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1.
Eur Radiol ; 33(1): 535-544, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35864349

RESUMO

OBJECTIVE: Liver lesion characterization is limited by the lack of an established gold standard for precise correlation of radiologic characteristics with their histologic features. The objective of this study was to demonstrate the feasibility of using an ex vivo MRI-compatible sectioning device for radiologic-pathologic co-localization of lesions in resected liver specimens. METHODS: In this prospective feasibility study, adults undergoing curative partial hepatectomy from February 2018 to January 2019 were enrolled. Gadoxetic acid was administered intraoperatively prior to hepatic vascular inflow ligation. Liver specimens were stabilized in an MRI-compatible acrylic lesion localization device (27 × 14 × 14 cm3) featuring slicing channels and a silicone gel 3D matrix. High-resolution 3D T1-weighted fast spoiled gradient echo and 3D T2-weighted fast-spin-echo images were acquired using a single channel quadrature head coil. Radiologic lesion coordinates guided pathologic sectioning. A final histopathologic diagnosis was prepared for all lesions. The proportion of successfully co-localized lesions was determined. RESULTS: A total of 57 lesions were identified radiologically and sectioned in liver specimens from 10 participants with liver metastases (n = 8), primary biliary mucinous cystic neoplasm (n = 1), and hepatic adenomatosis (n = 1). Of these, 38 lesions (67%) were < 1 cm. Overall, 52/57 (91%) of radiologically identified lesions were identified pathologically using the device. Of these, 5 lesions (10%) were not initially identified on gross examination but were confirmed histologically using MRI-guided localization. One lesion was identified grossly but not on MRI. CONCLUSIONS: We successfully demonstrated the feasibility of a clinical method for image-guided co-localization and histological characterization of liver lesions using an ex vivo MRI-compatible sectioning device. KEY POINTS: • The ex vivo MRI-compatible sectioning device provides a reliable method for radiologic-pathologic correlation of small (< 1 cm) liver lesions in human liver specimens. • The sectioning method can be feasibly implemented within a clinical practice setting and used in future efforts to study liver lesion characterization. • Intraoperative administration of gadoxetic acid results in enhancement in ex vivo MRI images of liver specimens hours later with excellent image quality.


Assuntos
Cistos , Neoplasias Hepáticas , Adulto , Humanos , Meios de Contraste/farmacologia , Estudos Prospectivos , Gadolínio DTPA , Fígado/diagnóstico por imagem , Fígado/cirurgia , Fígado/patologia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Imageamento por Ressonância Magnética/métodos , Cistos/patologia
2.
HPB (Oxford) ; 23(7): 1105-1112, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33317934

RESUMO

BACKGROUND: Unidimensional size is commonly used to risk stratify pancreatic cysts (PCs) despite inconsistent performance. The current study aimed to determine if unidimensional size, demonstrated by maximum axial diameter (MAD), is an appropriate surrogate measurement for volume and surface area. METHODS: Patients with cross-sectional imaging of PCs from 2012 to 2013 were identified. Cyst MAD, volume, and surface area were measured using quantitative imaging software. Non-pseudocystic PCs >1 cm were selected for inclusion to assess MAD correlation with volume and surface area. Cysts imaged twice >1 year apart were selected to evaluate volumetric growth rate. RESULTS: In total, 195 cysts were included. Overall, MAD was strongly correlated with volume (r = 0.83) and surface area (r = 0.93). However, cysts 1-2 cm and 2-3 cm were weakly correlated with volume and surface area: r = 0.78, 0.57 and 0.82, 0.61, respectively. Cyst volumes and surface areas varied widely within unidimensional size groups with 51% and 40% of volumes and surface areas overlapping unidimensional size groups, respectively. Estimated changes in volume poorly predicted measured changes in volume with 42% of cysts having >100% absolute percent difference. CONCLUSIONS: Pancreatic cyst volume and surface area may be useful adjunct measurements to risk stratify patients and surveil cyst changes and deserves further study.


