ANGELITA HABR GAMA
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Gastroenterologia, Faculdade de Medicina - Docente
13 resultados
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Agora exibindo 1 - 10 de 13
- Neoadjuvant chemoradiation therapy for rectal cancer: current status and perspectives for the surgeon(2017) ARAUJO, Sergio Eduardo Alonso; JULIAO, Guilherme Pagin Sao; HABR-GAMA, Angelita; VAILATI, Bruna Borba; PEREZ, Rodrigo OlivaModern management of rectal cancer has become increasingly complex over the last decades. The introduction of neoadjuvant chemoradiation to the treatment strategy of locally advanced and distal rectal cancers has added numerous variables that may ultimately affect final surgical or even non-surgical management. Specific chemoradiation regimens, intervals after neoadjuvant treatment completion and tools for the assessment of tumor response may all affect final surgical decision and should be interpreted with care. The present study attempts to provide a review of commonly used neoadjuvant chemoradiation regimens, specific intervals and final surgical or non-surgical management of rectal cancer in current clinical practice.
- Extralevator Abdominal Perineal Excision Versus Standard Abdominal Perineal Excision: Impact on Quality of the Resected Specimen and Postoperative Morbidity(2017) HABR-GAMA, Angelita; JULIO, Guilherme P. Sao; MATTACHEO, Adrian; CAMPOS-LOBATO, Luiz Felipe de; ALEMAN, Edgar; VAILATI, Bruna B.; GAMA-RODRIGUES, Joaquim; PEREZ, Rodrigo OlivaBackground Abdominal perineal excision (APE) has been associated with a high risk of positive circumferential resection margin (CRM+) and local recurrence rates in the treatment of rectal cancer. An alternative extralevator approach (ELAPE) has been suggested to improve the quality of resection by avoiding coning of the specimen decreasing the risk of tumor perforation and CRM+. The aim of this study is to compare the quality of the resected specimen and postoperative complication rates between ELAPE and ""standard"" APE. Methods All patients between 1998 and 2014 undergoing abdominal perineal excision for primary or recurrent rectal cancer at a single Institution were reviewed. Between 1998 and 2008, all patients underwent standard APE. In 2009 ELAPE was introduced at our Institution and all patients requiring APE underwent this alternative procedure (ELAPE). The groups were compared according to pathological characteristics, specimen quality (CRM status, perforation and failure to provide the rectum and anus in a single specimen-fragmentation) and postoperative morbidity. Results Fifty patients underwent standard APEs, while 22 underwent ELAPE. There were no differences in CRM+ (10.6 vs. 13.6%; p = 0.70) or tumor perforation rates (8 vs. 0%; p = 0.30) between APE and ELAPE. However, ELAPE were less likely to result in a fragmented specimen (42 vs. 4%; p = 0.002). Advanced pT-stage was also a risk factor for specimen fragmentation (p = 0.03). There were no differences in severe (Grade 3/4) postoperative morbidity (13 vs. 10%; p = 0.5). Perineal wound dehiscences were less frequent among ELAPE (52 vs 13%; p < 0.01). Despite short follow-up (median 21 mo.), 2-year local recurrence-free survival was better for patients undergoing ELAPE when compared to APE (87 vs. 49%; p = 0.04). Conclusions ELAPE may be safely implemented into routine clinical practice with no increase in postoperative morbidity and considerable improvements in the quality of the resected specimen of patients with low rectal cancers.
