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1.
HPB (Oxford) ; 24(7): 1153-1161, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-34987008

RESUMO

BACKGROUND: Standard of care for resectable pancreatic cancer is a combination of surgical resection (SR) and multiagent chemotherapy (MCT). We aim to determine whether SR or MCT is associated with superior survival for patients receiving only single-modality therapy. METHODS: Patients with stage I-IIb pancreatic head adenocarcinoma who received either MCT or SR were identified in the NCDB (2013-2015). Following a piecewise approach to estimating hazards over the course of follow-up, conditional overall survival (OS) at 30, 60, and 90 days after treatment initiation was estimated using landmark analyses. RESULTS: 3103 patients received MCT alone (60.3%) and 2043 underwent SR alone (39.7%). SR had an OS disadvantage at 30 (HR 3.99, 95% CI 3.12-5.11) and 60 days (HR 1.85, 95% CI 1.4-2.45), but an OS advantage after 90 days (HR 0.59, 95% CI 0.55-0.64). In a landmark analysis conditioned on 90 days survival post treatment initiation, median OS was improved for SR (17.0 vs. 12.2 months, p < 0.0001); SR improved 3-year OS by 21.3% (p < 0.05), despite patients being older (median 72 vs. 67 years, p < 0.0001) with higher Charlson-Deyo comorbidity scores (≥2: 11.2 vs. 8.6%, p = 0.006). CONCLUSION: For patients with resectable pancreatic cancer, SR is associated with superior long-term survival compared to MCT.


Assuntos
Adenocarcinoma , Neoplasias Pancreáticas , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/cirurgia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Humanos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas
2.
Cancer Med ; 8(10): 4678-4687, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31274231

RESUMO

BACKGROUND: E39, an HLA-A2-restricted, immunogenic peptide derived from the folate-binding protein (FBP), is overexpressed in multiple malignancies. We conducted a phase I/IIa trial of the E39 + GM-CSF vaccine with booster inoculations of either E39 or E39' (an attenuated version of E39) to prevent recurrences in disease-free endometrial and ovarian cancer patients(pts). Here, we present the final 24-month landmark analysis. PATIENTS AND METHODS: HLA-A2 + patients receiving E39 + GM-CSF were included in the vaccine group (VG), and HLA-A2- pts (or HLA-A2 + patients refusing vaccine) were followed as the control group (CG). VG group received 6 monthly inoculations as the primary vaccine series (PVS) and were randomized to receive either E39 or E39' booster inoculations. Demographic, safety, immunologic, and disease-free survival (DFS) data were collected and evaluated. RESULTS: Fifty-one patients were enrolled; 29 in the VG and 22 in the CG. Fourteen patients received <1000 µg and 15 received 1000 µg of E39. There were no clinicopathologic differences between VG and CG or between dose groups. E39 was well tolerated. At the 24 months landmark, DFS was 55.5% (VG) vs 40.0% (CG), P = 0.339. Patients receiving 1000 µg and boosted patients also showed improved DFS (P < 0.03). DFS was improved in the 1000 µg group after treatment of primary disease (90.0% vs CG:42.9%, P = 0.007), but not in recurrent patients. In low-FBP expressing patients, DFS was 100.0% (1000 µg), 50.0% (<1000 µg), and 25.0% (CG), P = 0.029. CONCLUSIONS: This phase I/IIa trial reveals that E39 + GM-CSF is safe and may be effective in preventing recurrence in high-risk ovarian and endometrial cancer when optimally dosed (1000 µg) to FBP low patients being treated for primary disease.


Assuntos
Vacinas Anticâncer/administração & dosagem , Neoplasias do Endométrio/prevenção & controle , Receptores de Folato com Âncoras de GPI/química , Recidiva Local de Neoplasia/prevenção & controle , Neoplasias Ovarianas/prevenção & controle , Vacinas de Subunidades Antigênicas/administração & dosagem , Idoso , Vacinas Anticâncer/imunologia , Relação Dose-Resposta a Droga , Neoplasias do Endométrio/imunologia , Feminino , Receptores de Folato com Âncoras de GPI/imunologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/administração & dosagem , Fator Estimulador de Colônias de Granulócitos e Macrófagos/imunologia , Antígeno HLA-A2/metabolismo , Humanos , Imunização Secundária , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/imunologia , Neoplasias Ovarianas/imunologia , Estudos Prospectivos , Análise de Sobrevida , Resultado do Tratamento , Vacinas de Subunidades Antigênicas/imunologia
3.
Clin Immunol ; 201: 48-54, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30817999

