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1.
Am Surg ; : 31348211060445, 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34766506

RESUMO

INTRODUCTION: Resection of colorectal liver metastases provides the best chance for survival in patients with Stage IV colorectal cancer; however, hepatic recurrence is frequent and the main cause of death. Multiple epidemiological studies have documented an association between metformin and anti-neoplastic effects in a variety of cancers. Given the vast literature, we evaluated the incidence on recurrence and survival of patients on metformin who undergo surgery for colorectal liver metastasis (CRLM). METHODS: We selected 270 consecutive patients with known CRLM who underwent hepatic metastases resection at our institution between January 1st 2012 and December 31st 2019. Patients were divided based on their use of metformin (n = 62) or no metformin (n = 208). Adjusted analysis of recurrence-free (RFS) and overall survival (OS) was performed. RESULTS: Patients on metformin had significantly longer RFS (HR: .44, 95% CI: .26-.75, P < .002; Median RFS: 49 months vs 33 months) and OS (HR .60, 95% CI .31-.97, P < .048, Median OS: 72 months vs 60 months). Additional factors associated with shorter RFS on univariate analysis included the following: CEA > 200 ng/ml (HR: 2.23, 95% CI 1.21-4.03, P < .010), positive liver margin (HR: 3.70, 95% CI 2.27-6.03, P < .001), and >1 tumor (HR: 1.98, 95% CI 1.26-3.09, P < .003). Liver margin remained a significant factor for predicting shorter OS (HR: 4.99, 95% CI 2.49-10.0, P < .001). CONCLUSION: In this study, we found that patients with CRLM on metformin have prolonged RFS and OS postliver resection. Further prospective randomized trials need to be carried out to evaluate the anti-neoplastic effect of metformin in diabetic and non-diabetic cancer patients.

2.
J Surg Oncol ; 124(3): 324-333, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33939838

RESUMO

BACKGROUND: Medicaid expansion under the Affordable Care Act has improved access to screening and treatment for certain cancers. It is unclear how this policy has affected the diagnosis and management of pancreatic cancer. METHODS: Using a quasi-experimental difference-in-differences (DID) approach, we analyzed Medicaid and uninsured patients in the National Cancer Data Base during two time periods: pre-expansion (2011-2012) and postexpansion (2015-2016). We investigated changes in cancer staging, treatment decisions, and surgical outcomes. RESULTS: In this national cohort, pancreatic cancer patients in expansion states had increased Medicaid coverage relative to those in nonexpansion states (DID = 17.49, p < 0.01). Medicaid expansion also led to an increase in early-stage diagnoses (Stage I/II, DID = 4.71, p = 0.03), higher comorbidity scores among surgical patients (Charlson/Deyo score 0: DID = -13.69, p = 0.02), a trend toward more neoadjuvant radiation (DID = 6.15, p = 0.06), and more positive margins (DID = 11.69, p = 0.02). There were no differences in rates of surgery, postoperative outcomes, or overall survival. CONCLUSION: Medicaid expansion was associated with improved insurance coverage and earlier stage diagnoses for Medicaid and uninsured pancreatic cancer patients, but similar surgical outcomes and overall survival. These findings highlight both the benefits of Medicaid expansion and the potential limitations of policy change to improve outcomes for such an aggressive malignancy.


Assuntos
Cobertura do Seguro/estatística & dados numéricos , Medicaid/estatística & dados numéricos , Neoplasias Pancreáticas/economia , Neoplasias Pancreáticas/mortalidade , Adulto , Idoso , Estudos de Coortes , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/cirurgia , Patient Protection and Affordable Care Act , Sistema de Registros , Estudos Retrospectivos , Estados Unidos/epidemiologia
3.
Pancreas ; 50(3): 386-392, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33835970