Assuntos
Cisto Pancreático , Humanos , Cisto Pancreático/diagnóstico por imagem
3.
Ann Surg Oncol ; 27(10): 3915-3923, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32328982

RESUMO

BACKGROUND: Pancreatic neuroendocrine tumors (PNETs) are often indolent; however, identifying patients at risk for rapidly progressing variants is critical, particularly for those with small tumors who may be candidates for expectant management. Specific growth rate (SGR) has been predictive of survival in other malignancies but has not been examined in PNETs. METHODS: A retrospective cohort study of adult patients who underwent PNET resection from 2000 to 2016 was performed utilizing the multi-institutional United States Neuroendocrine Study Group database. Patients with ≥ 2 preoperative cross-sectional imaging studies at least 30 days apart were included in our analysis (N = 288). Patients were grouped as "high SGR" or "low SGR." Demographic and clinical factors were compared between the groups. Kaplan-Meier and log-rank analysis were used for survival analysis. Cox proportional hazard analysis was used to assess the impact of various clinical factors on overall survival (OS). RESULTS: High SGR was associated with higher T stage at resection, shorter doubling time, and elevated HbA1c (all P ≤ 0.01). Patients with high SGR had significantly decreased 5-year OS (63 vs 80%, P = 0.01) and disease-specific survival (72 vs 91%, P = 0.03) compared to those with low SGR. In patients with small (≤ 2 cm) tumors (N = 106), high SGR predicted lower 5-year OS (79 vs 96%, P = 0.01). On multivariate analysis, high SGR was independently associated with worse OS (hazard ratio 2.67, 95% confidence interval 1.05-6.84, P = 0.04). CONCLUSION: High SGR is associated with worse survival in PNET patients. Evaluating PNET SGR may enhance clinical decision-making, particularly when weighing expectant management versus surgery in patients with small tumors.


Assuntos
Tumores Neuroendócrinos , Neoplasias Pancreáticas , Humanos , Estadiamento de Neoplasias , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/cirurgia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Estudos Retrospectivos , Taxa de Sobrevida , Estados Unidos/epidemiologia
4.
Ann Surg Oncol ; 27(9): 3147-3153, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32219725

RESUMO

BACKGROUND: Insurance status predicts access to medical care in the USA. Previous studies have shown uninsured patients with some malignancies have worse outcomes than insured patients. The impact of insurance status on patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) is unclear. PATIENTS AND METHODS: A retrospective cohort study of adult patients with resected GEP-NETs was performed using the US Neuroendocrine Tumor Study Group (USNETSG) database (2000-2016). Demographic and clinical factors were compared by insurance status. Patients ≥ 65 years were excluded, as these patients are almost universally covered by Medicare. Kaplan-Meier and log-rank analyses were used for survival analysis. Logistic regression was used to assess factors associated with overall survival (OS). RESULTS: The USNETSG database included 2022 patients. Of those, 1425 were aged 18-64 years at index operation and were included in our analysis. Uninsured patients were more likely to have an emergent operation (7.9% versus 2.5%, p = 0.01) and less likely to receive postoperative somatostatin analog therapy (1.6% versus 9.9%, p = 0.03). OS at 1, 5, and 10 years was significantly higher for insured patients (96.3%, 88.2%, and 73.8%, respectively) than uninsured patients (87.7%, 71.9%, and 44.0%, respectively) (p < 0.01). On Cox multivariate regression analysis controlling for T/M stage, tumor grade, ASA class, and income level, being uninsured was independently associated with worse OS [hazard ratio (HR) 2.69, 95% confidence interval (CI) 1.32-5.48, p = 0.006]. CONCLUSIONS: Insurance status is an independent predictor of survival in patients with GEP-NETs. Our study highlights the importance of access to medical care, disparities related to insurance status, and the need to mitigate these disparities.


Assuntos
Cobertura do Seguro , Tumores Neuroendócrinos , Adolescente , Adulto , Acessibilidade aos Serviços de Saúde/economia , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Humanos , Cobertura do Seguro/estatística & dados numéricos , Pessoas sem Cobertura de Seguro de Saúde/estatística & dados numéricos , Pessoa de Meia-Idade , Tumores Neuroendócrinos/economia , Tumores Neuroendócrinos/mortalidade , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/cirurgia , Estudos Retrospectivos , Estados Unidos/epidemiologia , Adulto Jovem
5.
J Surg Oncol ; 121(7): 1067-1073, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32153032

RESUMO

BACKGROUND AND OBJECTIVES: Lack of high-level evidence supporting adjuvant therapy for patients with resected gastroenteropancreatic neuroendocrine tumors (GEP NETs) warrants an evaluation of its non-standard of care use. METHODS: Patients with primary GEP NETs who underwent curative-intent resection at eight institutions between 2000 and 2016 were identified; 91 patients received adjuvant therapy. Recurrence-free survival (RFS) and overall survival (OS) were compared between adjuvant cytotoxic chemotherapy and somatostatin analog cohorts. RESULTS: In resected patients, 33 received cytotoxic chemotherapy, and 58 received somatostatin analogs. Five-year RFS/OS was 49% and 83%, respectively. Cytotoxic chemotherapy RFS/OS was 36% and 61%, respectively, lower than the no therapy cohort (P < .01). RFS with somatostatin analog therapy (compared to none) was lower (P < .01), as was OS (P = .01). On multivariable analysis, adjuvant cytotoxic therapy was negatively associated with RFS but not OS controlling for patient/tumor-specific characteristics (RFS P < .01). CONCLUSIONS: Our data, reflecting the largest reported experience to date, demonstrate that adjuvant therapy for resected GEP NETs is negatively associated with RFS and confers no OS benefit. Selection bias enriching our treatment cohort for individuals with unmeasured high-risk characteristics likely explains some of these results; future studies should focus on patient subsets who may benefit from adjuvant therapy.


