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CLINICAL IMPACT: Mechanical thrombectomy using a thromboaspiration catheter can be an effective alternative in the treatment of subacute pulmonary embolism.
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CONTEXT: DNA mismatch repair (MMR) deficiency (dMMR) testing is now recommended in endometrial cancer. Defect identification in the molecules participating in this pathway, or the presence of microsatellite instability, are commonly employed for this purpose. Novel methods are continuously evolving to report dMMR/microsatellite instability and to easily perform routine diagnoses. OBJECTIVE: The main aim of this study was to compare the concordance of the Idylla microsatellite instability test for the identification of dMMR endometrial cancer samples defined by immunohistochemistry and MMR genomic status. DESIGN: We applied the Idylla MSI test to 126 early-stage endometrial cancer cases with MMR testing by immunohistochemistry and genomic characterization (methylation in MLH1 and sequence alterations in MLH1, PMS2, MSH2 and MSH6). Individual markers and overall specific performance indicators were explored. RESULTS: The Idylla platform achieved a higher global concordance rate with MMR genomic status than with immunohistochemistry (75 % and 66 %, respectively). Sensitivity and specificity are also higher (75 % vs 66 % and 96 % vs 90 %, respectively). Clustering analysis split the patients into 2 well-differentiated clusters, the pMMR and the dMMR group, represented by MLH1/PMS2 loss and the MLH1 methylated promoter. Overall, immunohistochemistry and MMR genomic status identified more dMMR cases than did the Idylla test, although correlations were improved with a modified Idylla test cut-off. CONCLUSIONS: Performance of the Idylla test was better correlated with MMR genomic status than MMR immunohistochemistry status, which improved with a modified test cut-off. Further studies are needed to confirm the cut-off accuracy.
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OBJECTIVE: The aim of this study was to compare surgical complexity, post-operative complications, and survival outcomes between patients with minimal residual disease (completeness of cytoreduction (CC) score) CC-1 at the time of primary debulking surgery and those with complete cytoreduction (CC-0) at the time of interval debulking surgery. METHODS: A retrospective multicenter study was conducted of patients with advanced ovarian cancer (International Federation of Gynecology and Obstetrics stage IIIC-IV) who underwent cytoreductive surgery achieving either minimal or no residual disease between January 2008 and December 2015. Patients underwent either primary or interval debulking surgery after receiving ≥3 cycles of neoadjuvant chemotherapy. The sub-group of patients with primary debulking surgery/CC-1 was compared with those with interval debulking surgery/CC-0. Overall survival and disease-free survival were estimated using the Kaplan-Meier method. RESULTS: A total of 549 patients were included, with upfront surgery performed in 175 patients (31.9%) and 374 patients (68.1%) undergoing interval debulking surgery. After primary debulking surgery, 157/175 (89.7%) had complete cytoreduction and 18/175 (10.3%) had minimal residual disease (primary debulking surgery/CC-1 group), while after interval debulking surgery, 324/374 (86.6%) had complete cytoreduction (interval debulking surgery/CC-0 group) and 50/374 (13.4%) had minimal residual disease. The rate of patients with peritoneal cancer index >10 was 14/17 (82.4%) for the primary debulking surgery/CC-1 group and 129/322 (40.1%) for the interval debulking surgery/CC-0 (p<0.001). The rate of patients with an Aletti score of ≥8 was 11/18 (61.1%) and 132/324 (40.7%), respectively (p=0.09) and the rate of major post-operative complications was 5/18 (27.8%) and 64/324 (19.8%), respectively (p=0.38). Overall median disease-free and overall survival were 19.4 months (95% CI 18.0 to 20.6) and 56.7 months (95%CI 50.2 to 65.8), respectively. Median disease-free survival for the primary debulking surgery/CC-1 group was 16.7 months (95% CI 13.6 to 20.0) versus 18.2 months (95% CI 16.4 to 20.0) for the interval debulking surgery/CC-0 group (p=0.56). Median overall survival for the primary debulking surgery/CC-1 group was 44.7 months (95% CI 34.3 to not reached) and 49.4 months (95% CI 46.2 to 57.3) for the interval debulking surgery/CC-0 group (p=0.97). CONCLUSIONS: Patients with primary debulking surgery with minimal residual disease and those with interval debulking surgery with no residual disease had similar survival outcomes. Interval surgery should be considered when achieving absence of residual disease is challenging at upfront surgery, given the lower tumor burden found during surgery.