RESUMO

OBJECTIVES: The objective of this study was to create a composite measure, optimal oncologic surgery (OOS), for patients undergoing distal pancreatectomy for pancreatic adenocarcinoma and identify factors associated with OOS. METHODS: Adult patients undergoing distal pancreatectomy were identified from the National Cancer Database between 2010 and 2016. Patients were stratified based on receipt of OOS. Criteria for OOS included 90-day survival, no 30-day readmission, length of stay ≤7 days, negative resection margins, ≥12 lymph nodes harvested, and receipt of chemotherapy. Multivariate logistic regression was performed to identify predictors of OOS. Survival curves and a Cox proportional hazards model were created to compare survival and identify risk factors for mortality. RESULTS: Three thousand five hundred forty-six patients were identified. The rate of OOS was 22.3%. Diagnosis after 2012, treatment at an academic medical center, and a minimally invasive surgical approach (MIS) were associated with OOS. Survival was superior for patients undergoing OOS. Decreasing age at diagnosis, fewer comorbidities, surgery at an academic medical center, MIS, and lower pathologic stage were also associated with improved survival on multivariate analysis. CONCLUSIONS: Rates of OOS for distal pancreatectomy are low. Time trends show increasing rates of OOS that may be related to increasing MIS, adjuvant chemotherapy, and referrals to academic medical centers.

4.
Transpl Int ; 34(6): 1105-1122, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33780554

RESUMO

The prevalence of portal vein thrombosis (PVT), renal dysfunction (RD), and simultaneous PVT/RD in liver transplantation (LT) is poorly understood. We analyzed the prevalence of PVT, RD, simultaneous PVT/RD, and the outcomes of adult recipients of LT for nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) between 2006 and 2016 in the United States. We found that the prevalence of PVT (7.2% â†’ 11.3%), RD (33.8% â†’ 39.2%), and simultaneous PVT/RD (2.4% â†’ 4.5%) has increased significantly over the study period (all P-values <0.05). NAFLD patients had a higher proportion of PVT (14.8% vs. 9.2%), RD (45.0% vs. 42.1%), and simultaneous PVT/RD (6.5% vs. 3.9%; all P-values <0.05). 90-day mortality was 3.8%, 6.3%, 6.8%, and 9.8% for PVT(-)/RD(-), PVT(-)/RD(+), PVT(+)/RD(-), and PVT(+)/RD(+) recipients, respectively (P < 0.01). 5-year survival was 82.1%, 75.5%, 74.8%, and 71.1% for PVT(-)/RD(-), PVT(-)/RD(+), PVT(+)/RD(-), and PVT(+)/RD(+) recipients, respectively (P < 0.05). In conclusion, the prevalence of PVT, RD, and simultaneous PVT/RD has increased among LT recipients, especially for those with NAFLD. The short- and long-term outcomes of recipients with PVT, RD, and simultaneous PVT/RD were inferior to patients without those risk factors irrespective of their indication for LT. No differences in patient outcomes were found between ALD and NAFLD recipients after stratification by risk factors.


Assuntos
Nefropatias , Transplante de Fígado , Hepatopatia Gordurosa não Alcoólica , Trombose Venosa , Adulto , Humanos , Nefropatias/patologia , Cirrose Hepática , Cirrose Hepática Alcoólica , Hepatopatia Gordurosa não Alcoólica/complicações , Veia Porta/patologia , Estudos Retrospectivos , Fatores de Risco , Estados Unidos/epidemiologia , Trombose Venosa/epidemiologia , Trombose Venosa/etiologia
5.
Am Surg ; : 3134820988810, 2021 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-33517684

RESUMO

BACKGROUND: Colorectal adenocarcinoma is a leading cause of cancer mortality worldwide, often requiring patients to undergo anatomy-altering surgical interventions leading to increased postoperative readmission. Hospital readmission rates have been correlated with increased mortality. Therefore, it is important to understand the association between 30-day readmission rates and mortality as well as the factors associated with increased readmission rates. STUDY DESIGN: This is a retrospective review utilizing data from the National Cancer Database. Our primary outcomes of interest were 30- and 90-day mortality rates. Our primary independent variable of interest was 30-day readmission. RESULTS: Between 2010 and 2016, 207 299 patients underwent surgery for rectal cancer and 754 895 for colon cancer. The readmission rates within 30 days of discharge were 5.4% and 5.5% for patients after surgery for rectal or colon cancer, respectively. 30-day readmission was not associated with 30-day mortality, but it was independently associated with increased 90-day mortality and inferior long-term survival for both cohorts (P = .001). Independent risk factors significantly associated with increased readmission included race, non-private insurance, and low income. CONCLUSION: This study provides a large, up-to-date, and comprehensive analysis of readmission rates for colon and rectal cancers. We demonstrate that socioeconomic factors are associated with increased 30-day readmission. 30-day readmission is also independently associated with increased 90-day mortality as well as lower overall survival rates. Our study supports the need for implementation of programs that support patients of lower socioeconomic status undergoing surgery to further decrease readmission rates and mortality.

