JESUS PAULA CARVALHO
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Obstetrícia e Ginecologia, Faculdade de Medicina - Docente
LIM/58 - Laboratório de Ginecologia Estrutural e Molecular, Hospital das Clínicas, Faculdade de Medicina
LIM/58 - Laboratório de Ginecologia Estrutural e Molecular, Hospital das Clínicas, Faculdade de Medicina
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- Hereditary determinants of gynecological cancer and recommendations Number 8-August 2021(2021) CARVALHO, Jesus Paula; CARVALHO, Filomena Marino; CHAMI, Anisse Marques; SILVA FILHO, Agnaldo Lopes da; PRIMO, Walquiria Quida Salles Pereira
- Lactate secreted by cervical cancer cells modulates macrophage phenotype(2019) STONE, Simone Cardozo; ROSSETTI, Renata Ariza Marques; ALVAREZ, Karla Lucia Fernandez; CARVALHO, Jesus Paula; MARGARIDO, Paulo Francisco Ramos; BARACAT, Edmund Chada; TACLA, Maricy; BOCCARDO, Enrique; YOKOCHI, Kaori; LORENZI, Noely Paula; LEPIQUE, Ana PaulaCervical cancer continues to be a public health problem in developing countries. Previous studies have shown that cervical cancer cells display markers of aerobic glycolysis, indicating that these tumors are likely to secrete lactate. Mostly, lactate is recognized as a molecule capable of suppressing immune responses, through inhibition of T cells, M phi s, and dendritic cells. We and others have previously shown that M phi s are frequent cells infiltrating cervical cancers with the ability to inhibit antitumor immune responses and promote tumor growth through angiogenesis. Here, we have tested the hypothesis that lactate, secreted by cervical cancer cells, can modulate M phi phenotype. First, we showed higher lactate plasma concentrations in patients with increasing cervical lesion grades, with maximum concentration in the plasma of cancer patients, which supported our hypothesis. We then inhibited lactate production in tumor cell spheroids established from cervical cancer derived cell lines, using the lactate dehydrogenase inhibitor, oxamate, prior to co-culture with monocytes. Lactate mediated part of the crosstalk between tumor cells and M phi s, promoting secretion of IL-1, IL-10, IL-6, and up-regulation of hypoxia induced factor-1 expression, and down-regulation of p65-NFB phosphorylation in M phi s. We also showed that M phi s from co-cultures treated with oxamate were better inducers of T cell activation. Of note, experiments performed with inhibition of the monocarboxylate transporters rendered similar results. Our data confirms the hypothesis that lactate, secreted by cervical tumor cells, influences the phenotype of tumor M phi s, promoting a suppressive phenotype.
- Laparoscopic Sentinel Lymph Node Detection After Hysteroscopic Injection of Technetium-99 in Patients With Endometrial Cancer(2015) FAVERO, Giovanni; PFIFFER, Tatiana; RIBEIRO, Altamiro; CARVALHO, Jesus Paula; BARACAT, Edmund Chada; MECHSNER, Sylvia; CHIANTERA, Vito; KOEHLER, Christhardt; SCHNEIDER, AchimBackground 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 paraaortic 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.
- Secondary healing strategy for difficult wound closure in invasive vulvar cancer: a pilot case-control study(2019) DIAS-JR, Altamiro Ribeiro; SOARES-JR, Jose Maria; FARIA, Maria Beatriz Sartor de; GENTA, Maria Luiza Noqueira Dias; CARVALHO, Jesus Paula; BARACAT, Edmund C.OBJECTIVES: Despite the number of surgical advances and innovations in techniques over time, radical vulvectomy frequently results in substantial loss of tissue that cannot be primarily closed without tension, the mobilization of surrounding tissues or even the rotation of myocutaneous flaps. The aim of this study was to evaluate the feasibility of leaving the surgical vulvar open wound for secondary healing in situations where primary closure of the vulvar wound is not possible. METHODS: This case-control pilot study analyzed 16 women with a diagnosis of squamous cell carcinoma of the vulva who first underwent inguinofemoral lymphadenectomy, 6-week sessions of chemotherapy and 25 daily sessions of radiotherapy. Afterward, excision of the vulvar lesion with free margins was performed between January 2011 and July 2017. Twelve patients underwent primary closure of the wound (control), and in 4 patients, the surgical wound was left open for secondary healing by means of a hydrofiber (case). The inclusion criteria were a) FIGO-2009 stage II up to IIIC; b) squamous cell carcinoma; and c) no evidence of pelvic or extrapelvic disease or pelvic nodal involvement. The exclusion criteria were extrapelvic disease or pelvic nodal involvement, another primary cancer, or a poor clinical condition. ClinicalTrials.gov: NCT02067052. RESULTS: The mean age of the patients at the time of the intervention was 62.1. The distribution of the stages was as follows: II, n=6 (37 %); IIIA, n=1 (6%), IIIB, n=1 (6%) and IIIC, n=8 (51%). The mean operative time was 45 minutes. The hospital stay duration was 2 days. Full vulvar healing occurred after an average of 30 days in the control group and after an average of 50 days in the case group. CONCLUSION: A secondary healing strategy may be an option for the treatment of vulvar cancer in situations of non-extensive surgical wounds when primary closure of the wound is not possible.
