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1.
Nature ; 580(7802): 257-262, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32269339

RESUMO

Checkpoint blockade therapies have improved cancer treatment, but such immunotherapy regimens fail in a large subset of patients. Conventional type 1 dendritic cells (DC1s) control the response to checkpoint blockade in preclinical models and are associated with better overall survival in patients with cancer, reflecting the specialized ability of these cells to prime the responses of CD8+ T cells1-3. Paradoxically, however, DC1s can be found in tumours that resist checkpoint blockade, suggesting that the functions of these cells may be altered in some lesions. Here, using single-cell RNA sequencing in human and mouse non-small-cell lung cancers, we identify a cluster of dendritic cells (DCs) that we name 'mature DCs enriched in immunoregulatory molecules' (mregDCs), owing to their coexpression of immunoregulatory genes (Cd274, Pdcd1lg2 and Cd200) and maturation genes (Cd40, Ccr7 and Il12b). We find that the mregDC program is expressed by canonical DC1s and DC2s upon uptake of tumour antigens. We further find that upregulation of the programmed death ligand 1 protein-a key checkpoint molecule-in mregDCs is induced by the receptor tyrosine kinase AXL, while upregulation of interleukin (IL)-12 depends strictly on interferon-γ and is controlled negatively by IL-4 signalling. Blocking IL-4 enhances IL-12 production by tumour-antigen-bearing mregDC1s, expands the pool of tumour-infiltrating effector T cells and reduces tumour burden. We have therefore uncovered a regulatory module associated with tumour-antigen uptake that reduces DC1 functionality in human and mouse cancers.

2.
J Thorac Cardiovasc Surg ; 159(4): 1556, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31866086
3.
Ann Thorac Surg ; 108(6): 1724-1728, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31376378

RESUMO

BACKGROUND: Patients who have undergone curative surgery for stage I lung cancer require continued surveillance owing to the risk of a second primary lung cancer developing. Early diagnosis allows for prompt intervention. However, as in primary cancers, the role of wedge vs lobar resections remains controversial. METHODS: The Surveillance Epidemiology and End Results database was examined from 2004 to 2012 and all pathologically proven stage I lung cancer patients who underwent cancer-directed surgery were selected. Cases in which a second primary lung cancer developed 6 or more months after diagnosis of the first cancer were analyzed for survival after surgical treatment. RESULTS: Second primary lung cancer was identified in 625 patients, of whom 331 (53%) were diagnosed with stage I disease; 43.8% of patients underwent surgery alone, 30.9% received radiation alone, and 21.0% received neither surgery nor radiation. Of the patients who underwent surgery, 57.7% received wedge resection and 36.5% received a lobectomy. Surgical intervention was a positive predictor of survival-both wedge resection and lobectomy exhibited improved outcomes vs no surgery-but there was no statistically significant difference between the two surgical modalities. CONCLUSIONS: Wedge and lobar resections demonstrate similar survival for second primary lung cancers.

4.
Cancer Lett ; 459: 1-12, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31150822

RESUMO

High grade serous ovarian cancer (HGSOC) is the most frequent type of ovarian cancer. Most patients have primary response to platinum-based chemotherapy but frequently relapse, which leads to patient death. A lack of well documented and characterized patient-derived HGSOC cell lines is so far a major barrier to define tumor specific therapeutic targets and to study the molecular mechanisms underlying disease progression. We established 34 patient-derived HGSOC cell lines and characterized them at cellular and molecular level. Particularly, we demonstrated that a cancer-testis antigen PRAME and Estrogen Receptor could serve as therapeutic targets. Notably, data from the cell lines did not demonstrate acquired resistance due to tumor recurrence that matched with clinical observations. Finally, we presented that all HGSOC had no or very low CDKN1A (p21) expression due to loss of wild-type TP53, suggesting that loss of cell cycle control is the determinant for tumorigenesis and progression. In conclusion, patient-derived cell lines reveal that PRAME is a potential tumor specific therapeutic target in HGSOC and counteracting the down-regulation of p21 caused by loss of wild-type TP53 might be the key to impede disease progression.

