RESUMO
OBJECTIVE: To analyze recurrent factors in patients with clinical early-stage cervical cancer (ESCC) following hysterectomy and adjuvant radiotherapy. METHODS: We collected data from patients with ESCC, staged according to the 2009 Federation International of Gynecology and Obstetrics (FIGO) staging criteria, who underwent hysterectomy followed by adjuvant radiotherapy between 2012 and 2019. These patients were subsequently restaged using the 2018 FIGO criteria. Univariable and multivariable analyses, along with nomogram analyses, were conducted to explore factors associated with recurrence-free survival (RFS). RESULTS: A total of 310 patients met the inclusion criteria, with a median follow-up time of 46 months. Among them, 126 patients with ESCC were restaged to stage III C1 or III C2 after surgery due to lymph node metastasis (LNM) based on the 2018 FIGO staging criteria. Of these, 60 (19.3%) experienced relapse. The 1-, 3-, and 5-year RFS rates were 93.9%, 82.7%, and 79.3%, respectively. Multivariate analysis revealed that the number of positive lymph nodes (LNs), tumor diameter (TD) > 4 cm, and parametrial invasion (PI) were associated with recurrence. The nomogram indicated their predictive value for 3-year and 5-year RFS. Notably, the 5-year recurrence rate (RR) increased by 30.2% in patients with LNM, particularly those with ≥ 3 positive LNs (45.5%). Patients with stage III C2 exhibited a significantly higher RR than those with IIIC1 (56.5% vs. 24.3%, p < 0.001). The 5-year RFS for patients with TD > 4 cm was 65.8%, significantly lower than for those with TD ≤ 4 cm (88.2%). Subgroup analysis revealed higher 5-year RRs in patients with stage III C2 than that in patients with III-C1 (56.5% vs. 24.3%, p < 0.001), demonstrating a significant difference in the RFS survival curve. CONCLUSION: RR in patients with clinical ESCC after hysterectomy followed by adjuvant radiotherapy is correlated with the number of positive LNs, TD > 4 cm, and PI. Emphasis should be placed on the common high-risk factor of LNM association with recurrence after radical hysterectomy in ESCC.
Assuntos
Neoplasias do Colo do Útero , Feminino , Humanos , Radioterapia Adjuvante , Resultado do Tratamento , Intervalo Livre de Doença , Neoplasias do Colo do Útero/patologia , Estadiamento de Neoplasias , Estudos Retrospectivos , Recidiva Local de Neoplasia/patologia , Histerectomia , Excisão de LinfonodoRESUMO
BACKGROUND: HPV-independent cervical cancers (HPV-ind CCs) are uncommon with worse prognosis and poorly understood. This study investigated the molecular characteristics of HPV-ind CCs, aiming to explore new strategies for HPV-ind CCs. METHODS: HPV status of 1010 cervical cancer patients were detected by RT-PCR, PCR and RNA-sequencing (RNA-seq). Whole exome sequencing (WES) and RNA-seq were performed in identified HPV-ind CCs. The efficacy of PI3Kα inhibitor BYL719 in HPV-ind CCs was evaluated in cell lines, patient-derived organoids (PDOs) and patient-derived xenografts (PDXs). RESULTS: Twenty-five CCs were identified as HPV-ind, which were more common seen in older, adenocarcinoma patients and exhibited poorer prognosis as well as higher tumor mutation burden compared to HPV-associated CCs. HPV-ind CCs were featured with highly activated PI3K/AKT signaling pathway, particularly, PIK3CA being the most predominant genomic alteration (36%). BYL719 demonstrated superior tumor suppression in vitro and in vivo. Furthermore, HPV-ind CCs were classified into two subtypes according to distinct prognosis by gene expression profiles, the metabolism subtype and immune subtype. CONCLUSIONS: This study reveals the prevalence, clinicopathology, and molecular features of HPV-ind CCs and emphasizes the importance of PIK3CA mutations and PI3K pathway activation in tumorigenesis, which suggests the potential significance of PI3Kα inhibitors in HPV-ind CC patients.
