Jesus Paula Carvalho
University of São Paulo
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Featured researches published by Jesus Paula Carvalho.
Science Translational Medicine | 2013
Isaac Kinde; Chetan Bettegowda; Yuxuan Wang; Jian Wu; Nishant Agrawal; Ie Ming Shih; Robert J. Kurman; Fanny Dao; Douglas A. Levine; Robert L. Giuntoli; Richard Roden; James R. Eshleman; Jesus Paula Carvalho; Suely Kazue Nagahashi Marie; Nickolas Papadopoulos; Kenneth W. Kinzler; Bert Vogelstein; Luis A. Diaz
Mutant DNA from ovarian and endometrial tumors can be detected in Pap smear specimens through massively parallel sequencing. New Adventures of Old Pap Smear Patients generally do not enjoy getting a Pap smear, but the procedure has saved hundreds of thousands of lives in the decades since its inception. The now-routine smear, which allows doctors to detect abnormal cells in a woman’s cervix before they turn into an invasive cancer, was updated a decade ago to screen for DNA from human papillomavirus, the pathogen known to cause cervical cancer. Now, Kinde and coauthors have developed a technique that may make the Pap smear even more versatile by expanding it into a test for multiple cancers, including endometrial and the dreaded ovarian cancer, which is essentially untreatable unless it is caught early. The authors first assembled a catalog of common mutations in these cancers, drawing on previously published data for ovarian cancer and new data on 22 endometrial tumors. They tested 46 samples from patients with endometrial or ovarian cancers and confirmed that all 46 harbored at least some of the common genetic changes on their list. Kinde et al. then hypothesized that ovarian and endometrial cancers likely shed cells from their surfaces and that such cells may be detectable among the cervical cells in a Pap smear, if one knew how to identify them. Thus, the authors used massively parallel sequencing to test patients’ Pap specimens for some of the more common mutations found in the cancer cells. In the initial set of samples, 100% of endometrial cancers and 41% of ovarian cancers were detectable by this method. This new approach to Pap testing is not yet ready for clinical use and will not serve as a foolproof method of diagnosing genital tract tumors, particularly ovarian cancer. More research is needed to validate the current results in larger groups of patients and to improve the yield of screening for ovarian tumors, perhaps by modifying the technique doctors use to collect sample cells for the Pap test. Importantly, though, the new test has not misclassified any healthy woman as harboring a cancer, raising the possibility of its eventual use as a screening test for cancer. Even if this approach cannot identify every ovarian tumor, it may be able to detect more of them earlier and more accurately than is possible with existing methods. Once the findings of Kinde et al. are fully validated and the new test gains approval, women will have even more reasons to make sure they get their Pap smears routinely. Papanicolaou (Pap) smears have revolutionized the management of patients with cervical cancers by permitting the detection of early, surgically curable tumors and their precursors. In recent years, the traditional Pap smear has been replaced by a liquid-based method, which allows not only cytologic evaluation but also collection of DNA for detection of human papillomavirus, the causative agent of cervical cancer. We reasoned that this routinely collected DNA could be exploited to detect somatic mutations present in rare tumor cells that accumulate in the cervix once shed from endometrial or ovarian cancers. A panel of genes that are commonly mutated in endometrial and ovarian cancers was assembled with new whole-exome sequencing data from 22 endometrial cancers and previously published data on other tumor types. We used this panel to search for mutations in 24 endometrial and 22 ovarian cancers and identified mutations in all 46 samples. With a sensitive massively parallel sequencing method, we were able to identify the same mutations in the DNA from liquid Pap smear specimens in 100% of endometrial cancers (24 of 24) and in 41% of ovarian cancers (9 of 22). Prompted by these findings, we developed a sequence-based method to query mutations in 12 genes in a single liquid Pap smear specimen without previous knowledge of the tumor’s genotype. When applied to 14 samples selected from the positive cases described above, the expected tumor-specific mutations were identified. These results demonstrate that DNA from most endometrial and a fraction of ovarian cancers can be detected in a standard liquid-based Pap smear specimen obtained during routine pelvic examination. Although improvements need to be made before applying this test in a routine clinical manner, it represents a promising step toward a broadly applicable screening methodology for the early detection of gynecologic malignancies.
