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BACKGROUND: Laparoscopy is considered the method of choice in the operative treatment of type I endometrial carcinoma (EC). However, there is a paucity of data regarding the safety of endoscopy for type II EC because these malignancies have several biological similarities with ovarian cancer. OBJECTIVES: This study aimed to evaluate the feasibility, operative outcomes, and oncologic safety of laparoscopic surgery in patients with type II EC. METHODS: A retrospective study with histologically confirmed serous or clear-cell EC without peritoneal carcinomatosis treated by laparoscopy (G1) or laparotomy (G2) was conducted. Procedures included hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and pelvic and para-aortic lymphadenectomy. RESULTS: From 2009 to 2015, 89 patients were included; 53 women underwent laparoscopy and 36 underwent laparotomy. No relevant epidemiological or oncologic difference between groups was observed. The mean number of removed pelvic nodes was 16 [±10] and 12 [±13] in group 1 (G1) and group 2 (G2), respectively (P = 0.127). The mean number of dissected para-aortic nodes was significantly greater in the laparoscopic group (11 [±9] vs 6 [±9], P = 0.006). Para-aortic metastasis was significantly more often observed in the endoscopy group (26% vs 13%, P = 0.04). Adjuvant therapies were given to 86% of the patients in the study and 75% in the control group (P = 0.157). No excessive blood loss, casualty related to surgery, intraoperative complication, or conversion to laparotomy occurred in G1. Ten (18%) women from G1 and 36% (13/36) in G2 developed relevant postoperative complications (P = 0.03). The median duration of follow-up was 38 months for the laparoscopy and 47 months for the open surgery (P = 0.12). The 5-year overall and disease-free survival were similar, 86% versus 78% and 58% versus 51% for G1 and G2, respectively (P = 0.312). CONCLUSIONS: Laparoscopy is oncologically at least not inferior to laparotomy for the surgical treatment of type II EC. Endoscopic techniques are feasible, effective, result in significantly less morbidity, and improved quality staging. Although statistical significance was not reached, laparoscopy was associated with superior oncologic results.
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Carcinoma/terapia , Neoplasias do Endométrio/cirurgia , Laparoscopia/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND: Presently, the use of laparoscopy in advanced ovarian cancer (AOC) is extremely controversial. In the era of neoadjuvant chemotherapy (NACT), endoscopic debulking surgery could be a reasonable alternative for selected patients with primarily unresectable disease. OBJECTIVES: To evaluate the feasibility as well as the operative and oncologic safety of laparoscopic debulking surgery in patients with AOC submitted to NACT. METHODS: This is a pilot observational study on initially unresectable, high-grade serous ovarian cancer treated with a sequence of 6 cycles of carboplatin and paclitaxel followed by debulking surgery performed by laparoscopy (group 1) or laparotomy (group 2). The inclusion criteria were clinical complete response, CA-125 normalization, imaging without disease in critical areas, and optimal cytoreduction. RESULTS: From January 2011 to March 2014, 21 patients were included. Ten women underwent laparoscopy and 11 laparotomy. No epidemiological or oncologic differences were observed between the groups. No surgery-related casualties, intraoperative complications, conversion to laparotomy, or excessive blood loss or transfusion was detected in the laparoscopic procedures. The mean time of operation was 292 min. The length of hospital stay averaged 3.6 days. Two women in group 1 developed relevant complications. After a mean follow-up of 20 months, the recurrence rates were similar, i.e. 80% in group 1 versus 88% in group 2. Although statistical significance was not reached, the mortality related to cancer was considerably higher (20 vs. 0%; p = 0.086) and the mean chemotherapy-free interval was markedly shorter in group 1 (13.3 vs. 20.5 months; p = 0.288). CONCLUSION: Laparoscopic optimal debulking surgery after NACT is feasible and effective in selected patients. Nevertheless, laparoscopy was substantially associated with inferior oncologic results. Endoscopic cytoreduction in AOC should be cautiously suggested until larger prospective trials confirm the observed results.