Assuntos
Infecções por Papillomavirus , Tiazóis , Neoplasias do Colo do Útero , Feminino , Humanos , Idoso , Neoplasias do Colo do Útero/patologia , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/genética , Transdução de Sinais/genética , Genômica , Perfilação da Expressão Gênica , MutaçãoRESUMO
OBJECTIVE: Metastases in the supragastric lesser sac (SGLS) are not only occult but are also barriers to complete resection of ovarian cancer. We describe a cohort of patients with SGLS disease undergoing debulking surgery. METHODS: We identified all patients who underwent evaluation and eventual resection of SGLS disease as part of cytoreductive surgery for stage IIIC-IVB high-grade epithelial ovarian cancer at our institution from January 2018 to August 2022. RESULTS: Thirty-three of 286 patients (11.5%) underwent resection of SGLS disease. Metastases in the SGLS were identified by preoperative imaging in 4 of 33 patients (12.1%). The median peritoneal cancer index score was 22 (range, 9-33). Through surgical exploration, metastases were frequently seen in the right diaphragm (100%), hepatorenal recess (97%), lesser omentum (81.8%), left diaphragm (78.8%), supracolic omentum (75.8%), anterior transverse mesocolon (72.7%), splenic hilum (63.6%), ligamentum teres hepatis (60.6%), and gallbladder fossa (51.5%). The lesser omentum was normal in 6 of 33 (18.2%) patients, despite metastases within the SGLS. A total of 54.5% of patients underwent complex surgery (surgical complexity scores; median, 8; range, 3-14). Complete resections were achieved in 19 (57.6%) patients. No complications were related to the resection of SGLS disease. The median length of progression-free survival was 24.8 months (95% confidence interval=16.6-32.9). CONCLUSION: Metastases to the SGLS are not uncommon in advanced ovarian cancer, particularly those with widely disseminated disease. Disease in this recess is rarely identified by preoperative imaging and deserves systematic surgical exploration to attain complete cytoreduction.
Assuntos
Carcinoma Epitelial do Ovário , Procedimentos Cirúrgicos de Citorredução , Neoplasias Ovarianas , Neoplasias Peritoneais , Humanos , Feminino , Procedimentos Cirúrgicos de Citorredução/métodos , Pessoa de Meia-Idade , Neoplasias Ovarianas/cirurgia , Neoplasias Ovarianas/patologia , Idoso , Carcinoma Epitelial do Ovário/cirurgia , Carcinoma Epitelial do Ovário/patologia , Adulto , Neoplasias Peritoneais/cirurgia , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/patologia , Omento/cirurgia , Estudos Retrospectivos , Estadiamento de Neoplasias , Cavidade Peritoneal/cirurgia , Cavidade Peritoneal/patologia , Diafragma/cirurgia , Diafragma/patologia , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: Cervical cancer is and will remain to be an important health problem in China, especially with an increasing proportion of younger patients who has more specific needs. In China, surgery to remove tumor burden followed by postoperative treatment with radiotherapy and chemotherapy based on clinicopathologic factors may be the best choice for stages IB3 and IIA2 patients. Radical hysterectomy in cervical cancer has been a classic landmark surgery in gynecology. The current trial is designed to evaluate whether there is a difference between laparoscopic RH and abdominal RH in cervical cancer (stages IB3 and IIA2) patient survival under stringent operation standards and consistent surgical oncologic principles. This paper reports the rationale, design, and implementation of the trial. METHODS/DESIGN: This is an investigator-initiated, prospective, randomized, open, blinded endpoint (PROBE) controlled trial. A total of 1104 patients with stage IB3 and IIA2 cervical cancer will be enrolled over a period of 3 years. Patients are randomized (1:1) to either the laparoscopic RH or the abdominal RH group. Patients will then be followed up for at least 5 years. The primary end point will be 5-year overall survival, and secondary endpoints include 5-year progression-free survival, recurrence, and quality of life measurements. DISCUSSION: The study results will provide more convincing evidence-based information for stages IB3 and IIA2 cervical cancer patients and their gynecologic cancer surgeons in their choice of surgical method. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04939831 , retrospectively registered on 25 June 2021.
