RESUMEN
We aimed to examine the psychosocial well-being in the pancreas cancer patient-caregiver dyad, and determine patient and caregiver characteristics that predict caregiver distress. This was a cross-sectional, observational study. Demographics and caregiving characteristics were gathered from patients and caregivers. Caregivers completed validated instruments investigating anxiety, depression, perceived stress and caregiver burden. Over a period of eleven months, 128 patient-caregiver dyads were enrolled. Patient and caregiver distress scores were not associated with patient clinical disease burden. Patient distress was a significant predictor of concurrent caregiver distress, anxiety, depression, and perceived burden. Younger caregivers were also associated with higher caregiver anxiety and perceived burden. Additionally, number of caregiving activities and caregiver overall health status were predictors of concurrent caregiver depression and perceived stress. Certain pancreatic cancer patient and caregiver variables may negatively impact the well-being of caregivers. Future efforts should focus on development and implementation of comprehensive caregiver support programs for those at risk for psychosocial distress.
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Cuidadores , Neoplasias Pancreáticas , Humanos , Estudios Transversales , Ansiedad , Neoplasias PancreáticasRESUMEN
BACKGROUND/AIMS: During sepsis, an unchecked pro-inflammatory response can be detrimental to the host. We investigated the potential protective effect of amitriptyline (AT). METHODS: We used two murine models of sepsis: Cecal ligation and puncture and endotoxemia following LPS challenge. Aural temperatures were taken and cytokines quantified by cytometric bead assay. Lung injury was determined histologically and by protein determination in bronchoalveolar lavage fluid. Cell accumulation in the peritoneum was analyzed by flow cytometry, as well as cytokine production and p38-phosphorylation. Neutrophil chemotaxis was evaluated using an in vitro transwell assay. RESULTS: Our findings demonstrate that AT-treated septic mice have improved survival and are protected from pulmonary edema. Treatment with AT significantly decreased serum levels of KC and monocyte chemoattractant protein-1, as well as the accumulation of neutrophils and monocytes in the peritoneum of septic mice. Peritoneal IL-10 levels in septic mice were increased upon AT treatment. Direct treatment of septic mice with IL-10 recapitulated the effects of AT. Endotoxemic mice also exhibited enhanced IL-10 production upon AT-administration and peritoneal macrophages were identified as the ATinfluenced producers of IL-10. Treatment of these cells with AT in vitro resulted in increased p38-phosphorylation and IL-10 generation, whereas ceramide and p38 inhibition had the opposite effect. CONCLUSION: Altogether, AT treatment improved survival, increased IL-10 levels, and mitigated a pro-inflammatory response during sepsis. We conclude that AT is a promising therapeutic to temper inflammation during septic shock.
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Amitriptilina/uso terapéutico , Sepsis/tratamiento farmacológico , Amitriptilina/farmacología , Animales , Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/citología , Ceramidas/farmacología , Quimiocina CCL2/análisis , Citocinas/análisis , Modelos Animales de Enfermedad , Inflamación , Interleucina-10/sangre , Lipopolisacáridos/farmacología , Pulmón/patología , Macrófagos Peritoneales/citología , Macrófagos Peritoneales/efectos de los fármacos , Macrófagos Peritoneales/metabolismo , Masculino , Ratones , Neutrófilos/citología , Neutrófilos/inmunología , Fosforilación/efectos de los fármacos , Sepsis/metabolismo , Sepsis/mortalidad , Transducción de Señal/efectos de los fármacos , Tasa de Supervivencia , Proteínas Quinasas p38 Activadas por Mitógenos/antagonistas & inhibidores , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
During sepsis, the early innate response and inflammatory cytokine cascade are associated with activation of the coagulation cascade. Acute hypercoagulability can contribute to lethal sequela of vascular thrombosis, tissue ischemia, and organ failure. We investigated if amitriptyline (AMIT), an antidepressant drug with a number of anti-inflammatory effects, could ameliorate sepsis in a murine model of sepsis-cecal ligation and puncture (CLP). We hypothesized that AMIT treatment would reduce inflammation and mitigate sepsis-induced coagulopathy. Coagulation was measured using thromboelastometry and ferric chloride-induced carotid artery thrombosis. Our findings demonstrate a dynamic early hypercoagulability, followed by delayed hypocoagulability in septic mice. However, septic mice treated with AMIT were unaffected by these coagulation changes and exhibited a coagulation profile similar to sham mice. TNFα was markedly elevated in septic mice, but decreased in AMIT-treated mice. Exogenous administration of recombinant TNFα in naive mice recapitulated the acute sepsis-induced hypercoagulability profile. After sepsis and endotoxemia, peritoneal macrophages were the predominant source of TNFα expression. AMIT treatment significantly decreased macrophage TNFα expression and blunted M1 polarization. Altogether, during polymicrobial sepsis, AMIT treatment suppressed macrophage TNFα expression and the M1 phenotype, mitigating an initial hypercoagulable state, and protecting septic mice from delayed hypocoagulability. We propose that AMIT treatment is a promising therapeutic approach in the treatment of sepsis-associated coagulopathy and prevention of acute thromboembolic events or delayed bleeding complications.