5.
J Pharmacol Exp Ther ; 370(2): 269-277, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31175220

RESUMO

Cabotegravir, a novel integrase inhibitor under development for treatment and prevention of HIV, is primarily metabolized by UDP-glucuronosyltransferase (UGT)1A1 and UGT1A9 to a direct ether glucuronide metabolite. The aim of these studies was to elucidate the mechanistic basis of cabotegravir-glucuronide disposition in humans. Cabotegravir glucuronidation was predominantly hepatic (>95%) with minimal intestinal and renal contribution. Rat liver perfusions demonstrated that cabotegravir-glucuronide formed in the liver undergoes comparable biliary and sinusoidal excretion, consistent with high concentrations of the glucuronide in human bile and urine. Cabotegravir-glucuronide biliary excretion was mediated by multidrug resistance-associated protein (MRP)2 (not transported by breast cancer resistance protein or P-glycoprotein), whereas hepatic basolateral excretion into sinusoidal blood was via both MRP3 [fraction transport (Ft) = 0.81] and MRP4 (Ft = 0.19). Surprisingly, despite high urinary recovery of hepatically-formed cabotegravir-glucuronide, metabolite levels in circulation were negligible, a phenomenon consistent with rapid metabolite clearance. Cabotegravir-glucuronide was transported by hepatic uptake transporters organic anion-transporting (OAT) polypeptide (OATP)1B1 and OATP1B3; however, metabolite clearance by hepatic uptake from circulation was low (2.7% of hepatic blood flow) and unable to explain the minimal systemic exposure. Instead, circulating cabotegravir-glucuronide undergoes efficient renal clearance, where uptake into the proximal tubule would be mediated by OAT3 (not transported by OAT1), and subsequent secretion into urine by MRP2 (Ft = 0.66) and MRP4 (Ft = 0.34). These studies provide mechanistic insight into the disposition of cabotegravir-glucuronide, a hepatically-formed metabolite with appreciable urinary recovery and minimal systemic exposure, including fractional contribution of redundant transporters to any given process based on quantitative proteomics. SIGNIFICANCE STATEMENT: The role of membrane transporters in metabolite disposition, especially glucuronides, and as sites of unexpected drug-drug interactions, which alter drug efficacy and safety, has been established. Cabotegravir-glucuronide, formed predominantly by direct glucuronidation of parent drug in liver, was the major metabolite recovered in human urine (27% of oral dose) but was surprisingly not detected in systemic circulation. To our knowledge, this is the first mechanistic description of this phenomenon for a major hepatically-formed metabolite to be excreted in the urine to a large extent, but not circulate at detectable levels. The present study elucidates the mechanistic basis of cabotegravir-glucuronide disposition in humans. Specific hepatic and renal transporters involved in the disposition of cabotegravir-glucuronide, with their fractional contribution, have been provided.


Assuntos
Glucuronídeos/química , Inibidores de Integrase/química , Inibidores de Integrase/metabolismo , Piridonas/química , Piridonas/metabolismo , Animais , Transporte Biológico , Células HEK293 , Hepatócitos/metabolismo , Humanos , Fígado/citologia , Fígado/metabolismo , Microssomos/metabolismo , Ratos
6.
Comput Struct Biotechnol J ; 17: 537-560, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31049165

RESUMO

The sphingolipid and lysophosphatidate regulatory networks impact diverse mechanisms attributed to cancer cells and the tumor immune microenvironment. Deciphering the complexity demands implementation of a holistic approach combined with higher-resolution techniques. We implemented a multi-modular integrative approach consolidating the latest accomplishments in gene expression profiling, prognostic/predictive modeling, next generation digital pathology, and systems biology for epithelial ovarian cancer. We assessed patient-specific transcriptional profiles using the sphingolipid/lysophosphatidate/immune-associated signature. This revealed novel sphingolipid/lysophosphatidate-immune gene-gene associations and distinguished tumor subtypes with immune high/low context. These were characterized by robust differences in sphingolipid-/lysophosphatidate-related checkpoints and the drug response. The analysis also nominates novel survival models for stratification of patients with CD68, LPAR3, SMPD1, PPAP2B, and SMPD2 emerging as the most prognostically important genes. Alignment of proprietary data with curated transcriptomic data from public databases across a variety of malignancies (over 600 categories; over 21,000 arrays) showed specificity for ovarian carcinoma. Our systems approach identified novel sphingolipid-lysophosphatidate-immune checkpoints and networks underlying tumor immune heterogeneity and disease outcomes. This holds great promise for delivering novel stratifying and targeting strategies.