RESUMO

The development of HER2-targeted therapy has decreased recurrence rates and improved survival, transforming the natural history of HER2-positive breast cancer. However only a minority of breast cancer patients benefit as these agents are not used in patients with tumors expressing low levels of HER2. Preclinical data suggests a synergistic action of HER2-targeted vaccination with trastuzumab. We report the initial safety interim analysis of a phase II trial that enrolled patients with HER2 low-expressing (IHC 1+/2+) breast cancer who were clinically disease-free after standard therapy. Patients were randomized to receive the HER2-peptide vaccine nelipepimut-S + GM-CSF with trastuzumab (vaccine arm) or trastuzumab + GM-CSF (control arm) and were followed for recurrence. A planned analysis that occurred after enrollment of 150 patients showed no significant differences in toxicity between the two arms, including cardiac toxicity. The clinical efficacy of this combination will be reported 6 months after the final patient was enrolled.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Fator Estimulador de Colônias de Granulócitos e Macrófagos/efeitos adversos , Fatores Imunológicos/efeitos adversos , Fragmentos de Peptídeos/efeitos adversos , Trastuzumab/efeitos adversos , Neoplasias da Mama/metabolismo , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Receptor ErbB-2 , Volume Sistólico/efeitos dos fármacos , Função Ventricular Esquerda/efeitos dos fármacos
4.
Vaccine ; 36(23): 3247-3253, 2018 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-29724512

RESUMO

INTRODUCTION: Tumor vaccines use various strategies to generate immune responses, commonly targeting generic tumor-associated antigens. The tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine is produced from DC loaded with autologous tumor antigens, creating a patient-specific vaccine. Here, we describe initial phase I/IIa trial results. METHODS: This trial includes patients with any stage solid tumors, ECOG ≤1, and >4 months life-expectancy. A personalized vaccine is created using 1 mg of tumor and 120 ml blood (to isolate DC). Primary vaccination series (PVS) is four monthly inoculations. Patients are followed per standard of care (SOC). Endpoints include safety and tumor response (RECIST v1.1). RESULTS: 44 patients were enrolled and vaccinated consisting of 31 late stage patients with residual/measurable disease, and 13 disease-free patients after SOC therapies. While 4 patients progressed before completing the PVS, 12/31 (39%) demonstrated clinical benefit (2 complete responses, 4 partial responses, 6 stable disease). In the adjuvant setting, 46% of late stage patients remain disease free at a median of 22.5 months. CONCLUSIONS: The TLPLDC vaccine is scalable, generates a personalized DC vaccine, and requires little autologous tumor tissue and few DC. The vaccine is safe, with primarily grade 0-2 toxicities, and nearly 40% clinical benefit rate in varied tumors, warranting further study. TRIAL REGISTRATION: ISRCTN81339386, Registered 2/17/2016.


Assuntos
Vacinas Anticâncer/uso terapêutico , Células Dendríticas/imunologia , Imunoterapia/métodos , Neoplasias/terapia , Adulto , Vacinas Anticâncer/efeitos adversos , Vacinas Anticâncer/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/patologia , Medicina de Precisão/métodos , Resultado do Tratamento
5.
Immunotherapy ; 10(5): 373-382, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29473470

RESUMO

AIM: We developed a novel approach to efficiently deliver autologous tumor antigens to the cytoplasm of dendritic cells (DC) using yeast cell wall particles (YCWP). MATERIALS AND METHODS: Loading of YCWP, leakage of protein from loaded YCWP and cytoplasmic delivery of YCWP content was assessed using fluorescent-tagged experiments. Spectrophotometric analysis compared the epitope-specific T-cell responses following antigen presentation via YCWP versus exogenous loading. The in vivo effectiveness of tumor lysate (TL) particle loaded DC (TLPLDC) vaccine was assessed using murine melanoma models. RESULTS: In fluorescence-tagged experiments, YCWP efficiently delivered antigen to the cytoplasm of DC. TLPLDC loading was more effective than conventional exogenous loading of DC. Finally, in murine melanoma models, TLPLDC outperformed an analogous dendritoma vaccine. CONCLUSION: The TLPLDC vaccine is commercially scalable and holds the potential of producing personalized vaccines.