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Amitriptilina/farmacología , Trastornos de la Coagulación Sanguínea , Regulación de la Expresión Génica/efectos de los fármacos , Sepsis , Factor de Necrosis Tumoral alfa/sangre , Animales , Trastornos de la Coagulación Sanguínea/sangre , Trastornos de la Coagulación Sanguínea/patología , Trastornos de la Coagulación Sanguínea/prevención & control , Modelos Animales de Enfermedad , Macrófagos Peritoneales/metabolismo , Macrófagos Peritoneales/patología , Ratones , Sepsis/sangre , Sepsis/tratamiento farmacológico , Sepsis/patologíaRESUMEN
BACKGROUND: Due to disparities in access to care, patients with Medicaid or no health insurance are at risk of not receiving appropriate adjuvant treatment following resection of pancreatic cancer. We have previously shown inferior short-term outcomes following surgery at safety-net hospitals. Subsequently, we hypothesized that safety-net hospitals caring for these vulnerable populations utilize less adjuvant chemoradiation, resulting in inferior long-term outcomes. METHODS: The American College of Surgeons National Cancer Data Base was queried for patients diagnosed with pancreatic adenocarcinoma (n = 32,296) from 1998 to 2010. Hospitals were grouped according to safety-net burden, defined as the proportion of patients with Medicaid or no insurance. The highest quartile, representing safety-net hospitals, was compared to lower-burden hospitals with regard to patient demographics, disease characteristics, surgical management, delivery of multimodal systemic therapy, and survival. RESULTS: Patients at safety-net hospitals were less often white, had lower income, and were less educated. Safety-net hospital patients were just as likely to undergo surgical resection (OR 1.03, p = 0.73), achieving similar rates of negative surgical margins when compared to patients at medium and low burden hospitals (70% vs. 73% vs. 66%). Thirty-day mortality rates were 5.6% for high burden hospitals, 5.2% for medium burden hospitals, and 4.3% for low burden hospitals. No clinically significant differences were noted in the proportion of surgical patients receiving either chemotherapy (48% vs. 52% vs. 52%) or radiation therapy (26% vs. 30% vs. 29%) or the time between diagnosis and start of systemic therapy (58 days vs. 61 days vs. 53 days). Across safety-net burden groups, no difference was noted in stage-specific median survival (all p > 0.05) or receipt of adjuvant as opposed to neoadjuvant systemic therapy (82% vs. 85% vs. 85%). Multivariate analysis adjusting for cancer stage revealed no difference in survival for safety-net hospital patients who had surgery and survived > 30 days (HR 1.02, p = 0.63). CONCLUSION: For patients surviving the perioperative setting following pancreatic cancer surgery, safety-net hospitals achieve equivalent long-term survival outcomes potentially due to equivalent delivery of multimodal therapy at non-safety-net hospitals. Safety-net hospitals are a crucial resource that provides quality long-term cancer treatment for vulnerable populations.