7.
Cell Host Microbe ; 25(3): 377-388.e6, 2019 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-30850233

RESUMO

Inflammatory bowel disease (IBD) is characterized by alterations in the intestinal microbiota and altered immune responses to gut microbiota. Evidence is accumulating that IBD is influenced by not only commensal bacteria but also commensal fungi. We characterized fungi directly associated with the intestinal mucosa in healthy people and Crohn's disease patients and identified fungi specifically abundant in patients. One of these, the common skin resident fungus Malassezia restricta, is also linked to the presence of an IBD-associated polymorphism in the gene for CARD9, a signaling adaptor important for anti-fungal defense. M. restricta elicits innate inflammatory responses largely through CARD9 and is recognized by Crohn's disease patient anti-fungal antibodies. This yeast elicits strong inflammatory cytokine production from innate cells harboring the IBD-linked polymorphism in CARD9 and exacerbates colitis via CARD9 in mouse models of disease. Collectively, these results suggest that targeting specific commensal fungi may be a therapeutic strategy for IBD.


Assuntos
Colite/patologia , Colite/fisiopatologia , Doença de Crohn/patologia , Doença de Crohn/fisiopatologia , Trato Gastrointestinal/microbiologia , Malassezia/crescimento & desenvolvimento , Malassezia/isolamento & purificação , Animais , Proteínas Adaptadoras de Sinalização CARD/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Camundongos
8.
Carcinogenesis ; 40(4): 529-536, 2019 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-30649229

RESUMO

Malignant pleural mesothelioma (MPM) is a rare disease with a very poor prognosis. Previous studies have indicated that women experience longer survival compared with men. We analyzed 16 267 eligible patients (21.3% females) in the National Cancer Database to evaluate which clinical factors are independently predictive of longer survival. After adjusting for all covariates, survival was significantly better in females compared with males [HRadj: 0.81, 95% confidence interval (CI): 0.77-0.85]. Other factors significantly associated with better survival were younger age at diagnosis, higher income, lower comorbidity score, epithelial histology, earlier stage and receipt of surgical or medical treatment. After propensity matching, survival was significantly better for females compared with males [hazard ratio (HR): 0.86, 95% CI: 0.80-0.94]. After propensity matching within the epithelial group, survival remained significantly better for females compared with males (HR: 0.85, 95% CI: 0.74-0.97). This study adds information to the known significant gender survival difference in MPM by disentangling the effect of gender from the effect of age and histology, two known independent factors affecting survival. Circulating estrogen, present in young but not older women, and higher expression of the estrogen receptor beta in epithelial mesothelioma have been suggested to play a role in gender survival differences. These findings may lead to exploring new therapeutic options, such as targeting estrogen receptor beta, and considering hormonal therapy including estrogens for patients with otherwise limited prognosis.


Assuntos
Bases de Dados Factuais , Neoplasias Pulmonares/mortalidade , Mesotelioma/mortalidade , Neoplasias Pleurais/mortalidade , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Masculino , Mesotelioma/patologia , Mesotelioma/terapia , Pessoa de Meia-Idade , Neoplasias Pleurais/patologia , Neoplasias Pleurais/terapia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
9.
J Thorac Cardiovasc Surg ; 157(4): 1670-1679.e4, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30685165

