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2.
Surg Endosc ; 34(3): 1186-1190, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31139984

RESUMEN

BACKGROUND: In patients with cholangiocarcinoma (CC), management of biliary obstruction commonly involves either up-front percutaneous transhepatic biliary drainage (PTBD) or initial endoscopic retrograde cholangiopancreatography (ERCP) with stent placement. The objective of the study was to compare the efficacy and of initial ERCP with stent placement with efficacy of initial PTBD in management of biliary obstruction in CC. METHODS: A single-center database of patients with unresectable CC treated between 2006 and 2017 was queried for patients with biliary obstruction who underwent either PTBD or ERCP. Groups were compared with respect to patient, tumor, procedure, and outcome variables. RESULTS: Of 87 patients with unresectable CC and biliary obstruction, 69 (79%) underwent initial ERCP while 18 (21%) underwent initial PTBD. Groups did not differ significantly with respect to age, gender, or tumor location. Initial procedure success did not differ between the groups (94% ERCP vs 89% PTBD, p = 0.339). Total number of procedures did not differ significantly between the two groups (ERCP median = 2 vs. PTC median = 2.5, p = 0.83). 21% of patients required ERCP after PTBD compared to 25% of patients requiring PTBD after ERCP (p = 1.00). Procedure success rate (97% ERCP vs. 93% PTBD, p = 0.27) and rates of cholangitis (22% ERCP vs. 17% PTBD, p = 0.58) were similar between the groups. Number of hospitalizations since initial intervention did not differ significantly between the two groups (ERCP median = 1 vs. PTC median = 3.5, p = 0.052). CONCLUSIONS: In patients with CC and biliary obstruction, initial ERCP with stent placement and initial PTBD both represent safe and effective methods of biliary decompression. Initial ERCP and stenting should be considered for relief of biliary obstruction in such patients in centers with advanced endoscopic capabilities.


Asunto(s)
Neoplasias de los Conductos Biliares/complicaciones , Colangiocarcinoma/complicaciones , Colangiopancreatografia Retrógrada Endoscópica/métodos , Colestasis/terapia , Drenaje/métodos , Ictericia Obstructiva/terapia , Stents , Adulto , Anciano , Anciano de 80 o más Años , Conductos Biliares Intrahepáticos/patología , Colangiopancreatografia Retrógrada Endoscópica/efectos adversos , Colangitis/etiología , Colestasis/etiología , Femenino , Humanos , Ictericia Obstructiva/etiología , Masculino , Persona de Mediana Edad
3.
Sci Rep ; 9(1): 17739, 2019 11 28.
Artículo en Inglés | MEDLINE | ID: mdl-31780711

RESUMEN

Immunotherapies have demonstrated limited efficacy in pancreatic ductal adenocarcinoma (PDAC) patients despite their success in treating other tumor types. This limitation is largely due to the relatively immunosuppressive environment surrounding the tumor. A focal ablative technique called irreversible electroporation (IRE) has been shown to modulate this environment, enhancing the efficacy of immunotherapy. One enhancing factor related to improved prognosis is a decrease in regulatory T cells (Treg). This decrease has been previously unpredictable for clinicians using IRE, who currently have limited real-time metrics for determining the activation of the patient's immune response. Here, we report that larger overall changes in output current are correlated with larger decreases in T cell populations 24 hours post-treatment. This result suggests that clinicians can make real-time decisions regarding optimal follow-up therapy based on the range of output current delivered during treatment. This capability could maximize the immunomodulating effect of IRE in synergy with follow-up immunotherapy. Additionally, these results suggest that feedback from a preliminary IRE treatment of the local tumor may help inform clinicians regarding the timing and choice of subsequent therapies, such as resection, immunotherapy, chemotherapy, or follow-up thermal or non-thermal ablation.