Assuntos
Laparoscopia , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/cirurgia , Estudos Prospectivos , Qualidade de Vida , Laparoscopia/efeitos adversos , Histerectomia/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como AssuntoRESUMO
Targeting programmed death 1(PD-1) has been approved for relapsed cervical cancer with unsatisfactory clinical efficacy. This study aims to analyse the impact of PI3K pathway activation on tumour immune microenvironment and evaluates the immune sensitization effect by PI3K inhibition in cervical cancer. The effect of PIK3CA mutation on PD-L1 expression and CD8+ T cells differentiation was determined in cervical cancer tissues. Luciferase and ChIP-qPCR/PCR assays were used to determine the transcriptional regulation of PD-L1 by PIK3CA-E545K. The effects of PI3K inhibitor treatment on immune environment in vitro and in vivo were evaluated by RNA sequencing (RNA-seq) and flow cytometry. The efficacy of PI3K inhibitor and anti-PD-1 therapy was assessed in cell-derived xenografts (CDX) and patients-derived xenografts (PDX). PD-L1 overexpression is more frequently observed in elder women with squamous cervical carcinoma. It predicts longer progress-free survival and overall survival. PIK3CA mutation results in increased mRNA and protein levels of PD-L1, the repression of CD8+ T cell differentiation in cervical cancer. Here, we report a case that continuous pembrolizumab monotherapy treatment induced complete remission of a recurrent cervical cancer patient with systemic metastasis and PIK3CA-E545K mutation, implying that PIK3CA mutation is potentially a biomarker for pembrolizumab treatment in cervical cancer. Specifically, this mutation promotes the expression of PD-L1 by upregulating the transcription factor IRF1. PI3Kα-specific inhibitor markedly activates immune microenvironment by regulating the PD-1/L1-related pathways and promoting CD8+ T cell differentiation and proliferation in Caski-CDXs with PIK3CA-E545K mutation. PI3Kα inhibitor significantly enhances the anti-tumour efficacy of PD-1 blockade in CDXs and PDXs. PIK3CA mutations may predict the response of cervical cancer to PD-1 blockade. The efficacy of PI3Kα inhibitors combined with PD-1 antibodies is promising in cervical cancer and warrants additional clinical and mechanistic investigations.
Assuntos
Neoplasias do Colo do Útero , Humanos , Feminino , Idoso , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/genética , Antígeno B7-H1 , Receptor de Morte Celular Programada 1/metabolismo , Fosfatidilinositol 3-Quinases , Classe I de Fosfatidilinositol 3-Quinases/genética , Classe I de Fosfatidilinositol 3-Quinases/metabolismo , Microambiente TumoralRESUMO
Purpose: Anlotinib is a novel oral small-molecule multi-target tyrosine kinase inhibitor that has been approved for treating non-small cell lung cancer. However, its efficacy and safety among patients with advanced gynecological cancer have not been comprehensively evaluated. We conducted this study to address this issue in the real-world setting. Patients and Methods: Data from patients treated with Anlotinib for persistent, recurrent or metastatic gynecological cancer were collected from 17 centers from August 2018. The database lock-time was on March 2022. Anlotinib was administered orally on days 1-14 every 3 weeks until disease progression, severe toxicity occurred, or death. In this study, disease-specific advanced gynecological cancer was mainly referred to cervical, endometrial, and ovarian cancer. The outcomes included objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS). Results: A total of 249 patients were analyzed, with a median follow-up of 14.5 months. The overall ORR and DCR were 28.1% [95% confidence interval (CI) 22.6% to 34.1%] and 80.7% (95% CI 75.3% to 85.4%), respectively. Specifically, the ORR varied from 19.7% to 34.4% and the DCR differed from 81.7% to 90.0% in disease-specific advanced gynecological cancer. The median PFS was 6.1 months and ranged from 5.6 to 10.0 months in the overall and disease-specific advanced gynecological cancer, respectively. Larger cumulative dosage of Anlotinib (>700 mg) was in general associated with longer PFS in the overall and disease-specific advanced gynecological cancer. The most common adverse event related to Anlotinib treatment was pain/arthralgia (18.3%). Conclusion: In conclusion, Anlotinib holds promise in treating patients with advanced gynecological cancer including its disease-specific types, with reasonable efficacy and tolerable safety.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Neoplasias Ovarianas , Humanos , Feminino , Indóis/efeitos adversosRESUMO