Assuntos
Vacinas Anticâncer/uso terapêutico , Células Dendríticas/imunologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Melanoma Experimental/patologia , Animais , Antígenos de Neoplasias/imunologia , Vacinas Anticâncer/imunologia , Modelos Animais de Doenças , Feminino , Imunoterapia/métodos , Neoplasias Pulmonares/imunologia , Melanoma Experimental/imunologia , Camundongos , Camundongos Endogâmicos C57BL
6.
J Cancer ; 8(13): 2442-2448, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28900481

RESUMO

Introduction: Pre-operative MRI is being used with increasing frequency to evaluate breast cancer patients, but the debate surrounding risks and benefits of this use continues. At our institution, we instituted a standardized protocol for pre-operative MRI. Here, we compare patients seen prior to routine use of MRI to those seen after and examine effects on surgical choices, timing and outcomes. Methods: This is a retrospective review of a prospectively collected database of all new invasive breast cancers seen from January 2007 to December 2012. The control group (CG) did not receive MRI, while the MRI group (MRG) underwent MRI according to our pretreatment protocol. Groups were compared with regards to basic demographics, initial surgical choices, need for re-excision, and surgical timing. The electronic medical records of patients in the MRG who underwent mastectomy as their initial surgery were examined closely to determine the main factors leading to their choice of surgery. Finally, correlation between findings on MRI and final surgical pathology was analyzed. Results: Of 282 patients included, 38 were in the CG and 244 in the MRG; the groups were well matched. The MRG had a significantly higher percentage of patients choosing initial mastectomy (MRG: 47.1% vs CG 21.1%, p=0.003). Patients seen in the first 2 years of the study were less likely to choose mastectomy than those enrolled in the latter years (29.2%vs 48.6%, p=0.004). The MRG had a lower chance of return to the operating room for re-excision (15.2% vs 28.9%, p=0.035). The average time from initial imaging to initial surgery was approximately the same between groups (MRG: 39.7 days vs CG 42.1 days, p=0.45) and the MRG actually had shorter time to definitive (margin-negative) surgical management (MRG: 43.5 days vs CG: 50.3 days, p=0.079). One hundred-fifteen patients in the MRG underwent mastectomy as initial surgery. Of these, 64 (55.7%) had no additional findings on MRI and chose mastectomy based on patient preference; 30 patients (26.1%) (29 unilateral, 1 bilateral) had mastectomy because of MRI findings. Of the 31 breasts removed (29 unilateral and 1 bilateral mastectomies) because of MRI findings, 26 (83.9%) had histologic findings that correlated with the MRI findings, while 5 (16.1%) did not. Conclusion: Patients receiving routine pre-treatment MRI had an increased mastectomy rate, but had a lower re-excision rate. We found no delay to initial surgical therapy and, perhaps more importantly, a slight decrease in time to margin-negative surgical therapy in the MRI group. Women choosing mastectomy after MRI did so because of personal preference over half of the time, while MRI findings influenced this choice in 26% of these women. When MRI findings did lead to mastectomy, these findings were confirmed by pathology results in the vast majority of cases.

7.
Oncotarget ; 8(9): 15912-15923, 2017 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-27852036

RESUMO

BACKGROUND: Folate binding protein(FBP) is an immunogenic protein over-expressed in endometrial(EC) and ovarian cancer(OC). We are conducting a phase I/IIa trial of E39 (GALE 301)+GM-CSF, an HLA-A2-restricted, FBP-derived peptide vaccine to prevent recurrences in disease-free EC and OC patients. This interim analysis summarizes toxicity, immunologic responses, and clinical outcomes to date. METHODS: HLA-A2+ patients were vaccinated(VG), and HLA-A2- or -A2+ patients were followed as controls(CG). Six monthly intradermal inoculations of E39+250mcg GM-CSF were administered to VG. Demographic, safety, immunologic, and recurrence rate(RR) data were collected and evaluated. RESULTS: This trial enrolled 51 patients; 29 in the VG and 22 in the CG. Fifteen patients received 1000mcg E39, and 14 received <1000mcg. There were no clinicopathologic differences between groups(all p ≥ 0.1). E39 was well-tolerated regardless of dose. DTH increased pre- to post-vaccination (5.7±1.5 mm vs 10.3±3.0 mm, p = 0.06) in the VG, and increased more in the 1000mcg group (3.8±2.0 mm vs 9.5±3.5 mm, p = 0.03). With 12 months median follow-up, the RR was 41% (VG) vs 55% (CG), p = 0.41. Among the 1000mcg patients, the RR was 13.3% vs 55% CG, p = 0.01. Estimated 2-year DFS was 85.7% in the 1000mcg group vs 33.6% in the CG (p = 0.021). CONCLUSIONS: This phase I/IIa trial reveals that E39+GM-CSF is well-tolerated and elicits a strong, dose-dependent in vivo immune response. Early efficacy results are promising in the 1000 mcg dose cohort. This study proves the safety and establishes the dose of E39 for a larger prospective, randomized, controlled trial in HLA-A2+ EC and OC patients to prevent recurrence.