Assuntos
Neoplasias Intestinais/tratamento farmacológico , Neoplasias Intestinais/cirurgia , Tumores Neuroendócrinos/tratamento farmacológico , Tumores Neuroendócrinos/cirurgia , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/cirurgia , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Intestinais/mortalidade , Neoplasias Intestinais/patologia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Tumores Neuroendócrinos/mortalidade , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Somatostatina/análogos & derivados , Somatostatina/uso terapêutico , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia
6.
HPB (Oxford) ; 22(7): 1042-1050, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-31806388

RESUMO

BACKGROUND: Packed red blood cell (PRBC) transfusion has been associated with worse survival in multiple malignancies but its impact on pancreatic neuroendocrine tumors (PNETs) is unknown. The aim of this study was to determine the impact of PRBC transfusion on survival following PNET resection. METHODS: A retrospective cohort study of PNET patients was performed using the US Neuroendocrine Tumor Study Group database. Demographic and clinical factors were compared. Kaplan-Meier and log-rank analyses were performed. Factors associated with transfusion, overall (OS), recurrence-free (RFS) and progression-free survival (PFS) were assessed by logistic regression. RESULTS: Of 1129 patients with surgically resected PNETs, 156 (13.8%) received perioperative PRBC transfusion. Transfused patients had higher ASA Class, lower preoperative hemoglobin, larger tumors, more nodal involvement, and increased major complications (all p < 0.010). Transfused patients had worse median OS (116 vs 150 months, p < 0.001), worse RFS (83 vs 128 months, p < 0.01) in curatively resected (n = 1047), and worse PFS (11 vs 24 months, p = 0.110) in non-curatively resected (n = 82) patients. On multivariable analysis, transfusion was associated with worse OS (HR 1.80, p = 0.011) when controlling for TNM stage, tumor grade, final resection status, and pre-operative anemia. CONCLUSION: PRBC transfusion is associated with worse survival for patients undergoing PNET resection.


Assuntos
Tumores Neuroendócrinos , Neoplasias Pancreáticas , Transfusão de Sangue , Intervalo Livre de Doença , Humanos , Recidiva Local de Neoplasia , Tumores Neuroendócrinos/cirurgia , Neoplasias Pancreáticas/cirurgia , Estudos Retrospectivos , Taxa de Sobrevida
7.
J Surg Res ; 238: 240-247, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30776743

RESUMO

BACKGROUND: Although the surgical case series is a useful study design for surgical disciplines, elements of its presentation have not been standardized with a widely accepted reporting guideline. Hence, case series may not include all components necessary for surgeons to best interpret their results. We aimed to determine core elements of case series through qualitative analysis of discussions after presentations at national meetings. METHODS: Case series with accompanying discussions in three high-impact journals from 2010 to 2015 were analyzed with conventional content analysis. All interrogative sentences were selected for analysis and were classified by a redundant iterative process into descriptive categories and subcategories. RESULTS: Two hundred twenty-one case series were identified, 56 of which included discussion transcripts. Four hundred seventy six unique interrogatives were classified into 4 categories and 13 subcategories. The main categories identified were "Application of Results to Patient Care," "Clarification of Study Methodology," "Facilitation of Author Insight," and "Request for Additional Study-Specific Data." The most frequent subcategories of inquiry pertained to the changes to current standard of care, clarification of study variables, and subgroup data and outcomes. CONCLUSIONS: We determined major themes of inquiry that reflected core elements surgeons use to evaluate case series for relevance and applicability to their own practice. Discussants frequently questioned how the study's results changed the author's standard of care. Specifically encouraging surgical case series authors to comment on changes they made to their practice as a result of their findings would allow the surgical audience to quickly assess potential clinical applicability.