- Baseline T Classification Predicts Early Tumor Regrowth After Nonoperative Management in Distal Rectal Cancer After Extended Neoadjuvant Chemoradiation and Initial Complete Clinical Response(2017) HABR-GAMA, Angelita; JULIAO, Guilherme Pagin Sao; GAMA-RODRIGUES, Joaquim; VAILATI, Bruna Borba; ORTEGA, Cinthia; FERNANDEZ, Laura Melina; ARAUJO, Sergio Eduardo Alonso; PEREZ, Rodrigo OlivaBACKGROUND: Selected patients with rectal cancer and complete clinical response after neoadjuvant chemoradiation have been managed nonoperatively with acceptable outcomes. However, approximate to 20% of these patients will develop early tumor regrowth. Identification of these patients could select candidates for more intensive follow-up. OBJECTIVE: The purpose of this study was to investigate the influence of baseline radiological T classification on recurrences after a complete clinical response managed nonoperatively after chemoradiation. DESIGN: This was a retrospective review of a prospective collected database. SETTINGS: The study was conducted at a single center. PATIENTS: Patients with distal rectal cancer (cT2-4N0-2M0) undergoing extended chemoradiation (54 Gy + 5-fluorouracil-based chemotherapy) were eligible. Patients were reassessed for tumor response at 10 weeks after radiation completion. Patients with complete clinical response (clinical, radiological, and endoscopic) were managed nonoperatively and strictly followed. MAIN OUTCOMES MEASURES: Complete clinical response rates, early tumor regrowth rates (<12 mo), local recurrence-free survival, and distant metastases-free survival were measured. RESULTS: A total of 91 consecutive patients with rectal cancer underwent extended chemoradiation. Sixty-one patients developed initial complete clinical response (67%). cT2 patients developed similar initial complete clinical response rates compared with cT3/T4 (72% vs 63%; p = 0.403). Early tumor regrowths were more frequent among baseline cT3/4 when compared with cT2 patients (30% vs 3%; p = 0.007). There were no differences in late local recurrences (p = 0.593) or systemic recurrences (p = 0.387). Local recurrence-free survival was significantly better for cT2 patients at 1 year (96% vs 69%; p = 0.009). After Cox regression analysis, baseline T stage was an independent predictor of improved local recurrence-free survival at 1 year (p = 0.03; OR = 0.09 (95% CI, 0.01-0.81)). LIMITATIONS: This study was limited by its small sample size, retrospective nature, and short follow-up. CONCLUSIONS: cT2 patients who develop complete clinical response after extended chemoradiation managed nonoperatively are less likely to develop early tumor regrowths when compared with cT3/4 patients. cT3/4 patients should undergo more intensive follow-up after a complete clinical response to allow for early detection of early regrowths.
bookPart Tratamento da deiscência anastomótica colorretal(2017) JULIãO, Guilherme Pagin São; VAILATI, Bruna Borba; PEREZ, Rodrigo Oliva; HABR-GAMA, AngelitaconferenceObject NEOADJUVANT CHEMORADIATION MAY WORSEN RECTAL CANCER INTRATUMORAL HETEROGENEITY AMONG PATIENTS WHO DEVELOP INCOMPLETE RESPONSE TO TREATMENT.(2017) PEREZ, R.; HABR-GAMA, A.; BETTONI, F.; MASOTTI, C.; CORREA, B.; GALANTE, P.; JULIAO, G. Pagin Sao; VAILATI, B. Borba; GAMA-RODRIGUES, J.; AZEVEDO, R.; ARAUJO, S.; CAMARGO, A. AranhaconferenceObject DNA REPAIR GENES AND RESPONSE TO NEOADJUVANT CHEMORADIATION IN RECTAL CANCER: A PREDICTIVE SCORE TO IDENTIFY THE COMPLETE RESPONDER.(2017) PEREZ, R.; HABR-GAMA, A.; KOYAMA, F.; RESTREPO, J.; JULIAO, G. Pagin Sao; VAILATI, B. Borba; AZEVEDO, R.; ARAUJO, S.; CAMARGO, A. Aranha- Intratumoral Genetic Heterogeneity in Rectal Cancer Are Single Biopsies representative of the entirety of the tumor?(2017) BETTONI, Fabiana; MASOTTI, Cibele; HABR-GAMA, Angelita; CORREA, Bruna R.; GAMA-RODRIGUES, Joaquim; VIANNA, Maria R.; VAILATI, Bruna B.; JULIAO, Guilherme P. Sao; FERNANDEZ, Laura M.; GALANTE, Pedro A.; CAMARGO, Anamaria A.; PEREZ, Rodrigo O.Objective: Demonstrate intratumoral genetic heterogeneity in rectal cancer. Background: Several clinical management decisions in rectal cancer may be influenced by pretreatment biopsy information. However, in the setting of significant intratumoral heterogeneity, biopsies may not be representative of the entirety of the tumor and limit the reliability of the information provided from them for clinical decision management. Methods: Three fragments from a single rectal adenocarcinoma were chosen for whole-exome sequencing followed by mutation detection analysis. About 25 Gb of unambiguously mapped sequences were generated for each sample resulting in a median fold-coverage of 35x. Captured sequences mapped to the reference human genome were then used for the detection of somatic point mutations. Results: Overall, 193 unique somatic point mutations were identified. Only 53 (27%) of these were shared by all three fragments, including known genes involved in early phases of the adenoma-carcinoma sequence (such as, APC). Approximately, 115 (59%) mutations were exclusively present in only one of the fragments, including mutations in ""driver"" genes (DNAH12). Jaccard distances showed a median distance of 0.603 for pair-wise comparison of fragments indicating significant heterogeneity between them. Conclusions: Considerable intratumoral heterogeneity is present among naive rectal cancers. The majority of point mutations detected in different fragments from rectal cancers are frequently unique to a single fragment. These findings support that gene mutations found on single pretreatment biopsies will not necessarily be representative of mutations present in the entirety of the tumor and therefore may limit the utility of the biological information provided by single biopsy fragments for clinical management decisions.