Asunto(s)
Carcinoma Ductal Pancreático/terapia , Electroporación/métodos , Inmunoterapia/métodos , Neoplasias Pancreáticas/terapia , Linfocitos T/inmunología , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/inmunología , Humanos , Inmunomodulación , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/inmunología , Pronóstico , Linfocitos T Reguladores/inmunología , Resultado del Tratamiento
4.
Br J Surg ; 106(13): 1837-1846, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31424576

RESUMEN

BACKGROUND: Secondary resection of initially unresectable colorectal cancer liver metastases (CRLM) can prolong survival. The added value of selective internal radiotherapy (SIRT) to downsize lesions for resection is not known. This study evaluated the change in technical resectability of CRLM with the addition of SIRT to FOLFOX-based chemotherapy. METHODS: Baseline and follow-up hepatic imaging of patients who received modified FOLFOX (mFOLFOX6: fluorouracil, leucovorin, oxaliplatin) chemotherapy with or without bevacizumab (control arm) versus mFOLFOX6 (with or without bevacizumab) plus SIRT using yttrium-90 resin microspheres (SIRT arm) in the phase III SIRFLOX trial were reviewed by three or five (of 14) expert hepatopancreatobiliary surgeons for resectability. Reviewers were blinded to one another, treatment assignment, extrahepatic disease status, and information on clinical and scanning time points. Technical resectability was defined as at least 60 per cent of reviewers (3 of 5, or 2 of 3) assessing a patient's liver metastases as surgically removable. RESULTS: Some 472 patients were evaluable (SIRT, 244; control, 228). There was no significant baseline difference in the proportion of technically resectable liver metastases between SIRT (29, 11·9 per cent) and control (25, 11·0 per cent) arms (P = 0·775). At follow-up, significantly more patients in both arms were deemed technically resectable compared with baseline: 159 of 472 (33·7 per cent) versus 54 of 472 (11·4 per cent) respectively (P = 0·001). More patients were resectable in the SIRT than in the control arm: 93 of 244 (38·1 per cent) versus 66 of 228 (28·9 per cent) respectively (P < 0·001). CONCLUSION: Adding SIRT to chemotherapy may improve the resectability of unresectable CRLM.


ANTECEDENTES: La resección secundaria de metástasis hepáticas de cáncer colorrectal (colorectal cancer liver metastases, CRLM) inicialmente irresecables puede prolongar la supervivencia. Se desconoce el valor añadido de la radioterapia interna selectiva (selective internal radiation therapy, SIRT). Este estudio evaluó el cambio en la resecabilidad técnica de las CRLM secundario a la adición de SIRT a una quimioterapia tipo FOLFOX. MÉTODOS: Las pruebas de radioimagen basales y durante el seguimiento de pacientes tratados con un régimen FOLFOX modificado (mFOLFOX6: fluorouracilo, leucovorina, oxaliplatino) ± bevacizumab (grupo control) versus mFOLFOX6 (± bevacizumab) más SIRT usando microesferas de resina de yttrium-90, en el ensayo de fase III SIRFLOX, fueron revisadas por 3-5 (de 14) cirujanos expertos hepatobiliares para determinar la resecabilidad. Los expertos efectuaron la revisión de forma ciega unos respecto a otros en relación con la asignación al tratamiento, estado de la enfermedad extra-hepática y situación clínica en el momento del estudio radiológico. La resecabilidad técnica se definió como ≥ 60% de revisores evaluando las metástasis del paciente como quirúrgicamente resecables. RESULTADOS: Fueron evaluables un total de 472 pacientes (control, n = 228; SIRT, n = 244). No hubo diferencias significativas basales en la proporción de metástasis hepáticas técnicamente resecables entre SIRT (29/244; 11,9%) y el grupo control (25/228; 11,0%: P = 0,775). Durante el seguimiento y en ambos brazos de tratamiento, un número significativamente mayor de pacientes se consideraron técnicamente resecables en comparación con la situación basal (54/472 (11,4%) basal y 159/472 (33,7%) al seguimiento). Hubo más pacientes resecables en el grupo SIRT que en el control (93/244 (38,1%) y 66/228 (28,9%); P < 0,001, respectivamente). CONCLUSIÓN: La adición de SIRT a la quimioterapia puede mejorar la resecabilidad de las CRLM irresecables.


Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias Colorrectales/patología , Hepatectomía/métodos , Neoplasias Hepáticas/terapia , Neoplasias Colorrectales/terapia , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Radioterapia Adyuvante , Estudios Retrospectivos , Factores de Tiempo , Tomografía Computarizada por Rayos X , Resultado del Tratamiento
5.
Annu Int Conf IEEE Eng Med Biol Soc ; 2019: 5518-5521, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31947104

RESUMEN

Irreversible electroporation (IRE) is a focal ablation therapy that uses high voltage, short electrical pulses to destroy tumor tissue. The success of treatment directly depends on exposure of the entire tumor to a lethal electric field magnitude. However, this exposure is difficult to predict ahead of time and it is challenging for clinicians to determine optimal treatment parameters. One method clinicians rely upon for the cessation of pulse delivery is to monitor the resistance value of the tissue, as the cells within the tissue will undergo changes during electroporation. This work presents a computational model which incorporates human pancreatic tumor conductivity, and compares predicted and measured output currents from IRE treatments of human patients. The measured currents vary widely from patient to patient, suggesting there may areas of high local conductivity in the treatment area.