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Hospitales/estadística & datos numéricos , Neoplasias Pancreáticas/terapia , Calidad de la Atención de Salud/estadística & datos numéricos , Proveedores de Redes de Seguridad/estadística & datos numéricos , Anciano , Quimioterapia Adyuvante/estadística & datos numéricos , Bases de Datos Factuales , Femenino , Hospitales/clasificación , Humanos , Masculino , Medicaid/estadística & datos numéricos , Pacientes no Asegurados/estadística & datos numéricos , Terapia Neoadyuvante/estadística & datos numéricos , Estadificación de Neoplasias , Neoplasia Residual , Pancreatectomía , Radioterapia Adyuvante/estadística & datos numéricos , Factores de Tiempo , Estados UnidosRESUMEN
BACKGROUND: Red blood cell-derived microparticles are biologically active, submicron vesicles shed by erythrocytes during storage. Recent clinical studies have linked the duration of red blood cell storage with thromboembolic events in critically ill transfusion recipients. In the present study, we hypothesized that microparticles from aged packed red blood cell units promote a hypercoagulable state in a murine model of transfusion. METHODS: Microparticles were isolated from aged, murine packed red blood cell units via serial centrifugation. Healthy male C57BL/6 mice were transfused with microparticles or an equivalent volume of vehicle, and whole blood was harvested for analysis via rotational thromboelastometry. Serum was harvested from a separate set of mice after microparticles or saline injection, and analyzed for fibrinogen levels. Red blood cell-derived microparticles were analyzed for their ability to convert prothrombin to thrombin. Finally, mice were transfused with either red blood cell microparticles or saline vehicle, and a tail bleeding time assay was performed after an equilibration period of 2, 6, 12, or 24 hours. RESULTS: Mice injected with red blood cell-derived microparticles demonstrated an accelerated clot formation time (109.3 ± 26.9 vs 141.6 ± 28.2 sec) and increased α angle (68.8 ± 5.0 degrees vs 62.8 ± 4.7 degrees) compared with control (each P < .05). Clotting time and maximum clot firmness were not significantly different between the 2 groups. Red blood cell-derived microparticles exhibited a hundredfold greater conversion of prothrombin substrate to its active thrombin form (66.60 ± 0.03 vs 0.70 ± 0.01 peak OD; P<.0001). Additionally, serum fibrinogen levels were lower in microparticles-injected mice compared with saline vehicle, suggesting thrombin-mediated conversion to insoluble fibrin (14.0 vs 16.5 µg/mL, P<.05). In the tail bleeding time model, there was a more rapid cessation of bleeding at 2 hours posttransfusion (90.6 vs 123.7 sec) and 6 hours posttransfusion (87.1 vs 141.4 sec) in microparticles-injected mice as compared with saline vehicle (each P<.05). There was no difference in tail bleeding time at 12 or 24 hours. CONCLUSION: Red blood cell-derived microparticles induce a transient hypercoagulable state through accelerated activation of clotting factors.
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Micropartículas Derivadas de Células , Trombofilia , Reacción a la Transfusión , Animales , Transfusión Sanguínea , Masculino , Ratones Endogámicos C57BL , Modelos AnimalesRESUMEN
Chronic pancreatitis and incidentally discovered pancreatic lesions present significant diagnostic and therapeutic challenges for surgeons. While both decompressive and resection procedures have been described for treatment of chronic pancreatitis, optimal management must be tailored to each patient's individual disease characteristics, parenchymal morphology, and ductal anatomy. Surgeons should strive to achieve long-lasting pain relief while preserving native pancreatic function. For patients with incidentally discovered pancreatic lesions, differentiating benign, pre-malignant, and malignant lesions is critical as earlier treatment is thought to result in improved survival. The purpose of this evidence-based manuscript is to review the presentation, workup, surgical management, and associated outcomes for patients with chronic pancreatitis or incidentally discovered solid and cystic lesions of the pancreas.
