undergo lymphatic mapping using indocynanine green and will either receive no adjuvant treatment or vaginal brachytherapy only. Patients will be followed for 36 months. MAJOR INCLUSION/EXCLUSION CRITERIA: Patients will be enrolled in the study cohort if all the following criteria are met: (i) at time of surgery: hysterectomy with bilateral adnexectomy, and successful bilateral pelvic sentinel lymph node mapping; (ii) on final pathology: pathologic stage I, intermediate-risk endometrioid endometrial carcinoma (grade 1 or grade 2 with ≥50% myometrial invasion, or grade 3 with <50% myometrial invasion), negative pelvic peritoneal cytology, and bilateral sentinel lymph nodes negative for malignancy; (iii) recommended adjuvant treatment: vaginal brachytherapy or no adjuvant treatment. PRIMARY ENDPOINT: Incidence of pelvic/non-vaginal recurrence at 36 months. SAMPLE SIZE: 182 patients for study cohort ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Accrual will be completed in 2023 with results reported in 2026. TRIAL REGISTRATION: NCT04291612.
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Adenocarcinoma/patología , Neoplasias Endometriales/patología , Biopsia del Ganglio Linfático Centinela/métodos , Ganglio Linfático Centinela/patología , Femenino , Humanos , Metástasis Linfática/patología , Recurrencia Local de Neoplasia/diagnóstico , Estudios ProspectivosRESUMEN
OBJECTIVE: To evaluate the combination of positron emission tomography/computed tomography (PET/CT) and sentinel lymph node (SLN) biopsy in women with apparent early-stage endometrial carcinoma. The correlation between radiomics features extracted from PET images of the primary tumor and the presence of nodal metastases was also analyzed. METHODS: From November 2006 to March 2019, 167 patients with endometrial cancer were included. All women underwent PET/CT and surgical staging: 60/167 underwent systematic lymphadenectomy (Group 1) while, more recently, 107/167 underwent SLN biopsy (Group 2) with technetium-99m +blue dye or indocyanine green. Histology was used as standard reference. PET endometrial lesions were segmented (n=98); 167 radiomics features were computed inside tumor contours using standard Image Biomarker Standardization Initiative (IBSI) methods. Radiomics features associated with lymph node metastases were identified (Mann-Whitney test) in the training group (A); receiver operating characteristic (ROC) curves, area under the curve (AUC) values were computed and optimal cut-off (Youden index) were assessed in the test group (B). RESULTS: In Group 1, eight patients had nodal metastases (13%): seven correctly ridentified by PET/CT true-positive with one false-negative case. In Group 2, 27 patients (25%) had nodal metastases: 13 true-positive and 14 false-negative. Sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of PET/CT for pelvic nodal metastases were 87%, 94%, 93%, 70%, and 98% in Group 1 and 48%, 97%, 85%, 87%, and 85% in Group 2, respectively. On radiomics analysis a significant association was found between the presence of lymph node metastases and 64 features. Volume-density, a measurement of shape irregularity, was the most predictive feature (p=0001, AUC=0,77, cut-off 0.35). When testing cut-off in Group B to discriminate metastatic tumors, PET false-negative findings were reduced from 14 to 8 (-43%). CONCLUSIONS: PET/CT demonstrated high specificity in detecting nodal metastases. SLN and histologic ultrastaging increased false-negative PET/CT findings, reducing the sensitivity of the technique. PET radiomics features of the primary tumor seem promising for predicting the presence of nodal metastases not detected by visual analysis.