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PURPOSE: To evaluate the prevalence of deep and superficial dyspareunia in women with diagnosis of endometriosis. Secondly, to assess the temporal relation between deep and superficial dyspareunia in women reporting both symptoms (concomitant dyspareunia) and the impact on quality of life (QoL) and sexual function. METHODS: This is a cross-sectional cohort study that included fertile women with diagnosis of endometriosis. Enrolled subjects reported pain symptoms including dyspareunia and its temporal onset and completed two one-time validated questionnaires regarding sexual function (Female Sexual Function Index) and QoL (International QoL Assessment SF-36). RESULTS: Among the 334 enrolled patients, 75.7% (95%) reported dyspareunia. Women were divided into four groups according to the presence and type of dyspareunia: isolated superficial dyspareunia (6.3%), isolated deep dyspareunia (26.0%), concomitant dyspareunia (43.4%) and no dyspareunia (24.3%). Women with concomitant dyspareunia reported higher NRS scores than women with isolated dyspareunia or no dyspareunia (P ≤ 0.001). The majority of women with concomitant dyspareunia (56.6%) reported that deep dyspareunia developed before superficial dyspareunia. Women with concomitant dyspareunia reported worse QoL and worse sexual function than women with isolated dyspareunia or without dyspareunia (P ≤ 0.001). CONCLUSION: Dyspareunia is a common symptom in women with endometriosis, with many reporting concomitant deep and superficial dyspareunia. Concomitant dyspareunia can significantly impact sexual function and quality of life (QoL). Therefore, it is crucial to investigate dyspareunia thoroughly and differentiate between its types to tailor effective therapeutic strategies.
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The diagnosis of endometriosis by laparoscopy is delayed until advanced stages. In recent years, microRNAs have emerged as novel biomarkers for different diseases. These molecules are small non-coding RNA sequences involved in the regulation of gene expression and can be detected in peripheral blood. Our aim was to identify candidate serum microRNAs associated with endometriosis and their role as minimally invasive biomarkers. Serum samples were obtained from 159 women, of whom 77 were diagnosed with endometriosis by laparoscopy and 82 were healthy women. First, a preliminary study identified 29 differentially expressed microRNAs between the two study groups. Next, nine of the differentially expressed microRNAs in the preliminary analysis were evaluated in a new cohort of 67 women with endometriosis and 72 healthy women. Upon validation by quantitative real-time PCR technique, the circulating level of miR-30c-5p was significantly higher in the endometriosis group compared with the healthy women group. The area under the curve value of miR-30c-5p was 0.8437, demonstrating its diagnostic potential even when serum samples registered an acceptable limit of hemolysis. Dysregulation of this microRNA was associated with molecular pathways related to cancer and neuronal processes. We concluded that miR-30c-5p is a potential minimally invasive biomarker of endometriosis, with higher expression in the group of women with endometriosis diagnosed by laparoscopy.
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Endometriose , MicroRNAs , Humanos , Feminino , MicroRNAs/genética , Endometriose/diagnóstico , Endometriose/genética , Biomarcadores , Morte Celular , Reação em Cadeia da Polimerase em Tempo RealRESUMO
OBJECTIVE: Our study aimed to evaluate the association between timing of cytoreductive surgery and pattern of presentation of the first recurrence in patients with advanced ovarian cancer. We also aimed to assess the impact of the pattern of recurrence on post-relapse overall survival according to surgical timing. METHODS: This retrospective multicenter study evaluated patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIIC-IV ovarian cancer. Patients had undergone either primary debulking surgery, early interval debulking surgery after 3-4 cycles of neoadjuvant chemotherapy, or delayed debulking surgery after 6 cycles, with minimal or no residual disease, between January 2008 and December 2015. Survival analyses were conducted using the Log-rank test and the Cox model. Cumulative incidences of the different patterns of recurrence were estimated using a competing risks methodology. RESULTS: A total of 549 patients were included: 175 (31.9%) patients had primary, 224 (40.8%) early interval, and 150 (27.3%) delayed debulking surgery. The cumulative incidence of peritoneal recurrences at 2 years was higher with increasing neoadjuvant cycles (24.4%, 30.9% and 39.2%; p=0.019). For pleural or pulmonary recurrences, it was higher after early interval surgery (9.9%, 13.0% and 4.1%; p=0.022). Median post-relapse overall survival was 33.5 months (95% confidence interval (CI) (24.3 to 44.2)), 26.8 months (95% CI (22.8 to 32.6)), and 24.5 months (95% CI (18.6 to 29.4)) for primary, early interval, and delayed debulking surgery groups, respectively (p=0.025). The pattern of recurrence in a lymph node (hazard ratio (HR) 0.42, 95% CI (0.27 to 0.64)), delayed surgery (HR 1.53, 95% CI (1.11 to 2.13)) and time to first recurrence (HR 0.95, 95% CI (0.93 to 0.96)) were associated with post-relapse overall survival. For primary and early interval surgery, lymph node recurrences were associated with significantly longer post-relapse overall survival. CONCLUSIONS: The pattern of first recurrence was associated with timing of surgery, with peritoneal recurrences being more frequent with the increasing number of cycles of neoadjuvant chemotherapy. Lymph node recurrences were associated with better prognosis, having higher post-relapse overall survival. This improved prognosis of lymphatic recurrences was not observed in patients who underwent delayed surgery.