BACKGROUND: The Lymphadenectomy in Ovarian Neoplasms (LION) study revealed that systemic lymphadenectomy did not bring survival benefit for advanced ovarian cancer patients with clinically normal lymph nodes and was associated with a higher incidence of operative complications. However, there is no consensus on whether lymphadenectomy has survival benefit or not in early epithelial ovarian cancer (EOC). METHODS: We designed the LOVE study, a multicenter, randomized controlled, phase III trial to compare the efficacy and safety of comprehensive staging surgery with or without lymphadenectomy in stages IA-IIB EOC and fallopian tube carcinomas (FTC). The hypothesis is that the oncological outcomes provided by comprehensive staging surgery without lymphadenectomy are non-inferior to those of conventional completion staging surgery in early-stage EOC and FTC patients who have indications for post-operative adjuvant chemotherapy. Patients assigned to experimental group will undergo comprehensive staging surgery, but lymphadenectomy. Patients assigned to comparative group will undergo completion staging surgery including systematic pelvic and para-aortic lymphadenectomy. All subjects will receive 3-6 cycles of standard adjuvant chemotherapy. Major inclusion criteria are pathologic confirmed stage IA-IIB EOC or FTC, and patients have indications for adjuvant chemotherapy either confirmed by intraoperative fast frozen section or previous pathology after an incomplete staging surgery. Major exclusion criteria are non-epithelial tumors and low-grade serous carcinoma. Patients with severe rectum involvement which lead to partial rectum resection will be excluded. The sample size is 656 subjects. Primary endpoint is disease-free survival. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04710797.
Assuntos
Excisão de Linfonodo , Neoplasias Ovarianas , Humanos , Feminino , Estudos Prospectivos , Metástase Linfática/patologia , Excisão de Linfonodo/efeitos adversos , Linfonodos/cirurgia , Linfonodos/patologia , Carcinoma Epitelial do Ovário/cirurgia , Carcinoma Epitelial do Ovário/patologia , Neoplasias Ovarianas/patologia , Estadiamento de Neoplasias , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como Assunto , Ensaios Clínicos Fase III como AssuntoRESUMO
The mutation of glutamic acid 545 to lysine (E545K) in PIK3CA, as the most common missense mutation of this gene in various cancer types, is frequently observed in cervical cancer and has been shown to reduce cervical cancer radiosensitivity. However, the underlying mechanisms remain unclear. Here, we implicate the alterations of glutamine metabolism in PIK3CA-E545K-mediated radioresistance of cervical cancer. Specifically, PIK3CA mutation negatively regulated the expression of SIRT4 via the epigenetic regulator EP300 independently of the canonical mTORC1 pathway. PIK3CA-E545K-induced SIRT4 downregulation promoted cell proliferation, migration, and radiation-induced DNA repair and apoptosis, while SIRT4 overexpression reversed the radioresistance phenotype mediated by PIK3CA mutation. Mechanistically, SIRT4 modulated glutamine metabolism and thus cellular apoptosis by negatively regulating a glutamate pyruvate transaminase GPT1. Moreover, the PI3K inhibitor BYL719, but not mTOR inhibitors, exerted remarkable synergistic effects with radiotherapy by inhibiting glutamine metabolism in vitro and in vivo. Collectively, this study reveals the role of PIK3CA-E545K-SIRT4 axis in regulating glutamine metabolism and the radioresistance in cervical cancer, which provides a necessary preliminary basis for clinical research of PI3K inhibitors as radiosensitizing agents.