Assuntos
Congressos como Assunto , Cirurgia Geral/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Projetos de Pesquisa , Humanos , Pesquisa Qualitativa , Cirurgiões
8.
Clin Infect Dis ; 65(2): 268-275, 2017 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-28369287

RESUMO

BACKGROUND: Congenital Trypanosoma cruzi transmission is now estimated to account for 22% of new infections, representing a significant public health problem across Latin America and internationally. Treatment during infancy is highly efficacious and well tolerated, but current assays for early detection fail to detect >50% of infected neonates, and 9-month follow-up is low. METHODS: Women who presented for delivery at 2 urban hospitals in Santa Cruz Department, Bolivia, were screened by rapid test. Specimens from infants of infected women were tested by microscopy (micromethod), quantitative PCR (qPCR), and immunoglobulin (Ig)M trypomastigote excreted-secreted antigen (TESA)-blots at birth and 1 month and by IgG serology at 6 and 9 months. RESULTS: Among 487 infants of 476 seropositive women, congenital T. cruzi infection was detected in 38 infants of 35 mothers (7.8%). In cord blood, qPCR, TESA-blot, and micromethod sensitivities/specificities were 68.6%/99.1%, 58.3%/99.1%, and 16.7%/100%, respectively. When birth and 1-month results were combined, cumulative sensitivities reached 84.2%, 73.7%, and 34.2%, respectively. Low birthweight and/or respiratory distress were reported in 11 (29%) infected infants. Infants with clinical signs had higher parasite loads and were significantly more likely to be detected by micromethod. CONCLUSIONS: The proportion of T. cruzi-infected infants with clinical signs has fallen since the 1990s, but symptomatic congenital Chagas disease still represents a significant, albeit challenging to detect, public health problem. Molecular methods could facilitate earlier diagnosis and circumvent loss to follow-up but remain logistically and economically prohibitive for routine screening in resource-limited settings.


Assuntos
Doença de Chagas/congênito , Doença de Chagas/diagnóstico , Diagnóstico Precoce , Doenças Endêmicas , Trypanosoma cruzi/imunologia , Adulto , Anticorpos Antiprotozoários/sangue , Antígenos de Protozoários/sangue , Antígenos de Protozoários/imunologia , Doença de Chagas/imunologia , Doença de Chagas/transmissão , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Lactente , Recém-Nascido de Baixo Peso , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas , Masculino , Mães , Carga Parasitária , Reação em Cadeia da Polimerase em Tempo Real , Trypanosoma cruzi/genética
9.
Clin Infect Dis ; 61(6): 918-26, 2015 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-26063720

RESUMO

BACKGROUND: We studied women and their infants to evaluate risk factors for congenital transmission and cardiomyopathy in Trypanosoma cruzi-infected women. METHODS: Women provided data and blood for serology and quantitative polymerase chain reaction (PCR). Infants of infected women had blood tested at 0 and 1 month by microscopy, PCR and immunoblot, and serology at 6 and 9 months. Women underwent electrocardiography (ECG). RESULTS: Of 1696 women, 456 (26.9%) were infected; 31 (6.8%) transmitted T. cruzi to their infants. Women who transmitted had higher parasite loads than those who did not (median, 62.0 [interquartile range {IQR}, 25.8-204.8] vs 0.05 [IQR, 0-29.6]; P < .0001). Transmission was higher in twin than in singleton births (27.3% vs 6.4%; P = .04). Women who had not lived in infested houses transmitted more frequently (9.7% vs 4.6%; P = .04), were more likely to have positive results by PCR (65.5% vs 33.9%; P < .001), and had higher parasite loads than those who had lived in infested houses (median, 25.8 [IQR, 0-64.1] vs 0 [IQR, 0-12.3]; P < .001). Of 302 infected women, 28 (9.3%) had ECG abnormalities consistent with Chagas cardiomyopathy; risk was higher for older women (odds ratio [OR], 1.06 [95% confidence interval {CI}, 1.01-1.12] per year) and those with vector exposure (OR, 3.7 [95% CI, 1.4-10.2]). We observed a strong dose-response relationship between ECG abnormalities and reported years of living in an infested house. CONCLUSIONS: We hypothesize that repeated vector-borne infection sustains antigen exposure and the consequent inflammatory response at a higher chronic level, increasing cardiac morbidity, but possibly enabling exposed women to control parasitemia in the face of pregnancy-induced Th2 polarization.


