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1.
Ann Surg ; 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38568206

RESUMO

OBJECTIVES: Our objective was to investigate overall survival (OS) and length of stay (LOS) associated with differing management for high output (>1 liter over 24 h) leaks (HOCL) following cancer related esophagectomy. SUMMARY BACKGROUND: Although infrequent, chyle leak following esophagectomy is an event that can lead to significant perioperative sequelae. Low volume leaks appear to respond to non-operative measures, while HOCL often require invasive therapeutic interventions. METHODS: From a prospective single-institution database, we retrospectively reviewed patients treated from 2001-2021 who underwent esophagectomy for esophageal cancer. Within that cohort, we focused on a subgroup of patients who manifested a HOCL postoperatively. Clinicopathologic and operative characteristics were collected, including hospital length of stay and survival data. RESULTS: A total of 53/2299 patients manifested a HOCL. These were mostly males (77%), with a mean age of 62 years. Of this group, 15 patients received non-operative management, 15 patients received prompt (<72 h from diagnosis) interventional management, and 23 received late interventional management. Patients in the late intervention group had longer length of stay compared to early intervention (Slope=9.849, 95% Confidence Interval [CI] 3.431 to 16.267). Late intervention (Hazard Ratio (HR) 4.772, CI: 1.384 to 16.460) and non-operative management (HR 4.731, CI: 1.294 to 17.305) were associated with increased mortality compared to early intervention. Patients with early intervention for HOCL had an overall survival similar to patients without chyle leaks in survival analysis. CONCLUSIONS: Patients with HOCL should receive early intervention in order to possibly reverse the prognostic implications of this potentially detrimental complication.

2.
Plast Reconstr Surg ; 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38376232

RESUMO

BACKGROUND: This study explores the surgical management and reconstruction options for augmented breasts in the context of breast conservation therapy (BCT) for breast cancer. We hypothesized that there would be no difference in the rates of complications, revisions, or patient satisfaction in patients who maintained their breast augmentation versus those that had their implants removed in the context of BCT. METHODS: We conducted a retrospective review of 142 patients who underwent BCT at a single center from March 2016 to March 2022. The study included patients who had a preexistent cosmetic augmentation at the time of breast cancer diagnosis and BCT. Patient demographics, clinical and treatment characteristics, breast implant details, reconstructive technique, complications, and revisions were recorded. Patient-reported outcomes were assessed using the BREAST-Q Breast-Conserving Therapy module. RESULTS: Ninety-three (65.5%) patients chose to maintain their implants, while 49 (34.5%) elected to have them removed during BCT. Patients with submuscular implants were more likely to maintain their implants. Oncoplastic mastopexy was associated with higher complication rates, particularly in patients opting for implant downsizing. However, multivariate logistic regression did not identify implant management strategy as an independent predictor for complications or revisions. Surgical site infection was the only predictor of implant explantation. Patient-reported outcomes did not differ significantly between the different implant management cohorts. CONCLUSIONS: This study demonstrates that maintaining breast implants during BCT does not increase the risk of complications or revisions. Overall, BCT in augmented women was found to be a safe approach, with high patient satisfaction.

3.
J Plast Reconstr Aesthet Surg ; 89: 174-185, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38199219

RESUMO

PURPOSE: Reconstructing defects after resecting soft-tissue sarcoma (STS) can be challenging. The aim of this retrospective study was to analyze the reconstructive outcomes and identify the potential risk factors in patients undergoing reconstruction after excision of lower-extremity STS. METHODS: Patients with lower-extremity STS were included. This database was compiled of patients from a single, large National Cancer Institute-accredited academic hospital. In total, 302 patients were included between January 2016 to January 2022. Univariate and multivariate analyses were performed to calculate odds ratios (ORs) for developing complications for each patient and surgical characteristic. RESULTS: The following factors were independent predictors of any complication: benign pulmonary disease (OR = 4.2; p = 0.02), preoperative radiotherapy (RT; OR = 2.5; p = 0.047), a tumor in the medial thigh (OR = 1.9; p = 0.03), body mass index (BMI) > 30 kg/m2 (OR = 1.05; p = 0.037), and full-thickness skin graft (OR = 5.4; p = 0.01). In the preoperative RT subgroup, reconstructing a defect via undermining and layered closure alone was an independent predictor of dehiscence (OR = 2.1; p = 0.02) and seroma (OR = 3.1; p = 0.02), whereas pedicled flaps (OR = 0.08; p = 0.001) and free flaps (OR = 0.05; p = 0.001) were independent protectors against any complication. CONCLUSION: Information derived from this analysis will assist with accurate preoperative patient counseling, which is crucial for informed decision-making and expectation management in lower-extremity STS. BMI and pulmonary function should be optimized to the extent possible to reduce postoperative complications. Patients treated preoperatively with RT should be reconstructed with a pedicled or free flap to optimize recovery.