Clinics | 2012
Cristina Anton; Filomena Marino Carvalho; Elci Isabel Oliveira; Gustavo Arantes Rosa Maciel; Edmund Chada Baracat; Jesus Paula Carvalho
OBJECTIVE: 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.
Gynecologic Oncology | 2012
Giovanni Favero; Cristina Anton; Alexandre Silva e Silva; Altamiro Ribeiro; Marcia Pereira de Araujo; Giovanni Miglino; Edmund Chada Baracat; Jesus Paula Carvalho
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.
Gynecologic Oncology | 2014
Vanessa da Costa Miranda; Ângelo Bezerra de Souza Fêde; Carlos Henrique dos Anjos; Juliana Ribeiro da Silva; Fernando Barbosa Sanchez; Lyvia Rodrigues da Silva Bessa; Jesus Paula Carvalho; Elias Abdo Filho; Daniela de Freitas; Maria Del Pilar Estevez Diz
OBJECTIVE 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.
BMC Cancer | 2013
Cristina Mendes de Oliveira; José Humberto Tavares Guerreiro Fregnani; Jesus Paula Carvalho; Adhemar Longatto-Filho; José Eduardo Levi
BackgroundInvasive 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.MethodsFresh 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).Results170 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.ConclusionsTo 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.
Medical Hypotheses | 2008
Jesus Paula Carvalho; Filomena Marino Carvalho
Ovarian cancer is a highly lethal disease and its underlying biology is poorly understood. Prophylactic salpingo-oophorectomies in BRCA + women have recently implicated the fimbria as a site of origin for high-grade serous carcinoma and its intraepithelial precursors. This suggests that at least some ovarian cancers, probably the most aggressive ones, may not originate in the ovary itself, but rather may arise in the uterine tubes. Chronic inflammation is associated with carcinogenesis in several tissues, including liver, esophagogastric junction (cardia), and the uterine cervix. The mechanisms underlying the relationship between inflammation and cancer are complex and involve common pathways, in addition to DNA damage. A critical source of uterine tube inflammation is infection with Chlamydia trachomatis. We hypothesize that C.trachomatis infection may be involved in chronic tubal inflammation and subsequent fimbrial carcinogenesis. Fimbrial intraepithelial precursors can evolve into high grade serous carcinomas that spread rapidly to the ovarian surface and peritoneum; such tumors may appear to be primary ovarian neoplasia, though in reality being a secondary malignancy. This hypothesis must be further investigated to understand the intracellular signaling pathways involved in Chlamydia infection and its healing, and their relationship to carcinogenesis in order to discover potential therapeutic molecular targets. If our hypothesis were confirmed, salpingectomy instead of ovariectomy may also become the recommended surgery for high risk women.