Asunto(s)
Electroporación , Neoplasias Pancreáticas , Simulación por Computador , Conductividad Eléctrica , Humanos , Neoplasias Pancreáticas/terapia
6.
Annu Int Conf IEEE Eng Med Biol Soc ; 2018: 4170-4173, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-30441274

RESUMEN

Irreversible electroporation (IRE) is a cancer therapy that uses short, high-voltage electrical pulses to treat tumors. Due to its predominantly non-thermal mechanism and ability to ablate unresectable tumors, IRE has gained popularity in clinical treatments of both liver and pancreatic cancers. Existing computational models use electrical properties of animal tissue that are quantified a priori to predict the area of treatment in three dimensions. However, the changes in the electrical properties of human tissue during IRE treatment are so far unexplored. This work aims to improve models by characterizing the dynamic electrical behavior of human liver and pancreatic tissue. Fresh patient samples of each tissue type, both normal and tumor, were collected and IRE pulses were applied between two parallel metal plates at various voltages. The electrical conductivity was determined from the resistance using simple relations applicable to cylindrical samples. The results indicate that the percent change in conductivity during IRE treatments varies significantly with increasing electric field magnitudes. This percent change versus applied electric field behavior can be fit to a sigmoidal curve, as proposed in prior studies. The generic conductivity data from human patients from this work can be input to computational software using patient-specific geometry, giving clinicians a more accurate and personalized prediction of a given IRE treatment.


Asunto(s)
Electroporación , Neoplasias Pancreáticas , Animales , Conductividad Eléctrica , Humanos , Hígado , Metales
8.
Eur J Surg Oncol ; 43(4): 772-779, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28162818

RESUMEN

BACKGROUND: Improved preoperative immunonutrition has been shown to decrease the length of stay (LOS) and complications among patients undergoing elective gastrointestinal cancer surgeries. The purpose of this study was to determine whether preoperative immunonutrition supplementation decreases postoperative LOS, infectious complications, and morbidity in patients undergoing irreversible electroporation (IRE) surgery for locally advanced pancreatic cancer (LAPC). METHODS: At a regional hepatopancreatobiliary referral center within an academic medical center 71 patients receiving IRE treatment of LAPC were included in the study. The participants were divided into those receiving preoperative immunonutrition (n = 44) and those receiving no supplemental preoperative immunonutrition (n = 27). Main outcomes and measures were LOS, postoperative complications, nutritional risk index (NRI), and albumin levels. RESULTS: Patients in both groups were similar for preoperative nutrition parameters and operative therapy. Patients in the immunonutrition group experienced a statistically significant decrease in postoperative complications (p = 0.05) and LOS (10.7 vs. 17.4, p = 0.01), and less of a decrease in nutritional risk index (-12.6 vs. -16.2, p = 0.03) and albumin levels (-1.1 vs. -1.5, p < 0.01). CONCLUSION: Preoperative immunonutrition was clinically significant in decreasing postoperative complications, LOS, and improving post-surgery NRI and albumin levels in patients receiving elective IRE treatment of non-resectable pancreatic cancer. These results indicate that preoperative immunonutrition is effective and feasible in this subset of cancer patients.


Asunto(s)
Técnicas de Ablación , Adenocarcinoma/terapia , Suplementos Dietéticos , Electroporación , Nutrición Enteral/métodos , Neoplasias Pancreáticas/terapia , Complicaciones Posoperatorias/prevención & control , Cuidados Preoperatorios/métodos , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Aminoácidos de Cadena Ramificada/uso terapéutico , Arginina/uso terapéutico , Ácidos Grasos Omega-3/uso terapéutico , Femenino , Glutamina/uso terapéutico , Humanos , Inmunomodulación , Masculino , Persona de Mediana Edad , Nucleótidos/uso terapéutico , Estado Nutricional , Neoplasias Pancreáticas/patología , Proyectos Piloto , Resultado del Tratamiento , Pérdida de Peso
9.
Int J Hyperthermia ; 33(1): 43-50, 2017 02.
Artículo en Inglés | MEDLINE | ID: mdl-27405728