Assuntos
Doença de Chagas/epidemiologia , Doença de Chagas/transmissão , Transmissão Vertical de Doenças Infecciosas , Insetos Vetores/crescimento & desenvolvimento , Parasitemia/epidemiologia , Trypanosoma cruzi/isolamento & purificação , Adolescente , Adulto , Animais , Anticorpos Antiprotozoários/sangue , Bolívia , Doença de Chagas/congênito , Doença de Chagas/imunologia , DNA de Protozoário/sangue , Eletrocardiografia , Feminino , Humanos , Lactente , Recém-Nascido , Pessoa de Meia-Idade , Parasitemia/imunologia , Reação em Cadeia da Polimerase , Gravidez , Medição de Risco , Testes Sorológicos , Células Th2/imunologia , Trypanosoma cruzi/imunologia , Adulto Jovem
10.
J Surg Oncol ; 111(4): 389-95, 2015 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-25488568

RESUMO

BACKGROUND AND OBJECTIVES: Myeloid neoplasms are classified into five major categories. These patients may develop splenomegaly and require splenectomy to alleviate mechanical symptoms, to ameliorate transfusion-dependent cytopenias, or to enhance stem cell transplantation. The objective of this study was to determine which clinical variables significantly impacted morbidity, mortality, and survival in patients with myeloid neoplasms undergoing splenectomy, and to determine if operative outcomes have improved over time. METHODS: The records of all patients with myeloid neoplasms undergoing splenectomy from 1993 to 2010 were retrospectively reviewed. RESULTS: Eighty-nine patients (n = 89) underwent splenectomy for myeloid neoplasms. Over half of patients who had symptoms preoperatively had resolution of their symptoms post-splenectomy. The morbidity rate was 38%, with the most common complications being bleeding (14%) or infection (20%). Thirty-day mortality rate was 18% and median survival after splenectomy was 278 days. Decreased survival was associated with a diagnosis of myelodysplastic syndrome/myeloproliferative neoplasm, anemia, abnormal white blood cell count, and hypoalbuminemia. Patients who underwent stem cell transplantation did not show an increased risk for morbidity or mortality. CONCLUSIONS: Patients with myeloid neoplasms have a poor prognosis after splenectomy and the decision to operate is a difficult one, associated with high morbidity and mortality.


Assuntos
Leucemia Mieloide/mortalidade , Síndromes Mielodisplásicas/mortalidade , Transtornos Mieloproliferativos/mortalidade , Complicações Pós-Operatórias , Esplenectomia , Idoso , Anemia/mortalidade , Feminino , Humanos , Hipoalbuminemia/mortalidade , Leucemia Mieloide/terapia , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/terapia , Transtornos Mieloproliferativos/terapia , Reoperação , Estudos Retrospectivos
11.
Surg Clin North Am ; 103(5): 993-1010, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37709401

RESUMO

Parastomal hernias (PHs) are common and contribute to significant patient morbidity. Despite 45 years of evolution, mesh-based PH repairs continue to be challenging to perform and remain associated with high rates of postoperative complications and recurrences. In this article, the authors summarize the critical factors to consider when evaluating a patient for PH repair. The authors provide an overview of the current techniques for repair, including both open and minimally invasive approaches. The authors detail the mesh-based repair options and review the evidence for choice of mesh to use for repair.


Assuntos
Herniorrafia , Complicações Pós-Operatórias , Humanos , Complicações Pós-Operatórias/etiologia
12.
Abdom Radiol (NY) ; 47(1): 221-231, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34636933

RESUMO

PURPOSE: Current diagnostic and treatment modalities for pancreatic cysts (PCs) are invasive and are associated with patient morbidity. The purpose of this study is to develop and evaluate machine learning algorithms to delineate mucinous from non-mucinous PCs using non-invasive CT-based radiomics. METHODS: A retrospective, single-institution analysis of patients with non-pseudocystic PCs, contrast-enhanced computed tomography scans within 1 year of resection, and available surgical pathology were included. A quantitative imaging software platform was used to extract radiomics. An extreme gradient boosting (XGBoost) machine learning algorithm was used to create mucinous classifiers using texture features only, or radiomic/radiologic and clinical combined models. Classifiers were compared using performance scoring metrics. Shapely additive explanation (SHAP) analyses were conducted to identify variables most important in model construction. RESULTS: Overall, 99 patients and 103 PCs were included in the analyses. Eighty (78%) patients had mucinous PCs on surgical pathology. Using multiple fivefold cross validations, the texture features only and combined XGBoost mucinous classifiers demonstrated an area under the curve of 0.72 ± 0.14 and 0.73 ± 0.14, respectively. By SHAP analysis, root mean square, mean attenuation, and kurtosis were the most predictive features in the texture features only model. Root mean square, cyst location, and mean attenuation were the most predictive features in the combined model. CONCLUSION: Machine learning principles can be applied to PC texture features to create a mucinous phenotype classifier. Model performance did not improve with the combined model. However, specific radiomic, radiologic, and clinical features most predictive in our models can be identified using SHAP analysis.


