RESUMEN
BACKGROUND: The purpose of this study was to investigate the incidence of symptomatic and asymptomatic deep venous thrombosis in patients undergoing harvest of a free flap from the lower extremity who were receiving standard chemoprophylaxis while hospitalized. METHODS: A retrospective review of 65 consecutive patients undergoing surgery between 2011 and 2013 was performed to determine the incidence of symptomatic deep venous thrombosis. These patients were screened for deep venous thrombosis based on development of symptoms. Prospective evaluation of a similar consecutive population of 37 patients between 2014 and 2015 was then performed to determine the incidence of asymptomatic deep venous thrombosis. These patients underwent routine duplex ultrasonography of both legs at postoperative weeks 1 and 4. RESULTS: Symptomatic deep venous thrombosis occurred in 2.9 percent of all patients. In the prospective cohort, 8.1 percent of the patients were found to have an acute deep venous thrombosis by postoperative week 1. At postoperative week 4, 16.7 percent of the patients developed a new, acute deep venous thrombosis. The estimated costs of screening and treating deep venous thrombosis in the retrospective group and the prospective group were $222 and $2259, respectively. The cost of routine chemoprophylaxis without duplex screening for an additional 14 days after discharge was $125 per patient. CONCLUSIONS: The rate of asymptomatic deep venous thrombosis may be much higher than previously appreciated in this population of very high-risk patients, especially during the 2 weeks after discharge. Extending the duration of chemoprophylaxis to 4 weeks after surgery may be warranted. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.
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Quimioprevención/métodos , Colgajos Tisulares Libres , Heparina/uso terapéutico , Extremidad Inferior/irrigación sanguínea , Complicaciones Posoperatorias/prevención & control , Recolección de Tejidos y Órganos/efectos adversos , Trombosis de la Vena/prevención & control , Adulto , Anciano , Anticoagulantes/uso terapéutico , Colorado/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Estudios Prospectivos , Muslo/cirugía , Factores de Tiempo , Ultrasonografía Doppler Dúplex , Trombosis de la Vena/diagnóstico , Trombosis de la Vena/epidemiología , Trombosis de la Vena/etiologíaRESUMEN
SUMMARY: This study introduces the options for supercharging and augmenting venous drainage of an anterolateral thigh free flap. Clinical indications and options for additional microvascular anastomoses are reviewed in 5 consecutive patients. The indications were simultaneous mucosal and cutaneous defects, divergent mucosal defects, and extensively wide and long cutaneous defects. Three additional vascular pedicles were anastomosed: the transverse branch of the lateral circumflex (n = 3), a perforator coming directly off the superficial femoral artery (n = 1), and a posterior perforator from the profundus femoral artery (n = 1). The anastomosis of a separate pedicle from the superior, medial, and/or posterior-lateral thigh may be a useful technique when confronted with an extensive defect that may not reliably be reconstructed with a routine anterolateral thigh flap based on a single perforator.
RESUMEN
OBJECTIVES/HYPOTHESIS: The primary objective was to determine the incidence of pathologically positive lymph nodes in clinically N0 larynx cancer patients undergoing salvage surgery following nonsurgical primary therapy. Secondary aims included assessment of the impact of laryngeal subsite and neck dissection on disease status and survival. STUDY DESIGN: Retrospective chart review. METHODS: Sixty-eight patients with recurrent laryngeal cancer and no evidence of neck disease who underwent salvage laryngectomy and neck dissection after undergoing failed primary radiotherapy or chemoradiation were examined. Main outcome measures included: standard demographics, primary, clinical, radiologic, and pathologic recurrent TNM stage, laryngeal subsite, nodal neck level, surgical intervention, margin status, disease status, survival, and imaging results. RESULTS: Fifty-three men and 15 women, aged 33 to 88 years (mean=62.7 years) with recurrent laryngeal cancer were included. Overall, 28.3% of patients had pathologic nodal disease, with supraglottic cancer showing the highest rate (60%, P=.02). Survival was not associated with laryngectomy type (P=.35). However, on multivariate analysis, laryngeal subsite was significantly predictive of survival with transglottic recurrences demonstrating decreased mean survival (20.7 months, P=.02), and supraglottic recurrences demonstrating prolonged mean survival (37.1 months, P=.03). Metabolic imaging (negative predictive value=0.86) proved more reliable than anatomic imaging (negative predictive value=0.71). CONCLUSIONS: The incidence of pathologically positive lymph nodes in clinically negative patients with recurrent laryngeal carcinoma following nonsurgical therapy warrants standard selective neck dissection. Subsite of recurrence, specifically supraglottis and transglottis, correlates with pathologic neck node positivity and survival. Metabolic imaging proved more reliable than anatomic imaging in negative predictability for nodal disease. LEVEL OF EVIDENCE: 4.