International Journal of Gynecology & Obstetrics | 1999
Jesus Paula Carvalho; Jorge Saad Souen; J.A. Pinotti
The role of diagnostic laparoscopy in the staging of uterine malignancies is not well defined. Recent experimental studies suggest that laparoscopic surgery for abdominal malignancy may be w x associated with increased tumor implantation 1 . Clinical reports of port site metastasis following laparoscopic resection of intra-abdominal malignancy suggest that laparoscopy promotes tumor metastasis to wounds. We present a case of metastasis to four laparoscopic trochar sites in a 33-year-old patient with squamous cell cervical carcinoma, stage Ib2 FIGO submitted to pelvic laparoscopic lymphadenectomy, with positive lymph nodes metastasies in both pelvic lymph node chains. Six weeks after laparoscopy when the patient
Clinics | 2010
Filomena Marino Carvalho; Fabricia L. Zaganelli; Bernardo G.L. Almeida; Joao Carlos Sampaio Goes; Edmund Chada Baracat; Jesus Paula Carvalho
OBJECTIVE: To investigate the clinicopathological significance of podoplanin expression in the intratumoral stroma and neoplastic cells of early stage uterine cervical cancer. MATERIALS AND METHODS: A total of 143 patients with clinical stage I and IIA uterine cervical carcinomas underwent surgery between 2000 and 2007. Clinicopathological data and slides associated with these cases were retrospectively reviewed. Immunodetection of podoplanin expression in histologic sections of tissue microarray blocks was performed using the monoclonal antibody D2‐40. RESULTS: Expression of podoplanin was detected in neoplastic cells in 31/143 (21.6%) cases, with 29/31 (93.5%) of these cases diagnosed as squamous carcinoma. For all of the cases examined, the strongest signal for podoplanin expression was observed at the proliferating edge of the tumor nests. The rate of positive podoplanin expression for node‐positive cases was lower than that of node‐negative (18.9% vs. 22.6%, respectively). Furthermore, the rate of positive podoplanin expression in fatal cases was 10.5% vs. 21.6%, respectively. In 27/143 (18.8%) cases, podoplanin expression was detected in fibroblasts of the intratumoral stroma, and this expression did not correlate with patient age, clinical stage, tumor size, histologic type, depth of infiltration, or vascular involvement. Moreover, expression of podoplanin in intratumoral stroma fibroblasts was only negatively associated with nodal metastasis. A greater number of fatal cases was observed among negative intratumoral stroma fibroblasts (15.5% vs. 3.7%, respectively), although this difference was not significant. CONCLUSIONS: These preliminary results suggest that podoplanin may have a role in host‐tumor interactions and, as a result, may represent a favorable prognostic factor for squamous cervical carcinomas.
Revista do Hospital das Clínicas | 2000
Filomena Marino Carvalho; Jesus Paula Carvalho; Eduardo Vieira da Motta; Jorge Saad Souen
Müllerian adenosarcoma with sarcomatous overgrowth presented by a 52-year-old female patient after adjuvant tamoxifen treatment for breast carcinoma is described. The diagnosis was made on histological basis after curettage and complementary total hysterectomy with bilateral salpingo-oophorectomy. The immunohistochemical study showed high expression of estrogen receptors in the epithelial component of the lesion and irregularly positive findings in the stroma. The proliferative activity evaluated by Ki-67 immunoexpression was higher in the stroma than the epithelium. Some of the stromal cells showed rhabdomyoblastic differentiation. The association of tamoxifen use and development of mesenchymal neoplasms is discussed.
Clinics | 2011
Patrícia M. Diniz; Jesus Paula Carvalho; Edmund Chada Baracat; Filomena Marino Carvalho
INTRODUCTION: Serous carcinomas are the most frequent histologic type of ovarian and peritoneal cancers, and can also be detected in the endometrium and fallopian tubes. Serous carcinomas are usually high‐grade neoplasms when diagnosed, yet the identification of an associated precursor lesion remains challenging. Pathological examination of specimens obtained from prophylactic bilateral salpingo‐oophorectomies that were performed for patients harboring BRCA1/2 mutations suggests that high‐grade serous carcinomas may arise in the fallopian tubes rather than in the ovaries. OBJECTIVE: To investigate the presence and extent of fallopian tube involvement in cases of serous pelvic carcinomas. METHODS: Thirty‐four cases of serous pelvic carcinoma with clinical presentations suggesting an ovarian origin were analyzed retrospectively. Histologic samples of fallopian tube tissues were available for these cases and were analyzed. Probable primary site, type of tubal involvement, tissues involved in the neoplasia and vascular involvement were evaluated. RESULTS: Fallopian tube involvement was observed in 24/34 (70.6%) cases. In 4 (11.8%) of these cases, an intraepithelial neoplasia was present, and therefore these cases were hypothesized to be primary from fallopian tubes. For an additional 7/34 (20.6%) cases, a fallopian tube origin was considered a possible primary. CONCLUSIONS: Fallopian tubes can be the primary site for a subset of pelvic high‐grade serous carcinomas.