Assuntos
Sirtuínas , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/radioterapia , Glutamina/metabolismo , Fosfatidilinositol 3-Quinases/genética , Tolerância a Radiação , Classe I de Fosfatidilinositol 3-Quinases , Mutação , Linhagem Celular Tumoral , Proteínas Mitocondriais/metabolismo , Sirtuínas/genéticaRESUMO
OBJECTIVE: To investigate whether peritoneal disease extent can predict the survival benefit of intraperitoneal/intravenous (IP/IV) chemotherapy in ovarian cancer. DESIGN: A treatment-free survival (TFS) analysis. SETTING: Five-centre trial. POPULATION: An extended follow-up of the Additional Intraperitoneal Cisplatin and Etoposide in ovarian cancer (AICE) trial (NCT01669226), with data cut-off on 27 August 2020. Patients were categorised into subgroups with high tumour burden (HTB) and low tumour burden (LTB). METHODS: Overall survival (OS) was divided into time on protocol treatment exposure (T), time free of subsequent treatment or death (TFS) and time after the first subsequent therapy (REL). TFS analyses and quality-adjusted OS were calculated by multiplying the mean time in each health state by its assigned utility: quality-adjusted OS = ut × T + TFS + urel × REL. MAIN OUTCOME MEASURES: The area under each Kaplan-Meier curve was estimated using the 96-month restricted mean time, with threshold utility analyses used to illustrate quality-adjusted OS comparisons. RESULTS: In the HTB subgroup, the restricted mean TFS was 33.9 months and 18.7 months in the IP/IV and IV groups, respectively (p = 0.005), with a significant quality-adjusted OS gain (13.2-16.0 months). In the LTB subgroup, IP/IV therapy yielded no survival benefit in either TFS (p = 0.268) or quality-adjusted OS (range: 1.4-6.3 months). CONCLUSIONS: Both TFS and quality-adjusted OS was longer across all utility weight values with IP/IV than with standard IV therapy in the HTB subgroup, whereas patients in the LTB subgroup did not benefit from the therapy. The tumour burden of ovarian cancer should be assessed before deciding on IP/IV versus IV treatment.
Assuntos
Neoplasias Ovarianas , Feminino , Humanos , Carcinoma Epitelial do Ovário/patologia , Cisplatino/efeitos adversos , Intervalo Livre de Doença , Infusões Intravenosas , Estadiamento de Neoplasias , Neoplasias Ovarianas/patologia , Análise de SobrevidaRESUMO
The incidence of cervical cancer (CC) ranks the fourth in female malignant tumors globally. Chemoresistance is one of the main causes of treatment failure in advanced recurrent CC. Prolyl isomerase 1 (PIN1) is overexpressed in a variety of tumors, and is closely associated with the malignant potential of tumor cells, such as transformation, proliferation, invasion and metastasis. In the present study, we demonstrate that cell death induced by suppression of PIN1 could be inhibited by ferrostatin-1 (Fer-1) and ferroptosis biomarkers including lactate dehydrogenase (LDH) release, lipid peroxidation and malondialdehyde (MDA) are upregulated by downregulating PIN1. We then discover that abrogation of PIN1 greatly decreases the level of glutathione peroxidase 4 (GPX4) and the level of PIN1 is positively correlated with the level of GPX4. Furthermore, the knockdown of PIN1 promotes ferroptosis induced by RSL3. The mechanism involves PIN1 silencing which downregulates GPX4 by decreasing the level of nuclear factor E2-related factor 2 (NRF2). Furthermore, overexpression of NRF2 inhibits RSL3-mediated ferroptosis of CC cells when PIN1 is silenced. In addition, our results indicate that cisplatin (DDP) induces ferroptosis, which is restrained by overexpression of PIN1. The PIN1 inhibitor, KPT-6566, promotes the cytotoxic effect of DDP. The present study reveals that PIN1 affects ferroptosis and sensitivity to DDP in CC cells via the NRF2/GPX4 axis, thereby identifying PIN1 as a potential therapeutic target for CC.