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Neoplasias Endometriales/diagnóstico por imagen , Neoplasias Endometriales/patología , Ganglio Linfático Centinela/diagnóstico por imagen , Ganglio Linfático Centinela/patología , Neoplasias Endometriales/cirugía , Femenino , Fluorodesoxiglucosa F18 , Humanos , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/patología , Ganglios Linfáticos/cirugía , Metástasis Linfática , Persona de Mediana Edad , Estadificación de Neoplasias , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Radiofármacos , Biopsia del Ganglio Linfático Centinela/métodosRESUMEN
OBJECTIVES: To compare survival and progression outcomes between 2 nodal assessment approaches in patients with nonbulky stage IIIC endometrial cancer (EC). METHODS: Patients with stage IIIC EC treated at 2 institutions were retrospectively identified. At 1 institution, a historical series (2004-2008) was treated with systematic pelvic and para-aortic lymphadenectomy (LND cohort). At the other institution, more contemporary patients (2006-2013) were treated using a sentinel lymph node algorithm (SLN cohort). Outcomes (hazard ratios [HRs]) within the first 5â¯years after surgery were compared between cohorts using Cox models adjusted for type of adjuvant therapy. RESULTS: The study included 104 patients (48 LND, 56 SLN). The use of chemoradiotherapy was similar in the 2 cohorts (46% LND vs 50% SLN), but the use of chemotherapy alone (19% vs 36%) or radiotherapy alone (15% vs 2%) differed. Although there was evidence of higher risk of cause-specific death (HR, 2.10; 95% CI, 0.79-5.58; Pâ¯=â¯0.14) and lower risk of para-aortic progression (HR, 0.27; 95% CI, 0.05-1.42; Pâ¯=â¯0.12) for the LND group, the associations did not meet statistical significance. The risk of progression was not significantly different between the groups (HR, 1.27; 95% CI, 0.60-2.67; Pâ¯=0â¯.53). In parsimonious multivariable models, high-risk tumor characteristics and nonendometrioid type were independently associated with lower cause-specific survival and progression-free survival. CONCLUSIONS: In EC patients with nonbulky positive lymph nodes, use of the SLN algorithm with limited nodal dissection does not compromise survival compared with LND. Aggressive pathologic features of the primary tumor are the strongest determinants of prognosis.
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Neoplasias Endometriales/cirugía , Escisión del Ganglio Linfático/métodos , Anciano , Algoritmos , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Neoplasias Endometriales/patología , Femenino , Humanos , Metástasis Linfática , Invasividad Neoplásica , Estadificación de Neoplasias , Estudios Retrospectivos , Ganglio Linfático Centinela/patología , Resultado del TratamientoRESUMEN
BACKGROUND: The effect of chemotherapy exposure (CE) on ovarian function in young women with ovarian neoplasms undergoing fertility-sparing treatment (FST) remains unclear. We investigated whether CE is correlated with the outcomes (1) during-treatment and (2) post-treatment amenorrhea, (3) conception rate, (4) pregnancy outcome, and (5) spontaneous menopausal age. PATIENTS AND METHODS: Eligibility criteria were patients with a diagnosis of epithelial (EOC) or nonepithelial (no-EOC) invasive ovarian neoplasm, premenopausal age, undergoing FST⯱â¯CE, histopathology confirmation, and adequate follow-up. The groups' outcomes were compared by logistic and linear regression analysis. RESULTS: A total of 548 patients diagnosed during 1980 and 2014 were included, 198 in the EOC group and 350 in the no-EOC group, and 44% received chemotherapy, with a median follow-up of 15.9â¯years. In no-EOC patients, CE conferred a higher risk for Outcomes 1 (adjusted OR [aOR] 27; 95% CI 12 to 61; Pâ¯<â¯.0001) and 2 (aOR 5.42; 95% CI 1 to 24; Pâ¯=â¯.0256) and was associated with a younger menopausal age (adjusted ß -5.52; 95% CI -10.53 to -0.52; Pâ¯=â¯.0313). Overall, 57% of patients attempted pregnancy, with a conception rate of 89%. In EOC patients, no association between CE and a decreased fertility was demonstrated (aOR, 3.05; 95% CI 0.72 to 12.88; Pâ¯=â¯.1298). CONCLUSIONS: CE in no-EOC was associated with an increased risk of during-treatment amenorrhea, post-treatment amenorrhea, and earlier spontaneous menopausal age; CE in EOC was not associated with any item at study. Patients undergoing FST had reassuringly high conception rates and low premature ovarian failure rates; however, in pretreatment counseling, the risks of this approach in such young population should be discussed.