Assuntos
Proteínas de Transporte/genética , Neoplasias do Endométrio/genética , Fator Estimulador de Colônias de Granulócitos e Macrófagos/genética , Imunoterapia/métodos , Neoplasias Ovarianas/genética , Idoso , Feminino , Ácido Fólico , Humanos , Pessoa de Meia-Idade
8.
Cancer Immunol Immunother ; 65(4): 383-92, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26894495

RESUMO

BACKGROUND: Stage IV melanoma has high mortality, largely unaffected by traditional therapies. Immunotherapy including cytokine therapies and checkpoint inhibitors improves outcomes, but has significant toxicities. In this phase I/IIa trial, we investigated safety and efficacy of a dendritoma vaccine, an active, specific immunotherapy, in stage IV melanoma patients. METHODS: Autologous tumor lysate and dendritic cells were fused creating dendritoma vaccines for each patient. Phase I patients were vaccinated every 3 months with IL-2 given for 5 days after initial inoculation. Phase IIa patients were vaccinated every 6 weeks with IL-2 given on days 1, 3 and 5 after initial inoculation. Toxicity and clinical outcomes were assessed. RESULTS: Twenty-five patients were enrolled and inoculated. All dendritoma and IL-2 toxicities were

Assuntos
Vacinas Anticâncer/imunologia , Células Dendríticas/imunologia , Interleucina-2/imunologia , Melanoma/imunologia , Melanoma/terapia , Idoso , Artralgia/induzido quimicamente , Vacinas Anticâncer/efeitos adversos , Vacinas Anticâncer/uso terapêutico , Calafrios/induzido quimicamente , Terapia Combinada , Células Dendríticas/metabolismo , Relação Dose-Resposta a Droga , Esquema de Medicação , Eritema/induzido quimicamente , Feminino , Humanos , Interleucina-2/efeitos adversos , Interleucina-2/uso terapêutico , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Resultado do Tratamento
9.
HPB (Oxford) ; 17(12): 1058-65, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26385577

RESUMO

BACKGROUND: Mortality after major hepatectomy remains high and is frequently related to post-hepatectomy liver failure (PHLF). Other than pre-existing liver disease and a small future liver remnant, few patient factors or early postoperative indicators identify patients at elevated risk for PHLF and mortality. METHODS: Data on demographics, comorbidities, operative procedures and postoperative laboratory trends were reviewed for patients submitted to major hepatectomy (at least three Couinaud segments) for malignancy during 1998-2013. These factors were compared among patients who died within 90 days, survivors who met the 50-50 criteria and all remaining survivors. RESULTS: A total of 1528 patients underwent major hepatectomy during the study period. Of these, 947 had metastatic colorectal cancer and underwent resection of a median of four segments. Overall, 49 patients (3.2%) died within 90 days of surgery and 48 patients (3.1%) met the 50-50 criteria for PHLF; 30 of these patients survived 90 days. Operative blood loss was higher in patients who died within 90 days compared with survivors (1.0 l versus 0.5 l; P < 0.001). Despite equivalent perioperative resuscitation and urine output, non-survivors had higher creatinine and phosphate levels than survivors on postoperative day (PoD) 1 (1.1 mg/dl versus 0.9 mg/dl and 4.6 mg/dl versus 3.7 mg/dl, respectively; P < 0.001). CONCLUSIONS: Early trends in creatinine and phosphate (between the day of surgery and PoD 1) identify patients at risk for PHLF and mortality.