RESUMEN

BACKGROUND: The multimodality approach has significantly improved outcomes for hepatic malignancies. Microwave ablation is often used in isolation or succession, and seldom in combination with resection. Potential benefits and pitfalls from combined resection and ablation therapy in patients with complex and extensive bilobar hepatic disease have not been well defined. METHODS: A review of the University of Louisville prospective Hepato-Pancreatico-Biliary Patients database was performed with multi-focal bilobar disease that underwent microwave ablation with resection or microwave only included. RESULTS: One hundred and eight were treated with microwave only (MWA, n = 108) or combined resection and ablation (CRA, n = 84) and were compared with similar disease-burden patients undergoing resection only (n = 84). The groups were comparable except that the MWA group was older (p = .02) and with higher co-morbidities (diabetes, hepatitis). The resection group had larger tumours (4 vs. 3.2 and 3 cm) but the CRA group had more numerous lesions (4 vs. 3 and 2, p = .002). Short-term outcomes including morbidity (47.6% vs. 43%, p = .0715) were similar between the CRA and resection only groups. Longer operative time (164 vs. 126 min, p = .003) and need for blood transfusion (p = .001) were independent predictors of complications. Survival analyses for colorectal metastasis patients (n = 158) demonstrated better overall survival (OS) (43.9 vs. 37.6 and 30.5 months, p = .035), disease-free survival (DFS) (38 vs. 26.6 and 16.9 months, p = .028) and local recurrence-free survival (LRFS) (55.4 vs. 17 and 22.9 months, p < .001) with resection only. CONCLUSION: The use of microwave ablation in addition to surgical resection did not significantly increase the morbidities or short-term outcomes. In combination with systemic and other local forms of therapy, combined resection and ablation is a safe and effective procedure.


Asunto(s)
Técnicas de Ablación , Neoplasias Hepáticas/cirugía , Microondas/uso terapéutico , Anciano , Neoplasias Colorrectales/secundario , Neoplasias Colorrectales/cirugía , Terapia Combinada , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Resultado del Tratamiento
10.
Eur J Surg Oncol ; 43(2): 337-343, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-27727027

RESUMEN

INTRODUCTION: Irreversible electroporation (IRE) uses multiple needles and a series of electrical pulses to create pores in cell membranes and cause cell apoptosis. One of the demands of IRE is the precise needle spacing required. Two-dimensional intraoperative ultrasound (2-D iUS) is currently used to measure inter-needle distances but requires significant expertise. This study evaluates the potential of three-dimensional (3-D) image guidance for placing IRE needles and calculating needle spacing. PATIENTS AND METHODS: A prospective clinical evaluation of a 3-D needle localization system (Explorer™) was evaluated in consecutive patients from April 2012 through June 2013 for unresectable pancreatic adenocarcinoma. 3-D reconstructions of patients' anatomy were generated from preoperative CT images, which were aligned to the intraoperative space. RESULTS: Thirty consecutive patients with locally advanced pancreatic cancer were treated with IRE. The needle localization system setup added an average of 6.5 min to each procedure. The 3-D needle localization system increased surgeon confidence and ultimately reduced needle placement time. CONCLUSION: IRE treatment efficacy is highly dependent on accurate needle spacing. The needle localization system evaluated in this study aims to mitigate these issues by providing the surgeon with additional visualization and data in 3-D. The Explorer™ system provides valuable guidance information and inter-needle distance calculations.


Asunto(s)
Adenocarcinoma/terapia , Electroporación/instrumentación , Imagenología Tridimensional , Agujas , Neoplasias Pancreáticas/terapia , Adenocarcinoma/patología , Adulto , Femenino , Humanos , Periodo Intraoperatorio , Masculino , Neoplasias Pancreáticas/patología , Estudios Prospectivos , Encuestas y Cuestionarios , Tomografía Computarizada por Rayos X , Resultado del Tratamiento
11.
Br J Surg ; 103(8): 1048-54, 2016 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-27191368