- A comparison of CA125, HE4, risk ovarian malignancy algorithm (ROMA), and risk malignancy index (RMI) for the classification of ovarian masses(2012) ANTON, Cristina; CARVALHO, Filomena Marino; OLIVEIRA, Elci Isabel; MACIEL, Gustavo Arantes Rosa; BARACAT, Edmund Chada; CARVALHO, Jesus PaulaOBJECTIVE: Differentiation between benign and malignant ovarian neoplasms is essential for creating a system for patient referrals. Therefore, the contributions of the tumor markers CA125 and human epididymis protein 4 (HE4) as well as the risk ovarian malignancy algorithm (ROMA) and risk malignancy index (RMI) values were considered individually and in combination to evaluate their utility for establishing this type of patient referral system. METHODS: Patients who had been diagnosed with ovarian masses through imaging analyses (n = 128) were assessed for their expression of the tumor markers CA125 and HE4. The ROMA and RMI values were also determined. The sensitivity and specificity of each parameter were calculated using receiver operating characteristic curves according to the area under the curve (AUC) for each method. RESULTS: The sensitivities associated with the ability of CA125, HE4, ROMA, or RMI to distinguish between malignant versus benign ovarian masses were 70.4%, 79.6%, 74.1%, and 63%, respectively. Among carcinomas, the sensitivities of CA125, HE4, ROMA (pre-and post-menopausal), and RMI were 93.5%, 87.1%, 80%, 95.2%, and 87.1%, respectively. The most accurate numerical values were obtained with RMI, although the four parameters were shown to be statistically equivalent. CONCLUSION: There were no differences in accuracy between CA125, HE4, ROMA, and RMI for differentiating between types of ovarian masses. RMI had the lowest sensitivity but was the most numerically accurate method. HE4 demonstrated the best overall sensitivity for the evaluation of malignant ovarian tumors and the differential diagnosis of endometriosis. All of the parameters demonstrated increased sensitivity when tumors with low malignancy potential were considered low-risk, which may be used as an acceptable assessment method for referring patients to reference centers.
- Reassessment of low- and intermediate-risk endometrial cancer reports by gynecological pathologists increases risk classification without impacting outcome(2022) ANDRADE, Diocesio Alves Pinto de; SILVA, Vinicius Duval da; BAIOCCHI, Glauco; MATSUSHITA, Graziela de Macedo; LIMA, Marcos Alves de; CARVALHO, Jesus Paula; SANDRE, Leticia Batista; BROT, Louise De; REIS, Rui Manuel; REIS, Ricardo dosObjectives: A lack of agreement is often observed in pathological reviews performed by specialized and general pathologists. Four histopathological variables influence the risk classification of endometrial cancer: histological type; histological grade; myometrial invasion; lymph-vascular space invasion (LVSI). This study aimed to eval-uate if changes in the risk classification after a specialized pathological review of low-and intermediate-risk endometrial cancer (LIREC) samples may impact disease-free survival (DFS).Methods: A retrospective cohort of 195 patients diagnosed with LIREC at Barretos Cancer Hospital was obtained. Two gynecologic pathologists re-evaluated the pathological reports. Through the histology report reviewed, we could determine their new risk classification. The Kappa concordance score was used to verify the concordance between the general's and specialized pathologists' reports, and the new risk classification was correlated with the patients' DFS.Results: The final reports led to changes in the histological type, histological grade, myometrial invasion, and lymphovascular space invasion in 13.3 %, 62,8%, 18.3 %, and 11.1 % of cases, respectively. The Kappa concordance score for all variables was less than 0.7. In 54 patients (30 %), the risk classification was modified (Kappa = 0.396), of which 30 (55.5 %) cases upstaged. There was no difference in DFS for patients who had an upstaging in their European Society of Medical Oncology modified classification compared to those who maintained their initial risk classification (86.7 % vs 88.0 %, p = 0.77).Conclusion: Despite the differences in the reports reassessed by expert gynecological pathologists and the change (30%) in patients' risk classification, there was no difference in their DFS.
- Multiple HPV genotype infection impact on invasive cervical cancer presentation and survival(2017) GENTA, Maria Luiza Nogueira Dias; MARTINS, Toni Ricardo; LOPE, Rossana V. Mendoza; SADALLA, Jose Carlos; CARVALHO, Joao Paulo Mancusi de; BARACAT, Edmund Chada; LEVI, Jose Eduardo; CARVALHO, Jesus PaulaBackground Invasive cervical cancer (ICC) is the third most common malignant neoplasm affecting Brazilian women. Little is known about the impact of specific HPV genotypes in the prognosis of ICC. We hypothesized that HPV genotype would impact ICC clinical presentation and survival. Methods Women diagnosed with ICC at the Instituto do Ca A ncer do Estado de Sao Paulo (ICESP) between May 2008 and June 2012 were included in the study and were followed until December 2015. HPV genotype was detected from formalin-fixed paraffin-embedded (FFPE) tumor tissue samples using Onclarity (TM) system (BD Viper (TM) LT automated system). Results 292 patients aged 50 +/- 14 years were analyzed. HPVDNA was detected in 84% of patients. The HPV genotypes studied were: HPV16 (64%), HPV18 (10%), HPV33-58 (7%), HPV45 (5%), HPV31 (4%) and other high-risk HPV genotypes (11%). HPV genotypes showed different distributions regarding histological type and clinical stage. Patients were followed for 35-21 months. The overall survival at 5 years after diagnosis of cervical cancer was 54%. Age, clinical staging, histological type and multiple HPV genotypes infection detected in the same tumor specimen were associated with poorer overall survival on multivariate Cox proportional hazard analysis (p<0.05). No specific HPV genotype affected survival. Conclusion Multiple HPV genotype infection was associated with poorer ICC survival in our study, compared with single genotype infection. HPV genotyping from FFPE tumor tissue using an automated assay such as the Onclarity BD (TM) assay provides a simpler alternative for routine clinical use.