Assuntos
Retalhos de Tecido Biológico , Procedimentos de Cirurgia Plástica , Sarcoma , Neoplasias de Tecidos Moles , Humanos , Procedimentos de Cirurgia Plástica/efeitos adversos , Estudos Retrospectivos , Retalhos de Tecido Biológico/transplante , Extremidade Inferior/cirurgia , Extremidade Inferior/patologia , Sarcoma/patologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/cirurgia , Neoplasias de Tecidos Moles/cirurgia , Neoplasias de Tecidos Moles/patologia , Fatores de Risco
4.
Breast Cancer Res Treat ; 203(2): 397-406, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37851289

RESUMO

PURPOSE: Mastectomy, breast reconstruction (BR) and breast conserving therapy (BCT) are core components of the treatment paradigm for early-stage disease but are differentially associated with significant financial burdens. Given recent price transparency regulations, we sought to characterize rates of disclosure for breast cancer-related surgery, including mastectomy, BCT, and BR (oncoplastic reconstruction, implant, pedicled flap and free flap) and identify associated factors. METHODS: For this cross-sectional analysis, cost reports were obtained from the Turquoise Health price transparency platform for all U.S. hospitals meeting national accreditation standards for breast cancer care. The Healthcare Cost Report Information System was used to collect facility-specific data. Addresses were geocoded to identify hospital referral and census regions while data from CMS was also used to identify the geographic practice cost index. We leveraged a Poisson regression model and relevant Medicare billing codes to analyze factors associated with price disclosure and the availability of an OOP price estimator. RESULTS: Of 447 identified hospitals, 221 (49.4%) disclosed prices for mastectomy and 188 42.1%) disclosed prices for both mastectomy and some form of reconstruction including oncoplastic reduction (n = 184, 97.9%), implants (n = 187, 99.5%), pedicled flaps (n = 89, 47.3%), and free flaps (n = 81, 43.1%). Non-profit status and increased market competition were associated with price nondisclosure. 121 hospitals (27.1%) had an out-of-pocket price estimator that included at least one breast surgery. CONCLUSIONS: Most eligible hospitals did not disclose prices for breast cancer surgery. Distinct hospital characteristics were associated with price disclosure. Breast cancer patients face persistent difficulty in accessing costs.


Assuntos
Neoplasias da Mama , Retalhos de Tecido Biológico , Mamoplastia , Humanos , Idoso , Estados Unidos/epidemiologia , Feminino , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/cirurgia , Mastectomia , Revelação , Estudos Transversais , Medicare
5.
Ann Am Thorac Soc ; 21(1): 38-46, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37796618