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Procedimentos Cirúrgicos de Citorredução/métodos , Procedimentos Cirúrgicos em Ginecologia/métodos , Laparoscopia/efeitos adversos , Terapia Neoadjuvante/métodos , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/cirurgia , Adulto , Idoso , Biomarcadores Tumorais/sangue , Carboplatina/administração & dosagem , Quimioterapia Adjuvante , Cistadenocarcinoma Seroso/tratamento farmacológico , Cistadenocarcinoma Seroso/cirurgia , Estudos de Viabilidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Laparoscopia/mortalidade , Laparotomia , Tempo de Internação , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/prevenção & controle , Estadiamento de Neoplasias , Duração da Cirurgia , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/prevenção & controle , Paclitaxel/administração & dosagem , Projetos Piloto , Vigilância da População/métodos , Estudos Prospectivos , Tamanho da Amostra , Resultado do TratamentoAssuntos
Ascite Quilosa/cirurgia , Excisão de Linfonodo/efeitos adversos , Imagem Óptica , Neoplasias Ovarianas/cirurgia , Aorta , Ascite Quilosa/etiologia , Corantes , Procedimentos Cirúrgicos de Citorredução , Feminino , Humanos , Verde de Indocianina , Metástase Linfática , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia , Pelve , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgiaRESUMO
BACKGROUND AND OBJECTIVES: Endometrial cancer (EC) has an increasing incidence worldwide. Despite the unequivocal prognostic importance of nodal status, systematic lymphadenectomy is associated to elevated morbidity. Sentinel lymph node (SLN) biopsy is designed to avoid extensive nodal dissection and provide crucial oncologic information. The goal of this prospective study was to determine the feasibility, safety, and accuracy of laparoscopic SLN biopsy in EC obtained through hysteroscopic injection of technetium-99 (Tc-99). METHODS: From January 2008 to December 2012, a total of 42 women with EC were included in the study. We injected 20 mBq of Tc-99 hysteroscopically underneath the tumor minutes before definitive surgery. Thereafter, laparoscopic SLN identification /biopsy followed by pelvic and para-aortic lymphadenectomy, hysterectomy, and bilateral salpingo-oophorectomy were executed. RESULTS: The total number of removed nodes was 970. The detection rate of the method was 73% (31/42). Among the 70 isolated SLNs, 35% (24) were exclusively identified in the para-aortic area. Fourteen patients (45%) had SLN only in the pelvic region, whereas 11 (35%) had SLN in both pelvic and para-aortic areas and 6 women (20%) had isolated para-aortic SNL. Nodal metastases were histologically confirmed in 9 patients (22%), and SLN was identified in 7 of 9 patients (78%). Although the obtained specificity was 100% and the negative predictive value was 89%, the sensitivity was only 58% (false-negative rate of 42%). CONCLUSIONS: We could demonstrate that endoscopic SLN biopsy obtained through hysteroscopic injection of Tc-99 is a feasible and safe method. Despite the restricted number of included patients in this series, the obtained sensitivity and false-negative rates raise some questions about the real accuracy of the procedure in EC. Larger validation trials requiring quality pelvic and para-aortic lymphadenectomy are essential to correctly evaluate the method.