RESUMEN

BACKGROUND: Patients undergoing liver resection combined with microwave ablation (MWA) for bilobar colorectal metastasis may have similar overall survival to patients who undergo two-stage hepatectomy, but with less morbidity. METHODS: This was a multi-institutional evaluation of patients who underwent MWA between 2003 and 2012. Morbidity (90-day) and mortality were compared between patients who had MWA alone and those who underwent combined resection and MWA (CRA). Mortality and overall survival after CRA were compared with published data on two-stage resections. RESULTS: Some 201 patients with bilobar colorectal liver metastasis treated with MWA from four high-volume institutions were evaluated (100 MWA alone, 101 CRA). Patients who had MWA alone were older, but the groups were otherwise well matched demographically. The tumour burden was higher in the CRA group (mean number of lesions 3·9 versus 2·2; P = 0·003). Overall (31·7 versus 15·0 per cent; P = 0·006) and high-grade (13·9 versus 5·0 per cent; P = 0·030) complication rates were higher in the CRA group. Median overall survival was slightly shorter in the CRA group (38·4 versus 42·2 months; P = 0·132) but disease-free survival was similar (10·1 versus 9·3 months; P = 0·525). The morbidity and mortality of CRA compared favourably with rates in the existing literature on two-stage resection, and survival data were similar. CONCLUSION: Single-stage hepatectomy and MWA resulted in survival similar to that following two-stage hepatectomy, with less overall morbidity.


Asunto(s)
Técnicas de Ablación , Neoplasias Colorrectales/patología , Hepatectomía/métodos , Neoplasias Hepáticas/cirugía , Microondas/uso terapéutico , Anciano , Neoplasias Colorrectales/mortalidad , Supervivencia sin Enfermedad , Femenino , Hepatectomía/efectos adversos , Humanos , Tiempo de Internación/estadística & datos numéricos , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Complicaciones Posoperatorias , Carga Tumoral
12.
J Eur Acad Dermatol Venereol ; 29(12): 2423-8, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26370585

RESUMEN

BACKGROUND: A Virtual Lesion Clinic (VLC) using teledermatoscopy was established to improve efficiency of the melanoma referral pathway. OBJECTIVES: To assess diagnostic accuracy and to compare wait-times and costs of VLC and conventional clinics. METHODS: Patients with suspected melanoma referred from primary care into a publicly funded health system attended local skin imaging centres, rather than hospital outpatient clinics. A teledermatologist assessed each lesion choosing specialist assessment/excision, General Practitioner (GP) follow-up, to re-image in 3 months, or self-monitoring/no concern. RESULTS: 613 skin lesions in 310 patients were evaluated over 12 months. Median time between receipt of referral and attendance at the VLC was 9 days compared to 26.5 days for standard outpatient assessment. Sixty-six percent (404/613) of lesions were considered benign, and 12% (73/613) were suspicious for melanoma. Of 129 lesions excised, 98 were skin cancers including 48 histologically confirmed melanomas with one spitzoid tumour of unknown malignant potential (STUMP), i.e. one melanoma per 1.59 suspected lesions biopsied and one melanoma in every 12.8 referred to the service. There were 49 non-melanoma skin cancers (NMSC). Teledermatoscopic diagnosis of melanomas was found to have a positive predictive value (PPV) of 63%. Compared to the conventional clinic, cost reductions from running the VLC for 1 year were in excess of NZ$364,000 (or NZ$1174/patient seen). CONCLUSIONS: The VLC offered an efficient, accurate and cost effective way of processing suspected melanoma referrals to the public health system.


Asunto(s)
Carcinoma Basocelular/patología , Carcinoma de Células Escamosas/patología , Dermoscopía/métodos , Melanoma/patología , Neoplasias Cutáneas/patología , Telemedicina , Triaje/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Ahorro de Costo , Femenino , Humanos , Masculino , Melanoma/cirugía , Persona de Mediana Edad , Nueva Zelanda , Valor Predictivo de las Pruebas , Derivación y Consulta , Neoplasias Cutáneas/cirugía , Telemedicina/economía , Factores de Tiempo , Triaje/economía , Listas de Espera , Adulto Joven
13.
Cancer Gene Ther ; 22(10): 481-6, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26384137