Assuntos
Aprendizado de Máquina , Cisto Pancreático , Algoritmos , Humanos , Cisto Pancreático/diagnóstico por imagem , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos
13.
J Biol Chem ; 285(49): 38415-27, 2010 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-20889977

RESUMO

Opioid receptor signaling via EGF receptor (EGFR) transactivation and ERK/MAPK phosphorylation initiates diverse cellular responses that are cell type-dependent. In astrocytes, multiple µ opioid receptor-mediated mechanisms of ERK activation exist that are temporally distinctive and feature different outcomes. Upon discovering that chronic opiate treatment of rats down-regulates thrombospondin 1 (TSP1) expression in the nucleus accumbens and cortex, we investigated the mechanism of action of this modulation in astrocytes. TSP1 is synthesized in astrocytes and is released into the extracellular matrix where it is known to play a role in synapse formation and neurite outgrowth. Acute morphine (hours) reduced TSP1 levels in astrocytes. Chronic (days) opioids repressed TSP1 gene expression and reduced its protein levels by µ opioid receptor and ERK-dependent mechanisms in astrocytes. Morphine also depleted TSP1 levels stimulated by TGFß1 and abolished ERK activation induced by this factor. Chronic morphine treatment of astrocyte-neuron co-cultures reduced neurite outgrowth and synapse formation. Therefore, inhibitory actions of morphine were detected after both acute and chronic treatments. An acute mechanism of morphine signaling to ERK that entails depletion of TSP1 levels was suggested by inhibition of morphine activation of ERK by a function-blocking TSP1 antibody. This raises the novel possibility that acute morphine uses TSP1 as a source of EGF-like ligands to activate EGFR. Chronic morphine inhibition of TSP1 is reminiscent of the negative effect of µ opioids on EGFR-induced astrocyte proliferation via a phospho-ERK feedback inhibition mechanism. Both of these variations of classical EGFR transactivation may enable opiates to diminish neurite outgrowth and synapse formation.


Assuntos
Astrócitos/metabolismo , Morfina/farmacologia , Entorpecentes/farmacologia , Neuritos/metabolismo , Sinapses/metabolismo , Trombospondina 1/biossíntese , Animais , Linhagem Celular Transformada , Proliferação de Células , Córtex Cerebral/metabolismo , Ativação Enzimática/efeitos dos fármacos , Receptores ErbB , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Núcleo Accumbens/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores Opioides mu/agonistas , Receptores Opioides mu/metabolismo , Fatores de Tempo , Fator de Crescimento Transformador beta1/metabolismo
14.
J Neurochem ; 112(6): 1431-41, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19895666

RESUMO

As embryonic stem cell-derived neural progenitors (NPs) have the potential to be used in cell replacement therapy, an understanding of the signaling mechanisms that regulate their terminal differentiation is imperative. In previous studies, we discovered the presence of functional mu opioid receptors (MOR) and kappa opioid receptors (KOR) in mouse embryonic stem cells and NPs. Here, MOR and KOR immunoreactivity was detected in NP-derived oligodendrocytes during three stages of their maturation in vitro. Moreover, we examined the modulation of retinoic acid-induced NP differentiation to astrocytes and neurons by mu, [D-ala(2), mephe(4), gly-ol(5)] enkephalin, or kappa, U69, 593, opioids. Both opioid agonists inhibited NP-derived neurogenesis and astrogenesis via their corresponding receptors as determined by immunocytochemistry. By administering selective inhibitors, we found that opioid inhibition of NP-derived astrogenesis was driven via extracellular-signal regulated kinase (ERK), while the p38 mitogen-activated protein kinase pathway was implicated in opioid attenuation of neurogenesis. In addition, mu and kappa opioids stimulated oligodendrogenesis from NP-derived NG2(+) oligodendrocyte progenitors via both ERK and p38 signaling pathways. Accordingly, both opioids induced ERK phosphorylation in NG2(+) cells. These results indicate that small molecules, such as MOR and KOR agonists may play a modulatory role in NP terminal differentiation.