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Carcinoma Epitelial de Ovario/fisiopatología , Carcinoma Epitelial de Ovario/terapia , Preservación de la Fertilidad/métodos , Menopausia/fisiología , Ovario/fisiopatología , Adulto , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Carcinoma Epitelial de Ovario/cirugía , Femenino , Humanos , Embarazo , Resultado del Embarazo , Estudios RetrospectivosRESUMEN
OBJECTIVE: This study is designed to identify genes and pathways that could promote metastasis to the bowel in high-grade serous ovarian cancer (OC) and evaluate their associations with clinical outcomes. METHODS: We performed RNA sequencing of OC primary tumors (PTs) and their corresponding bowel metastases (nâ¯=â¯21 discovery set; nâ¯=â¯18 replication set). Differentially expressed genes (DEGs) were those expressed at least 2-fold higher in bowel metastases (BMets) than PTs in at least 30% of patients (Pâ¯<â¯.05) with no increased expression in paired benign bowel tissue and were validated with quantitative reverse transcription PCR. Using an independent OC cohort (nâ¯=â¯333), associations between DEGs in PTs and surgical and clinical outcomes were performed. Immunohistochemistry and mouse xenograft studies were performed to confirm the role of LRRC15 in promoting metastasis. RESULTS: Among 27 DEGs in the discovery set, 21 were confirmed in the replication set: SFRP2, Col11A1, LRRC15, ADAM12, ADAMTS12, MFAP5, LUM, PLPP4, FAP, POSTN, GRP, MMP11, MMP13, C1QTNF3, EPYC, DIO2, KCNA1, NETO1, NTM, MYH13, and PVALB. Higher expression of more than half of the genes in the PT was associated with an increased requirement for bowel resection at primary surgery and an inability to achieve complete cytoreduction. Increased expression of LRRC15 in BMets was confirmed by immunohistochemistry and knockdown of LRRC15 significantly inhibited tumor progression in mice. CONCLUSIONS: We identified 21 genes that are overexpressed in bowel metastases among patients with OC. Our findings will help select potential molecular targets for the prevention and treatment of malignant bowel obstruction in OC.
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Carcinoma Epitelial de Ovario/genética , Carcinoma Epitelial de Ovario/patología , Neoplasias Intestinales/genética , Neoplasias Intestinales/secundario , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Animales , Línea Celular Tumoral , Estudios de Cohortes , Femenino , Técnicas de Silenciamiento del Gen , Xenoinjertos , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Proteínas de la Membrana/genética , Ratones , Ratones Desnudos , ARN Neoplásico/genética , Transcriptoma , Regulación hacia ArribaRESUMEN
OBJECTIVE: The role of lymphadenectomy in endometrial cancer is still uncertain. We aimed to evaluate the survival outcomes of two different strategies in apparent uterine confined disease by comparing sentinel lymph node (SLN) mapping and selective lymphadenectomy (LD). METHODS: We retrospectively reviewed women with preoperative stage I endometrial cancer underwent surgical staging with either SLN mapping, or LD in two Italian centers. RESULTS: Eight hundred and two women underwent surgical staging for preoperative stage I endometrial cancer were revised (145 Monza; 657 Rome). All patients underwent peritoneal washing, simple hysterectomy with bilateral salpingo-oophorectomy and nodal staging including SLN mapping, or LD. Overall 8229 lymph nodes were removed (1595 in Monza, 6634 in Rome). Pelvic lymphadenectomy was performed in 33.1% and 52.4% in Monza and Rome, respectively (p<0.001). Patients with positive pelvic LN were 16.7% and 7.3%, in SLN and LD groups, respectively (p=0.002). Disease-free survival (DFS) curves did not showed a statistically significant difference between centers and strategies adopted (SLN mapping, LD, SLN+LD) with a HR of 0.87 (95% CI 0.63-2.16; p=0.475). CONCLUSIONS: Survival outcomes were similar for both strategies. The SLN strategy allowed to identify a higher rate of stage IIIC1 disease even with a lower median number of lymph node removed in SLN group. Applying a SLN algorithm does not impair the prognosis of endometrial cancer patients. The clinical impact and management of low volume metastasis in high-risk patients should be further clarify.