Assuntos
Cisplatino , Neoplasias do Colo do Útero , Feminino , Humanos , Cisplatino/farmacologia , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/genética , Recidiva Local de Neoplasia , Peptidilprolil Isomerase de Interação com NIMA/genéticaRESUMO
BACKGROUND: A retrospective study and a randomized controlled trial published in a high quality journal in late 2018 have shown that laparoscopic radical hysterectomy (RH) was associated with worse survival than abdominal RH among patients with early stage cervical cancer. Radical hysterectomy in cervical cancer has been a classic landmark surgery in gynecology, therefore this conclusion is pivotal. The current trial is designed to reconfirm whether there is a difference between laparoscopic RH and abdominal RH in cervical cancer (stage IA1 with LVSI, IA2) patient survival under stringent operation standards and consistent tumor-free technique. This paper reports the rationale, design, and implementation of the trial. METHODS: This is an investigator-initiated, prospective, randomized, open, blinded endpoint (PROBE) controlled trial. A total of 690 patients with stage IA1 (with intravascular), and IA2 cervical cancer will be enrolled over a period of three years. Patients are randomized (1:1) to either the laparoscopic RH or the abdominal RH group. Patients will then be followed-up for at least five years. The primary endpoint will be 5-year progression-free survival. Secondary endpoints will include 5-year overall survival rates, recurrence rates, operation time, intraoperative blood loss, surgery-related complications, and quality of life. DISCUSSION: The results of the trial will provide valuable evidence for guiding clinical decision of choosing appropriate treatment strategies for stage IA1 (LVSI) and stage IA2 cervical cancer patients. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT04934982 , Registered on 22 June 2021).
Assuntos
Histerectomia , Laparoscopia , Neoplasias do Colo do Útero , Intervalo Livre de Doença , Feminino , Humanos , Histerectomia/efeitos adversos , Histerectomia/métodos , Laparoscopia/efeitos adversos , Estudos Multicêntricos como Assunto , Estadiamento de Neoplasias , Estudos Prospectivos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Neoplasias do Colo do Útero/cirurgiaRESUMO
BACKGROUND: To investigate the alterations of peripheral lymphocyte subpopulations in ovarian cancer patients compared to benign or borderline counterparts. The possible clinicopathological implications were also evaluated. METHODS: We enrolled 112 treatment-naive ovarian cancer patients, 14 borderline tumor patients and 44 benign tumor patients between 09/2016 and 01/2019. Flow cytometry was used to measure the peripheral lymphocyte subsets consisting of T cells (CD3+, CD3+CD4+, CD3+CD8+ and CD8+CD28+), regulatory T cells (Tregs, CD4+CD25+CD127-), natural killer cells (NK cells, CD3-CD56+) and B cells (CD19+). RESULTS: Most ovarian cancer patients were high-grade serous carcinoma (84.8%), followed by clear cell carcinoma (8.03%). Late-stage tumor (FIGO III + IV) accounted for 82.1%. The study showed that the proportions of peripheral lymphocyte subsets underwent apparent changes in ovarian cancer patients. We observed elevated levels of Treg cells in patients with both ovarian borderline and malignant tumor compared to those with benign tumors, which achieved statistic significance. In contrast, CD3+CD8+ T and CD8+CD28+ T cells were significantly lower in ovarian cancer patients. Interestingly, low level of B cells was correlated to clear cell carcinoma (P = 0.024), advanced tumor (P = 0.028) and platinum-resistant recurrence (P = 0.014). Regarding the changes of lymphocyte subsets after surgery, CD8+CD28+ T cells had a significant decreasing tendency (P = 0.007) while B cells were the opposite (P < 0.001). CONCLUSIONS: Ovarian cancer patients have altered circulating lymphocyte profile (elevated Treg cell, depressed CD3+CD8+ T and CD8+CD28+ T cells). Low level of B cells might be related to disease aggressiveness, and it recovered after the removal of tumor, which merits further study.