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Neoplasias Ovarianas , Humanos , Feminino , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/cirurgia , Neoplasias Ovarianas/patologia , Estadiamento de Neoplasias , Recidiva Local de Neoplasia/patologia , Carcinoma Epitelial do Ovário/patologia , Prognóstico , Terapia Neoadjuvante , Estudos Retrospectivos , Procedimentos Cirúrgicos de Citorredução/métodos , Quimioterapia AdjuvanteRESUMO
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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BACKGROUND: The SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) pandemic changed the distribution of healthcare resources, leading in many cases to the suspension of all non-essential treatments and procedures and representing a challenge for medical professionals. The objective of this study was to evaluate whether clinical protocols in gynecologic oncology care were modified as a result of the pandemic and to assess surgeons' perceptions regarding the management of gynecologic cancers". METHODS: Data were collected through an anonymous and voluntary survey sent via email to healthcare professionals in the field of gynecologic oncology in Spain. RESULTS: A total of 75 gynecologic oncologists completed the online survey. Of these, 93.2% (69) reported working in public hospitals and 62.5% (45) in tertiary care hospitals. 97.3% (71) were affiliated with hospitals treating patients infected with SARS-CoV-2. 85.1% (63) of the respondents expressed concern about the SARS-CoV-2 pandemic and 52.1% (38) indicated that the pandemic impacted the diagnostic and therapeutic quality of care for oncology patients. SARS-CoV-2 nasopharyngeal swab PCR (Polymerase Chain Reaction) testing was always performed before surgical interventions by 97.3% (71), being considered a best practice in triage by 94.4% (68). 87.5% (63) reported no change in the type of surgical approach during the pandemic. 62.5% (45) experienced limitations in accessing special personal protective equipment for SARS-CoV-2. An impact on the follow-up of patients with gynecologic cancers due to the pandemic was reported by 70.4% (50). CONCLUSIONS: Most of the Spanish gynecologic oncologists who responded to our survey reported that the SARS-CoV-2 pandemic had affected their clinical practice. The primary measures implemented were an increase in telemedicine, restricting outpatient visits to high-risk or symptomatic patients and the use of SARS-CoV-2 screening prior to surgery. No major changes in the surgical approach or management of the treatment of ovarian, endometrial or cervical cancer during the pandemic were reported.
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COVID-19 , Neoplasias dos Genitais Femininos , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias dos Genitais Femininos/epidemiologia , Neoplasias dos Genitais Femininos/terapia , SARS-CoV-2 , PandemiasRESUMO
Approximately 20-30% of endometrial carcinomas (EC) are characterized by mismatch repair (MMR) deficiency (dMMR) or microsatellite instability (MSI), and their testing has become part of the routine diagnosis. The aim of this study was to establish and compare the MMR status using various approaches. Immunohistochemistry (IHC), PCR-based MSI, and the detection of defects in the four key MMR genes (MLH1, PMS2, MSH2, and MSH6) via methylation-specific multiplex ligation-dependent probe amplification (MLPA) and targeted next-generation sequencing (NGS) were performed. MSH3 expression was also evaluated. A set of 126 early-stage EC samples were analyzed, 53.2% of which were dMMR and 46.8% of which were proficient MMR (pMMR) as determined using IHC, whereas 69.3% were classified as microsatellite stable, while 8.8% and 21.9% were classified MSI-low (MSI-L) and MSI-high (MSI-H), respectively. In total, 44.3% of the samples showed genetic or epigenetic alterations in one or more genes; MLH1 promoter methylation was the most common event. Although acceptable concordance was observed, there were overall discrepancies between the three testing approaches, mainly associated with the dMMR group. IHC had a better correlation with MMR genomic status than the MSI status determined using PCR. Further studies are needed to establish solid conclusions regarding the best MMR assessment technique for EC.