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Descompresión Quirúrgica , Hallazgos Incidentales , Páncreas/cirugía , Pancreatectomía , Quiste Pancreático/cirugía , Neoplasias Pancreáticas/cirugía , Pancreatitis Crónica/cirugía , Rol del Médico , Cirujanos , Colangiopancreatografia Retrógrada Endoscópica , Pancreatocolangiografía por Resonancia Magnética , Endosonografía , Humanos , Imagen por Resonancia Magnética , Neoplasias Pancreáticas/diagnóstico , Pancreatitis Crónica/diagnóstico , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Pseudomonas aeruginosa is a major cause of morbidity and mortality among burn patients, despite antibiotic therapy. There is a need to identify innate immune defenses that prevent P aeruginosa infection in injured adults in an effort to find therapeutic alternatives to antibiotics. Here, we tested our hypothesis that microvesicles (MVs) in bronchoalveolar (BAL) fluid have a role in the immunity of the lung in response to pathogens. STUDY DESIGN: Microvesicles were isolated from murine BAL fluid, quantified using Nanoparticle Tracking Analysis, and injected into burn-injured mice before P aeruginosa infection. Survival was assessed and BAL bacterial loads enumerated. Neutrophil number and interleukin 6 activity were determined. Lungs were harvested and sphingosine (SPH) content analyzed via immunohistochemistry. Antimicrobial effects of MVs and SPH-enriched MVs were assessed in an in vitro assay. RESULTS: Burn-injured mice have reduced BAL MV number and SPH content compared with sham. When BAL MVs from healthy mice are administered to injured mice, survival and bacterial clearance are improved robustly. We also observed that intranasal administration of MVs restores SPH levels after burn injury, MVs kill bacteria directly, and this bacterial killing is increased when the MVs are supplemented with SPH. CONCLUSIONS: Using a preclinical model, BAL MVs are reduced after scald injury and BAL MV restoration to injured mice improves survival and bacterial clearance. The antimicrobial mechanisms leading to improved survival include the quantity and SPH content of BAL MVs.
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Lavado Broncoalveolar , Quemaduras/complicaciones , Quemaduras/terapia , Micropartículas Derivadas de Células , Neumonía Bacteriana/prevención & control , Infecciones por Pseudomonas/prevención & control , Pseudomonas aeruginosa , Animales , Modelos Animales de Enfermedad , Masculino , Ratones , Neumonía Bacteriana/microbiologíaRESUMEN
BACKGROUND: Despite randomized trials addressing adjuvant therapy (AT) for pancreas cancer, the ideal time to initiate therapy remains undefined. Retrospective analyses of the ESPAC-3 trial demonstrated that time to initiation of AT did not impact overall survival (OS). Given the absence of confirmatory data outside of a clinical trial, we sought to determine if AT timing in routine clinical practice is associated with OS differences. METHODS: Perioperative data of pancreatectomies for ductal adenocarcinoma from five institutions (2005-2015) were assessed. Delay in AT was defined as initiation >12 weeks after surgery. Multivariate analysis was performed to identify predictors of mortality. RESULTS: Of 867 patients, 172 (19.8%) experienced omission of AT. Improved OS was observed in patients who received AT compared with patients who did not (24.8 vs. 19.1 months, p < 0.01). Information on time to initiation of AT was available in 488 patients, of whom 407 (83.4%) and 81 (16.6%) received chemotherapy ≤12 and >12 weeks after surgery, respectively. There were no differences in recurrence-free survival or OS (all p > 0.05) between the timely and delayed AT groups. After controlling for perioperative characteristics and tumor pathology, patients who initiated AT ≤ 12 or > 12 weeks after surgery had a 50% lower odds of mortality than patients who only underwent resection (p < 0.01). CONCLUSIONS: In a multi-institutional experience of resected pancreas cancer, delayed initiation of AT was not associated with poorer survival. Patients who do not receive AT within 12 weeks after surgery are still appropriate candidates for multimodal therapy and its associated survival benefit.