6.
Hepatology ; 73(6): 2494-2509, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32924145

RESUMO

BACKGROUND AND AIMS: Liver ischemia/reperfusion injury (IRI) induces local and systemic inflammation in which neutrophil extracellular traps (NETs) are major drivers. IRI markedly augments metastatic growth, which is consistent with the notion that the liver IRI can serve as a premetastatic niche. Exercise training (ExT) confers a sustainable protection, reducing IRI in some animal models, and has been associated with improved survival in patients with cancer; however, the impact of ExT on liver IRI or development of hepatic metastases is unknown. APPROACH AND RESULTS: Mice were randomized into exercise (ExT) and sedentary groups before liver IRI and tumor injection. Computerized dynamic network analysis of 20 inflammatory mediators was used to dissect the sequence of mediator interactions after ischemia/reperfusion (I/R) that induce injury. ExT mice showed a significant decrease in hepatic IRI and tissue necrosis. This coincided with disassembly of complex networks among inflammatory mediators seen in sedentary mice. Neutrophil infiltration and NET formation were decreased in the ExT group, which suppressed the expression of liver endothelial cell adhesion molecules. Concurrently, ExT mice revealed a distinct population of infiltrating macrophages expressing M2 phenotypic genes. In a metastatic model, fewer metastases were present 3 weeks after I/R in the ExT mice, a finding that correlated with a marked increase in tumor-suppressing T cells within the tumor microenvironment. CONCLUSIONS: ExT preconditioning mitigates the inflammatory response to liver IRI, protecting the liver from injury and metastases. In light of these findings, potential may exist for the reduction of liver premetastatic niches induced by liver IRI through the use of ExT as a nonpharmacologic therapy before curative surgical approaches.

7.
Am J Surg ; 221(2): 345-350, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33187628

RESUMO

BACKGROUND: The purpose of this study was to investigate the feasibility of a simulated teaching activity as an assessment of surgical knowledge and teaching competencies. METHODS: In this prospective observational study, 15 residents and 1 fellow in the Department of Surgery watched three video clips of laparoscopic cholecystectomies and provided feedback to a participant learner. Qualitative and statistical analysis identified differences in surgical knowledge and teaching strategies. RESULTS: As compared to senior trainees, junior trainees were more likely to speculate on the learner's actions (p = 0.033), identify which actions looked correct (p = 0.028), and speculate more on the learner's thoughts (p = 0.02). Senior trainees noted case difficulty more frequently (p = 0.028), identified more actions that looked incorrect (p = 0.004), and speculated more about the learner's emotions (p = 0.033). CONCLUSIONS: A simulated teaching scenario successfully assessed operative and teaching competencies, suggesting a novel assessment method.


Assuntos
Competência Clínica , Cirurgia Geral/educação , Internato e Residência/métodos , Aprendizagem , Ensino/educação , Centros Médicos Acadêmicos , Adolescente , Colecistectomia Laparoscópica/educação , Colecistectomia Laparoscópica/normas , Feedback Formativo , Cirurgia Geral/normas , Humanos , Internato e Residência/normas , Estudos Prospectivos , Treinamento por Simulação , Gravação em Vídeo , Adulto Jovem
8.
J Gastrointest Surg ; 25(9): 2307-2316, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33269460

RESUMO

AIM: To assess the predictors and influence of resection margins and the role of neoadjuvant and adjuvant therapy on survival for a national cohort of patients with resected pancreatic cancer. METHODS: Using the National Cancer Data Base between 2004 and 2016, 56,532 patients were identified who underwent surgical resection for pancreatic adenocarcinoma. Univariate and multivariate models were employed to identify factors predicting R0/R1 resection and assess the impact on survival. RESULTS: In total, 48,367 (85.6%) patients were found to have negative margins (R0) compared to 8165 (14.4%) who had microscopic residual tumor (R1). Factors predicting positive margin on univariate analysis included male gender, Medicare, advanced stage, moderately or poorly differentiated tumor, lymphovascular invasion, and tumors > 2 cm. Factors predicting R0 resection included receipt of neoadjuvant therapy and treatment at an Academic/Research Center. Following adjustment for other factors, margin status remained an independent predictor for overall survival (HR: 1.24; 95% CI 1.22-1.27, p < 0.001) (1-, 3-, and 5-year overall survival rates (R0: 77%, 37%, and 25% vs R1: 62%, 19%, and 10%). CONCLUSIONS: A positive margin predicts a poorer survival than R0 resections regardless of stage and receipt of adjuvant therapy. Several modifiable factors significantly predict the likelihood of R0 resection including neoadjuvant treatment and treatment at Academic/Research Programs. Knowledge about these factors can help guide patient management by offering neoadjuvant treatment modalities at Academic as well as Community hospitals.