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Neoplasias Colorretais , Neoplasias do Endométrio , Síndromes Neoplásicas Hereditárias , Feminino , Humanos , Reparo de Erro de Pareamento de DNA/genética , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/patologia , Neoplasias Colorretais/diagnóstico , Síndromes Neoplásicas Hereditárias/diagnóstico , Instabilidade de MicrossatélitesRESUMO
BACKGROUND: the association between ovarian endometriosis (OE) and endometriosis-associated ovarian cancer (EAOC) is extensively documented, and misfunction of the immune system might be involved. The primary objective of this study was to identify and compare the spatial distribution of tumour-infiltrating lymphocytes (TILs) and tumour-associated macrophages (TAMs) in OE and EAOC. Secondary objectives included the analysis of the relationship between immunosuppressive populations and T-cell exhaustion markers in both groups. METHODS: TILs (CD3, CD4, and CD8) and macrophages (CD163) were assessed by immunochemistry. Exhaustion markers (PD-1, TIM3, CD39, and FOXP3) and their relationship with tumour-associated macrophages (CD163) were assessed by immunofluorescence on paraffin-embedded samples from n = 43 OE and n = 54 EAOC patients. RESULTS: we observed a predominantly intraepithelial CD3+ distribution in OE but both an intraepithelial and stromal pattern in EAOC (p < 0.001). TILs were more abundant in OE (p < 0.001), but higher TILs significantly correlated with a longer overall survival and disease-free survival in EAOC (p < 0.05). CD39 and FOXP3 significantly correlated with each other and CD163 (p < 0.05) at the epithelial level in moderate/intense CD4 EAOC, whereas in moderate/intense CD8+, PD-1+ and TIM3+ significantly correlated (p = 0.009). Finally, T-cell exhaustion markers FOXP3-CD39 were decreased and PD-1-TIM3 were significantly increased in EAOC (p < 0.05). CONCLUSIONS: the dysregulation of TILs, TAMs, and T-cell exhaustion might play a role in the malignization of OE to EAOC.
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Endometriose , Neoplasias Ovarianas , Humanos , Feminino , Endometriose/complicações , Endometriose/patologia , Receptor Celular 2 do Vírus da Hepatite A , Receptor de Morte Celular Programada 1 , Neoplasias Ovarianas/patologia , Complexo CD3 , Linfócitos do Interstício Tumoral/patologia , Fatores de Transcrição ForkheadRESUMO
There is uncertainty regarding Wilson's disease (WD) management. OBJECTIVES: To assess, in a multicenter Spanish retrospective cohort study, whether the approach to WD is homogeneous among centers. METHODS: Data on WD patients followed at 32 Spanish hospitals were collected. RESULTS: 153 cases, 58% men, 20.6 years at diagnosis, 69.1% hepatic presentation, were followed for 15.5 years. Discordant results in non-invasive laboratory parameters were present in 39.8%. Intrahepatic copper concentration was pathologic in 82.4%. Genetic testing was only done in 56.6% with positive results in 83.9%. A definite WD diagnosis (Leipzig score ≥4) was retrospectively confirmed in 92.5% of cases. Chelating agents were standard initial therapy (75.2%) with frequent modifications (57%), particularly to maintenance zinc. Enzyme normalization was not achieved by one third, most commonly in the setting of poor compliance, lack of genetic mutations and/or presence of cardiometabolic risk factors. Although not statistically significant, there were trends for sex differences in number of diagnosed cases, age at diagnosis and biochemical response. CONCLUSIONS: Significant heterogeneity in diagnosis and management of WD patients emerges from this multicenter study that includes both small and large reference centers. The incorporation of genetic testing will likely improve diagnosis. Sex differences need to be further explored.
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Degeneração Hepatolenticular , Humanos , Feminino , Masculino , Degeneração Hepatolenticular/diagnóstico , Degeneração Hepatolenticular/genética , Estudos Retrospectivos , Quelantes/uso terapêutico , Zinco , Cobre , Penicilamina/uso terapêuticoRESUMO
Patients with endometrial cancer differ in terms of the extent of T-cell infiltration; however, the association between T-cell subpopulations and patient outcomes remains unexplored. We characterized 285 early-stage endometrial carcinoma samples for T-cell infiltrates in a tissue microarray format using multiplex fluorescent immunohistochemistry. The proportion of T cells and their subpopulations were associated with clinicopathological features and relapse-free survival outcomes. CD3+ CD4+ infiltrates were more abundant in the patients with higher grade or non-endometrioid histology. Cytotoxic T cells (CD25+, PD-1+, and PD-L1+) were strongly associated with longer relapse-free survival. Moreover, CD3+ PD-1+ stromal cells were independent of other immune T-cell populations and clinicopathological factors in predicting relapses. Patients with high stromal T-cell fraction of CD3+ PD-1+ cells were associated with a 5-year relapse-free survival rate of 93.7% compared to 79.0% in patients with low CD3+ PD-1+ fraction. Moreover, in patients classically linked to a favorable outcome (such as endometrioid subtype and low-grade tumors), the stromal CD3+ PD-1+ T-cell fraction remained prognostically significant. This study supports that T-cell infiltrates play a significant prognostic role in early-stage endometrial carcinoma. Specifically, CD3+ PD-1+ stromal cells emerge as a promising novel prognostic biomarker.