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Antimetabolitos Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma Ductal Pancreático/tratamiento farmacológico , Desoxicitidina/análogos & derivados , Neoplasias Pancreáticas/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Carcinoma Ductal Pancreático/cirugía , Quimioterapia Adyuvante , Desoxicitidina/administración & dosificación , Desoxicitidina/uso terapéutico , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pancreatectomía/efectos adversos , Neoplasias Pancreáticas/cirugía , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Albúmina Sérica/metabolismo , Tasa de Supervivencia , Factores de Tiempo , GemcitabinaRESUMEN
BACKGROUND: Although increased hospital volume has been correlated with improved outcomes in certain surgical procedures, the effect of center volume on pancreas transplantation (PT) is less understood. Our study aims to establish whether a volume-outcome effect exists for PT. METHODS: Through an established linkage between the University HealthSystem Consortium and the Scientific Registry of Transplant Recipients (SRTR) databases, we performed a retrospective cohort analysis of adult PT recipients between 2009 and 2012. Surgical volume was divided equally into low volume (LV), middle volume (MV), and high volume (HV) tertiles for each year that was studied. Hospital outcomes were measured through University HealthSystem Consortium, and long-term outcomes were measured through Scientific Registry of Transplant Recipients. Statistical analysis was performed using regression analyses and the Kaplan-Meier method. Median follow-up period was 2 y. RESULTS: Among the 2309 PT recipients included, 815 (35.3%) were performed at LV centers, 755 (32.7%) at MV centers, and 739 (32.0%) at HV centers. Compared with MV and LV centers, organs transplanted at HV centers were more frequently donation after cardiac death (5.1% versus 2.4% versus 3.3%, P = 0.01) and from older donors (2.8% [>50 y] versus 0.8% versus 0.1%, P < 0.001). In addition, HV recipients were older (31.5% [>50 y] versus 20.9% versus 19.7%, P < 0.001) and had worse functional status (39.5% dependent versus 9.7% versus 9.9%, P < 0.001). Patient and graft survival were similar across hospital volume tertiles. Center volume was not predictive of readmission rates, total length of stay, intensive care unit length of stay, or total direct cost on multivariate analysis (all P > 0.05). CONCLUSIONS: Short- and long-term outcomes after PT are not affected by hospital volume. Although LV centers confine their cases to low-risk patients, HV centers transplant a higher percentage of high-risk donor and recipient combinations with equivalent outcomes.
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Hospitales de Alto Volumen/estadística & datos numéricos , Hospitales de Bajo Volumen/estadística & datos numéricos , Trasplante de Páncreas , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Bases de Datos Factuales , Femenino , Estudios de Seguimiento , Supervivencia de Injerto , Humanos , Estimación de Kaplan-Meier , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Trasplante de Páncreas/mortalidad , Trasplante de Páncreas/estadística & datos numéricos , Readmisión del Paciente/estadística & datos numéricos , Estudios Retrospectivos , Estados Unidos , Adulto JovenRESUMEN
BACKGROUND: A disconnected distal pancreas (DDP) remnant is a morbid sequela of necrotizing pancreatitis. Definitive surgical management can be accomplished by either fistulojejunostomy (FJ) or distal pancreatectomy (DP). It is unclear which operative approach is superior with regard to short- and long-term outcomes. METHODS: Between 2002 and 2014, patients undergoing either FJ or DP for DDP were retrospectively identified at a center specializing in pancreatic diseases. Patient demographics, perioperative, and postoperative variables were evaluated. RESULTS: Forty-two patients with DDP secondary to necrotizing pancreatitis underwent either a FJ (n = 21) or DP (n = 21). Between the two cohorts, there were no significant differences in overall lengths of stay, pancreatic leak rates, or readmission rates (all p > 0.05). DP was associated with higher estimated blood loss, increased transfusion requirements, and worsening endocrine function (all p < 0.05). At a median follow-up of 18 months, four patients that underwent a FJ developed a recurrent fluid collection requiring re-intervention. Overall, FJ was successful in 80% of patients as compared to a 95% success rate for DP (p = 0.15). CONCLUSIONS: Although DP was associated with higher intraoperative blood loss, increased transfusion requirements, and worsening of preoperative diabetes, this procedure provides superior long-term resolution of a DDP when compared to FJ.