RESUMO

OBJECTIVE: Although the incidence of lung cancer has decreased over the past decades, disparities in survival and treatment modalities have been observed for black and white patients with early-stage non-small cell lung cancer, despite the fact that surgical resection has been established as the standard of care. Possible contributors to these disparities are stage at diagnosis, comorbidities, socioeconomic factors, and patient preference. This study examines racial disparities in treatment, adjusting for clinicodemographic factors. METHODS: The Surveillance, Epidemiology, and End Results-Medicare dataset was queried to identify patients diagnosed with primary stage I non-small cell lung cancer between 1992 and 2009. Multivariable logistic regressions were performed to assess the association between race and treatment modalities within 1 year of diagnosis, adjusted for clinical and demographic factors. Adjusted Cox proportional hazards models were performed to evaluate disparities in survival, accounting for mode of treatment. RESULTS: We identified 22,724 patients; 21,230 (93.4%) white and 1494 (6.6%) black. Black patients were less likely to receive treatment (odds ratio [OR]adj, 0.62; 95% confidence interval [CI], 0.53-0.73) and less likely to receive surgery only when treated (ORadj, 0.70, 95% CI, 0.61-0.79). Although univariate survival for black patients was worse, when accounting for treatment mode, there was no difference in survival (hazard ratioadj, 0.97; 95% CI, 0.90-1.04 for all patients, hazard ratioadj, 0.98; 95% CI: 0.90-1.06 for treated patients). CONCLUSIONS: Treatment disparities persist, even when adjusting for clinical and demographic factors. However, when black patients receive similar treatment, survival is comparable with white patients.


Assuntos
Afro-Americanos , Carcinoma Pulmonar de Células não Pequenas/terapia , Grupo com Ancestrais do Continente Europeu , Disparidades em Assistência à Saúde/etnologia , Neoplasias Pulmonares/terapia , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/etnologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Neoplasias Pulmonares/etnologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Medicare , Estadiamento de Neoplasias , Medição de Risco , Fatores de Risco , Programa de SEER , Fatores de Tempo , Resultado do Tratamento , Estados Unidos/epidemiologia
11.
BMC Cancer ; 18(1): 1188, 2018 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-30497433

RESUMO

BACKGROUND: Few studies have focused on quality of life (QoL) after treatment of malignant pleural mesothelioma (MPM). There are still questions as to which surgical procedure, extrapleural pneumonectomy (EPP) or pleurectomy decortication (P/D) is most effective and results in better survival outcomes, involves fewer complications, and results in better QoL. Here we performed a literature review on MPM patients to assess and compare QoL changes after P/D and EPP. METHODS: Research articles concerning QoL after mesothelioma surgery were identified through May 2018 in Medline. For inclusion, studies were 1) cohort or randomized controlled trials (RCT) design, 2) included standardized QoL instruments, 3) reported QoL measurement after surgery, 4) described the type of surgery performed (EPP or P/D), 5) were written in English. Measures of lung function (FEV1, FVC) and measures from the EORTC-C30 were compared 6 months following surgery with preoperative values. RESULTS: QoL data was extracted from 17 articles (14 datasets), encompassing 659 patients (102 EPP, 432 P/D); the available evidence was of low quality. While two studies directly compared QoL between the two surgical procedures, additional data was available from one arm of two RCTs, as the RCTs were not comparing EPP and P/D. The remaining data was reported from observational studies. While QoL was still compromised 6 months following surgery, from the limited and low quality data available it would appear that P/D patients had better QoL than EPP patients across all measures. Physical function, social function and global health were better at follow-up for P/D than for EPP, while other indicators such as pain and cough were similar. Forced Expiratory Volume (FEV1) and Forced Vital Capacity (FVC) were reported in one study only, and were higher at follow-up for P/D compared to EPP. CONCLUSIONS: Although the existing evidence is limited and of low quality, it suggests that P/D patients have better QoL than EPP patients following surgery. QoL outcomes should be factored into the choice of surgical procedure for MPM patients, and the possible effects on lung function and QoL should be discussed with patients when presenting surgical treatment options.