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Neoplasias do Endométrio , Linfócitos do Interstício Tumoral , Antígeno B7-H1 , Neoplasias do Endométrio/patologia , Feminino , Humanos , Imuno-Histoquímica , Recidiva Local de Neoplasia/patologia , PrognósticoRESUMO
OBJECTIVE: To assess the impact on survival of major postoperative complications and to identify the factors associated with these complications in patients with advanced ovarian cancer after cytoreductive surgery. METHODS: We designed a retrospective multicenter study collecting data from patients with IIIC-IV FIGO Stage ovarian cancer who had undergone either primary debulking surgery (PDS), early interval debulking surgery (IDS) after 3-4 cycles of neoadjuvant chemotherapy, or delayed debulking surgery (DDS) after 6 cycles, with minimal or no residual disease, from January 2008 to December 2015. Univariable and multivariable analyses were conducted to identify factors associated with major surgical complications (≥Grade 3). We assessed disease-free survival (DFS) and overall survival (OS) rates according to the occurrence of major postoperative complications. RESULTS: 549 women were included. The overall rate of major surgical complications was 22.4%. Patients who underwent PDS had a higher rate of major complications (28.6%) than patients who underwent either early IDS (23.2%) or DDS (14.0%). Multivariable analysis revealed that extensive peritonectomy and surgical timing were associated with the occurrence of major complications. Median DFS and OS were 16.9 months (95%CI = [13.7-18.4]) and 48.0 months (95%CI = [37.2-73.1]) for the group of patients with major complications, and 20.1 months (95%CI = [18.6-22.4]) and 56.7 months (95%CI = [51.2-70.4]) for the group without major complications. Multivariable analysis revealed that major surgical complications were significantly associated with DFS, but not with OS. CONCLUSIONS: Patients who experienced major surgical complications had reduced DFS, compared with patients without major morbidity. Extensive peritonectomy and surgical timing were predictive factors of postoperative morbidity.
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Procedimentos Cirúrgicos de Citorredução , Neoplasias Ovarianas , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/cirurgia , Quimioterapia Adjuvante , Procedimentos Cirúrgicos de Citorredução/efeitos adversos , Feminino , Humanos , Terapia Neoadjuvante , Estadiamento de Neoplasias , Neoplasias Ovarianas/patologia , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/epidemiologia , Estudos RetrospectivosRESUMO
STUDY OBJECTIVE: To evaluate laparoscopic pelvic lymph node debulking during extraperitoneal aortic lymphadenectomy in diagnosis, therapeutic planning, and prognosis of patients with locally advanced cervical cancer and enlarged lymph nodes on imaging before chemoradiotherapy. DESIGN: Retrospective, multicenter, comparative cohort study. SETTING: The study was carried out at 11 hospitals with specialized gynecologic oncology units in Spain. PATIENTS: Total of 381 women with locally advanced cervical cancer and International Federation of Gynecology and Obstetrics 2018 stage IIIC 1r (radiologic) and higher who received primary treatment with chemoradiotherapy. INTERVENTIONS: Patients underwent pelvic lymph node debulking and para-aortic lymphadenectomy (group 1), only para-aortic lymphadenectomy (group 2), or no lymph node surgical staging (group 3). On the basis of pelvic node histology, group 1 was subdivided as negative (group 1A) or positive (group 1B). MEASUREMENTS AND MAIN RESULTS: False positives and negatives of imaging tests, disease-free survival, overall survival, and postoperative complications were evaluated. In group 1, pelvic lymph node involvement was 43.3% (71 of 164), and aortic involvement was 24.4% (40 of 164). In group 2, aortic nodes were positive in 29.7% (33 of 111). Disease-free survival and overall survival were similar in the 3 groups (p = .95) and in groups 1A and 1B (p = .25). No differences were found between groups 1 and 2 in intraoperative (3.7% vs 2.7%, p = .744), early postoperative (8.0% vs 6.3%, p = .776), or late postoperative complications (6.1% vs 2.7%, p = .252). Fewer early and late complications were attributed to radiotherapy in group 1A than in the others (p = .022). CONCLUSION: Laparoscopic pelvic lymph node debulking during para-aortic staging surgery in patients with locally advanced cervical cancer with suspicious nodes allows for the confirmation of metastatic lymph nodes without affecting survival or increasing surgical complications. This information improves the selection of patients requiring boost irradiation, thus avoiding overtreatment of patients with negative nodes.