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Yeyunostomía/efectos adversos , Pancreatectomía/efectos adversos , Pancreatitis Aguda Necrotizante/cirugía , Complicaciones Posoperatorias/etiología , Adulto , Anciano , Anastomosis Quirúrgica , Pérdida de Sangre Quirúrgica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Páncreas/cirugía , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Cell-derived nanoparticles (CDNPs) containing cytosolic proteins and RNAs/DNAs can be isolated from stressed eukaryotic cells. Previously, CDNPs isolated from cultured cells exerted immunomodulatory activities in different infections. Here, we sought to elucidate the role of CDNPs using a murine model of cecal ligation and puncture (CLP). We hypothesized that CDNPs influence the immune response at the site of infection, where severe cellular stress occurs. We observed early CDNP accumulation in the peritoneum after 4âh and continued CDNP presence 24âh after CLP. To determine whether CDNPs influence the host response to sepsis, we isolated CDNPs from a murine fibroblast cell line stressed by nutrient-deprivation, and injected them into septic mice. CDNP-treated mice demonstrated decreased peritoneal interleukin 6 levels and an approximately 2-log lower bacterial load compared with control mice 24âh after CLP. Additionally, a 20% CFU reduction was observed when incubating CDNPs with Pseudomona aeroginosa, indicating that CDNPs are bactericidal. To identify CDNP-responsive cells, CFSE-labeled CDNPs were injected into mice at the time of CLP. We observed that CDNPs were preferentially ingested by F4/80 macrophages, and to a lesser degree, associated with inflammatory monocytes and neutrophils. Strikingly, CDNP-ingesting cells demonstrated elevated CD11b and MHCII expression compared with control cells. Altogether, our data indicate that CDNPs enhance the immune response at the site of infection and promote bacterial clearance, by direct bacterial killing and increasing phagocyte activation. Thus, CDNPs represent a novel, unexplored endogenous sepsis modulator with therapeutic potential.
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Micropartículas Derivadas de Células/trasplante , Nanopartículas , Sepsis/terapia , Animales , Micropartículas Derivadas de Células/metabolismo , Micropartículas Derivadas de Células/patología , Modelos Animales de Enfermedad , Masculino , Ratones , Peritoneo/metabolismo , Peritoneo/patología , Sepsis/metabolismo , Sepsis/patologíaRESUMEN
BACKGROUND AND OBJECTIVES: In patients with borderline resectable pancreas cancers, clinicians frequently consider radiographic response as the primary driver of whether patients should be offered surgical intervention following neoadjuvant therapy (NT). We sought to determine any correlation between radiographic and pathologic response rates following NT. METHODS: Between 2005 and 2015, 38 patients at a tertiary care referral center underwent NT followed by pancreaticoduodenectomy for borderline resectable pancreas cancer. Radiographic response after the completion of NT and pathologic response after surgery were graded according to RECIST and Evans' criteria, respectively. RESULTS: Preoperatively, 50% of patients underwent chemotherapy alone and 50% underwent chemotherapy and chemoradiation. Radiographically, one patient demonstrated a complete radiologic response, 68.4% (n = 26) of patients had stable disease (SD), 26.3% (n = 10) demonstrated a partial response, and one patient had progressive. Among patients without radiographic response, 77.7% (n = 21) achieved a R0 resection. Of patients with SD on imaging, 26.9% (n = 7) had Evans grade IIB or greater pathologic response. CONCLUSIONS: Our data indicate that approximately one-fourth of patients who did not have a radiologic response had a grade IIB or greater pathologic response. In the absence of metastatic progression, lack of radiographic down-staging following NT should not preclude surgery.