9.
J Trauma Acute Care Surg ; 90(3): 477-483, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33075028

RESUMO

BACKGROUND: The significance of pneumatosis intestinalis (PI) remains challenging. While certain clinical scenarios are predictive of transmural ischemia, risk models to assess the presence of pathologic PI are needed. The aim of this study was to determine what patient factors at the time of radiographic diagnosis of PI predict the risk for pathologic PI. METHODS: We conducted a retrospective cohort study examining patients with PI from 2010 to 2016 at a multicenter hospital network. Multivariate logistic regression was used to develop a predictive model for pathologic PI in a derivation cohort. Using regression-coefficient-based methods, the final multivariate model was converted into a five-factor-based score. Calibration and discrimination of the score were then assessed in a validation cohort. RESULTS: Of 305 patients analyzed, 102 (33.4%) had pathologic PI. We identified five factors associated with pathologic PI at the time of radiographic diagnosis: small bowel PI, age 70 years or older, heart rate 110 bpm or greater, lactate of 2 mmol/L or greater, and neutrophil-lymphocyte ratio 10 or greater. Using this model, patients in the validation cohort were assigned risk scores ranging from 0 to 11. Low-risk patients were categorized when scores are 0 to 4; intermediate, score of 5 to 6; high, score of 7 to 8; and very high risk, 9+. In the validation cohort, very high-risk patients (n = 17; 18.1%) had predicted rates of pathologic pneumatosis of 88.9% and an observed rate of 82.4%. In contrast, patients labeled as low risk (n = 37; 39.4%) had expected rates of pathologic pneumatosis of 1.3% and an observed rate of 0%. The model showed excellent discrimination (area under the curve, 0.90) and good calibration (Hosmer-Lemeshow goodness-of-fit, p = 0.37). CONCLUSION: Our score accurately stratifies patient risk of pathologic pneumatosis. This score has the potential to target high-risk individuals for expedient operation and spare low-risk individuals invasive interventions. LEVEL OF EVIDENCE: Prognostic Study, Level III.


Assuntos
Pneumatose Cistoide Intestinal/diagnóstico , Pneumatose Cistoide Intestinal/etiologia , Idoso , Feminino , Hospitalização , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Pneumatose Cistoide Intestinal/cirurgia , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Risco , Tomografia Computadorizada por Raios X
10.
HPB (Oxford) ; 23(2): 309-320, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32811764

RESUMO

BACKGROUND: The incidence of primary hepatic malignancies including Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) is on the rise. (i) Surgery remains the mainstay of potential curative treatment, however the vast majority of patients will recur and not be amenable to curative therapy. (ii) Inflammation has been associated with poor prognosis, however there is no preoperative marker that can predict recurrence-free- or overall survival. Our aim is to correlate inflammation measured as neutrophil extracellular traps (NETs) with survival. METHODS: A retrospective analysis was performed using sera/tissue from patients with hepatic malignancies. NET levels were measured in the serum (MPO-DNA) or tumor (Cit-H3). Log rank analysis for RFS/OS was performed. RESULTS: Cancer patients had higher pre-surgery MPO-DNA levels compared to healthy individuals (healthy vs cancer: 2.6 ± 1.0 ng/ml vs 34.7 ± 2.13 ng/ml; p < 0.0001). High pre-surgery serum NET levels were associated with shorter RFS/OS compared to those with low levels (RFS-HCC: HR: 2.91, 95% CI: 1.61-5.26, p < 0.0001, RFS-CC: HR: 3.22, 95% CI: 1.33-7.77 p < 0.0093). High Cit-H3 tumor levels similarly predicted shorter RFS/OS. CONCLUSION: The current study shows a correlation between pre-operative NET levels and survival. Studying NET formation as a biomarker pre-surgery can help identify patients that could benefit from closer follow-up due to higher risk for recurrence.