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Adenocarcinoma/secundário , Neoplasias do Endométrio/patologia , Excisão de Linfonodo , Biópsia de Linfonodo Sentinela/métodos , Tecnécio/administração & dosagem , Adenocarcinoma/cirurgia , Adulto , Idoso , Neoplasias do Endométrio/cirurgia , Reações Falso-Negativas , Estudos de Viabilidade , Feminino , Humanos , Histeroscopia , Laparoscopia , Metástase Linfática , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Biópsia de Linfonodo Sentinela/efeitos adversosRESUMO
OBJECTIVE: To evaluate the operative and oncologic outcomes of an innovative technique for organ morcellation in patients scheduled for laparoscopic treatment of uterine malignancies. BACKGROUND: Endoscopy is currently considered the standard of care for the operative treatment of endometrial cancer; however, the use of minimal invasive surgery (MIS) is restricted in patients with a bulky uterus or narrow vagina. Conventional unprotected intraperitoneal uterine fragmentation is indeed contraindicated in these cases. Consequently, oncologically safe methods to render these patients eligible for MIS are urgently needed. INTERVENTION: Prospective study of women with histologically proven endometrial cancer in which uterus removal was a realistic concern owing to both organ size and proportionality. The patients underwent laparoscopic staging, including retroperitoneal lymphadenectomy, total hysterectomy, and bilateral salpingo-oophorectomy, followed by vaginal morcellation of the uterus inside a protective pouch (LapSac). RESULTS: In our series of 30 cases, we achieved successful completion in all patients, without conversion to laparotomy. No surgery-related casualty or intraoperative morbidity was observed. The mean organ size was 246 g (range, 148-420 g), and the average additional operative time related to vaginal morcellation was 16 minutes (range, 9-28 minutes). Proper histopathological staging according to 2009 FIGO staging guidelines could be performed in all specimens. Two patients (6%) presented with significant postoperative complications, 1 each with vesicovaginal fistula and vaginal vault dehiscence. Fourteen patients (46%) needed adjuvant therapy. After a median follow-up of 20 months (range, 6-38 months), the 12-month and 24-month overall survival was 100% and 73.4% (95% confidence interval, 51%-96%), respectively. Four patients with positive lymph nodes died of distant metastasis. No case of pelvic or local relapse was observed. CONCLUSION: Vaginal morcellation following oncologic principles is a feasible method that permits rapid uterine extraction and potentially avoids unnecessary laparotomies. This series suggests that the technique may be oncologically safe and also can be used in cases of uterine pathology of uncertain malignancy.
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Neoplasias do Endométrio/cirurgia , Histerectomia/métodos , Laparoscopia , Morcelação/métodos , Neoplasias Uterinas/cirurgia , Vagina , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Endométrio/patologia , Estudos de Viabilidade , Feminino , Humanos , Laparoscopia/métodos , Excisão de Linfonodo/métodos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Segurança do Paciente , Estudos Prospectivos , Neoplasias Uterinas/patologiaRESUMO
OBJECTIVE: This study aimed to evaluate the feasibility and safety of laparoscopic extrafascial hysterectomy and bilateral salpingo-oophorectomy after primary chemoradiation (CRT) in patients with locally advanced cervical cancer (LACC) without evidence of nodal metastasis. BACKGROUND: Currently, the standard of care for patients with advanced cervical cancer is concurrent CRT. There is an unequivocal correlation between presence of residual disease and risk of local relapse. Nevertheless, the importance of hysterectomy in adjuvant setting remains controversial. METHODS: Prospective study with patients affected by bulky LACC (International Federation of Gynecology and Obstetrics stage IB2 up to IIB) treated initially with radical CRT who underwent laparoscopic surgery 12 weeks after therapy conclusion. Inclusion criteria were absence of signs for extrapelvic or nodal involvement on initial imaging staging, as well as complete clinical and radiologic response. RESULTS: From January 2011 to March 2013, 33 patients were endoscopically operated. The mean age was 44 years (range, 21-77 years). Histologic finding revealed squamous cell carcinoma in 19 (60%) cases and adenocarcinoma in 14 (40%) cases. International Federation of Gynecology and Obstetrics stages distribution were as follow: 1B2, n = 3 (9%); IIA, n = 4 (11%); and IIB, n = 26 (80%). The mean pretherapeutic tumor size was 5.2 cm (range, 4-10.2 cm). Estimated blood loss was 80 mL (range, 40-150 mL), and mean operative time was approximately 104 minutes (range, 75-130 minutes). No casualty or conversion to laparotomy occurred. Hospital stay was in average 1.7 days (range, 1-4 days). Significant complication occurred in 12% of the cases; 2 vaginal vault dehiscence, 1 pelvic infection, and 1 ureterovaginal fistula. Nine (27%) patients had pathologic residual disease, and in 78% of these cases, histologic finding was adenocarcinoma (P = -0.048). All patients had free margins. After median follow-up of 16 months, all women have no signs of local recurrence. CONCLUSIONS: Laparoscopic extrafascial hysterectomy (completion surgery) after primary CRT in patients with apparent node-negative LACC is a feasible and safe strategy to improve tumor local control mainly in cases of adenocarcinoma.