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Terapia Neoadyuvante , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/patología , Anciano , Albúminas/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Antígeno CA-19-9/sangre , Quimioradioterapia Adyuvante , Quimioterapia Adyuvante , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Clorhidrato de Erlotinib/administración & dosificación , Femenino , Fluorouracilo/uso terapéutico , Humanos , Leucovorina/uso terapéutico , Masculino , Persona de Mediana Edad , Compuestos Organoplatinos/uso terapéutico , Paclitaxel/administración & dosificación , Neoplasias Pancreáticas/terapia , Pancreaticoduodenectomía , Estudios Retrospectivos , Centros de Atención Terciaria , GemcitabinaAsunto(s)
Adenocarcinoma , Neoplasias Gástricas , Adenocarcinoma/diagnóstico , Adenocarcinoma/etiología , Adenocarcinoma/cirugía , Endoscopía , Gastrectomía , Humanos , Escisión del Ganglio Linfático , Estadificación de Neoplasias , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/etiología , Neoplasias Gástricas/cirugíaRESUMEN
BACKGROUND: Sequencing therapy for patients with periampullary malignancy is controversial. Clinical trial data report high rates of adjuvant therapy completion, though contemporary, real-world rates remain incomplete. We sought to identify patients who failed to receive adjuvant therapy and those at risk for early recurrence (ER) who might benefit most from neoadjuvant therapy (NT). METHODS: We retrospectively reviewed medical records of 201 patients who underwent pancreaticoduodenectomy for periampullary malignancies between 1999 and 2015; patients receiving NT were excluded. Univariate and multivariate analyses were performed to identify predictors of failure to receive adjuvant therapy and ER (within 6 months) as the primary end points. RESULTS: The median age at the time of surgery was 65.5 years (interquartile range 57-74 years). The majority of tumors were pancreatic ductal adenocarcinoma (76.6 %), and 71.6 % of patients received adjuvant therapy after resection. Univariate predictors of failure to undergo adjuvant therapy were advanced age, age-adjusted Charlson comorbidity index, operative transfusion, reoperation, length of stay, and 30- to 90-day readmissions (all p < 0.05). Advanced age, specifically among patients >70 years, persisted as a significant preoperative predictor on multivariate analysis (p < 0.01). Patients who failed to receive adjuvant therapy and/or developed ER had significantly worse overall survival rates compared to all other patients (27.8 vs. 9.7 months; p < 0.01). CONCLUSIONS: Approximately one-third of surgery-first patients undergoing pancreaticoduodenectomy at our institution did not receive adjuvant therapy and/or demonstrated ER. This substantial subset of patients may particularly benefit from NT, ensuring completion of multimodal therapy and/or avoiding futile surgical intervention.
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Ampolla Hepatopancreática , Carcinoma Ductal Pancreático/terapia , Terapia Combinada/estadística & datos numéricos , Neoplasias del Conducto Colédoco/terapia , Neoplasias Duodenales/terapia , Recurrencia Local de Neoplasia/diagnóstico por imagen , Neoplasias Pancreáticas/terapia , Factores de Edad , Anciano , Carcinoma Ductal Pancreático/secundario , Neoplasias del Conducto Colédoco/patología , Neoplasias Duodenales/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/patología , Pancreaticoduodenectomía , Estudios Retrospectivos , Tasa de Supervivencia , Factores de TiempoRESUMEN
BACKGROUND: For patients with chronic pancreatitis, duodenum-sparing head resections and pancreaticoduodenectomy are effective operations to relieve abdominal pain. For patients who develop recurrent symptoms after their index operation, the long-term management remains controversial. METHODS: Between 2002 and 2014, patients undergoing operative intervention for chronic pancreatitis were identified retrospectively. Patients requiring reoperation after their index operation were reviewed. RESULTS: A total of 121 patients with chronic pancreatitis underwent an index operation. At a median time of 33 months, 85 patients underwent no further operative intervention, while 36 patients underwent reoperation. A reoperative procedure was completed with acceptable perioperative morbidity and blood loss. After a revision operation, 25% of patients became narcotic independent. Narcotic requirements decreased from 143 morphine equivalent milligrams per day (MEQ/d) to 80 MEQ/d, and 58% of patients required less than 50 MEQ/d. Insulin requirements were not increased from preoperative levels. Multivariate analysis demonstrated only narcotic requirement and exocrine insufficiency after the index operation to be predictive for the need for a revision operation. CONCLUSION: Our data demonstrate the following: (1) A significant number of patients undergoing duodenum-sparing head resections (26%) or pancreaticoduodenectomy (29%) required reoperation for recurrent abdominal pain; and (2) a revisional operation can be effective in relieving recurrent abdominal symptoms. Patients with recurrent symptoms should be considered for additional operative intervention.