Assuntos
Neoplasias Pulmonares/epidemiologia , Mesotelioma/epidemiologia , Neoplasias Pleurais/epidemiologia , Qualidade de Vida , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/cirurgia , Masculino , Mesotelioma/diagnóstico , Mesotelioma/cirurgia , Neoplasias Pleurais/diagnóstico , Neoplasias Pleurais/cirurgia , Pneumonectomia/métodos , Resultado do Tratamento
12.
J Surg Oncol ; 118(7): 1178-1187, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30293239

RESUMO

BACKGROUND/OBJECTIVES: We evaluated postoperative mortality and complications after extrapleural pneumonectomy (EPP) and pleurectomy decortication (P/D) to better understand their effectiveness in malignant pleural mesothelioma (MPM). METHODS: A meta-analysis was done to evaluate 30-day mortality and postoperative complications. In addition, in-patients data of 500 eligible patients with MPM who underwent EPP or P/D was extracted from the New York Statewide Planning and Research Cooperative System (SPARCS). Multivariate analyses and propensity matching were used to compare in-hospital mortality and postoperative complications in EPP vs P/D. RESULTS: The meta-analysis showed a statistically significant difference in 30-day mortality (5% [95% CI: 4-6] vs P/D 2% [95% CI: 1-3]), proportion of complications (46% [95% CI: 36-56] vs 24% [95% CI: 15-34]) and postoperative arrhythmias (20% [95% CI: 12-31] vs 5% [95% CI: 2-8]) for EPP vs P/D. In-hospital mortality (OR adj : 2.6; 95% CI: 0.86-7.75) and postoperative complications (OR adj : 1.1; 95% CI: 0.68-1.86) were not different in EPP compared with P/D while supraventricular arrhythmia was significantly more frequent after EPP vs P/D (OR adj : 5.2; 95% CI: 2.34-11.33). CONCLUSIONS: Postoperative mortality, postoperative complications, and particularly supraventricular arrhythmia are less frequent after P/D vs EPP. P/D, a less invasive surgery, may provide a better option when technically feasible for patients with MPM.


Assuntos
Mortalidade Hospitalar , Mesotelioma/cirurgia , Pleura/cirurgia , Neoplasias Pleurais/cirurgia , Pneumonectomia/efeitos adversos , Idoso , Arritmias Cardíacas/epidemiologia , Bases de Dados Factuais , Feminino , Humanos , Masculino , Mesotelioma/mortalidade , Pessoa de Meia-Idade , New York/epidemiologia , Neoplasias Pleurais/mortalidade , Complicações Pós-Operatórias , Pontuação de Propensão
13.
Brain Behav Immun ; 73: 21-33, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30041013

RESUMO

The accumulation of neurotoxic amyloid-beta (Aß) in the brain is a characteristic hallmark of Alzheimer's disease (AD). The blood-brain barrier (BBB) provides a large surface area and has been shown to be an important mediator for removal of brain Aß. Both, the ABC transporter P-glycoprotein (ABCB1/P-gp) and the receptor low-density lipoprotein receptor-related protein 1 (LRP1) have been implicated to play crucial roles in Aß efflux from brain. Here, with immunoprecipitation experiments, co-immunostainings and dual inhibition of ABCB1/P-gp and LRP1, we show that both proteins are functionally linked, mediating a concerted transcytosis of Aß through endothelial cells. Late-onset AD risk factor Phosphatidylinositol binding clathrin assembly protein (PICALM) is associated with both ABCB1/P-gp and LRP1 representing a functional link and guiding both proteins through the brain endothelium. Together, our results give more mechanistic insight on Aß transport across the BBB and show that the functional interplay of different clearance proteins is needed for the rapid removal of Aß from the brain.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Proteínas Monoméricas de Montagem de Clatrina/fisiologia , Receptores de LDL/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/fisiologia , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Peptídeos beta-Amiloides/fisiologia , Animais , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/fisiologia , Encéfalo/metabolismo , Modelos Animais de Doenças , Células Endoteliais/metabolismo , Células Endoteliais/fisiologia , Masculino , Camundongos , Camundongos Knockout , Proteínas Monoméricas de Montagem de Clatrina/metabolismo , Fragmentos de Peptídeos/metabolismo , Cultura Primária de Células , Receptores de LDL/fisiologia , Suínos , Transcitose/fisiologia , Proteínas Supressoras de Tumor/fisiologia
14.
Int J Pharm ; 548(1): 104-112, 2018 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-29936200