RESUMEN

Manganese superoxide dismutase (MnSOD) expression has been found to be low in human pancreatic ductal adenocarcinoma (PDAC). Previously, we have reported that microRNA-301a (miR-301a) was found being upregulated via nuclear factor-κB (NF-κB) feedback loop in human PDAC. In this study, we investigate whether the miR-301a expression level is associated with MnSOD expression in human PDAC. We established a xenograft PDAC mouse model using transfected PanC-1 cells (miR-301a antisense or scrambled control) to investigate tumor growth and the interaction between MnSOD and miR-301a. The animal study indicated that miR-301a antisense transfection could significantly decrease the growth rate of inoculated PDAC cells, and this decrease in tumor growth rate is associated with increased MnSOD expression. To evaluate the MnSOD-miR-301a correlation in human PDAC, we have analyzed a total of 60 PDAC specimens, along with 20 normal pancreatic tissue (NPT) specimens. Human specimens confirmed a significant decrease of MnSOD expression in PDAC specimens (0.88±0.38) compared with NPT control (2.45±0.76; P<0.05), whereas there was a significant increase in miR-301a levels in PDAC specimens (0.89±0.28) compared with NPT control (0.25±0.41; P<0.05). We conclude that MnSOD expression is negatively associated with miR-301a levels in PDAC tissues, and lower miR-301a levels are associated with increased MnSOD expression and inhibition of PDAC growth.


Asunto(s)
Carcinoma Ductal Pancreático/genética , MicroARNs/genética , Neoplasias Pancreáticas/genética , Superóxido Dismutasa/genética , Animales , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patología , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Técnicas de Inactivación de Genes , Humanos , Inmunohistoquímica , Hibridación in Situ , Ratones Endogámicos BALB C , Ratones Desnudos , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , Superóxido Dismutasa/metabolismo , Trasplante Heterólogo , Carga Tumoral/genética , Neoplasias Pancreáticas
14.
Cogn Neuropsychol ; 32(5): 243-65, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26216232

RESUMEN

Prior research has shown that patients with damage to the left inferior frontal gyrus (LIFG) can have difficulties in executive control as well as understanding syntactic garden-paths, that is, sentences with a temporary syntactic ambiguity that resolve towards a less preferred interpretation. The present study tested two LIFG patients on object/subject garden path and matched syntactically unambiguous sentences. Besides syntactic ambiguity, support for the preferred but ultimately inappropriate interpretation was manipulated via verb bias, using verbs that were neutral between alternative analyses and verbs that were biased towards the context-inappropriate option. The LIFG patients, a non-LIFG patient, and healthy controls were tested on a sentence interpretation task (Experiment 1) and grammaticality judgement (Experiment 2). In contrast to the non-LIFG patient and controls, the LIFG patients showed impaired thematic role assignment across garden-path as well as unambiguous sentences, which tended to be worse with biased verbs. The results argue for a role of executive control in overcoming verb bias across diverse sentence processing situations, including, but not limited to, garden-path revision.


Asunto(s)
Comprensión/fisiología , Función Ejecutiva/fisiología , Lóbulo Frontal/fisiología , Lenguaje , Anciano , Estudios de Casos y Controles , Femenino , Humanos , Pruebas del Lenguaje , Masculino , Persona de Mediana Edad , Semántica
16.
Br J Surg ; 101(9): 1113-21, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24961953

RESUMEN

BACKGROUND: Irreversible electroporation (IRE) is a new technique for tumour cell ablation that is reported to involve non-thermal-based energy using high voltage at short microsecond pulse lengths. In vivo assessment of the thermal energy generated during IRE has not been performed. Thermal injury can be predicted using a critical temperature model. The aim of this study was to assess the potential for thermal injury during IRE in an in vivo porcine model. METHODS: In vivo continuous temperature assessments of 86 different IRE procedures were performed on porcine liver, pancreas, kidney and retroperitoneal tissue. Tissue temperature was measured continuously throughout IRE by means of two thermocouples placed at set distances (0·5 cm or less, and 1 cm) from the IRE probes within the treatment field. Thermal injury was defined as a tissue temperature of 54°C lasting at least 10 s. Tissue type, pulse length, probe exposure length, number of probes and retreatment were evaluated for associations with thermal injury. In addition, IRE ablation was performed with metal clips or metal stents within the ablation field to determine their effect on thermal injury. RESULTS: An increase in tissue temperature above the animals' baseline temperature (median 36·0°C) was generated during IRE in all tissues studied, with the greatest increase found at the thermocouple placed within 0·5 cm in all instances. On univariable and multivariable analysis, ablation in kidney tissue (maximum temperature 62·8°C), ablation with a pulse length setting of 100 µs (maximum 54·7°C), probe exposure of at least 3·0 cm (maximum 52·0°C) and ablation with metal within the ablation field (maximum 65·3°C) were all associated with a significant risk of thermal injury. CONCLUSION: IRE can generate thermal energy, and even thermal injury, based on tissue type, probe exposure lengths, pulse lengths and proximity to metal. Awareness of probe placement regarding proximity to critical structures as well as probe exposure length and pulse length are necessary to ensure safety and prevent thermal injury. A probe exposure of 2·5 cm or less for liver IRE, and 1·5 cm or less for pancreas, with maximum pulse length of 90 µs will result in safe and non-thermal energy delivery with spacing of 1·5-2·3 cm between probe pairs.