11.
HPB (Oxford) ; 23(6): 927-936, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33189566

RESUMO

BACKGROUND: We assessed if the risk of post-liver transplant mortality within 24 h could be stratified at the time of listing using the liver transplant risk score (LTRS). Secondary aims were to assess if the LTRS could stratify the risk of 30-day, 1-year mortality, and survival beyond the first year. METHODS: MELD, BMI, age, diabetes, and the need for dialysis were the five variables used to calculate the LTRS during patients' evaluation for liver transplantation. Mortality rates at 24 h, 30 days, and 1-year were compared among groups of patients with different LTRS. Patients with ABO-incompatibility, redo, multivisceral, partial graft and malignancies except for hepatocellular carcinoma were excluded. Data of 48,616 adult liver transplant recipients were extracted from the Scientific Registry of Transplant Recipients between 2002 and 2017. RESULTS: 24-h mortality was 0.9%, 1.0%, 1.1%, 1.7%, 2.3%, 2.0% and 3.5% for patients with LTRS of 0,1,2,3,4, 5 and ≥ 6, respectively (P < 0.001). 30-day mortality was 3.5%, 4.2%, 4.9%, 6.2%, 7.6%, 7.2% and 10.1% respectively (P < 0.001). 1-year mortality was 8.6%, 10.8%, 12.9%, 13.9%, 18.5%, 20.3% and 28.6% respectively (P < 0.001). 10-year survival was 61%, 56%, 57%, 54%, 47%, and 31% for patients with 0, 1, 2, 3, 4, 5 and ≥ 6 points respectively (P < 0.001). CONCLUSION: Perioperative mortality and long-term survival of patients undergoing LT can be accurately estimated at the time of listing by the LTRS.

12.
Am Surg ; 87(7): 1145-1154, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33342268

RESUMO

INTRODUCTION: With advances in multimodal therapy, survival rates in gastric cancer have significantly improved over the last two decades. Neoadjuvant therapy increases the likelihood of achieving negative margins and may even lead to pathologic complete response (pCR). However, the impact of pCR on survival in gastric cancer has been poorly described. We analyzed the rate and predictors of pCR in patients receiving neoadjuvant therapy as well as impact of pCR on survival. METHODS: We conducted a National Cancer Database (NCDB) analysis (2004-2016) of patients with gastric adenocarcinoma who received neoadjuvant chemotherapy followed by surgical resection. RESULTS: The pCR rate was 2.2%. Following adjustment, only neoadjuvant chemoradiation, non-signet histology, and tumor grade remained as significant factors predicting pCR. pCR was a statistically significant predictor of survival. CONCLUSION: In this NCDB study, pCR was a predictor of survival. Though chemoradiation rather than chemotherapy alone was a predictor of pCR, it was not a predictor of survival. Further studies are needed to elucidate the role of radiation in the neoadjuvant setting and to discern the impact of pCR on survival.


Assuntos
Adenocarcinoma/patologia , Adenocarcinoma/terapia , Gastrectomia , Terapia Neoadjuvante , Neoplasias Gástricas/patologia , Neoplasias Gástricas/terapia , Adenocarcinoma/mortalidade , Idoso , Bases de Dados Factuais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Neoplasias Gástricas/mortalidade , Taxa de Sobrevida , Resultado do Tratamento , Estados Unidos
13.
Am Surg ; : 3134820976080, 2020 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-33342275

RESUMO

AIM: We performed a single-center teaching intervention with nursing providers on nasogastric tube (NG tube) clinical practice. The initial purpose of this study was the validation of whether the training was sufficient enough to be retained at a later time point. METHODS: We performed a prospective pre-post study examining participants' knowledge before, immediately after, and 4 weeks after training in NG tube management. Training was delivered in face-to-face classroom sessions. Knowledge was assessed using a multiple-choice test (pretest, posttest #1and #2). RESULTS: A total of 137 nursing providers participated in the training intervention. Immediately after training (posttest #1) and again 4 weeks later (posttest #2), participants overwhelmingly recalled and retained the knowledge of NG tube management as compared to pretest results. Paired t-tests showed each participant increased their test score from pretest to posttest #1, t (134) = 12.64, P = .0001. Similarly, participants who took posttest #2 significantly improved their scores from the pretest to posttest #2, t (71) = 10.629, P < .0001. Secondary analysis showed that the NG tube management comfort level and age of provider were not significant in predicting test results. However, years of professional experience and frequency of NG tube care were significant predictors for higher test scores. CONCLUSION: To minimize the risk of NG tubes for patients, it is critical to follow clinical guidelines. This study shows that teaching interventions for providers to increase knowledge on NG tubes are beneficial. In addition, the knowledge is retained at later time points.