Assuntos
Antígenos CD28 , Neoplasias Ovarianas , Linfócitos T CD8-Positivos , Carcinoma Epitelial do Ovário , Feminino , Citometria de Fluxo , Humanos , Células Matadoras Naturais , Contagem de Linfócitos , Subpopulações de LinfócitosRESUMO
BACKGROUND: A retrospective study and a randomized controlled trial published in late 2018 have shown that laparoscopic radical hysterectomy (RH) was associated with worse survival than abdominal RH among patients with early-stage cervical cancer. Radical hysterectomy in cervical cancer has been a classic landmark surgery in gynecology; therefore, this conclusion is pivotal. The current trial is designed to reconfirm whether there is a difference between laparoscopic RH and abdominal RH in cervical cancer (stages IB1, IB2, and IIA1) patient survival under stringent operation standards and consistent surgical oncologic principles. METHODS/DESIGN: This is an investigator-initiated, Prospective, Randomized, Open, Blinded End-point (PROBE)-controlled non-inferiority trial. A total of 780 patients with stage IB1, IB2, and IIA1 cervical cancer will be enrolled over a period of 3 years. Patients are randomized (1:1) to either the laparoscopic RH or the abdominal RH group. Patients will then be followed up for at least 5 years. The primary endpoint will be 5-year progression-free survival, and secondary endpoints include 5-year overall survival, recurrence, and quality of life measurements. DISCUSSION: The debate on laparoscopic versus abdominal RH is still ongoing, and high-quality evidences are needed to guide clinical practice. The study results will provide more convincing evidence-based information for early-stage cervical cancer patients and their gynecologic cancer surgeons in their choice of surgical method. TRIAL REGISTRATION: ClinicalTrials.gov NCT04929769 . Registered on 18 June 2021.
Assuntos
Laparoscopia , Neoplasias do Colo do Útero , Intervalo Livre de Doença , Feminino , Humanos , Histerectomia/efeitos adversos , Histerectomia/métodos , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Estudos Multicêntricos como Assunto , Estadiamento de Neoplasias , Estudos Prospectivos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Neoplasias do Colo do Útero/patologiaRESUMO
BACKGROUND: To review the utilization of bowel resection in ovarian cancer surgery in our institution. METHODS: All ovarian cancer patients who received bowel resection between 2006/01 and 2018/12 were identified. Postoperative morbidities were assessed according to the Clavien-Dindo classification (CDC). RESULTS: There were 182 patients in the anastomosis group and 100 patients in the ostomy group, yielding a total of 282 patients. The median age was 57 years, and most patients had high-grade serous histology (88.7%). Forty-nine (17.3%) patients received neoadjuvant chemotherapy. During the operation, 78.7% of patients had ascites, and the median volume was 800 mL. Extensive bowel resection (at least two-segment) and upper abdominal operation were performed in 29 (10.2%) and 69 (24.4%) patients, respectively. The rectosigmoid colon was the most commonly resected (83.8%) followed by right hemicolectomy (5.9%) and small bowel resection (2.8%). No macroscopic residual disease was observed in 42.9% of the patients, whereas 87.9% had residual disease ≤ 1 cm. Among the entire cohort, 23.0% (65/282) experienced different complications. Severe complications (CDC 3-5) accounted for 9.2% of complications and were mostly categorized as pleural effusion requiring drainage (3.5%) followed by wound dehiscence requiring delayed repair in the operating room (1.8%). Nine patients experienced anastomotic leakage (AL): one in the ostomy group with extensive bowel resection and eight in the anastomosis group. The overall AL rate was 4.2% (9/212) per anastomosis. CONCLUSIONS: The execution of bowel resection as part of debulking surgery in patients with newly diagnosed ovarian cancer resulted in a severe morbidity rate of 9.2%.