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Neoplasias Endometriales/diagnóstico , Neoplasias Endometriales/mortalidad , Escisión del Ganglio Linfático/métodos , Biopsia del Ganglio Linfático Centinela/métodos , Adulto , Anciano , Anciano de 80 o más Años , Algoritmos , Neoplasias Endometriales/patología , Neoplasias Endometriales/cirugía , Femenino , Humanos , Italia/epidemiología , Ganglios Linfáticos/patología , Ganglios Linfáticos/cirugía , Metástasis Linfática , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios RetrospectivosRESUMEN
"Non-communicable diseases cause more than 80% of deaths in europe and, among these, 20% are caused by cancer. Modifiable lifestyle factors considered in the italian national programme "Guadagnare salute" (Gaining health), such as tobacco smoking, unhealthy diet, physical inactivity, overweight, and excessive alcohol use, are amongst the major causes of cancer deaths. The aims of this study was to estimate the number of deaths attributable to lifestyle factors for italy and for italian regions in 2013 and to describe its variation in relation to the regional prevalence of risk factors exposure. For Italy and for each italian region, deaths attributable to lifestyle factors were estimated using the methodology of the Global Burden of disease (GBd) study. italian mortality data of 2013 and risks attributable to these lifestyle factors for each cancer site for italy from the GBd study were used. Prevalence of exposure to lifestyles in Italy and in each Italian Region was collected for the period 2008-2013. In 2013, at least 66,605 cancer deaths in italy were attributable to lifestyle factors, accounting for 37.9% of all cancer deaths: 34.1% of cancer deaths in men and 9.0% in women were attributable to smoking; in men and women, respectively, 3.3% and 2.8% were attributable to excessive alcohol consumption; 5.3 % and 6.7% to overweight; 10.1% and 7.1% to dietary risk factors; 1.9% and 4.2% to physical inactivity. A moderate variability of percentage of deaths attributable to modifi able lifestyle factors by region was also detected due to different prevalence values of exposure to lifestyles occurred in last decades. At least 45,000 cancer deaths in men and 21,000 in women occurred in 2013 were attributable to modifi able risk factors, whose prevalence varied by region and which could be averted through the implementation of primary prevention interventions."
Asunto(s)
Consumo de Bebidas Alcohólicas/efectos adversos , Estilo de Vida , Neoplasias/mortalidad , Neoplasias/prevención & control , Fumar Tabaco/efectos adversos , Índice de Masa Corporal , Dieta/efectos adversos , Humanos , Italia/epidemiología , Neoplasias/epidemiología , Sobrepeso/epidemiología , Prevalencia , Factores de Riesgo , Distribución por SexoRESUMEN
Indocyanine green (ICG) represents a feasible alternative to the more traditional methods of sentinel lymph node (SLN) mapping, and interest in this promising tracer is growing. This report outlines our experience with ICG in a minimally invasive laparoscopic approach in women with endometrial cancer and cervical cancer using the Storz SPIES ICG near-infrared fluorescence imaging technology. A total of 49 patients with clinical stage I endometrial cancer (n = 40) or stage I cervical cancer (n = 9) were retrospectively reviewed. All patients had undergone simple or radical laparoscopic hysterectomy with pelvic and/or aortic lymphadenectomy and SLN mapping by means of an intracervical injection of ICG dye at the 3 o'clock and 9 o'clock locations after the induction of general anesthesia. The detection rate of ICG was 100% (49 of 49). The rate of bilateral SLN detection was 86% (42 of 49). Positive lymph nodes were found in 6 patients (12%), with at least 1 positive SLN. The sensitivity and negative predictive value of SLN detection were 100%. All procedures were successfully completed without conversion to open laparotomy, and no intraoperative or postoperative complications occurred. In our preliminary experience, ICG showed a high overall detection rate, and bilateral mapping appears to be a feasible alternative to the more traditional methods of SLN mapping in patients with endometrial cancer and cervical cancer. Laparoscopic SLN mapping with ICG appears to be safe, easy, and reproducible, with a positive impact on patient management.