Assuntos
Creatinina/sangue , Hepatectomia/mortalidade , Neoplasias Hepáticas/cirurgia , Fosfatos/sangue , Idoso , Biomarcadores/sangue , Perda Sanguínea Cirúrgica , Comorbidade , Bases de Dados Factuais , Feminino , Hepatectomia/efeitos adversos , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Regulação para Cima
10.
Ann Plast Surg ; 64(1): 52-4, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20023455

RESUMO

The Triangular Intermuscular Space is defined by borders of the teres major, teres minor, and long head of the triceps. Through this space pass the descending circumflex scapular artery, vena comitants, and lymphatics. We report 3 patients with truncal melanoma, presenting with recurrent disease in the TIS. These cases suggest that in patients with melanoma of the back, the Triangular Intermuscular Space, as the gateway to the axilla, may be an important site of metastatic disease.


Assuntos
Metástase Linfática/diagnóstico por imagem , Melanoma/secundário , Neoplasias Musculares/secundário , Músculo Esquelético/cirurgia , Dorso , Humanos , Excisão de Linfonodo , Masculino , Melanoma/diagnóstico por imagem , Melanoma/metabolismo , Pessoa de Meia-Idade , Neoplasias Musculares/diagnóstico por imagem , Neoplasias Musculares/metabolismo , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/metabolismo , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons , Biópsia de Linfonodo Sentinela , Neoplasias Cutâneas/patologia , Tomografia Computadorizada por Raios X
11.
Am J Surg ; 197(5): 595-8; discussion 598, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19306984

RESUMO

BACKGROUND: Ventral hernia is a common complication of open Roux-en-Y gastric bypass (RYGB). The aim of this study was to determine whether prophylactic mesh placement during RYGB would reduce the incidence of postoperative hernias. METHODS: Obese patients undergoing RYGB by a single surgeon had prosthetic mesh placed in a subfascial location at the conclusion of the procedure. The incidences of recurrent hernia and morbidity associated with the placement of mesh were assessed. RESULTS: Sixteen patients underwent RYGB with prophylactic mesh placement over 6 months. The average preoperative body mass index was 46.6 kg/m(2). Half of the patients were diabetics. None were smokers. During mean follow-up of 6 months, 4 patients (25%) required mesh excision, 3 for infection and 1 for a persistently symptomatic seroma. One patient was explanted incidentally in the course of reexploration for intractable nausea and vomiting. Another developed an incisional hernia despite prophylactic mesh. CONCLUSIONS: In the investigators' experience, the use of prophylactic new-generation mesh at the time of open RYGB led to an unacceptable rate of local complications. They caution against this technique in patients undergoing open RYGB.


Assuntos
Derivação Gástrica/efeitos adversos , Hérnia Ventral/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Telas Cirúrgicas , Índice de Massa Corporal , Hérnia Ventral/epidemiologia , Hérnia Ventral/etiologia , Humanos , Complicações Pós-Operatórias/epidemiologia , Recidiva
12.
Arch Surg ; 143(8): 783-7, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18711039

RESUMO

OBJECTIVES: To describe arterial and venous injuries and their management and short-term outcomes in a wartime hospital. DESIGN: Retrospective review of patients with vascular injuries. Mechanism, location, method of repair, and outcomes were analyzed with descriptive and inferential statistics. SETTING: The 31st Combat Support Hospital, Operation Iraqi Freedom. PATIENTS: A total of 153 patients with 218 vascular injuries from January 1, 2004, to December 30, 2004. MAIN OUTCOME MEASURES: Limb salvage and mortality rates. RESULTS: The overall limb salvage rate was 80%, while all-cause mortality was 6%. Most vascular injuries were sustained by blast and fragmentation mechanisms. Not surprisingly, most vascular injuries were in lower extremity vessels (57% arterial, 50% venous), with a high predominance of superficial femoral vessel injuries. Vascular injuries to the upper extremities were associated with a higher limb salvage rate (95%) than injuries to the lower extremities (71%). Variable follow-up data for 63 (41%) patients revealed that 32 underwent further procedures outside the combat theater, 12 of which were delayed amputations. Of all arterial injuries, 36% were primarily repaired, 34% were repaired with a vein interposition graft, 29% were ligated, and 2% were repaired with a prosthetic graft. A majority of venous injuries (56%) were ligated. CONCLUSIONS: There is an acceptable early patency and limb salvage rate in combat vascular repairs. A majority of penetrating vascular injuries occur in the lower extremities. Overall, penetrating vascular trauma is often a survivable injury.


