Hospital Provincial Neuquen

Neuquén, Argentina

Hospital Provincial Neuquen

Neuquén, Argentina
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Avila S.A.,Hospital Provincial Neuquen | Penaloza J.,Hospital Provincial Neuquen | Gonzalez F.,Hospital Provincial Neuquen | Abdo I.,Hospital Provincial Neuquen | And 3 more authors.
Acta Gastroenterologica Latinoamericana | Year: 2014

Gastrointestinal stromal tumors (GIST) are the most common mesenchymatous neoplasms of the human digestive tract. They locate preferentially in stomach, duodenum or small bowel. Usually sporadic, familial cases unrelated to neurofibromatosis may be due to germline mutations in KIT or PDGFRA. We describe the first Argentine family with GIST in which we found, diffuse cutaneous melanosis, lentiginosis, and dysphagia. Dysphagia was not observed in the four families previously described with the same mutation. Histopathology resulted consistent with GIST, and tumor immunohistochemistry was likewise positive for DOG-1, CD117 (KIT) and CD34. The search for germline mutations identified the KIT c.1697T>C (p.559V>A) substitution in exon 11. Treatment with imatinib is furnishing positive results.


Leone J.,Hospital Provincial Neuquen | Leone J.,National University of the South | Perez J.E.,National University of the South | Dominguez M.E.,National University of the South | And 11 more authors.
International Journal of Biological Markers | Year: 2016

Background: Several mechanisms are involved in the development of resistance to therapy in locally advanced cervical squamous cell carcinoma (LACSCC). Studies have shown that CD44 and Lewis Y antigen (LeY) form a complex that is associated with chemoresistance, tumor invasion and metastasis. We assessed the role of CD44 and LeY in the outcome of LACSCC patients treated with different chemotherapy regimens. Methods: 126 LACSCC patients at FIGO stages IIB-IVA were selected from the GOCS database: 74 patients included in 3 different prospective phase II trials in the neoadjuvant setting (vinorelbine, docetaxel, ifosfamide-vinorelbine-cisplatin) and 52 patients treated with standard radiochemotherapy based on cisplatin (RCBC). Clinical data at baseline, disease-free survival (DFS) and overall survival (OS) were recorded. Univariate and multivariate Cox models were employed. Results: Median age was 45.6 years (range: 24.9-80.5). Sixty-three and 47 tumors were CD44+ and LeY+, respectively. Tumors with expansive growth showed higher grade (p = 0.0024), mitotic index (p = 0.0505), tumor necrosis (p = 0.0191), LeY+ (p = 0.0034) and CD44+/LeY+ coexpression (p = 0.0334). CD44+ cells were present in 91.3% of patients with local recurrence (p = 0.0317). Advanced stage was associated with LeY+ tumors. Patients treated with RCBC had worse DFS and OS when their tumors expressed LeY (p = 0.0083 and p = 0.0137, respectively). Pre-treatment hemoglobin level, FIGO stage and tumor response remained the most significant prognostic factors in Cox regression. Conclusions: In our cohort of LACSCC patients, the coexpression of CD44 and LeY was not associated with worse outcome. However, in the subgroup of patients receiving RCBC, LeY expression was correlated with shorter DFS and OS. © 2016 Wichtig Publishing.


PubMed | Hospital Provincial Neuquen and National University of the South
Type: Journal Article | Journal: The International journal of biological markers | Year: 2016

Several mechanisms are involved in the development of resistance to therapy in locally advanced cervical squamous cell carcinoma (LACSCC). Studies have shown that CD44 and Lewis Y antigen (LeY) form a complex that is associated with chemoresistance, tumor invasion and metastasis. We assessed the role of CD44 and LeY in the outcome of LACSCC patients treated with different chemotherapy regimens.126 LACSCC patients at FIGO stages IIB-IVA were selected from the GOCS database: 74 patients included in 3 different prospective phase II trials in the neoadjuvant setting (vinorelbine, docetaxel, ifosfamide-vinorelbine-cisplatin) and 52 patients treated with standard radiochemotherapy based on cisplatin (RCBC). Clinical data at baseline, disease-free survival (DFS) and overall survival (OS) were recorded. Univariate and multivariate Cox models were employed.Median age was 45.6 years (range: 24.9-80.5). Sixty-three and 47 tumors were CD44+ and LeY+, respectively. Tumors with expansive growth showed higher grade (p = 0.0024), mitotic index (p = 0.0505), tumor necrosis (p = 0.0191), LeY+ (p = 0.0034) and CD44+/LeY+ coexpression (p = 0.0334). CD44+ cells were present in 91.3% of patients with local recurrence (p = 0.0317). Advanced stage was associated with LeY+ tumors. Patients treated with RCBC had worse DFS and OS when their tumors expressed LeY (p = 0.0083 and p = 0.0137, respectively). Pre-treatment hemoglobin level, FIGO stage and tumor response remained the most significant prognostic factors in Cox regression.In our cohort of LACSCC patients, the coexpression of CD44 and LeY was not associated with worse outcome. However, in the subgroup of patients receiving RCBC, LeY expression was correlated with shorter DFS and OS.