RESUMO

d-ß-hydroxybutyrate and melatonin (BHB/MLT) infusion improves survival in hemorrhagic shock models. The original BHB/MLT formulation contains dimethyl sulfoxide (DMSO) to increase melatonin solubility. We formulated BHB/MLT solutions wherein DMSO was replaced either with 10% polyvinylpyrrolidone (BHB/MLT/PVP) or with 5% hydroxypropyl-ß-cyclodextrin/2.5% PVP/2.5% polyethylene glycol 400 (BHB/MLT/CD). Safety and efficacy of the new and the original BHB/MLT solution were tested in a lethal rat hemorrhagic shock model, with seven groups: 1) sham, 2) shock, untreated, 3) shock, lactated Ringer's solution (LR), 4) shock, 4 M BHB/MLT/DMSO, 5) shock, 2 M BHB/MLT/DMSO, 6) shock, BHB/MLT/PVP and 7) shock, BHB/MLT/CD. BHB/MLT/DMSO was given at full strength and 1:1 dilution to match the concentration of the novel formulations. Rats were anesthetized, instrumented, and 40% of the total blood volume was withdrawn in three steps, followed by four-hour long shock. Treatment boluses were infused half-way throughout hemorrhage. Survival was highest in BHB/MLT/CD-treated rats (8/10), followed by the BHB/MLT/PVP (6/10), 4 M BHB/MLT/DMSO (5/10) or 2 M BHB/MLT/DMSO (5/10), LR (3/10) and the untreated group (0/11). Survival did not differ significantly between BHB/MLT groups (p > 0.05), but was significantly higher in BHB/MLT/CD than in LR-treated animals (p = 0.018). BHB/MLT/PVP and BHB/MLT/CD constitute promising candidates for clinical hemorrhagic shock treatment.


Assuntos
Ácido 3-Hidroxibutírico/administração & dosagem , Melatonina/administração & dosagem , Choque Hemorrágico/tratamento farmacológico , 2-Hidroxipropil-beta-Ciclodextrina/administração & dosagem , 2-Hidroxipropil-beta-Ciclodextrina/química , 2-Hidroxipropil-beta-Ciclodextrina/farmacocinética , Ácido 3-Hidroxibutírico/química , Ácido 3-Hidroxibutírico/farmacocinética , Animais , Dimetil Sulfóxido/administração & dosagem , Dimetil Sulfóxido/química , Dimetil Sulfóxido/farmacocinética , Modelos Animais de Doenças , Masculino , Melatonina/química , Melatonina/farmacocinética , Povidona/administração & dosagem , Povidona/química , Povidona/farmacocinética , Ratos Sprague-Dawley , Choque Hemorrágico/sangue , Choque Hemorrágico/fisiopatologia
15.
Ann Thorac Surg ; 106(5): 1548-1555, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29928852

RESUMO

BACKGROUND: There are no published reports on predictors of oxygen (O2) use after lung cancer surgery. The prospect of O2 use after lung cancer surgery may affect a patient's therapy choice. METHODS: The Surveillance, Epidemiology, and End Results (SEER)-Medicare data set was queried to identify patients diagnosed with primary lung cancer (stage I/II) who underwent surgical resection from 1994 to 2010. Patients with a second resection within 6 months of their first and those with preoperative O2 use were excluded. Multivariable logistic regression was performed to evaluate the odds ratios and 95% confidence intervals of O2 use (defined as being billed for home O2) after discharge for lung cancer surgery. RESULTS: Of 21,245 eligible patients from 1994 to 2010, 3,255 (15.3%) were billed for O2 use in the first month of discharge. Of these, 13.7% (447 of 3,255) stopped using within 1 month, and 1.47% died. By 6 months, an additional 6.7% died, and 46.27% (1,384 of 2,991) were still alive and using O2. Discharge on O2 was associated with higher odds of death within 6 months (odds ratio, 1.35; 95% confidence interval, 1.17 to 1.55). The significant, independent risk factors for O2 use at discharge were procedure, sex, race, histology, pulmonary comorbidities, obesity, length of stay, pulmonary complications, and discharge mode. CONCLUSIONS: Home O2 use after lung cancer surgery comprises a sizable portion of this population and is correlated with death in the first 6 months. Various predictors significantly increased the risk of O2 use at discharge. However, 49.3% of those originally discharged on O2 were alive and off O2 at 6 months.