Assuntos
Diferenciação Celular/fisiologia , Células-Tronco Embrionárias/fisiologia , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Receptores Opioides kappa/metabolismo , Receptores Opioides mu/metabolismo , Analgésicos Opioides/farmacologia , Animais , Antígenos/metabolismo , Benzenoacetamidas/farmacologia , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Interações Medicamentosas , Embrião de Mamíferos , Células-Tronco Embrionárias/efeitos dos fármacos , Ala(2)-MePhe(4)-Gly(5)-Encefalina/farmacologia , Inibidores Enzimáticos/farmacologia , Proteína Glial Fibrilar Ácida/metabolismo , Camundongos , Naltrexona/análogos & derivados , Naltrexona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Oligodendroglia/efeitos dos fármacos , Oligodendroglia/fisiologia , Peptídeos/farmacologia , Proteoglicanas/metabolismo , Pirrolidinas/farmacologia , Receptores Opioides kappa/agonistas , Receptores Opioides mu/antagonistas & inibidores , Fatores de Tempo , Tretinoína/farmacologia , Tubulina (Proteína)/metabolismo
15.
OBM Transplant ; 4(1)2020.
Artigo em Inglês | MEDLINE | ID: mdl-32582882

RESUMO

Brazilian-born British biologist Dr. Peter Medawar played an integral role in developing the concepts of immunologic rejection and tolerance, which led to him receiving the Nobel Prize "for the discovery of acquired immunologic tolerance" and eventually made organ transplantation a reality. However, at the time of his early work in tolerance, a paradox to his theories was brought to his attention; how was pregnancy possible? Pregnancy resembles organ transplantation in that the fetus, possessing paternal antigens, is a semi-allogeneic graft that can survive without immunosuppression for 9 months. To answer this question, Medawar proposed three hypotheses of how a mother supports her fetus in utero, now known as "Medawar's Paradox." The mechanisms that govern fetomaternal tolerance are still incompletely understood but may provide critical insight into how to achieve immune tolerance in organ transplantation. Here, we review current understanding of the immune factors responsible for fetomaternal tolerance during pregnancy and discuss the potential implications for advances in transplantation science.

16.
Pancreas ; 49(3): 301-312, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32168248

RESUMO

Radiologic characterization of pancreatic lesions is currently limited. Computed tomography is insensitive in detecting and characterizing small pancreatic lesions. Moreover, heterogeneity of many pancreatic lesions makes determination of malignancy challenging. As a result, invasive diagnostic testing is frequently used to characterize pancreatic lesions but often yields indeterminate results. Computed tomography texture analysis (CTTA) is an emerging noninvasive computational tool that quantifies gray-scale pixels/voxels and their spatial relationships within a region of interest. In nonpancreatic lesions, CTTA has shown promise in diagnosis, lesion characterization, and risk stratification, and more recently, pancreatic applications of CTTA have been explored. This review outlines the emerging role of CTTA in identifying, characterizing, and risk stratifying pancreatic lesions. Although recent studies show the clinical potential of CTTA of the pancreas, a clear understanding of which specific texture features correlate with high-grade dysplasia and predict survival has not yet been achieved. Further multidisciplinary investigations using strong radiologic-pathologic correlation are needed to establish a role for this noninvasive diagnostic tool.


Assuntos
Neoplasias Pancreáticas/diagnóstico por imagem , Interpretação de Imagem Radiográfica Assistida por Computador , Tomografia Computadorizada por Raios X , Intervalo Livre de Doença , Humanos , Gradação de Tumores , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/terapia , Valor Preditivo dos Testes , Medição de Risco , Fatores de Risco
17.
J Patient Exp ; 7(6): 1568-1576, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33457616

RESUMO

BACKGROUND: Although provider-derived surgical complication severity grading systems exist, little is known about the patient perspective. OBJECTIVE: To assess patient-rated complication severity and determine concordance with existing grading systems. METHODS: A survey asked general surgery patients to rate the severity of 21 hypothetical postoperative events representing grades 1 to 5 complications from the Accordion Severity Grading System. Concordance with the Accordion scale was examined. Separately, descriptive ratings of 18 brief postoperative events were ranked. RESULTS: One hundred sixty-eight patients returned a mailed survey following their discharge from a general surgery service. Patients rated grade 4 complications highest. Grade 1 complications were rated similarly to grade 5 and higher than grades 2 and 3 (P ≤ .01). Patients rated one event not considered an Accordion scale complication higher than all but grade 4 complications (P < .001). The brief events also did not follow the Accordion scale, other than the grade 6 complication ranking highest. CONCLUSION: Patient-rated complication severity is discordant with provider-derived grading systems, suggesting the need to explore important differences between patient and provider perspectives.