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Adenocarcinoma/cirurgia , Carcinoma de Células Escamosas/cirurgia , Quimiorradioterapia , Histerectomia Vaginal/métodos , Neoplasias do Colo do Útero/cirurgia , Adulto , Idoso , Feminino , Humanos , Laparoscopia/métodos , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Invasive cervical cancer is the second most common malignant tumor affecting Brazilian women. Knowledge on Human Papillomavirus (HPV) genotypes in invasive cervical cancer cases is crucial to guide the introduction and further evaluate the impact of new preventive strategies based on HPV. We aimed to provide updated comprehensive data about the HPV types' distribution in patients with invasive cervical cancer. METHODS: Fresh tumor tissue samples of histologically confirmed invasive cervical cancer were collected from 175 women attending two cancer reference hospitals from São Paulo State: ICESP and Hospital de Câncer de Barretos. HPV detection and genotyping were performed by the Linear Array HPV Genotyping Test (Roche Molecular Diagnostics, Pleasanton,USA). RESULTS: 170 out of 172 valid samples (99%) were HPV DNA positive. The most frequent types were HPV16 (77.6%), HPV18 (12.3%), HPV31 (8.8%), HPV33 (7.1%) and HPV35 (5.9%). Most infections (75%) were caused by individual HPV types. Women with adenocarcinoma were not younger than those with squamous cell carcinoma, as well, as women infected with HPV33 were older than those infected by other HPV types. Some differences between results obtained in the two hospitals were observed: higher overall prevalence of HPV16, absence of single infection by HPV31 and HPV45 was verified in HC-Barretos in comparison to ICESP patients. CONCLUSIONS: To our knowledge, this is one of the largest studies made with fresh tumor tissues of invasive cervical cancer cases in Brazil. This study depicted a distinct HPV genotype distribution between two centers that may reflect the local epidemiology of HPV transmission among these populations. Due to the impact of these findings on cervical cancer preventive strategies, extension of this investigation to routine screening populations is warranted.
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Infecções por Papillomavirus/genética , Infecções por Papillomavirus/virologia , Neoplasias do Colo do Útero/virologia , Adulto , Idoso , Brasil , DNA Viral/análise , DNA Viral/genética , Feminino , Genótipo , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Papillomaviridae/genética , Neoplasias do Colo do Útero/patologiaRESUMO
Cervical cancer is one of the most frequent gynecological malignancies in Brazil, and most of the patients require pelvic radiotherapy as part of oncological treatment. Pelvic radiotherapy induces ovarian premature insufficiency in pre-menopausal women. This condition impacts the life quality and increases the risk of osteoporosis, obesity, cardiovascular, and neurodegenerative diseases in the middle and long term. Most of these patients have no access to hormonal replacement therapy. Techniques such as ovarian transposition have questionable results when aiming to preserve ovarian function. In this context, a promising alternative is the implantation of fresh ovarian tissue, outside the radiotherapy field, in the abdominal cavity (orthotopic implantation) or in other sites such as the forearm, breast, or subcutaneous tissue (heterotopic implantation). Here we report a successful case of autologous implantation of fresh ovarian tissue in the inner thigh of a young patient with advanced cervical cancer, who was a candidate for concurrent chemoradiotherapy.