Assuntos
Causas de Morte , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/cirurgia , Oxigenoterapia/métodos , Pneumonectomia/métodos , Qualidade de Vida , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Continuidade da Assistência ao Paciente , Feminino , Seguimentos , Humanos , Incidência , Modelos Logísticos , Neoplasias Pulmonares/patologia , Masculino , Medicare/estatística & dados numéricos , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Oxigenoterapia/estatística & dados numéricos , Pneumonectomia/mortalidade , Cuidados Pós-Operatórios/métodos , Estudos Retrospectivos , Medição de Risco , Programa de SEER , Análise de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Estados Unidos
17.
Am J Clin Oncol ; 41(12): 1149-1153, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29642076

RESUMO

OBJECTIVE: Sublobar resection is often used as an alternative surgical approach in lung cancer patients who are unlikely to tolerate a full lobe resection. This study aims to assess outcomes of video-assisted thoracoscopic surgeries (VATS) sublobar resection as a surgical technique. MATERIALS AND METHODS: The SEER-Medicare database was queried to identify patients with primary lung cancer who had VATS or open sublobar resection. Baseline clinical differences between VATS and open patients were adjusted for in logistic regression and by propensity score matching to investigate surgical outcomes. RESULTS: Patients undergoing VATS had a greater number of comorbidities (adjusted odds ratio [ORadj], 0.90; 95% confidence interval [CI], 0.85-0.96) and were less likely to have later stage cancer (ORadj, 0.80; 95% CI, 0.67-0.95), squamous compared with adenocarcinoma (ORadj, 0.82; 95% CI, 0.68-0.99), large (>30 mm) tumor size (ORadj, 0.56; 95% CI, 0.0.41-0.75). VATS patients were less likely to have nodes removed for examination during surgery (ORadj, 0.76; 95% CI, 0.64-0.90). After propensity matching (n=2148), patients who underwent VATS were less likely to experience in-hospital complications, blood transfusions, and a prolonged length of hospital stay than those who had open surgery. There was no statistically significant difference in in-hospital or long-term mortality between patients with VATS and open surgery. CONCLUSION: In the most compromised lung cancer patients, VATS sublobar resection might be the best option.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/cirurgia , Tempo de Internação/estatística & dados numéricos , Neoplasias Pulmonares/cirurgia , Pneumonectomia/métodos , Complicações Pós-Operatórias , Cirurgia Torácica Vídeoassistida/métodos , Idoso , Carcinoma de Células Grandes/patologia , Carcinoma de Células Grandes/cirurgia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Estudos de Coortes , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/patologia , Masculino , Prognóstico , Programa de SEER
18.
Am J Surg ; 215(3): 467-470, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29395023

RESUMO

BACKGROUND: Selective internal radiation therapy (SIRT) with Ytrrium-90 (Y-90) has been used to treat hepatic malignancies with success. This study focuses on the efficacy and safety of Y-90 in the treatment of unresectable and metastatic intrahepatic cholangiocarcinoma (ICC). METHODS: A single-institution retrospective case review was performed for patients with unresectable and metastatic ICC treated with Y-90 between 2006 and 2016. RESULTS: Seventeen patients with ICC underwent 21 Y-90 treatments. Four patients had undergone prior liver resection, and six patients had extrahepatic disease at the time of treatment. Five year overall survival was 26.8%, with a median survival of 33.6 months. One patient underwent margin negative liver resection after a single treatment. Complications were appreciated in two cases. Ninety-day mortality was 0%. CONCLUSION: Treatment of ICC using Y-90 is a safe and promising procedure. Further research is needed to clarify its role in the treatment of unresectable and metastatic ICC.