RESUMO

Rationale: Pulmonary function testing (PFT) is performed to aid patient selection before surgical resection for non-small cell lung cancer (NSCLC). The interpretation of PFT data relies on normative equations, which vary by race, but the relative strength of association of lung function using race-specific or race-neutral normative equations with postoperative pulmonary complications is unknown. Objectives: To compare the strength of association of lung function, using race-neutral or race-specific equations, with surgical complications after lobectomy for NSCLC. Methods: We studied 3,311 patients who underwent lobectomy for NSCLC and underwent preoperative PFT from 2001 to 2021. We used Global Lung Function Initiative equations to generate race-specific and race-neutral normative equations to calculate percentage predicted forced expiratory volume in 1 second (FEV1%). The primary outcome of interest was the occurrence of postoperative pulmonary complications within 30 days of surgery. We used unadjusted and race-adjusted logistic regression models and least absolute shrinkage and selection operator analyses adjusted for relevant comorbidities to measure the association of race-specific and race-neutral FEV1% with pulmonary complications. Results: Thirty-one percent of patients who underwent surgery experienced pulmonary complications. Higher FEV1, whether measured with race-neutral (odds ratio [OR], 0.98 per 1% change in FEV1% [95% confidence interval (CI), 0.98-0.99]; P < 0.001) or race-specific (OR, 0.98 per 1% change in FEV1% [95% CI, 0.98-0.98]; P < 0.001) normative equations, was associated with fewer postoperative pulmonary complications. The area under the receiver operator curve for pulmonary complications was similar for race-adjusted race-neutral (0.60) and race-specific (0.60) models. Using least absolute shrinkage and selection operator regression, higher FEV1% was similarly associated with a lower rate of pulmonary complications in race-neutral (OR, 0.99 per 1% [95% CI, 0.98-0.99]) and race-specific (OR, 0.99 per 1%; 95% CI, 0.98-0.99) models. The marginal effect of race on pulmonary complications was attenuated in all race-specific models compared with all race-neutral models. Conclusions: The choice of race-specific or race-neutral normative PFT equations does not meaningfully affect the association of lung function with pulmonary complications after lobectomy for NSCLC, but the use of race-neutral equations unmasks additional effects of self-identified race on pulmonary complications.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma Pulmonar de Células não Pequenas/complicações , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/complicações , Estudos Retrospectivos , Pneumonectomia/efeitos adversos , Pulmão/cirurgia , Volume Expiratório Forçado , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/cirurgia
6.
J Thorac Cardiovasc Surg ; 167(1): 329-337.e4, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37116780

RESUMO

OBJECTIVES: Disparities in cancer care are omnipresent and originate from a multilevel set of barriers. Our objectives were to describe the likelihood of undergoing surgery for early-stage non-small cell lung cancer at minority-serving hospitals (MSHs), and evaluate the association of race/ethnicity with resection based on MSH status. METHODS: A retrospective study using the National Cancer Database (2008-2016) was conducted including patients with clinical stage I non-small cell lung cancer. MSHs were defined as hospitals in the top decile of providing care to Hispanic or African American patients. The primary outcome evaluated was receipt of definitive surgery at MSHs vs non-MSHs. Outcomes related to race/ethnicity stratified by hospital type were also investigated. RESULTS: A total of 142,580 patients were identified from 1192 hospitals (120 MSHs and 1072 non-MSHs). Most patients (85% [n = 121,240]) were non-Hispanic White, followed by African American (9% [n = 12,772]), and Hispanic (3%, [n= 3749]). MSHs cared for 7.4% (n = 10,491) of the patients included. In adjusted analyses, patients treated at MSHs were resected less often than those at non-MSHs (odds ratio, 0.87; 95% CI, 0.76-1.00; P = .0495). African American patients were less likely to receive surgery in the overall analysis (P < .01), and at MSHs specifically (P < .01), compared with non-Hispanic White patients. Hispanic patients had similar rates of resection in the overall analysis (P = .11); however, at MSHs, they underwent surgery more often compared with non-Hispanic White patients (P = .02). Resected patients at MSHs had similar overall survival (median, 91.7 months; 95% CI, 86.6-96.8 months) compared with those resected at non-MSHs (median, 85.7 months; 95% CI, 84.5-86.8 months). CONCLUSIONS: Patients with early-stage non-small cell lung cancer underwent resection less often at MSHs compared with non-MSHs. Disparities related to underutilization of surgery for African American patients continue to persist, regardless of hospital type.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Estudos Retrospectivos , Neoplasias Pulmonares/cirurgia , Hospitais , Disparidades em Assistência à Saúde , Brancos
7.
Org Biomol Chem ; 21(46): 9128-9132, 2023 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-37966723

RESUMO

The remarkable biological activities of γ-lactams have stimulated the search for efficient synthetic methods to achieve these scaffolds. In this work, we have developed a simple one-pot diastereoselective synthesis of new γ-lactams from ketoaziridines with moderate to good yields via the Horner-Wadsworth-Emmons reaction, followed by an intramolecular ester-aziridine cyclization and its opening in situ. Preliminary efforts towards an enantioselective version of this method are also reported.