Asunto(s)
Técnicas de Ablación/efectos adversos , Quemaduras/etiología , Electroporación/métodos , Riñón/lesiones , Hígado/lesiones , Páncreas/lesiones , Técnicas de Ablación/instrumentación , Animales , Electroporación/instrumentación , Diseño de Equipo , Calor/efectos adversos , Stents/efectos adversos , Instrumentos Quirúrgicos/efectos adversos , Porcinos , Factores de Tiempo
17.
World J Surg ; 38(8): 2138-44, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24663483

RESUMEN

BACKGROUND: Studies have shown that somatostatin reduces the occurrence of postoperative pancreatic fistula. However, no study to date has analyzed the cost effectiveness of this treatment. The purpose of this study was to analyze the cost effectiveness of prophylactic somatostatin use with respect to pancreatectomy. METHODS: Review of prospectively collected 2002 patient hepato-pancreatico-biliary database from January 2007 to May 2012. Patients received somatostatin prophylactically at the discretion of their surgeon. Data were analyzed using univariate analysis to determine if somatostatin had an effect on imaging costs, lab costs, "other" costs, PT/OT costs, surgery costs, room and board costs, and total hospital costs. RESULTS: A total of 179 patients underwent pancreatectomy at a single teaching institution. Median total hospital costs were 90,673.50 (59,979-743,667) for patients who developed a postoperative pancreatic fistula versus 86,563 (39,190-463,601) for those who did not (p = 0.004). Median total hospital costs were 89,369 (39,190-743,667) for patients who were administered somatostatin versus 85,291 (40,092-463,601) for patients who did not (p = 0.821). CONCLUSIONS: Pancreatic fistulas significantly increase hospital costs, and somatostatin has been shown to decrease the rate of pancreatic fistula formation. Somatostatin has no significant effect on hospital costs.


Asunto(s)
Hormonas/economía , Costos de Hospital , Pancreatectomía/efectos adversos , Fístula Pancreática/prevención & control , Somatostatina/economía , Adulto , Anciano , Anciano de 80 o más Años , Análisis Costo-Beneficio , Femenino , Hormonas/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Fístula Pancreática/economía , Fístula Pancreática/etiología , Periodo Posoperatorio , Estudios Retrospectivos , Somatostatina/uso terapéutico , Adulto Joven
18.
Animal ; 7(11): 1875-83, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23896042

RESUMEN

The effects of feeding total mixed ration (TMR) or pasture forage from a perennial sward under a management intensive grazing (MIG) regimen on grain intake and enteric methane (EM) emission were measured using chambers. Chamber measurement of EM was compared with that of SF6 employed both within chamber and when cows grazed in the field. The impacts of the diet on farm gate greenhouse gas (GHG) emission were also postulated using the results of existing life cycle assessments. Emission of EM was measured in gas collection chambers in Spring and Fall. In Spring, pasture forage fiber quality was higher than that of the silage used in the TMR (47.5% v. 56.3% NDF; 24.3% v. 37.9% ADF). Higher forage quality from MIG subsequently resulted in 25% less grain use relative to TMR (0.24 v. 0.32 kg dry matter/kg milk) for MIG compared with TMR. The Fall forage fiber quality was still better, but the higher quality of MIG pasture was not as pronounced as that in Spring. Neither yield of fat-corrected milk (FCM) which averaged 28.3 kg/day, nor EM emission which averaged 18.9 g/kg dry matter intake (DMI) were significantly affected by diet in Spring. However, in the Fall, FCM from MIG (21.3 kg/day) was significantly lower than that from TMR (23.4 kg/day). Despite the differences in FCM yield, in terms of EM emission that averaged 21.9 g/kg DMI was not significantly different between the diets. In this study, grain requirement, but not EM, was a distinguishing feature of pasture and confinement systems. Considering the increased predicted GHG emissions arising from the production and use of grain needed to boost milk yield in confinement systems, EM intensity alone is a poor predictor of the potential impact of a dairy system on climate forcing.