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The radiation recall phenomenon is a rare, massive inflammatory reaction induced by some chemotherapeutic agents in previously irradiated areas. When it occurs in the pelvis it looks like a recurrence. Recognizing this phenomenon is paramount to avoiding unnecessary surgical intervention and complications. Symptoms manifest as dermatitis, mucositis, myositis, esophagitis, colitis, proctitis, and pneumonitis in areas within the irradiation field. Most patients respond to clinical treatment with corticosteroids. Here, we describe a 47-year-old patient with cervical carcinoma, FIGO stage IIB, submitted to external beam radiotherapy and concomitant chemotherapy with cisplatin (40 mg/m2 weekly), followed by intracavitary brachytherapy. One month after the end of radiotherapy and chemotherapy, the patient underwent laparoscopic completion hysterectomy plus bilateral salpingo-oophorectomy, followed by three cycles of cisplatin 50 mg/m2 D1 and gemcitabine 1,000 mg/m2 D1 and D8. Four months after the surgery, she presented with a suspicious mass in the vaginal dome that proved to be an exuberant inflammatory reaction that regressed after treatment with corticosteroids.
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Isthmocele is a discontinuation of the myometrium at the uterine scar site in a patient with a previous cesarian section (CS). The cause of isthmocele appears to be multifactorial. Poor surgical technique, low incision location, uterine retroflection, obesity, smoking, inadequate healing of scars, and maternal age are possible related factors. Most patients with this condition are asymptomatic. However, women can present with postmenstrual bleeding, pelvic pain, subfertility, dysmenorrhea, infertility, and scar abscess. Brazil has one of the world's highest cesarean section rates. One of the consequences of the rising rate of CS is the isthmocele, an emerging female health problem. Here we report a case of mucinous cystadenoma arising in a uterine isthmocele, a complication, as far as we could investigate, not yet described in the literature.
Istmocele é a descontinuidade do miométrio no local da cicatriz uterina em paciente com cesariana anterior. A causa da istmocele parece ser multifatorial. Má técnica cirúrgica, baixa localização da incisão, retroflexão uterina, obesidade, tabagismo, cicatrização inadequada de cicatrizes e idade materna são possíveis fatores relacionados. A maioria dos pacientes com esta condição é assintomática. No entanto, as mulheres podem apresentar sangramento pós-menstrual, dor pélvica, subfertilidade, dismenorreia, infertilidade e abscesso cicatricial. O Brasil tem uma das maiores taxas de cesariana do mundo. Uma das consequências da taxa crescente de cesarianas é a istmocele, um problema emergente de saúde feminina. Aqui relatamos um caso de cistoadenoma mucinoso originado em uma istmocele uterina, uma complicação ainda não descrita, até onde pudemos investigar.
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Cistadenoma Mucinoso , Doenças Uterinas , Feminino , Humanos , Gravidez , Doenças Uterinas/cirurgia , Cicatriz/etiologia , Cesárea/efeitos adversos , Cistadenoma Mucinoso/complicações , Cistadenoma Mucinoso/diagnóstico , Cistadenoma Mucinoso/cirurgia , Útero/cirurgiaRESUMO
DNA mismatch repair protein deficiency (MMRd) in endometrial carcinoma is associated with the risk of Lynch syndrome and response to immune checkpoint inhibitors. It is also related to microsatellite instability and corresponds to a molecular subtype of endometrial tumor with an unclear prognosis. Here, we evaluated the clinicopathological characteristics and prognosis of 312 consecutive endometrial carcinoma cases submitted to complete surgical staging at a single institution. We compared MMRd and mismatch repair protein-proficient (MMRp) tumors and examined the effects of the MMR protein loss type (MLH1/PMS2 vs. MSH2/MSH6) and influence of L1CAM and p53 expression. The median follow-up period was 54.5 (range, 0-120.5) months. No difference was observed between MMRd [n = 166 (37.2%)] and MMRp [n = 196 (62.8%)] cases in terms of age, body mass index, FIGO stage, tumor grade, tumor size, depth of myometrial infiltration, or lymph node metastasis. More MMRd than MMRp tumors had endometrioid histology (87.9% vs. 75.5%) and despite MMRd had more lymphovascular space invasion (LVSI; 27.2% vs. 16.9%), they presented fewer recurrences and no difference in lymph node metastasis and disease-related death. Relative to those with MLH1/MSH6 loss, tumors with MSH2/MSH6 loss were diagnosed at earlier FIGO stages, were smaller, and had less ≥50% myometrial invasion, LVSI and lymph node metastasis. Outcomes, however, did not differ between these groups. L1CAM positivity and mutation-type p53 expression were more common in MMRp than in MMRd tumors and did not differ between the MLH1/PMS2 and MSH2/MSH6 loss groups. In the entire cohort, L1CAM and mutation p53 expression were associated with worse prognosis, but only non-endometrioid histology, FIGO stage III/IV, and deep myometrial infiltration were significant predictors. In the subgroup of endometrioid carcinomas, only FIGO stage III/IV was associated with poor outcomes. The risk of lymph node metastasis was associated with tumor size, non-endometrioid histology, and multifocal LVSI. For MMRd tumors, only tumor size and myometrial invasion depth were predictive of lymph node involvement. In our cohort, MMRd tumors were associated with greater recurrence-free, but not overall, survival. The precise identification of MMRd status, present in a substantial proportion of endometrial cancer cases, is a challenge to be overcome for proper patient management. MMRd status serves as a marker for Lynch syndrome, and a significant number of these tumors are high risk and candidate to immunotherapy.
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OBJECTIVE: Evaluate feasibility and safety of a novel technique for uterine morcellation in patients scheduled for laparoscopic treatment of gynecologic malignances. BACKGROUND: The laparoscopic management of uterine malignancies is progressively gaining importance and popularity over laparotomy. Nevertheless, minimal invasive surgery is of limited use when patients have enlarged uterus or narrow vagina. In these cases, conventional uterus morcellation could be a solution but should not be recommended due to risks of tumor dissemination. METHODS: Prospective pilot study of women with endometrial cancer in which uterus removal was a realistic concern due to both organ size and proportionality. Brief technique description: after completion of total laparoscopic hysterectomy and bilateral anexectomy, a nylon with polyurethane Lapsac® is vaginally inserted into the abdomen; the specimen is placed inside the pouch that will be closed and rotated 180° toward the vaginal vault and, posteriorly, pushed into the vaginal canal; in the transvaginal phase, the surgeon pulls the edges of the bag up to vaginal introitus and all vaginal walls will be covered; inside the pouch, the operator performs a uterus bisection-morcellation. RESULTS: In our series of 8 cases, we achieved successful completion in all patients, without conversion to laparotomy. Average operative time, blood loss and length of hospitalization were favorable. One patient presented with a vesicovaginal fistula. CONCLUSION: The vaginal morcellation following oncologic principles is a feasible method that permits a rapid uterine extraction and may avoid a number of unnecessary laparotomies. Further studies are needed to confirm the oncological safety of the technique.
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Adenocarcinoma/cirurgia , Carcinossarcoma/cirurgia , Neoplasias do Endométrio/cirurgia , Laparoscopia/métodos , Excisão de Linfonodo , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Aorta , Carcinossarcoma/patologia , Neoplasias do Endométrio/patologia , Feminino , Humanos , Histerectomia/efeitos adversos , Histerectomia/métodos , Laparoscopia/efeitos adversos , Metástase Linfática , Pessoa de Meia-Idade , Ovariectomia/efeitos adversos , Ovariectomia/métodos , Pelve , Projetos Piloto , Estudos Prospectivos , Salpingectomia/efeitos adversos , Salpingectomia/métodos , Vagina/cirurgiaRESUMO
Female adnexal tumor of probable Wolffian origin (FATWO) are a rare type of cancer that originates from Wolffian duct remnants. Due to its rarity, no standard systemic treatment is established for cases of recurrent or metastatic disease. Previous literature reported the use of platinum-based chemotherapy and c-Kit tyrosine kinase inhibitors for FATWO cases with c-Kit positive expression. Currently, however, the broader availability of next-generation sequencing (NGS) tests allows a better molecular characterization of rare cancer such as FATWO and a possibility for the use of personalized, targeted therapy. Previous case series that performed NGS for FATWO patients described the presence of STK11 mutations in a considerable number of cases, representing a potential target in this population. To our knowledge, we describe here the first case report of a patient with FATWO and STK11 mutation exhibiting a considerable and durable response after treatment with an mTOR inhibitor plus endocrine therapy.