8.
Ann Thorac Surg ; 2023 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-37806335

RESUMO

BACKGROUND: The presence of lymphovascular invasion (LVI) in early esophageal adenocarcinoma (EAC) is associated with more aggressive disease. Molecular markers associated with LVI are still largely unknown. Using a combination of transcriptomic analysis and validation experiments, we sought to describe markers for LVI and survival. METHODS: We performed NanoString expression profiling using RNA from 60 EAC specimens collected from surgery-only cases between 2000 and 2012. Differentially expressed genes (DEGs) were correlated with pathologic characteristics (T and N status and presence of LVI). Kaplan-Meier and Cox regression analyses were used to correlate gene expression with overall survival. Expression of alanyl aminopeptidase, membrane (ANPEP)/CD13 was validated by immunohistochemistry (IHC) in EAC tissue microarray and in EAC cell lines. RESULTS: We identified >20 up-regulated DEGs in tumor samples containing LVI. Multivariable analysis showed depth of invasion and ANPEP/CD13 expression were independently associated with overall survival, whereas nodal status was not. IHC analysis demonstrated overexpression of the ANPEP/CD13 protein in dysplastic Barrett esophagus and EAC tumors. Kaplan-Meier analysis showed that patients with higher RNA expression and strongly positive ANPEP/CD13 membrane IHC-Histoscore staining have shorter survival (P = .002). Down-regulation of ANPEP/CD13 expression by short hairpin RNA vector reduces colony formation, migration, and invasion of FLO-1 EAC cells. Overexpression of CD13 in SKGT4 EAC cells increases colony formation, motility, and invasion in vitro. CONCLUSIONS: Elevated expression of ANPEP/CD13 indicates shorter survival of EAC patients and a more invasive phenotype of cancer cells in vitro. Validation in a larger sample group is required to better understand the clinical significance of ANPEP/CD13 and other candidate genes.

9.
ChemistryOpen ; 12(6): e202300070, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37287423

RESUMO

Indole derivatives substituted at the C-2 position have shown important biological activities. Due to these properties, several methods have been described for the preparation of structurally diverse indoles. In this work, we have synthesized highly functionalized indole derivatives via Rh(III)-catalyzed C-2 alkylation with nitroolefins. Under the optimized condition, 23 examples were prepared with 39-80 % yield. Moreover, the nitro compounds were reduced and submitted to the Ugi four-component reaction, furnishing a series of new indole-peptidomimetics in moderate to good overall yields.

10.
J Org Chem ; 88(13): 8781-8790, 2023 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-37272775

RESUMO

Reactions involving C(sp3)-H bonds of azaarenes have been widely studied in recent years as they allow direct functionalization of these N-heterocycles without the use of harsh reaction conditions. In this work, we describe the C(sp3)-H functionalization of 4-methylquinazolines and 1-benzylisoquinolines, employing α-substituted ß-nitrostyrenes catalyzed by inexpensive copper acetate. Under the optimized condition, 21 pyrrolo[1,2-c]quinazolines, as well as an imidazo[1,2-c]quinazoline and 4 pyrrolo[2,1-a]isoquinolines, were obtained in moderate to good yields. Furthermore, the biological activity of the pyrrolo[1,2-c]quinazolines was evaluated against Plasmodium falciparum, and promising results were obtained.


Assuntos
Antimaláricos , Quinazolinas , Cobre/farmacologia , Cobre/química , Isoquinolinas/química , Catálise
11.
JTO Clin Res Rep ; 3(11): 100420, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36389133

RESUMO

Introduction: Complete pathologic response (CPR) is an acceptable surrogate for survival in clinical trials but it occurs infrequently in patients with NSCLC receiving neoadjuvant chemotherapy (NCT). Therefore, we studied the impact of major pathologic response (MPR) for predicting survival of patients with NSCLC receiving NCT. We also tested a newly reported scoring system-the prognostic score (PRSC)-which combines T category, lymph node status, and MPR status. Methods: We analyzed CPR and MPR, defined as 0% and less than or equal to 10% viable tumor cells, respectively, in 339 patients with NSCLC with various histologic types who had been treated with NCT followed by complete surgical resection. We evaluated the relationships between CPR, MPR, or PRSC and overall survival using the Kaplan-Meier method and Cox regression multivariate models, accounting for known prognostic factors, such as age, gender, histologic subtype, and pathologic stage. Results: Among all 339 patients, the Kaplan-Meier method revealed that patients with CPR and MPR had better survival. MPR identified a favorable group of patients who experienced survival similar to patients with CPR. Nevertheless, patients with no MPR had a significantly reduced probability of survival. Furthermore, univariate and multivariate Cox proportional hazards regression analysis revealed that MPR and PRSC were significantly associated with overall survival. Conclusions: Our data suggest that MPR can be used as an end point for overall survival in different histologic types for evaluation of therapeutic agents in clinical trials exploring NCT. We also confirmed that PRSC had a prognostic impact, differentiating patients into three prognostic groups, but not superior compared with MPR alone or the TNM8 systems.