conferenceObject WATCH & WAIT AFTER COMPLETE CLINICAL RESPONSE TO NEOADJUVANT CRT: ARE CT3/4 TUMORS MORE LIKELY TO DEVELOP EARLY TUMOR RECURRENCE THAN CT2?(2017) HABR-GAMA, A.; JULIAO, G. Pagin Sao; VAILATI, B. Borba; ORTEGA, C.; FERNANDEZ, L.; ARAUJO, S.; AZEVEDO, R.; PEREZ, R.- E2F1 somatic mutation within miRNA target site impairs gene regulation in colorectal cancer(2017) LOPES-RAMOS, Camila M.; BARROS, Bruna P.; KOYAMA, Fernanda C.; CARPINETTI, Paola A.; PEZUK, Julia; DOIMO, Nayara T. S.; HABR-GAMA, Angelita; PEREZ, Rodrigo O.; PARMIGIANI, Raphael B.Background Genetic studies have largely concentrated on the impact of somatic mutations found in coding regions, and have neglected mutations outside of these. However, 3' untranslated regions (3' UTR) mutations can also disrupt or create miRNA target sites, and trigger oncogene activation or tumor suppressor inactivation. Methods We used next-generation sequencing to widely screen for genetic alterations within predicted miRNA target sites of oncogenes associated with colorectal cancer, and evaluated the functional impact of a new somatic mutation. Target sequencing of 47 genes was performed for 29 primary colorectal tumor samples. For 71 independent samples, Sanger methodology was used to screen for E2F1 mutations in miRNA predicted target sites, and the functional impact of these mutations was evaluated by luciferase reporter assays. Results We identified germline and somatic alterations in E2F1. Of the 100 samples evaluated, 3 had germline alterations at the MIR205-5p target site, while one had a somatic mutation at MIR136-5p target site. E2F1 gene expression was similar between normal and tumor tissues bearing the germline alteration; however, expression was increased 4-fold in tumor tissue that harbored a somatic mutation compared to that in normal tissue. Luciferase reporter assays revealed both germline and somatic alterations increased E2F1 activity relative to wild-type E2F1. Conclusions We demonstrated that somatic mutation within E2F1: MIR136-5p target site impairs miRNAmediated regulation and leads to increased gene activity. We conclude that somatic mutations that disrupt miRNA target sites have the potential to impact gene regulation, highlighting an important mechanism of oncogene activation.
- Magnetic resonance imaging following neoadjuvant chemoradiation and transanal endoscopic microsurgery for rectal cancer(2017) JULIAO, G. P. Sao; ORTEGA, C. D.; VAILATI, B. B.; HABR-GAMA, A.; FERNANDEZ, L. M.; GAMA-RODRIGUES, J.; ARAUJO, S. E.; PEREZ, R. O.Aim Full-thickness local excision after neoadjuvant chemoradiotherapy (CRT) for patients with rectal cancer and incomplete clinical response has been a treatment strategy for organ preservation. Follow-up of these patients is challenging since anatomic distortion and postoperative changes may be clinically indistinguishable from tumour recurrence. MRI may have a role in detecting recurrence. The aim of this study was to describe the MRI findings during follow-up in patients having local excision following CRT with and without local recurrence. Method The data were collected retrospectively from a single centre. Fifty-three patients with rectal cancer who had full-thickness local excision after neoadjuvant CRT and near-complete response were eligible for the study. Patients with local recurrence were treated by radical salvage surgery. The main outcome was local MRI assessment findings during follow-up. Results Fifteen patients (five who developed local recurrence and 10 with no evidence of local recurrence) had MR images available for review and were included in the study. High signal intensity and thickening of the rectal wall were present in all patients with recurrent disease within the rectal wall. Overall, 80% of the patients with recurrence showed diffusion restriction. MRI mesorectal fascia status and circumferential resection margin showed agreement in all cases. A low signal intensity scar was seen in all patients without recurrent disease. Conclusion MRI shows high signal intensity and thickening of the rectal wall in recurrent disease in comparison to a low signal intensity fibrotic scar in non-recurrent disease. These findings may be useful in surveillance of these patients.