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Squamous cell carcinoma (SCC) and adenocarcinoma (ADC) are the most common histological types of cervical cancer (CC). The worse prognosis of ADC cases highlights the need for better molecular characterization regarding differences between these CC types. RNA-Seq analysis of seven SCC and three ADC human papillomavirus 16-positive samples and the comparison with public data from non-tumoral human papillomavirus-negative cervical tissue samples revealed pathways exclusive to each histological type, such as the epithelial maintenance in SCC and the maturity-onset diabetes of the young (MODY) pathway in ADC. The transcriptional regulatory network analysis of cervical SCC samples unveiled a set of six transcription factor (TF) genes with the potential to positively regulate long non-coding RNA genes DSG1-AS1, CALML3-AS1, IGFL2-AS1, and TINCR. Additional analysis revealed a set of MODY TFs regulated in the sequence predicted to be repressed by miR-96-5p or miR-28-3p in ADC. These microRNAs were previously described to target LINC02381, which was predicted to be positively regulated by two MODY TFs upregulated in cervical ADC. Therefore, we hypothesize LINC02381 might act by decreasing the levels of miR-96-5p and miR-28-3p, promoting the MODY activation in cervical ADC. The novel TF networks here described should be explored for the development of more efficient diagnostic tools.
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BACKGROUND: The molecular profile of endometrial cancer has become an important tool in determining patient prognosis and their optimal adjuvant treatment. In addition to The Cancer Genome Atlas (TCGA), simpler tools have been developed, such as the Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE). We attempted to determine a genetic signature to build a recurrence risk score in patients diagnosed with low- and intermediate-risk endometrial cancer. METHODS: A case-control study was conducted. The eligible patients were women diagnosed with recurrence low- and intermediate-risk endometrial cancer between January 2009 and December 2014 at a single institution; the recurrence patients were matched to two nonrecurrence patients with the same diagnosis by age and surgical staging. Following RNA isolation of 51 cases, 17 recurrence and 34 nonrecurrence patients, the expression profile was determined using the nCounter® PanCancer Pathways Panel, which contains 770 genes. RESULTS: The expression profile was successfully characterized in 49/51 (96.1%) cases. We identified 12 genes differentially expressed between the recurrence and nonrecurrence groups. The ROC curve for each gene was generated, and all had AUCs higher than 0.7. After backward stepwise logistic regression, four genes were highlighted: FN1, DUSP4, LEF1, and SMAD9. The recurrence risk score was calculated, leading to a ROC curve of the 4-gene model with an AUC of 0.93, sensitivity of 100%, and specificity of 72.7%. CONCLUSION: We identified a four-gene signature that may be associated with recurrence in patients with low- and intermediate-risk endometrial cancer. This finding suggests a new prognostic factor in this poorly explored group of patients with endometrial cancer.
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PEComas are rare neoplasms that are sometimes associated with the tuberous sclerosis complex. They typically contain perivascular epithelioid cells that coexpress muscle and melanocytic markers. However, apart from these classical features, considerable clinical, pathologic, and immunohistochemical variation has been reported. WT1, the Wilms tumor gene product, can be expressed in various tumors from different anatomical sites, including sex-cord and other ovarian tumors with a sertoliform pattern. Neither a sex-cord-like pattern nor WT1 expression has been described in PEComas. Here, we describe a case of uterine PEComa with a pattern of infiltration into the myometrium that is similar to stromal sarcomas, characterized by tongues and endovascular growing. The architecture and cellular morphology were similar to sex-cord tumors, and the PEComa was diffusely and strongly positive for WT1. We reviewed, from our files, an additional 9 cases of PEComa from different sites, and found WT1 expression in one more soft tissue tumor. We discuss the relationship between PEComas and other uterine sarcomas.