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Am Surg ; 85(9): 944-948, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31638504


The incidence of esophageal cancer in the United States seems to have significantly increased since the 1970s. In undertaking this study, we sought to describe changes in the incidence, histologic type, and presenting stage of esophageal cancer over the past four decades. With Institutional Review Board approval, the Surveillance, Epidemiology, and End Results database of the National Cancer Institute was queried. Regression analysis was used to analyze data, and significance was accepted with 95 per cent probability. Forty-two thousand seven hundred thirty-nine patients had squamous cell carcinoma or adenocarcinoma located in their upper, middle, and/or lower esophagus from 1973 through 2010, reflecting a 7.5-fold annual increase from 1973 through 2010. Squamous cell carcinoma increased annually 2.5-fold (P < 0.001) and esophageal adenocarcinoma increased annually 57-fold from 1973 through 2010 (P < 0.001), whereas the overall population in the United States increased only 43 per cent (215,092,900 to 308,745,538) in the same period. From 1973 through 2010, there was a significant increase in the incidence of esophageal cancer in the United States. This increase was much greater than the increase in the population in the United States. The incidence of adenocarcinoma increased much more than that of squamous cell carcinoma of the esophagus from 1973 through 2010.

Adenocarcinoma/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Neoplasias Esofágicas/epidemiologia , Adenocarcinoma/patologia , Idoso , Carcinoma de Células Escamosas/patologia , Comorbidade , Neoplasias Esofágicas/patologia , Feminino , Refluxo Gastroesofágico/epidemiologia , Humanos , Incidência , Masculino , Estadiamento de Neoplasias , Obesidade/epidemiologia , Fatores de Risco , Programa de SEER , Estados Unidos/epidemiologia
Am Surg ; 85(1): 115-119, 2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30760356


Robotic liver resection is being introduced with its potential to overcome limitations of conventional laparoscopy. This study was undertaken to document early experience and learning curve of robotic liver resection in our institution. All patients undergoing liver resection between 2013 and 2017 were prospectively followed. Patients were divided into three consecutive tertiles (cohort I-III). Thirty-three patients underwent robotic liver resection within the study period. Twenty-four per cent of patients underwent formal right or left hemihepatectomy, 21 per cent underwent sectionectomy, 6 per cent underwent central hepatectomy, and the remainder underwent nonanatomical liver resection. Formal hemihepatectomy and right posterosuperior segment resection were undertaken in two patients in cohort I, four patients in cohort II, and four patients in cohort III. Two cases were converted to "open" operation. Operative time was 172 (194.5 ± 65.1) minutes in cohort I, 222 (247.8 ± 109.8) minutes in cohort II, and 280 (302.5 ± 84.9) minutes in cohort III, reflecting increasing degree of technical complexity. Estimated blood loss decreased significantly throughout the cohorts, being 400 mL, 200 mL, and 100 mL in cohorts I to III, respectively. Major intraoperative complications were not seen. Three patients experienced postoperative complications, resulting in a single mortality. Length of hospital stay was three days, with two patients being readmitted within 30 days. Robotic technique for liver resection is feasible and safe. It offers good short-term clinical outcomes, including for patients who require major liver resection. As the proficiency developed, a notable improvement in technically ability to undertake more complex resections with decreasing blood loss and minimal morbidity was seen.

Hepatectomia/educação , Curva de Aprendizado , Neoplasias Hepáticas/cirurgia , Complicações Pós-Operatórias/epidemiologia , Procedimentos Cirúrgicos Robóticos/educação , Adulto , Idoso , Estudos de Coortes , Feminino , Hepatectomia/efeitos adversos , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Procedimentos Cirúrgicos Robóticos/efeitos adversos
J Immunother ; 41(7): 313-318, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29985207


Adoptive cell transfer therapy for cancer has existed for decades and is experiencing a resurgence in popularity that has been facilitated by improved methods of production, techniques for genetic modification, and host preconditioning. The trafficking of adoptively transferred lymphocytes and infiltration into the tumor microenvironment is sine qua non for successful tumor eradication; however, the paradox of extremely poor trafficking of lymphocytes into the tumor microenvironment raises the issue of how best to deliver these cells to optimize entry into tumor tissue. We examined the route of administration as a potential modifier of both trafficking and antitumor efficacy. Femoral artery cannulation and tail vein injection for the intra-arterial (IA) and IV delivery, respectively, were utilized in the B16-OVA/OT-I mouse model system. Both IV and IA infusions showed decreased tumor growth and prolonged survival. However, although significantly increased T-cell tumor infiltration was observed in IA mice, tumor growth and survival were not improved as compared with IV mice. These studies suggest that IA administration produces increased early lymphocyte trafficking, but a discernable survival benefit was not seen in the murine model examined.