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Causas de Muerte , Pancreatectomía/métodos , Pancreaticoduodenectomía/métodos , Pancreatitis Crónica/mortalidad , Pancreatitis Crónica/cirugía , Reoperación/mortalidad , Adulto , Factores de Edad , Anciano , Toma de Decisiones Clínicas , Intervalos de Confianza , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Pancreatectomía/efectos adversos , Pancreaticoduodenectomía/efectos adversos , Pancreatitis Crónica/diagnóstico , Selección de Paciente , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/cirugía , Pronóstico , Recurrencia , Reoperación/métodos , Medición de Riesgo , Índice de Severidad de la Enfermedad , Factores Sexuales , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
Currently, over 10% of the US population is taking antidepressants. Numerous antidepressants such as amitriptyline are known to inhibit acid sphingomyelinase (Asm), an enzyme that is known to mediate leukocyte function and homeostasis. Severe burn injury can lead to an immunosuppressive state that is characterized by decreased leukocyte function and numbers as well as increased susceptibility to infection. Based upon the intersection of these facts, we hypothesized that amitriptyline-treated, scald-injured mice would have an altered immune response to injury as compared with untreated scald mice. Prior to burn, mice were pretreated with amitriptyline. Drug- or saline-treated mice were subjected full thickness dorsal scald- or sham-injury. Immune cells from spleen, thymus, and bone marrow were subsequently harvested and characterized. We first observed that amitriptyline prior to burn injury increased body mass loss and spleen contraction. Both amitriptylinetreatment and burn injury resulted in a 40% decrease of leukocyte Asm activity. Following scald injury, we demonstrate increased reduction of lymphocyte precursors in the bone marrow and thymus, as well as mature leukocytes in the spleen in mice that were treated with amitriptyline. We also demonstrate that amitriptyline treatment prior to injury reduced neutrophil accumulation following peptidoglycan stimulus in scald-injured mice. These data show that Asm alterations can play a significant role in mediating alterations to the immune system after injury. The data further suggest that those taking antidepressants may be at a higher risk for complications following burn injury.
Asunto(s)
Amitriptilina/uso terapéutico , Quemaduras/tratamiento farmacológico , Quemaduras/inmunología , Animales , Antidepresivos Tricíclicos/uso terapéutico , Western Blotting , Quemaduras/metabolismo , Quimiocinas/metabolismo , Citocinas/metabolismo , Ensayo de Inmunoadsorción Enzimática , Citometría de Flujo , Terapia de Inmunosupresión , Linfocitos/efectos de los fármacos , Linfocitos/metabolismo , Masculino , Ratones , Infiltración Neutrófila/efectos de los fármacos , Bazo/efectos de los fármacos , Bazo/metabolismoRESUMEN
Hemorrhagic shock is a leading cause of mortality within the trauma population, and blood transfusion is the standard of care. Leukoreduction filters remove donor leukocytes prior to transfusion of blood products. While the benefits of leukocyte depletion are well documented in scientific literature, these benefits do not translate directly to the clinical setting. This review summarizes current research regarding leukoreduction in the clinical arena, as well as studies performed exclusively in the trauma population.
RESUMEN
INTRODUCTION: The incidence of cancer of the esophagus/GE junction is dramatically increasing but continues to have a dismal prognosis. Esophagectomy provides the best opportunity for long-term cure but is hampered by increased rates of perioperative morbidity. We reviewed our large institutional experience to evaluate the impact of postoperative complications on the long-term survival of patients undergoing resection for curative intent. METHODS: We identified 237 patients who underwent esophagogastrectomy, with curative intent, for cancer between 1994 and 2008. Complications were graded using the previously published Clavien scale. Survival was calculated using Kaplan-Meier methodology and survival curves were compared using log-rank tests. Multivariate analysis was performed with continuous and categorical variables as predictors of survival, and examined with logistic regression and odds ratio confidence intervals. RESULTS: There were 12 (5 %) perioperative deaths. The average age of all patients was 62 years, and the majority (82 %) was male. Complication grade did not significantly affect long-term survival, although patients with grade IV (serious) complications did have a decreased survival (p = 0.15). Predictors of survival showed that the minimally invasive type esophagectomy (p = 0.0004) and pathologic stage (p = 0.0007) were determining factors. There was a significant difference in overall survival among patients who experienced pneumonia (p = 0.00016) and respiratory complications (p = 0.0004), but this was not significant on multivariate analysis. CONCLUSIONS: In this single-institution series, we found that major perioperative morbidity did not have a negative impact on long-term survival which is different than previous series. The impact of tumor characteristics at time of resection on long-term survival is of most importance.