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Laparoscopia , Neoplasias do Colo do Útero , Estudos de Coortes , Procedimentos Cirúrgicos de Citorredução , Feminino , Humanos , Excisão de Linfonodo , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Linfonodos/cirurgia , Metástase Linfática , Estadiamento de Neoplasias , Sobretratamento , Estudos Retrospectivos , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/cirurgiaRESUMO
Different steroid pre-treatments have been used to schedule the start of the ovarian stimulation in IVF cycles. Currently, there is controversy about their effects on gestational outcomes. We designed a three-armed randomised controlled trial (RCT). Eighty-six normoresponder patients undergoing IVF treatment with antagonist GnRH protocol were allocated to three different groups. In the group 1, 34 patients received oral contraceptive pill (OCP) from the first day of the cycle to five days before starting ovarian stimulation, in the group 2, 25 patients received 2 mg/12 hours of oral E2 valerate from day 25 of the previous cycle until the day before starting stimulation, and finally, in the group 3, 27 patients did not receive any treatment. There are no statistically significant differences neither in clinical pregnancy rate (CPR) (40.9% OCP vs. 28.6% E2 vs. 53.3% no treatment group, p=.388) nor live birth rate (LBR) (31.8% OCP vs. 28.6% E2 vs. 46.7% no treatment group, p=.537) between groups in fresh embryo transfer. Likewise, no differences were found in the cumulative CPR, nor in cumulative LBR. However, there is a tendency to worst outcomes in the E2 group. In this E2 group, we observed better results with longer exposition, although no significant differences are reached (E2 mean days in the pregnant group 8.29 vs. 6.83 in the non-pregnant group, p=.08). Our study shows no significant differences in pregnancy rates between groups, but the E2 group is trending at worse gestational results. Trial registration number: Eudra-CT registration number is 2014-001809-40.Impact StatementWhat is already known on this subject? Nowadays, there is much controversy about how pregnancy rates could be affected by the selection of steroid pre-treatments used in order to schedule IVF cycles. However, these treatments are widely utilised in clinical practice.What the results of this study add? The results support the clinical findings of most of the studies previously published. No significant differences in gestational outcomes were found between the groups treated with steroid pre-treatments and the control group. Additionally, oestrogen pre-treatment seems to be related to better pregnancy outcomes when the exposition is longer. Thus, an earlier start of this treatment in the luteal phase could be the optimal approach.What the implications are of these findings for clinical practice and/or further research? This study pretends to provide clarity about the treatment guidelines of steroid pre-treatments to schedule the clinical work without impact on gestational outcomes.
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Resultado da Gravidez , Injeções de Esperma Intracitoplásmicas , Feminino , Fertilização in vitro/métodos , Hormônio Liberador de Gonadotropina , Humanos , Indução da Ovulação/métodos , Gravidez , Taxa de Gravidez , Injeções de Esperma Intracitoplásmicas/métodos , EsteroidesRESUMO
OBJECTIVE: To determine whether the extraperitoneal approach for paraaortic staging lymphadenectomy results in a lower rate of surgical complications compared to the transperitoneal approach, without compromising oncological outcomes. METHODS: Prospective randomized multicenter study of patients with early endometrial or ovarian cancer undergoing paraaortic lymphadenectomy in 2010-2019. Patients were randomized to minimally invasive surgery (laparoscopy or robotic-assisted) using an extraperitoneal or a transperitoneal approach. The primary end point measure was a composite outcome that included developing one or more of the following surgical complications: bleeding during paraaortic lymphadenectomy ≥500â¯mL, any intraoperative complication related to paraaortic lymphadenectomy, severe postoperative complication (Dindoâ¯≥â¯IIIA), impossibility to complete the procedure, or conversion to laparotomy. RESULTS: There were 103 patients in the extraperitoneal group and 100 in the transperitoneal group. Differences in the composite outcome (transperitoneal 26.0% vs, extraperitoneal 18.4%; P = 0.195) were not found. Differences in the operative time, conversion to laparotomy, intraoperative bleeding, or survival were not observed. A higher number of lymph nodes were retrieved through the extraperitoneal approached (median, interquartile range [IQR] 12 [7-17] vs, 14 [10-19]: P = 0.026). Older age and greater body mass index (BMI) or waist-to-hip ratio (WHR) increased the risk for surgical complications independently of the laparoscopic approach. CONCLUSIONS: The extraperitoneal approach did not show differences regarding surgical and oncological parameters compared with the transperitoneal approach, although the number of aortic nodes retrieved was higher. The decision to use one or another laparoscopic route is a matter of the surgeon preference. Trial registration ClinicalTrials.gov.identifier: NCT02676726.