18.
J Surg Educ ; 77(5): 1088-1096, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32546388

RESUMO

OBJECTIVE: Ample evidence exists that one's internal state (e.g., mindset, emotion) impacts one's performance. Both the military and sports organizations have focused on optimizing internal states of their service members and athletes, respectively, to improve performance and wellbeing. The internal states of surgical residents and the factors that influence their internal states have not yet been examined. Our goal is to better understand whether certain internal states are beneficial for resident operative performance, and how to optimize these during surgical training. DESIGN: A 17-question survey, containing both open-ended and multiple-choice questions, was distributed to all (n = 134) surgical residents at the University of Wisconsin. In open-ended questions, recurring themes were identified utilizing content analysis. Recurring themes stated by 25% or more of the respondents are reported. SETTING: Department of Surgery at the University of Wisconsin-Madison. PARTICIPANTS: Surgical residents at the University of Wisconsin. RESULTS: The survey response rate varied between n = 47 (35%) and n = 32 (24%), as not all respondents answered all questions. (1) Effective surgical educators were identified to demonstrate humanism and focus on teaching. (2) Nearly all residents affirmed that certain mindsets help them excel in the OR, including positive and confident mindsets. (3) Nearly all residents affirmed that faculty and senior residents influence their mindsets. (4) Constructive resident mindsets were promoted by positive faculty behaviors and personal preparation, while negative faculty behaviors were identified to stifle constructive mindsets. (5) Factors contributing to favorable OR performance included personal preparation and positive OR environments. (6) Factors contributing to poor OR performance included inadequate preparation and negative interactions with faculty. CONCLUSIONS: Residents near unanimously believe that certain mindsets help them excel, and that faculty impact their mindsets. As teachers, we must strive to better understand how to foster constructive mindsets in residents to optimize learning, performance, and wellbeing.


Assuntos
Incivilidade , Internato e Residência , Docentes de Medicina , Humanos , Aprendizagem , Inquéritos e Questionários , Universidades
19.
Am Surg ; 85(12): 1369-1375, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31908220

RESUMO

Multidisciplinary management of chronic wounds using comprehensive wound centers improves outcomes. With an increasing need for wound providers, little is known about surgeons' roles in wound centers. An online survey of two national surgical organization members covered demographics, wound center characterization, and surgeons' perspectives of wound centers and wound care. Surgeon perspectives were compared by age, gender, and relationship status. Three hundred sixty-four surgeons responded. Respondents were mostly older than 50 years, male, in practice older than 10 years, and used wound centers. Most respondents reported favorable experiences with wound centers but uncertainty about financial details. Most respondents were interested in formal wound care certification and participation in a wound practice, particularly as a transition to the retirement option for older surgeons. Surgeons are interested in pursuing a career focus in wound care. Further efforts are needed to educate surgeons and create a pathway for surgeons to become wound center directors. In a nationwide survey, surgeon perspectives on wound centers and wound specialization were positive, although financial understanding was limited. The importance of this finding is the support of wound care pathways for surgeons.


Assuntos
Cirurgiões/estatística & dados numéricos , Centros de Traumatologia , Ferimentos e Lesões/terapia , Adulto , Atitude do Pessoal de Saúde , Escolha da Profissão , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Centros de Traumatologia/economia , Centros de Traumatologia/estatística & dados numéricos , Estados Unidos , Ferimentos e Lesões/cirurgia
20.
J Gastrointest Surg ; 23(11): 2225-2231, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-30941685

RESUMO

BACKGROUND: In a changing health care environment where patient outcomes will be more closely scrutinized, the ability to predict surgical complications is becoming increasingly important. The American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) online risk calculator is a popular tool to predict surgical risk. This paper aims to assess the applicability of the ACS NSQIP calculator to patients undergoing surgery for pancreatic neuroendocrine tumors (PNETs). METHODS: Using the US Neuroendocrine Tumor Study Group (USNET-SG), 890 patients who underwent pancreatic procedures between 1/1/2000-12/31/2016 were evaluated. Predicted and actual outcomes were compared using C-statistics and Brier scores. RESULTS: The most commonly performed procedure was distal pancreatectomy, followed by standard and pylorus-preserving pancreaticoduodenectomy. For the entire group of patients studied, C-statistics were highest for discharge destination (0.79) and cardiac complications (0.71), and less than 0.7 for all other complications. The Brier scores for surgical site infection (0.1441) and discharge to nursing/rehabilitation facility (0.0279) were below the Brier score cut-off, while the rest were equal to or above and therefore not useful for interpretation. CONCLUSION: This work indicates that the ACS NSQIP risk calculator is a valuable tool that should be used with caution and in coordination with clinical assessment for PNET clinical decision-making.


Assuntos
Tumores Neuroendócrinos/cirurgia , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia/métodos , Complicações Pós-Operatórias/epidemiologia , Melhoria de Qualidade , Medição de Risco/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
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