Assuntos
Vasos Sanguíneos/lesões , Guerra do Iraque 2003-2011 , Procedimentos Cirúrgicos Vasculares/estatística & dados numéricos , Ferimentos Penetrantes/epidemiologia , Ferimentos Penetrantes/cirurgia , Adulto , Feminino , Hospitais Militares/estatística & dados numéricos , Humanos , Salvamento de Membro , Masculino , Estudos Retrospectivos
13.
J Trauma ; 64(2 Suppl): S28-37; discussion S37, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18376169

RESUMO

BACKGROUND: Up to 9% of casualties killed in action during the Vietnam War died from exsanguination from extremity injuries. Retrospective reviews of prehospital tourniquet use in World War II and by the Israeli Defense Forces revealed improvements in extremity hemorrhage control and very few adverse limb outcomes when tourniquet times are less than 6 hours. HYPOTHESIS: We hypothesized that prehospital tourniquet use decreased hemorrhage from extremity injuries and saved lives, and was not associated with a substantial increase in adverse limb outcomes. METHODS: This was an institutional review board-approved, retrospective review of the 31st combat support hospital for 1 year during Operation Iraqi Freedom. Inclusion criteria were any patient with a traumatic amputation, major extremity vascular injury, or documented prehospital tourniquet. RESULTS: Among 3,444 total admissions, 165 patients met inclusion criteria. Sixty-seven patients had prehospital tourniquets (TK); 98 patients had severe extremity injuries but no prehospital tourniquet (No TK). Extremity Acute Injury Scores were the same (3.5 TK vs. 3.4 No TK) in both groups. Differences (p < 0.05) were noted in the numbers of patients with arm injuries (16.2% TK vs. 30.6% No TK), injuries requiring vascular reconstruction (29.9% TK vs. 52.5% No TK), traumatic amputations (41.8% TK vs. 26.3% No TK), and in those patients with adequate bleeding control on arrival (83% TK vs. 60% No TK). Secondary amputation rates (4 (6.0%) TK vs. 9 (9.1%) No TK); and mortality (3 (4.4%) TK vs. 4 (4.1%) No TK) did not differ. Tourniquet use was not deemed responsible for subsequent amputation in severely mangled extremities. Analysis revealed that four of seven deaths were potentially preventable with functional prehospital tourniquet placement. CONCLUSIONS: Prehospital tourniquet use was associated with improved hemorrhage control, particularly in the worse injured (Injury Severity Score >15) subset of patients. Fifty-seven percent of the deaths might have been prevented by earlier tourniquet use. There were no early adverse outcomes related to tourniquet use.


Assuntos
Traumatismos do Braço/terapia , Serviços Médicos de Emergência , Hemorragia/prevenção & controle , Guerra do Iraque 2003-2011 , Traumatismos da Perna/terapia , Torniquetes , Adulto , Traumatismos do Braço/complicações , Feminino , Hemorragia/etiologia , Humanos , Traumatismos da Perna/complicações , Masculino , Estudos Retrospectivos , Resultado do Tratamento , Estados Unidos
14.
Surg Clin North Am ; 87(5): 1115-34, ix, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17936478

RESUMO

This article briefly reviews the various etiologies, presentation, and diagnosis of different types of mesenteric ischemia. Operative management techniques and the applicability of percutaneous endovascular intervention are discussed. Finally, the authors explore emerging technologies that have the potential to further improve diagnosis and treatment of this frequently lethal disease process.


Assuntos
Isquemia/etiologia , Artérias Mesentéricas/fisiopatologia , Veias Mesentéricas/fisiopatologia , Doença Aguda , Angioplastia com Balão , Doença Crônica , Colo/irrigação sanguínea , Diagnóstico por Imagem , Humanos , Isquemia/diagnóstico , Isquemia/cirurgia , Circulação Esplâncnica/fisiologia , Tromboembolia/complicações , Terapia Trombolítica
15.
Am J Surg ; 193(5): 547-50; discussion 550, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17434352