- Surgical treatment of endometrial cancer in developing countries: reasons to consider systematic two-step surgical treatment(2015) ANTON, Cristina; FAVERO, Giovanni Mastrantonio di; KOEHLER, Christhardt; CARVALHO, Filomena Marino; BARACAT, Edmund Chada; CARVALHO, Jesus PaulaOBJECTIVE : The aim of this study was to determine the lymph node status in a large cohort of women with endometrial cancer from the public health system who were referred to an oncology reference center in Brazil to identify candidates for the omission of lymphadenectomy based on clinicopathological parameters. METHODS : We retrospectively analyzed a cohort of 310 women with endometrial cancer (255 endometrioid, 40 serous, and 15 clear cell tumors) treated between 2009 and 2014. We evaluated the histological type, grade (low vs. high), tumor size (cm), depth of myometrial invasion (<= 50%, > 50%) and lymphovascular space invasion to determine which factors were correlated with the presence of lymph node metastasis. RESULTS : The factors related to lymph node involvement were tumor size (p =0.03), myometrial invasion (p < 0.01), tumor grade (p < 0.01), and lymphovascular space invasion (p < 0.01). The histological type was not associated with the nodal status (p = 0.52). Only twelve of 176 patients (6.8%) had low-grade endometrioid carcinoma, tumor size <= 2 cm and < 50% myometrial infiltration. CONCLUSIONS : The omission of lymphadenectomy based on the histological type, grade, tumor size and depth of myometrial invasion is not likely to have a large impact on the surgical treatment of endometrial cancer in our population because most patients present with large and advanced tumors. New strategies are proposed that prioritize hysterectomy performed in a general hospital as soon as possible after diagnosis, followed by an evaluation of the need for lymph node dissection at a reference center.
- Gemcitabine-Induced Radiation Recall Phenomenon in Cervical Cancer: A Case Report(2023) CARVALHO, Jesus Paula; FREITAS, Daniela; HANNA, Samir; VELHO, Isabela A.; CARVALHO, Filomena M.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.
- Neoadjuvant chemotherapy with six cycles of carboplatin and paclitaxel in advanced ovarian cancer patients unsuitable for primary surgery: Safety and effectiveness(2014) MIRANDA, Vanessa da Costa; FEDE, Angelo Bezerra de Souza; ANJOS, Carlos Henrique dos; SILVA, Juliana Ribeiro da; SANCHEZ, Fernando Barbosa; BESSA, Lyvia Rodrigues da Silva; CARVALHO, Jesus de Paula; ABDO FILHO, Elias; FREITAS, Daniela de; DIZ, Maria del Pilar EstevezObjective. Three cycles of neoadjuvant chemotherapy (NACT) followed by interval debulking (ID) surgery is an alternative for patients with advanced ovarian cancer unresectable disease. This study aimed to determine the efficacy and safety of six cycles of NACT followed by cytoreduction. Methods. Retrospective analysis of all patients with advanced epithelial ovarian cancer, tubal carcinoma, or primary peritoneal carcinoma treated with platinum based NACT between January 2008 and February 2012. Results. Eighty-two patients underwent NACT; 78% and 18.2% had extensive stage IIIC or IV disease at diagnosis, respectively. Their median age was 60 years (41-82). On histology, serous adenocarcinoma was found in 90.2%. Patients did not receive chemotherapy after debulking surgery. 35.4% suffered grade 3/4 toxicity; the most commonly observed toxicities were hematologic and nausea. After NACT, 23.1% experienced clinical complete response, 57.4% partial response, and 12.1% disease progression. Complete resection of all macroscopic and microscopic disease (R0) was performed in 63.7%. Surgical complications were uncommon; however, four (6.2%) patients needed a second procedure due to operative complications and 18 (27.3%) needed blood transfusion after debulking. Over a median follow-up period of 19.2 months, median overall survival and chemotherapy-free interval were 37.5 months (confidence interval not reached) and 16 months, respectively. Conclusion. Six cycles of neoadjuvant carboplatin and paclitaxel was safe and effective and did not increase perioperative or postoperative complications in patients with stage IIIC/IV disease who were unsuitable for optimal PDS. The overall survival of this cohort was higher than that of those treated with ID surgery.