14.
Am Surg ; : 3134820973739, 2020 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-33369487

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality worldwide. Liver resections and transplantations have increasingly become feasible options for potential cure. These complex surgeries are inherently associated with increased rates of readmission. In the meanwhile, hospital readmission rates are rapidly becoming an important quality of care metric. Therefore, it is very important to understand the effect of 30-day readmission on mortality and the factors associated with increased 30- and 90-day mortality rates. METHODS: This is a retrospective cohort study utilizing data from the National Cancer Database. Patients included were 18 years or older who underwent liver resection or liver transplantation for HCC between 2003 and 2011. Our primary outcomes of interest were 30- and 90-day mortality rates. Our primary independent variable of interest was 30-day readmission. RESULTS: 16 658 patients underwent either a liver resection or transplantation for HCC between 2003 and 2011. For patients with liver transplantations, increased readmission rates were associated with lower risks of 30-day mortality (P = .012) but a trend toward higher 90-day mortality (P = .057). Patients who underwent liver resection for HCC also demonstrated increased readmission rates to be associated with lower risk of 30-day mortality (P = .014) but higher 90-day mortality (P ≤ .001). CONCLUSION: This is the only study to utilize a national database to investigate the association between readmission rates and mortality rates of both liver transplantations and resections for patients with HCC. We demonstrate 30-day readmission to show no increase in 30-day mortality, but rather higher 90-day mortality.

15.
PLoS One ; 15(11): e0239119, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33137133

RESUMO

Autophagy is an important factor in liver ischemia-reperfusion injury. In the current study we investigate the function of interferon regulatory factor-1 (IRF1) in regulating autophagy to promote hepatic ischemia reperfusion injury (IR). The high expression of IRF1 during hepatic IR exhibited increased liver damage and was associated with activation of autophagy shown by Western blot markers, as well as immunofluorescent staining for autophagosomes. These effects were diminished by IRF1 deficiency in IRF1 knock out (KO) mice. Moreover, the autophagy inhibitor 3-MA decreased IR-induced liver necrosis and markedly abrogated the rise in liver injury tests (AST/ALT). ß-catenin expression decreased during liver IR and was increased in the IRF1 KO mice. Immunoprecipitation assay showed the binding between IRF1 and ß-catenin. Overexpression of IRF1 induced autophagy and also inhibited the expression of ß-catenin. ß-catenin inhibitor increased autophagy while ß-catenin agonist suppressed autophagy in primary mouse hepatocytes. These results indicate that IRF1 induced autophagy aggravates hepatic IR injury in part by inhibiting ß-catenin and suggests that targeting IRF1 may be an effective strategy in reducing hepatic IR injury.


Assuntos
Autofagia/fisiologia , Fator Regulador 1 de Interferon/metabolismo , Hepatopatias/metabolismo , Fígado/metabolismo , Traumatismo por Reperfusão/metabolismo , beta Catenina/metabolismo , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout
16.
Transplantation ; 104(12): e332-e341, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32675743