Linfócitos do Interstício Tumoral/imunologia , Melanoma/terapia , Linfócitos T/imunologia , Administração Intravenosa , Transferência Adotiva , Animais , Movimento Celular , Modelos Animais de Doenças , Artéria Femoral/cirurgia , Humanos , Imunoterapia Adotiva , Injeções Intra-Arteriais , Melanoma/imunologia , Melanoma Experimental , Camundongos , Camundongos Endogâmicos C57BL , Neoplasias Experimentais , Carga Tumoral , Microambiente Tumoral
Cancer Res ; 76(22): 6620-6630, 2016 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-27680682


Isolated limb perfusion (ILP) with the chemotherapeutic agent melphalan is an effective treatment option for extremity in-transit melanoma but is toxic and technically challenging to deliver locoregionally. CBL0137 is an experimental clinical drug with broad anticancer activity in animal models, owing to its ability to bind DNA in a nongenotoxic manner and inactivate the FACT chromatin modulator essential for tumor cell viability. Here, we report that CBL0137 delivered by ILP in a murine melanoma model is as efficacious as melphalan, displaying antitumor activity at doses corresponding to only a fraction of the systemic MTD of CBL0137. The ability to bind DNA quickly combined with a favorable safety profile made it possible to substitute CBL0137 in the ILP protocol, using an intra-arterial infusion method, to safely achieve effective tumor suppression. Our findings of a preclinical proof of concept for CBL0137 and its administration via intra-arterial infusion as a superior treatment compared with melphalan ILP allows for locoregional treatment anywhere a catheter can be placed. Cancer Res; 76(22); 6620-30. ©2016 AACR.

Extremidades/patologia , Bombas de Infusão , Melanoma/tratamento farmacológico , Animais , Feminino , Humanos , Melanoma/patologia , Camundongos , Camundongos Endogâmicos C57BL , Resultado do Tratamento , Estudos de Validação como Assunto
J Neurooncol ; 126(1): 37-45, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26376657


Historically, intra-arterial (IA) drug administration for malignant brain tumors including glioblastoma multiforme (GBM) was performed as an attempt to improve drug delivery. With the advent of percutaneous neuorovascular techniques and modern microcatheters, intracranial drug delivery is readily feasible; however, the question remains whether IA administration is safe and more effective compared to other delivery modalities such as intravenous (IV) or oral administrations. Preclinical large animal models allow for comparisons between treatment routes and to test novel agents, but can be expensive and difficult to generate large numbers and rapid results. Accordingly, we developed a murine model of IA drug delivery for GBM that is reproducible with clear readouts of tumor response and neurotoxicities. Herein, we describe a novel mouse model of IA drug delivery accessing the internal carotid artery to treat ipsilateral implanted GBM tumors that is consistent and reproducible with minimal experience. The intent of establishing this unique platform is to efficiently interrogate targeted anti-tumor agents that may be designed to take advantage of a directed, regional therapy approach for brain tumors.

Antineoplásicos/administração & dosagem , Neoplasias Encefálicas/tratamento farmacológico , Glioblastoma/tratamento farmacológico , Infusões Intra-Arteriais , Animais , Encéfalo/patologia , Neoplasias Encefálicas/patologia , Linhagem Celular , Modelos Animais de Doenças , Sistemas de Liberação de Medicamentos/instrumentação , Proteína Glial Fibrilar Ácida/metabolismo , Glioblastoma/patologia , Humanos , Masculino , Camundongos , Camundongos Nus , Exame Neurológico , Ensaios Antitumorais Modelo de Xenoenxerto
Am Surg ; 81(11): 1125-33, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26672582


Duodenal adenocarcinoma is rare. We aimed to evaluate survival outcome and prognostic factors for survival in patients with duodenal adenocarcinoma in recent years, marked by advancement in chemotherapy for gastrointestinal cancers. All patients treated for duodenal adenocarcinoma at our institution between January 2000 and July 2013 were reviewed. Thirty-nine patients were identified: 27 operative patients [21(53.8%) curative and 6 (15.4%) palliative operations] and 12 nonoperative patients [primary systemic chemotherapy, 4 (10.3%), palliative radiotherapy, 1 (2.6%), and no treatment, 7 (17.9%)]. Curative resections included 13 pancreaticoduodenectomies and eight segmental resections. Median overall survival (OS) for entire cohort was 14.4 months. Median OS and one-, three-, and five-year OS were operative group (41.4 months; 79.1%, 50.6%, and 10.6%, respectively); nonoperative group (7.4 months; 25.0%, 8.3%, and 0%, respectively); curative surgery (45.4 months; 92.9%, 62.5%, and 16.7%, respectively) and palliative surgery (5.4 months; 33.3%, 16.7%, and 0%, respectively). Female gender (P = 0.04), curative resection (P = 0.03), nodal metastasis (P = 0.047) and advanced T stage (P = 0.047) were predictive of OS. Two factors were independently predictive of OS--female gender and curative resection. Overall survival still hinges on curative resection. This favors early detection. Adjuvant treatment modalities such as chemotherapy and radiation require further investigation.

Adenocarcinoma/mortalidade , Neoplasias Duodenais/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Idoso , Neoplasias Duodenais/terapia , Feminino , Humanos , Metástase Linfática , Masculino , Estadiamento de Neoplasias , Prognóstico , Fatores Sexuais , Resultado do Tratamento