Asunto(s)
Contaminantes Atmosféricos/metabolismo , Bovinos/fisiología , Industria Lechera/métodos , Conducta Alimentaria , Metano/metabolismo , Alimentación Animal/análisis , Animales , Dieta/veterinaria , Gases/metabolismo , Efecto Invernadero , Nueva Escocia
19.
Minerva Chir ; 67(4): 297-308, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23022754

RESUMEN

AIM: Systemic hormonal and cytotoxic chemotherapy still remains the optimal treatment for metastatic breast cancer with the role of surgery being strictly limited for palliation of metastatic complications or locoregional relapse. However there has been a greater awareness of liver dominant and liver only metastatic disease that remains more refractory to systemic chemotherapy alone. A systematic review was undertaken to define its safety, efficacy and to identify prognostic factors associated with liver only or liver dominant metastatic breast cancer. METHODS: Electronic search of the MEDLINE, PubMed and Scopus databases (January 2000-January 2012) to identify studies reporting outcomes for liver dominant breast cancer metastasis. Two reviewers independently appraised each study using a predetermined protocol. Safety and clinical efficacy was synthesized through a narrative review with full tabulation of results of all included studies. RESULTS: A total of 61 studies were identified that reported liver dominant metastatic breast cancer and comprised a total of 8260 patients. Chemotherapy alone was reported in 27 studies involving 4958 patients with a median overall survival of 17.9 months (range 6 to 29.2). Surgical resection of liver metastasis was reported in 24 studies involving 2552 patients with a median overall survival of 38.1 months (range 10.9 to 57). Hepatic arterial therapy was reported in six studies involving 373 patients with a median overall survival of 27.9 months (range 18.5 to 47). CONCLUSION: Liver dominant or liver only metastatic breast cancer is a common presentation and clinical problem in a subset of patients. Consideration of hepatic resection, ablation or hepatic arterial therapy should be considered, but are still rarely performed. Continued review and identification of liver only-liver dominant is needed to ensure this subset of patients with metastatic breast cancer can achieve optimal improvement in quality of life time.


Asunto(s)
Neoplasias de la Mama/patología , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/terapia , Femenino , Arteria Hepática , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/cirugía , Resultado del Tratamiento
20.
Ann Surg Oncol ; 19(12): 3926-32, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-22669449

RESUMEN

BACKGROUND: The aim of this study was to review the management of cervical lymph nodes in patients with cutaneous melanoma and to analyze factors influencing prognosis. METHODS: This was a retrospective cohort study of patients who had cervical node surgery at the Sydney Melanoma Unit from 1990 to 2004. RESULTS: Of 716 patients who met the study criteria, 339 had a sentinel node biopsy (SNB) and 396 had a neck dissection. Locoregional recurrence occurred in 27.6 % of those undergoing therapeutic neck dissection and 60 % eventually developed distant metastases. Radiotherapy was given as adjuvant treatment in 110 of the patients who had a therapeutic neck dissection (41 %), but this was not associated with improved regional control (p = .322). Multivariate analysis showed that nodal positivity (p < .001) and primary tumor ulceration (p = < .027) were the most important predictors of locoregional recurrence and that primary tumor Breslow thickness (p = .009) and node positivity (p = .046) were the most important factors predicting survival. SNB-positive patients who underwent immediate completion lymphadenectomy had a 5-year survival advantage over those who had a therapeutic neck dissection for macroscopic disease (54 % vs 47 %, p = .028). CONCLUSIONS: Nodal status was the most important factor predicting disease-free and overall survival in patients with melanoma of the head and neck. Adjuvant radiotherapy was not associated with better locoregional control in the non-randomized cohorts of patients in this study.


Asunto(s)
Escisión del Ganglio Linfático , Ganglios Linfáticos/cirugía , Melanoma/cirugía , Recurrencia Local de Neoplasia/patología , Neoplasias Cutáneas/cirugía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Manejo de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Ganglios Linfáticos/patología , Metástasis Linfática , Masculino , Melanoma/mortalidad , Melanoma/patología , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/cirugía , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Neoplasias Cutáneas/mortalidad , Neoplasias Cutáneas/secundario , Tasa de Supervivencia , Adulto Joven
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