Assuntos
Neoplasias dos Ductos Biliares/radioterapia , Ductos Biliares Intra-Hepáticos , Colangiocarcinoma/radioterapia , Compostos Radiofarmacêuticos/uso terapêutico , Radioisótopos de Ítrio/uso terapêutico , Adulto , Idoso , Neoplasias dos Ductos Biliares/mortalidade , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/patologia , Colangiocarcinoma/mortalidade , Colangiocarcinoma/patologia , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estudos Retrospectivos , Resultado do Tratamento
19.
Ann Thorac Surg ; 105(3): 886-891, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29397101

RESUMO

BACKGROUND: Studies reporting the benefits of video-assisted thoracoscopic surgery (VATS) lung cancer resection over thoracotomy have been subject to selection bias. We evaluated patient and hospital characteristics associated with type of surgery and the independent effect of VATS on outcomes. METHODS: The Statewide Planning and Research Cooperative System of New York State database was queried to identify all lung cancer patients undergoing lobectomy or sublobar resection between 2007 and 2012. Multivariable logistic regression was performed to identify patient (age, sex, race, comorbidities, year, and insurance) and hospital (urban, teaching, and total lung surgery volume) cofactors associated with surgical technique and propensity scores were used to evaluate whether technique was independently associated with complications or in-hospital mortality. RESULTS: There were 5,505 lobectomy and 4,282 sublobar resection patients, with 2,318 (42%) and 2,416 (56%) undergoing VATS, respectively. For lobectomy, VATS was associated with being female, lower comorbidity index, private insurance, older age, surgery in recent year, nonteaching hospital, and higher annual lung surgery volume. For sublobar resection, VATS was associated with black race, lower comorbidity index, Medicaid or other insurance, surgery in recent year, rural hospital, and higher annual lung surgery volume. Complication rate was significantly lower for VATS lobectomy and not sublobar resection, whereas in-hospital mortality was lower for VATS in both resection groups. CONCLUSIONS: Numerous patient- and hospital-related variables that affect morbidity and mortality also affect whether a patient undergoes VATS or open lung resection. Studies evaluating VATS must account more accurately for selection bias and adjust for these confounders.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/cirurgia , Pneumonectomia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Cirurgia Torácica Vídeoassistida/efeitos adversos , Toracotomia/efeitos adversos , Idoso , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Bases de Dados Factuais , Feminino , Mortalidade Hospitalar , Humanos , Modelos Logísticos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Estudos Retrospectivos
20.
Gastroenterol Clin North Am ; 47(1): 155-177, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29413010

RESUMO

Nutritional strategies have been explored as primary or adjunct therapies for inflammatory bowel disease (IBD). Exclusive enteral nutrition is effective for the induction of remission in Crohn disease and is recommended as a first-line therapy for children. Dietary strategies focus on adjusting the ratio of consumed nutrients that are proinflammatory or antiinflammatory. Treatments with dietary supplements focus on the antiinflammatory effects of the individual supplements (eg, curcumin, omega-3 fatty acids, vitamin D) or their positive effects on the intestinal microbiome (eg, prebiotics, probiotics). This article discusses the role of diets and dietary supplements in the treatment of IBD.


Assuntos
Colite Ulcerativa/terapia , Doença de Crohn/terapia , Dieta , Açúcares da Dieta/administração & dosagem , Suplementos Nutricionais , Curcumina/uso terapêutico , Dieta Livre de Glúten , Fibras na Dieta/administração & dosagem , Nutrição Enteral , Ácidos Graxos Ômega-3/uso terapêutico , Glutamina/uso terapêutico , Humanos , Imunoglobulina G/sangue , Nutrição Parenteral , Prebióticos , Probióticos/uso terapêutico , Vitamina D/uso terapêutico
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