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Neoplasias do Endométrio/cirurgia , Excisão de Linfonodo/efeitos adversos , Excisão de Linfonodo/métodos , Linfonodos/cirurgia , Neoplasias Ovarianas/cirurgia , Neoplasias do Endométrio/patologia , Feminino , Humanos , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Linfonodos/patologia , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Estadiamento de Neoplasias , Neoplasias Ovarianas/patologia , Cavidade Peritoneal/cirurgia , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Procedimentos Cirúrgicos Robóticos/métodosRESUMO
OBJECTIVE: Despite radical surgery and chemotherapy, most patients with ovarian cancer die due to disease progression. M-Trap is an implantable medical device designed to capture peritoneal disseminated tumor cells with the aim to focalize the disease. This trial analyzed the safety and performance of the device. METHODS: This first-in-human prospective, multi-center, non-blinded, single-arm study enrolled 23 women with high-grade serous advanced ovarian cancer. After primary or interval debulking surgery, 3 M-Trap devices were placed in the peritoneum of the abdominal cavity. 18-months post-implantation or at disease progression, devices were initially removed by laparoscopy. The primary safety endpoint was freedom from device and procedure-related major adverse events (MAEs) through 6-months post-implantation compared to an historical control. The primary performance endpoint was histopathologic evidence of tumor cells capture. RESULTS: Only one major adverse event was attributable to the device. 18 women were free of device and procedure related MAEs (78.3%). However, the primary safety endpoint was not achieved (p = 0.131), primarily attributable to the greater surgical complexity of the M-Trap patient population. 62% of recurrent patients demonstrated tumor cell capture in at least one device with a minimal tumor cell infiltration. No other long-term device-related adverse events were reported. The secondary performance endpoint demonstrated a lack of disease focalization. CONCLUSIONS: The M-Trap technology failed to meet its primary safety objective, although when adjusted for surgical complexity, the study approved it. Likewise, the devices did not demonstrate the anticipated benefits in terms of tumor cell capture and disease focalization in recurrent ovarian cancer.
Assuntos
Carcinoma Epitelial do Ovário/cirurgia , Procedimentos Cirúrgicos de Citorredução/instrumentação , Recidiva Local de Neoplasia/cirurgia , Neoplasias Ovarianas/cirurgia , Neoplasias Peritoneais/cirurgia , Adulto , Idoso , Carcinoma Epitelial do Ovário/secundário , Feminino , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia/patologia , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/secundário , Estudos Prospectivos , Espanha , Resultado do TratamentoRESUMO
OBJECTIVE: Voiding dysfunctions represent a leading morbidity after radical hysterectomy performed in patients with early-stage cervical cancer. The aim of this study was to perform ad hoc analysis of factors influencing voiding recovery in SENTIX (SENTinel lymph node biopsy in cervIX cancer) trial. METHODS: The SENTIX trial (47 sites, 18 countries) is a prospective study on sentinel lymph node biopsy without pelvic lymphadenectomy in patients with early-stage cervical cancer. Overall, the data of 300 patients were analysed. Voiding recovery was defined as the number of days from surgery to bladder catheter/epicystostomy removal or to post-voiding urine residuum ≤50 mL. RESULTS: The median voiding recovery time was three days (5th-95th percentile: 0-21): 235 (78.3%) patients recovered in <7 days and 293 (97.7%) in <30 days. Only seven (2.3%) patients recovered after >30 days. In the multivariate analysis, only previous pregnancy (p = 0.033) and type of parametrectomy (p < 0.001) significantly influenced voiding recovery >7 days post-surgery. Type-B parametrectomy was associated with a higher risk of delayed voiding recovery than type-C1 (OR = 4.69; p = 0.023 vs. OR = 3.62; p = 0.052, respectively), followed by type-C2 (OR = 5.84; p = 0.011). Both previous pregnancy and type C2 parametrectomy independently prolonged time to voiding recovery by two days. CONCLUSIONS: Time to voiding recovery is significantly related to previous pregnancy and type of parametrectomy but it is not influenced by surgical approach (open vs minimally invasive), age, or BMI. Type B parametrectomy, without direct visualisation of nerves, was associated with longer recovery than nerve-sparing type C1. Importantly, voiding dysfunctions after radical surgery are temporary, and the majority of the patients recover in less than 30 days, including patients after C2 parametrectomy.