Assuntos
Procedimentos Cirúrgicos de Citorredução , Neoplasias Ovarianas , Colectomia/métodos , Colo Sigmoide/patologia , Procedimentos Cirúrgicos de Citorredução/métodos , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: To investigate changes in peripheral lymphocyte subsets after splenectomy during cytoreductive surgery for advanced or recurrent ovarian cancers. METHODS: We enrolled 83 patients with advanced or recurrent ovarian cancer who underwent cytoreductive surgery. Twenty patients who also underwent splenectomy were assigned to the splenectomy cohort and the rest were assigned to the non-splenectomy cohort. Flow cytometry was used to measure peripheral lymphocyte subsets consisting of T cells, regulatory T cells, natural killer cells, B cells, and activation antigens before and after surgery. RESULTS: There was no difference in the number and distribution of peripheral lymphocyte subsets between the two cohorts before surgery. After surgery, we observed elevated levels of T cells (CD3+, CD3+CD8+) in the splenectomy cohort compared to those in the non-splenectomy cohort, and the difference was statistically significant. CD8+CD28+ T cells had a significant decreasing tendency (P = 0.011) while CD3+/HLA-DR+ T cells showed the opposite trend (P = 0.001) in the splenectomy cohort. The proportion of Tregs (P = 0.005) and B cells (P < 0.001) including CD3-/HLA-DR+ B cells (P = 0.007) increased after surgery, and the absolute number of T cells and NK cells decreased to different extents (P < 0.001) in the non-splenectomy cohort. The post-operative percentage of CD8+CD28+ T cells was less than the pre-operative percentage (P = 0.022), which was similar to the splenectomy cohort. There was no significant difference in progression-free survival or overall survival between the groups after a median follow-up time of 41 months. CONCLUSIONS: The changes in peripheral lymphocyte populations were different between patients with and those without splenectomy during cytoreductive surgery for ovarian cancers. T cells were increased and activated in the splenectomy cohort, whereas, B cells were increased and activated in the non-splenectomy cohort.
Assuntos
Procedimentos Cirúrgicos de Citorredução/métodos , Contagem de Linfócitos/métodos , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/cirurgia , Esplenectomia/métodos , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: Small cell neuroendocrine carcinoma of the cervix (SCNEC) is a lethal malignancy and little treatment progress has been made for decades. We sought to map its genetic profiles, and identify whether SCNEC harbor mutations and potential targets for therapeutic interventions. METHODS: Primary tumor tissue and blood samples were obtained from 51 patients with SCNEC. The next-generation sequencing was carried out to detect mutations of 520 cancer-related genes, including the entire exon regions of 312 genes and the hotspot mutation regions of 208 genes. Quantitative multiplex PCR was performed for the detection of seven high-risk HPV types. RESULTS: Of the 51 detected patients, 92.16% were positive for HPV 18. Ninety-eight percent of cases harbored genetic alterations. Two cases were observed with hypermutated phenotype and determined as MSI-H/dMMR. Genetic mutations were clustering in RTK/RAS(42.86%), PI3K-AKT(38.78%), p53 pathway(22.45%) and MYC family(20.41%). Mutations in genes involved in the p53 pathway indicate a poorer prognosis (3-year OS, 33.5% vs 59.9%, p = 0.031). A total of seven patients harboring mutations in homogeneous recombination repair (HRR) genes were reported. In addition, IRS2 and SOX2 were amplified in 14.9% and 6.12% of SCNEC patients, respectively. CONCLUSIONS: SCNEC is specifically associated with HPV 18 infection. Its genetic alterations are characterized by a combined feature of high-risk HPV driven events and mutations observed in common neuroendocrine carcinoma. We identified several targetable mutated genes, including KRAS, PIK3CA, IRS2, SOX2, and HRR genes, indicating the potential efficacy of target therapies in these patients. MSI-H/dMMR individuals may benefit from checkpoint blockade therapies.