Zwenger A.O.,Hospital Provincial Neuquen | Zwenger A.O.,Oncologic Cooperative Southern Group GOCS | Grosman G.,Hospital Provincial Neuquen | Iturbe J.,Hospital Provincial Neuquen | And 10 more authors.
International Journal of Biological Markers | Year: 2015

Background: Several studies in solid tumors have shown that expression of excision repair cross-complementation group 1 (ERCC1) and class III β-tubulin (TUBB3) can predict response to chemoradiotherapy and might be prognostic factors. We assessed the role of ERCC1 and TUBB3 expressions as predictive and prognostic factors in locally advanced cervical squamous cell carcinoma (LACSCC) patients treated with different neoadjuvant regimens. Methods: ERCC1 and TUBB3 were detected in 88 patients with LACSCC by immunohistochemical analysis. Sixtytwo patients were included in 3 different prospective trials and grouped as follows: vinorelbine or docetaxel (group A, n = 44) and ifosfamide-vinorelbine-cisplatin (group B, n = 18). Both groups were compared with standard cisplatin chemoradiotherapy (group C, n = 26). Clinical data at baseline, disease-free survival (DFS) and overall survival (OS) were also collected. Univariate and multivariate Cox models were used to analyze the risk factors. Results: Thirty-five patients (39.8%) and 18 (20.5%) had high ERCC1 and TUBB3 expression, respectively. Both proteins were overexpressed in tumors with unfavorable characteristics. High ERCC1 was associated with advanced FIGO stage (p = 0.034) and progressive disease (49% vs. 28%). Poor DFS (p = 0.021) and OS (p = 0.005) were observed in group C patients with high ERCC1 expression. Multivariate analysis showed that ERCC1 expression, FIGO stage and pretreatment hemoglobin level were significant prognostic factors (p = 0.002, p = 0.008 and p = 0.005, respectively). Conclusions: ERCC1 expression could be a predictive and prognostic factor in LACSCC patients who receive cisplatin monotherapy. Conversely, TUBB3 had no impact on survival in patients treated with antimicrotubule agents. © 2015 Wichtig Publishing.


Leone J.P.,University of Pittsburgh | Leone J.,Grupo Oncologico Cooperativo Del sur GOCS | Leone J.,Hospital Provincial Neuquen | Vallejo C.T.,Grupo Oncologico Cooperativo Del sur GOCS | And 13 more authors.
Breast Cancer Research and Treatment | Year: 2014

Neoadjuvant chemotherapy (NAC) allows direct evaluation of the tumor's sensitivity to therapy, eradication of micrometastatic disease and the possibility of performing breast conserving surgery. The aim of this study was to describe long-term results of NAC in stage III breast cancer patients. We evaluated 126 patients that participated in a phase II randomized trial of neoadjuvant FAC compared with CMF. Chemotherapy was administered for three cycles prior to definitive surgery and radiotherapy, and then for six cycles as adjuvant. Median follow-up was 4.5 years (range 0.2-16.4). Objective response rate (OR) was similar in both groups (61 % for FAC, 66 % for CMF, P = NS). There were no differences in median disease free survival (DFS) or overall survival (OS) (5.1 vs 3.3 years and 6.7 vs 6.3 years for FAC and CMF, respectively). After 16 years of follow-up, 53 patients are still alive. Multivariate analysis showed that the number of pathologically involved lymph nodes (pLN) was the only factor associated with both, DFS and OS (P = 0.0003 and P = 0.0005, respectively). Both regimens were well tolerated, CMF had higher incidence of grade 3-4 leukopenia, thrombocytopenia, and stomatitis, whereas alopecia was more common in FAC. To the best of our knowledge, this is the first study to report long-term outcomes of FAC and CMF in the neoadjuvant setting. Within the sensitivity of our study, both regimens showed similar OR, long-term toxicity, DFS, and OS rate at 16 years. After 5 years, the hazard of death seems to decline. The prolonged follow-up of this study provides a unique opportunity to evaluate factors that predict long-term outcomes. After 16 years of follow-up, the number of pLN remains the most powerful predictor of survival. © 2013 Springer Science+Business Media New York.


Palma S.,National University of La Plata | Zwenger A.O.,Hospital Provincial Neuquen | Croce M.V.,National University of La Plata | Abba M.C.,National University of La Plata | Lacunza E.,National University of La Plata
Clinical Colorectal Cancer | Year: 2016

During the past years, molecular studies through high-throughput technologies have led to the confirmation of critical alterations in colorectal cancer (CRC) and the discovery of some new ones, including mutations, DNA methylations, and structural chromosomal changes. These genomic alterations might act in concert to dysregulate specific signaling pathways that normally exert their functions on critical cell phenotypes, including the regulation of cellular metabolism, proliferation, differentiation, and survival. Targeted therapy against key components of altered signaling pathways has allowed an improvement in CRC treatment. However, a significant percentage of patients with CRC and metastatic CRC will not benefit from these targeted therapies and will be restricted to systemic chemotherapy. Mechanisms of resistance have been associated with specific gene alterations. To fully understand the nature and significance of the genetic and epigenetic defects in CRC that might favor a tumor evading a given therapy, much work remains. Therefore, a dynamic link between basic molecular research and preclinical studies, which ultimately constitute the prelude to standardized therapies, is very important to provide better and more effective treatments against CRC. We present an updated revision of the main molecular features of CRC and their associated therapies currently under study in clinical trials. Moreover, we performed an unsupervised classification of CRC clinical trials with the aim of obtaining an overview of the future perspectives of preclinical studies. © 2016 Elsevier Inc. All rights reserved.

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