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Colorantes/uso terapéutico , Neoplasias Endometriales/patología , Verde de Indocianina/uso terapéutico , Ganglios Linfáticos/patología , Imagen Óptica , Biopsia del Ganglio Linfático Centinela/métodos , Neoplasias del Cuello Uterino/patología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Histerectomía , Laparoscopía/métodos , Persona de Mediana Edad , Imagen Óptica/métodos , Estudios RetrospectivosRESUMEN
The implementation of sentinel lymph node (SLN) biopsy is changing the scenario in the surgical treatment of early-stage cervical cancer, and the oncologic safety of replacing bilateral pelvic lymphadenectomy with SLN biopsy is currently under investigation. Part of the undisputed value of SLN biopsy is its diagnostic accuracy in detecting low-volume metastases (LVM) via pathologic ultrastaging. In early-stage cervical cancer, the reported incidence of LVM ranges from 4 to 20%. The prognostic impact and the role of adjuvant treatment in patients with LVM is still unclear. Some non-prespecified analyses in prospective studies showed no impact on the oncologic outcomes compared to node-negative disease. However, the heterogeneity of the studies, the differences in the disease stage and the use of adjuvant treatment, and the concomitant pelvic lymphadenectomy (PLND) make reaching any conclusions on this topic hard. Current guidelines suggest considering micrometastases (MIC) as a node-positive disease, while considering isolated tumor cells (ITC) as a node-negative disease with a low level of evidence. This review aims to highlight the unanswered questions about the definition, identification, and prognostic and therapeutic roles of LVM and to underline the present and future challenges we are facing. We hope that this review will guide further research, giving robust evidence on LVM and their impacts on clinical practice.
RESUMEN
OBJECTIVE: The standard surgical treatment of advanced ovarian carcinoma is primary debulking surgery (PDS) aiming to complete cytoreduction. The need to achieve complete cytoreduction has shifted the surgical paradigm to more complex procedures, whose impact on morbidity is controversial. The objective of this retrospective analysis is to explore the impact of extensive PDS on morbidity and oncologic outcomes in a real-world scenario. METHODS: A retrospective single-center analysis was performed on 137 patients with advanced high-grade ovarian carcinoma (HGOC) who received PDS in 2015-2020. Patients treated in 2015-2017 (Group 1) were compared to patients treated in 2018-2020 (Group 2). The two periods were chosen according to the higher complexity of surgical procedures introduced in 2018. RESULTS: The increase in complete cytoreduction observed in Group2 (RD 0: 33 % vs 61 %, p = 0,008) was related to a higher surgical complexity (Aletti Score: 4 vs 6, p = 0,003) and did not reflect an increase in peri-operative complications (CCI: 20,9 vs 20,9, p = 0,11). After a median FUP of 44 months, PFS and OS at 24 months were 33,60 % vs 47,33 % (p = 0,288) and 72,10 % vs 80,37 % (p = 0,022) in Group 1 and 2, respectively. CONCLUSIONS: An extensive surgical effort leads to a significant increase in complete cytoreduction with acceptable morbidity. Arm-in-arm with novel maintenance therapies, it contributes to increasing the outcomes of patients with advanced HGOC.