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Neoplasias Laríngeas/patología , Neoplasias Laríngeas/cirugía , Laringectomía , Disección del Cuello , Recurrencia Local de Neoplasia/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Neoplasias Laríngeas/terapia , Metástasis Linfática , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Terapia Recuperativa , Insuficiencia del TratamientoRESUMEN
Targeted therapy development in head and neck squamous cell carcinoma (HNSCC) is challenging given the rarity of activating mutations. Additionally, HNSCC incidence is increasing related to human papillomavirus (HPV). We sought to develop an in vivo model derived from patients reflecting the evolving HNSCC epidemiologic landscape, and use it to identify new therapies. Primary and relapsed tumors from HNSCC patients, both HPV+ and HPV-, were implanted on mice, giving rise to 25 strains. Resulting xenografts were characterized by detecting key mutations, measuring protein expression by IHC and gene expression/pathway analysis by mRNA-sequencing. Drug efficacy studies were run with representative xenografts using the approved drug cetuximab as well as the new PI3K inhibitor PX-866. Tumors maintained their original morphology, genetic profiles and drug susceptibilities through serial passaging. The genetic makeup of these tumors was consistent with known frequencies of TP53, PI3KCA, NOTCH1 and NOTCH2 mutations. Because the EGFR inhibitor cetuximab is a standard HNSCC therapy, we tested its efficacy and observed a wide spectrum of efficacy. Cetuximab-resistant strains had higher PI3K/Akt pathway gene expression and protein activation than cetuximab-sensitive strains. The PI3K inhibitor PX-866 had anti-tumor efficacy in HNSCC models with PIK3CA alterations. Finally, PI3K inhibition was effective in two cases with NOTCH1 inactivating mutations. In summary, we have developed an HNSCC model covering its clinical spectrum whose major genetic alterations and susceptibility to anticancer agents represent contemporary HNSCC. This model enables to prospectively test therapeutic-oriented hypotheses leading to personalized medicine.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Carcinoma de Células Escamosas/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Alphapapillomavirus/patogenicidad , Animales , Western Blotting , Carcinoma de Células Escamosas/virología , Cetuximab , Biología Computacional , Receptores ErbB/genética , Receptores ErbB/metabolismo , Gonanos/farmacología , Neoplasias de Cabeza y Cuello/virología , Humanos , Inmunohistoquímica , Ratones , Fosfatidilinositol 3-Quinasas/metabolismo , Inhibidores de las Quinasa Fosfoinosítidos-3 , Receptor Notch1/genética , Receptor Notch1/metabolismo , Receptor Notch2/genética , Receptor Notch2/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Extracellular heat-shock proteins (eHsp) such as those belonging to the 70-kDa family of Hsp (eg, Hsp72) have been hypothesized to act as a "danger signal" to immune cells, promote immune responses, and improve host defense. The current study tested this hypothesis. Adult male F344 rats were exposed to an acute laboratory stressor (100, 5-second, 1.6-mA inescapable tail shocks) and challenged with Escherichia coli. The number of colony-forming units (CFU) of bacteria at the site of injection, the levels of eHsp72, the immune response to eHsp72 and E. coli-derived lipopolysaccharide (LPS), and the amount of time required to recover from in vivo bacterial challenge were measured. CFUs were reduced 2, 4, and 6 hours after injection of E. coli in rats exposed to stress. Rats exposed to stress had elevated eHsp72 that was elevated rapidly (25 minutes) and remained elevated in the circulation and at the inflammatory site (2 hours after stressor termination). Both stressor exposure and eHsp72 administration in the absence of stress resulted in a facilitated pattern of recovery after bacterial inflammation induced by subcutaneous E. coli injection. Rats exposed to acute restraint (100 minutes) did not demonstrate elevated circulating eHsp72 or a facilitated pattern of recovery after bacterial challenge. In vitro stimulation of rat splenocytes and macrophages with eHsp72 elevated nitric oxide (NO), tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-1beta, and IL-6, and this effect was specific to eHsp72 because it was not diminished by polymyxin B and was reduced by earlier heat-denature treatment. Stimulation of cells with eHsp72 combined with LPS resulted in a greater NO and cytokine response than that observed after stimulation with eHsp72 or LPS alone. In vivo, at the inflammatory site, the bacterial-induced NO response was potentiated by stress, and NO inhibition (L-NIO) reduced the stress-induced facilitation but had no effect on the control kinetics of bacterial inflammation recovery. Thus, these results lend support to the hypothesis that intense stressor exposure increases eHsp72, which acts as a danger signal to potentiate the NO response to bacterial challenge and facilitate recovery from bacterial inflammation.