RESUMO

BACKGROUND: The liver transplant risk score (LTRS) was developed to stratify 90-day mortality of patients referred for liver transplantation (LT). We aimed to validate the LTRS using a new cohort of patients. METHODS: The LTRS stratifies the risk of 90-day mortality of LT recipients based on their age, body mass index, diabetes, model for end-stage liver disease (MELD) score, and need for dialysis. We assessed the performance of the LTRS using a new cohort of patients transplanted in the United States between July 2013 and June 2017. Exclusion criteria were age <18 years, ABO incompatibility, redo or multivisceral transplants, partial grafts, malignancies other than hepatocellular carcinoma and fulminant hepatitis. RESULTS: We found a linear correlation between the number of points of the LTRS and 90-day mortality. Among 18 635 recipients, 90-day mortality was 2.7%, 3.8%, 5.2%, 4.8%, 6.7%, and 9.3% for recipients with 0, 1, 2, 3, 4, and ≥5 points (P < 0.001). The LTRS also stratified 1-year mortality that was 5.5%, 7.7%, 9.9%, 9.3%, 10.8%, and 15.4% for 0, 1, 2, 3, 4, and ≥5 points (P < 0.001). An inverse correlation was found between the LTRS and 4-year survival that was 82%, 79%, 78%, 82%, 78%, and 66% for patients with 0, 1, 2, 3, 4, and ≥5 points (P < 0.001). The LTRS remained an independent predictor after accounting for recipient sex, ethnicity, cause of liver disease, donor age, cold ischemia time, and waiting time. CONCLUSIONS: The LTRS can stratify the short- and long-term outcomes of LT recipients at the time of their evaluations irrespective of their gender, ethnicity, and primary cause of liver disease.


Assuntos
Técnicas de Apoio para a Decisão , Indicadores Básicos de Saúde , Hepatopatias/cirurgia , Transplante de Fígado/mortalidade , Idoso , Feminino , Humanos , Hepatopatias/diagnóstico , Hepatopatias/mortalidade , Transplante de Fígado/efeitos adversos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Sistema de Registros , Reprodutibilidade dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Estados Unidos
17.
Am J Surg ; 220(6): 1605-1612, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32680623

RESUMO

AIM: Surgery with or without chemotherapy represent the only curative option for patients with colon cancer. However, some patients refuse treatment despite the recommendation. This study aims to identify the incidence, risk factors and impact on survival associated with refusal. METHODS: A National Cancer Data Base (NCDB) analysis between 1998 and 2012 was performed. We identified 924,290 patients with potentially treatable colon cancer. Patients who underwent treatment were compared with patients that refused. RESULTS: 7152 patients refused surgery. On multivariable analysis, patients were more likely to refuse if they were older (OR = 1.14; 95% CI 1.14-1.15), female (OR = 1.20; 95% CI 1.12-1.28), African American (vs White, OR = 2.30; 95% CI 2.10-2.51) or on Medicaid (vs private, OR = 3.06; 95% CI 2.49-43.77). Overall survival was worse in patients that refused surgery [median survival 6.8 vs 24 months, Cox hazard ratio (HR) 3.41; 95%CI 3.12-3.60]. Furthermore, 11,334 patients with path. stage III disease refused adjuvant chemotherapy. CONCLUSIONS: Refusal of treatment affects survival and is independently associated with several variables (gender, race, insurance status), therefore raising the concern that socioeconomic factors may drive decisions.


Assuntos
Neoplasias do Colo/mortalidade , Neoplasias do Colo/terapia , Recusa do Paciente ao Tratamento/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
18.
Biochem Biophys Res Commun ; 524(2): 273-279, 2020 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-31987500

RESUMO

Hepatocellular carcinoma (HCC) tumors evade death in part by downregulating expression of the tumor suppressor gene Interferon regulatory factor-1 (IRF-1). However, the molecular mechanisms accounting for IRF-1 suppression in HCC have not been well described. In this study, we identified a novel microRNA-301a (miR-301a) binding site in the 3'-untranslated region (3'- UTR) of the human IRF-1 gene and hypothesized a functional role for miR-301a in regulating HCC growth. We show that miR-301a is markedly upregulated in primary HCC tumors and HCC cell lines, while IRF-1 is down-regulated in a post-transcriptional manner. MiR-301a regulates basal and inducible IRF-1 expression in HCC cells with an inverse relationship between miR-301a and IRF-1 expression in HCC cells. Chronic hypoxia induces miR-301a in HCC in vitro and decreases IRF-1 expression. Finally, miR-301a inhibition increases apoptosis and decreases HCC cell proliferation. These findings suggest that targeting of IRF-1 by miR-301a contributes to the molecular basis for IRF-1 downregulation in HCC and provides new insight into the regulation of HCC by miRNAs.