RESUMO

BACKGROUND: Telomerase is not expressed in most somatic tissues, but activity has been shown in breast carcinoma and up to 90% of solid tumors. We sought to determine whether activation of telomerase, as shown by immunohistochemical staining for human telomerase reverse transcriptase (hTERT), held prognostic significance in core breast biopsy specimens. METHODS: We identified women with atypical ductal hyperplasia (ADH) on core biopsy who either had underlying cancer or ADH. Immunohistochemistry with anti-hTERT antibody was performed on biopsy specimens, and staining was evaluated. RESULTS: Core biopsy specimens stained strongly with the hTERT antibody in 7 (70%) specimens with ADH on open biopsy and 6 (86%) with underlying cancer. The difference was not statistically significant (P = .43). CONCLUSIONS: Our study suggests telomerase may be activated early in the pathogenesis of breast cancer. The immunohistochemical evaluating expression of hTERT does not reliably identify those patients with ADH on core biopsy who are likely to have cancer.


Assuntos
Neoplasias da Mama/enzimologia , Neoplasias da Mama/patologia , Telomerase/metabolismo , Biópsia , Feminino , Humanos , Pessoa de Meia-Idade , Prognóstico
16.
Am J Surg ; 193(5): 571-3; discussion 573-4, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17434357

RESUMO

BACKGROUND: Isolated tumor cells (ITCs), often detectable only with immunohistochemical techniques, have an unknown significance in the prognosis of breast cancer. The American Joint Committee on Cancer guidelines classify such patients as N0 (immunohistochemistry +), staging them with node-negative patients. We sought to further elucidate the impact of ITCs on survival. METHODS: We conducted a retrospective review of all women at our institution with breast cancer from 1996 to 2005. Of 514 patients, 16 had isolated tumor cells detected only with immunohistochemical staining. Survival then was compared with historical survival rates for women with node-free disease. RESULTS: The 16 women with N0 (i+) disease had stage I or II disease. There was no documented recurrence among these women, with an average follow-up period of 2.5 years. CONCLUSIONS: Our data suggest that ITCs detected in lymph nodes do not adversely impact survival or disease-free survival compared with women with node-negative disease. Larger studies will be required to confirm these findings.


Assuntos
Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Adulto , Idoso , Feminino , Seguimentos , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Biópsia de Linfonodo Sentinela , Taxa de Sobrevida
17.
Curr Surg ; 63(5): 322-5, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16971202

RESUMO

OBJECTIVE: Intestinal fatty acid binding protein (I-FABP), a protein released by necrotic enterocytes, is a useful marker for the detection of ischemia from mechanical small bowel obstruction. DESIGN: Validation cohort. SETTING: Academic medical center. PARTICIPANTS: Cohort of 21 patients admitted with a clinical diagnosis of mechanical small bowel obstruction. Plasma and urine samples were collected from patients upon hospital admission and again immediately before laparotomy if surgical intervention was delayed. RESULTS: Plasma and urine I-FABP levels (pg/ml by enzyme-linked immunosorbent assay) in patients found to have small bowel necrosis at the time of laparotomy were compared with those without significant ischemia upon laparotomy and those that did not require laparotomy and, by default, did not have small bowel ischemia. A positive test was defined as 1000-pg/ml I-FABP in urine and 100-pg/ml I-FABP in plasma. Small bowel necrosis was confirmed in 3 of 21 enrolled patients. Urine I-FABP levels were positive in 3 of 3 patients with necrosis and 3 of 18 patients without necrosis (sensitivity 100%, specificity 83%, PPV 50%, NPV 100%). Plasma I-FABP levels were positive in 3 of 3 patients with necrosis and 4 of 18 patients without necrosis (sensitivity 100%, specificity 78%, PPV 43%, NPV 100%). CONCLUSIONS: I-FABP is a sensitive marker for ischemia in mechanical small bowel obstruction. Additional work should be done to validate I-FABP in a variety of clinical settings and to develop a rapid I-FABP laboratory assay.


Assuntos
Biomarcadores/sangue , Biomarcadores/urina , Proteínas de Ligação a Ácido Graxo/sangue , Proteínas de Ligação a Ácido Graxo/urina , Obstrução Intestinal/diagnóstico , Intestino Delgado/irrigação sanguínea , Isquemia/diagnóstico , Idoso , Área Sob a Curva , Feminino , Humanos , Ácido Láctico/sangue , Masculino , Pessoa de Meia-Idade , Necrose , Curva ROC , Sensibilidade e Especificidade
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