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Infecciones por Escherichia coli/inmunología , Proteínas de Choque Térmico/biosíntesis , Estrés Fisiológico/inmunología , Animales , Citocinas/biosíntesis , Infecciones por Escherichia coli/complicaciones , Proteínas del Choque Térmico HSP72 , Proteínas de Choque Térmico/sangre , Inflamación/microbiología , Masculino , Óxido Nítrico/biosíntesis , Ratas , Ratas Endogámicas F344 , Estrés Fisiológico/complicaciones , Factores de Tiempo , Distribución TisularRESUMEN
The mechanism(s) for how physically active organisms are resistant to many damaging effects of acute stressor exposure is unknown. Cellular induction of heat-shock proteins (e.g., HSP72) is one successful strategy used by the cell to survive the damaging effects of stress. It is possible, therefore, that the stress-buffering effect of physical activity may be due to an improved HSP72 response to stress. Thus the purpose of the current study was to determine whether prior voluntary freewheel running facilitates the stress-induced induction of HSP72 in central (brain), peripheral, and immune tissues. Adult male Fischer 344 rats were housed with either a mobile running wheel (Active) or a locked, immobile wheel [sedentary (Sed)] for 8 wk before stressor exposure. Rats were exposed to either inescapable tail-shock stress (IS; 100 1.6-mA tail shocks, 5-s duration, 60-s intertrial interval), exhaustive exercise stress (EXS; treadmill running to exhaustion), or no stress (controls). Blood, brain, and peripheral tissues were collected 2 h after stressor termination. The kinetics of HSP72 induction after IS was determined in cultured mesenteric lymph node cells. Activation of the stress response was verified by measuring serum corticosterone (RIA). Tissue and cellular HSP72 content were measured using HSP72 ELISA in cell lysates. Both Active and Sed rats had elevated levels of serum corticosterone after stress. In contrast, Active but not Sed rats exposed to IS and/or EXS had elevated HSP72 in dorsal vagal complex, frontal cortex, hippocampus, pituitary, adrenal, liver, spleen, mesenteric lymph nodes, and heart. In addition, Active rats exposed to IS demonstrated a faster induction of lymphocyte HSP72 compared with Sed rats. Thus Active rats responded to stress with both greater and faster HSP72 responses compared with Sed rats. These results indicate that previous physical activity potentiates HSP72 expression after a wide range of stressors. Facilitated induction of HSP72 may contribute to the increased stress resistance previously reported in physically active organisms.
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Encéfalo/metabolismo , Proteínas de Choque Térmico/metabolismo , Sistema Inmunológico/metabolismo , Actividad Motora/fisiología , Condicionamiento Físico Animal/fisiología , Estrés Fisiológico/fisiopatología , Regulación hacia Arriba , Glándulas Suprarrenales/metabolismo , Animales , Peso Corporal , Células Cultivadas , Corticosterona/sangre , Proteínas del Choque Térmico HSP72 , Proteínas de Choque Térmico/análisis , Proteínas de Choque Térmico/sangre , Hígado/metabolismo , Ganglios Linfáticos/metabolismo , Linfocitos/metabolismo , Masculino , Miocardio/metabolismo , Ratas , Ratas Endogámicas F344 , Bazo/metabolismo , Estrés Fisiológico/sangre , Factores de TiempoRESUMEN
Exposure to acute stress modulates immune function. Most research regarding stress and immunity has described the deleterious effects of stress. Recent studies, however, indicate that acute stress enhances many features of innate immunity. For example, exposure to acute stress reduced the time required to resolve inflammation produced by subcutaneous injection of streptomycin-killed, benign bacteria. It is unclear if this change in inflammation would be advantageous to the organism if challenged with living, infectious bacteria. Thus, the current experiments examined the effect of acute stressor exposure on inflammation development and resolution after a naturalistic, live bacterial challenge. In addition, nitric oxide (NO), an important bactericidal mediator, was measured at the inflammatory site. Rats (F344) were exposed to acute stress (100, 5-s, 1.6 mA tailshocks) and subcutaneously injected with live Escherichia coli ( approximately 2.5 x 10(9) colony forming units [CFU]). Stressed rats attained their peak inflammatory size quicker, resolved their inflammation 10-14 days faster, experienced less bacterial-induced weight loss and released 300% greater NO at the inflammatory site than nonstressed controls. Thus, acute stress improved recovery from bacterially induced inflammation possibly due to local elevations in NO.
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Inflamación/patología , Óxido Nítrico/fisiología , Estrés Psicológico/patología , Enfermedad Aguda , Animales , Ensayo de Unidades Formadoras de Colonias , Electrochoque , Escherichia coli/metabolismo , Infecciones por Escherichia coli/patología , Masculino , Ratas , Ratas Endogámicas F344RESUMEN
Most previous stress-immune research focused on the immunosuppressive effects of stress on acquired immunity. More recently, it has become clear that acute stressor exposure can potentiate innate, as well as suppress acquired, immunity. For example, acute stress improves recovery from bacterial inflammation, a classic in vivo measure of innate immunity. The previous work was done in sedentary organisms. Physical activity status can modulate the impact of stress on immune function. The following studies tested the hypothesis that the effect of stress on inflammation after subcutaneous challenge with bacteria (Escherichia coli) is facilitated by physical activity. The results were that sedentary, stressed rats resolved their inflammation 1-2 days faster and have increased circulating neutrophils compared with their nonstressed, sedentary counterparts. In contrast, physically active, stressed rats resolve their inflammation 3-4 days faster and have increased circulating and inflammatory site neutrophils compared with their nonstressed counterparts. Importantly, the beneficial impact of stress on inflammation recovery and neutrophil migration was greater in the physically active, than sedentary, stressed rats. Thus physical activity status facilitates the positive effect of acute stress on innate immunity.