Assuntos
Carcinoma Hepatocelular/genética , Regulação Neoplásica da Expressão Gênica , Fator Regulador 1 de Interferon/genética , Neoplasias Hepáticas/genética , MicroRNAs/genética , Animais , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células , Regulação para Baixo , Células Hep G2 , Humanos , Neoplasias Hepáticas/patologia , Camundongos , Regulação para Cima
19.
Ann Surg ; 2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31850985

RESUMO

PURPOSE: Time to surgery (TTS) is of concern to patients diagnosed with cancer and their physicians. Controversy surrounds the impact of TTS on colon cancer survival. There are limited national data evaluating the association; thus, our aim was to estimate the overall survival (OS) impact from increasing TTS for patients with colon cancer. METHODS: Using the National Cancer Data Base (NCDB), we assessed OS as a function of time between diagnosis and surgery by evaluating intervals encompassing <7, 7 to 30, 31 to 60, 61 to 90, 91 to 120, and 121 to 180 days in length. All patients were diagnosed with nonmetastatic colon cancer and underwent surgery as initial treatment. Our main outcome was OS as a function of time between diagnosis and surgery, after adjusting for patient, demographic, and tumor-related factors using Cox regression models and propensity score-based weighting. RESULTS: A total of 514,103 patients diagnosed between 1998 and 2012 were included. Individuals having <7, 7 to 30, 31 to 60, 61 to 90, 91 to 120, and 121 to 180 days between diagnosis and surgery comprised 35.4%, 45%, 15.1%, 2.9%, 1%, and 0.6% of the patients, respectively. There was a steady increase in median TTS across the years. On multivariable analysis, TTS >30 days or within the first week independently increased mortality risk. There was a significant increase in mortality with TTS 31 to 60 [hazard ratio (HR) 1.13], 61 to 90 (HR 1.49), <7 (HR 1.56), 91 to 120 (HR 2.28), and 121 to 180 (HR 2.46) compared to surgery performed 7 to 30 days after diagnosis (P < 0.001). CONCLUSIONS: TTS is independently associated with OS and this represents a public health issue that should be addressed at a national level. Although time is required for evaluation before surgery, efforts to reduce TTS should be pursued.

20.
Ann Surg Oncol ; 25(12): 3427-3435, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30043318

RESUMO

AIM: To identify factors associated with refusal of surgery in patients with early-stage pancreatic cancer and estimate the impact of this decision on survival. METHODS: Using the National Cancer Data Base, 26,358 patients were identified with potentially resectable tumors (pretreatment clinical stage I: T1 or T2 N0M0). Multivariate models were employed to identify factors predicting failure to undergo surgery and assess the impact on survival. RESULTS: Of early-stage patients who were recommended surgery, 7.8% (N = 992) refused surgery for resectable early-stage pancreatic cancer. On multivariable analysis, patients were more likely to refuse surgery if they were older [odds ratio (OR) = 1.18; 95% confidence interval (CI) 1.16-1.19], female (OR = 1.52; 95% CI 1.33-1.73), African American (vs White, OR = 1.79; 95% CI 1.37-2.34), on Medicare/Medicaid (vs private, OR = 2.75; 95% CI 1.54-4.92) or had higher Charlson-Deyo score (2 vs 0, OR = 1.33; 95% CI 1.03-1.72). Patients were also significantly more likely to refuse surgery if they were seen at a center that is not an academic/research program (OR 1.9; 95% CI 1.6-2.27). Patients who were recommended surgery but refused had significantly worse survival than those with stage I who received surgery [median survival 6.8 vs 24 months, Cox hazard ratio (HR) 3.41; 95% CI 3.12-3.60]. CONCLUSIONS: The percentage of patients refusing surgery for operable early-stage pancreatic cancer has been decreasing in the last decade but remains a significant issue that affects survival. Disparities in refusal of surgery are independently associated with several variables including gender, race, and insurance. To mitigate national disparities in surgical care, future studies should focus on exploring potential reasons for refusal and developing communication interventions.


Assuntos
Adenocarcinoma/etnologia , Afro-Americanos/psicologia , Grupo com Ancestrais do Continente Europeu/psicologia , Disparidades em Assistência à Saúde , Pancreatectomia/psicologia , Neoplasias Pancreáticas/etnologia , Recusa do Paciente ao Tratamento/etnologia , Adenocarcinoma/cirurgia , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/cirurgia , Prognóstico , Estudos Retrospectivos , Fatores Socioeconômicos , Taxa de Sobrevida , Recusa do Paciente ao Tratamento/psicologia
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