Assuntos
Histerectomia/efeitos adversos , Neoplasias do Colo do Útero/cirurgia , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
INTRODUCTION: Recent evidence has shown adverse oncological outcomes when minimally invasive surgery is used in early-stage cervical cancer. The objective of this study was to compare disease-free survival in patients that had undergone radical hysterectomy and pelvic lymphadenectomy, either by laparoscopy or laparotomy. METHODS: We performed a multicenter, retrospective cohort study of patients with cervical cancer stage IA1 with lymph-vascular invasion, IA2, and IB1 (FIGO 2009 classification), between January 1, 2006 to December 31, 2017, at seven cancer centers from six countries. We included squamous, adenocarcinoma, and adenosquamous histologies. We used an inverse probability of treatment weighting based on propensity score to construct a weighted cohort of women, including predictor variables selected a priori with the possibility of confounding the relationship between the surgical approach and survival. We estimated the HR for all-cause mortality after radical hysterectomy with weighted Cox proportional hazard models. RESULTS: A total of 1379 patients were included in the final analysis, with 681 (49.4%) operated by laparoscopy and 698 (50.6%) by laparotomy. There were no differences regarding the surgical approach in the rates of positive vaginal margins, deep stromal invasion, and lymphovascular space invasion. Median follow-up was 52.1 months (range, 0.8-201.2) in the laparoscopic group and 52.6 months (range, 0.4-166.6) in the laparotomy group. Women who underwent laparoscopic radical hysterectomy had a lower rate of disease-free survival compared with the laparotomy group (4-year rate, 88.7% vs 93.0%; HR for recurrence or death from cervical cancer 1.64; 95% CI 1.09-2.46; P=0.02). In sensitivity analyzes, after adjustment for adjuvant treatment, radical hysterectomy by laparoscopy compared with laparotomy was associated with increased hazards of recurrence or death from cervical cancer (HR 1.7; 95% CI 1.13 to 2.57; P=0.01) and death for any cause (HR 2.14; 95% CI 1.05-4.37; P=0.03). CONCLUSION: In this retrospective multicenter study, laparoscopy was associated with worse disease-free survival, compared to laparotomy.
Assuntos
Histerectomia/métodos , Laparoscopia/métodos , Neoplasias do Colo do Útero/cirurgia , Adulto , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias do Colo do Útero/mortalidade , Adulto JovemRESUMO
STUDY OBJECTIVE: To evaluate if extraperitoneal para-aortic lymphadenectomy (PALND) using a robot-assisted approach was associated with fewer complications than all other approaches (conventional laparoscopic transperitoneal or extraperitoneal and robot-assisted transperitoneal) without compromising lymph node yield, operative time, or length of stay. DESIGN: Post hoc analysis of the prospective randomized open-label multicenter trial (STELLA-2). SETTING: Three academic referral hospitals. PATIENTS: Two hundred and three eligible patients from the STELLA-2 trial were included. INTERVENTIONS: The patients were randomized to extraperitoneal or transperitoneal PALND using a minimally invasive approach (either laparoscopic or robot-assisted) for surgical staging of endometrial or ovarian cancer. The minimally invasive approaches were not subjected to randomization. MEASUREMENTS AND MAIN RESULTS: The primary end point was evaluated through a composite variable that included at least 1 of the following events: blood loss ≥500 mL during PALND, any intraoperative complication related to PALND, severe postoperative complication (Clavien-Dindo ≥grade IIIA), impossibility of completing the procedure, or conversion to laparotomy. Of the 203 patients analyzed, 68 were assigned to the extraperitoneal laparoscopic group (X-L), 62 to the transperitoneal laparoscopic group (T-L), 35 to the extraperitoneal robotic group (X-R), and 38 to the transperitoneal robotic group (T-R). A reduced trend in complications was observed in the extraperitoneal robot-assisted arm when considering the primary end point (X-L: 25.0%, T-L: 24.2%, X-R: 5.7%, T-R: 28.9%; p = .073). In a multivariable analysis, age (odds ratio [OR] 1.05; 95% confidence interval [CI], 1.00-1.09), body mass index (OR 1.09; 95% CI, 1.03-1.16), and waist-to-hip ratio (OR 1.66; 95% CI, 1.12-2.47) were found to independently increase the risk of PALND complications, whereas the extraperitoneal robotic approach (OR 0.13; 95% CI, 0.02-0.64) was an independent protective factor for complication occurrence. CONCLUSION: Robot-assisted extraperitoneal PALND is associated with fewer surgical complications, without compromising lymph node retrieval, operative time, or length of stay. Robot-enhanced 3D visualization, surgeon ergonomics, or hemostatic precision could explain our results.