12.
Molecules ; 28(1)2022 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-36615207

RESUMO

BINOL derivatives have shown relevant biological activities and are important chiral ligands and catalysts. Due to these properties, their asymmetric synthesis has attracted the interest of the scientific community. In this work, we present an overview of the most efficient methods to obtain chiral BINOLs, highlighting the use of metal complexes and organocatalysts as well as kinetic resolution. Further derivatizations of BINOLs are also discussed.


Assuntos
Naftóis , Estereoisomerismo , Catálise , Ligantes
13.
Pharmaceuticals (Basel) ; 14(11)2021 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-34832907

RESUMO

Viral infections cause many severe human diseases, being responsible for remarkably high mortality rates. In this sense, both the academy and the pharmaceutical industry are continuously searching for new compounds with antiviral activity, and in addition, face the challenge of developing greener and more efficient methods to synthesize these compounds. This becomes even more important with drugs possessing stereogenic centers as highly enantioselective processes are required. In this minireview, the advances achieved to improve synthetic routes efficiency and sustainability of important commercially antiviral chiral drugs are discussed, highlighting the use of organocatalytic methods.

14.
Am Surg ; 87(12): 1934-1945, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34553636

RESUMO

BACKGROUND: Little is known regarding the impact of operating room (OR) personnel generation on their perceptions to various surgeon behaviors. We aimed to characterize these relationships by evaluating their responses to 5 realistic intraoperative scenarios. METHODS: Operating room personnel were asked to assess surgeon OR behavior across a standardized set of 5 scenarios via an online survey. For each scenario, respondents were asked to identify the behavior as either acceptable, unacceptable but would ignore, unacceptable and would confront the surgeon, or unacceptable and would report to management. Chi-squared analyses were used to compare responses to surgeon behavior with respondent generation. RESULTS: There were 3101 respondents, of which 41% of respondents were baby boomers (n = 1280), 31% were generation (Gen) X (n = 955), and 28% were Gen Y (n = 866). Overall, when compared to Gen X or Gen Y, baby boomers were significantly more likely to find surgeon behaviors of impatience (P < .001), being late for a case (P < .001), swearing in the OR (P < .001), and shouting with a bleeding patient (P = .001) to be inappropriate and would talk to the surgeon. Alternatively, Gen Y respondents were more likely to find fault with surgeon behaviors that deviate from rules and regulations, such as forgetting a time-out (P = .001), when compared to baby boomers and Gen X respondents. DISCUSSION: Results of our study demonstrate that OR personnel generation affects their perceptions and response to surgeon behavior. Understanding these tendencies can guide efforts to improve OR interactions among team members.


Assuntos
Atitude do Pessoal de Saúde , Comportamento , Corpo Clínico Hospitalar/psicologia , Recursos Humanos de Enfermagem Hospitalar/psicologia , Salas Cirúrgicas , Cirurgiões/psicologia , Estudos Transversais , Feminino , Humanos , Relação entre Gerações , Masculino , Equipe de Assistência ao Paciente
15.
Ultrason Sonochem ; 78: 105704, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34454180

RESUMO

Ultrasound is an essential technique to improve organic synthesis from the point of view of green chemistry, as it can promote better yields and selectivities, in addition to shorter reaction times when compared to the conventional methods. Heterogeneous catalysis is another pillar of sustainable chemistry being the recycling and reuse of the catalysts one of its great advantage. In the other hand, multicomponent reactions provide the synthesis of structurally diverse compounds, in a one-pot fashion, without isolation and purification of intermediates. Thus, the combination of these protocols has proved to be a powerful tool to obtain biologically active organic compounds with lower costs, time and energy consumption. Herein, we provide a comprehensive overview of advances on methods of organic synthesis that have been reported over the past ten years with focus on ultrasound-assisted multicomponent reactions under heterogeneous catalysis. In particular, we present pharmacologically important N- and O-heterocyclic compounds, considering their synthetic methods using green solvents, and catalyst recycling.


Assuntos
Compostos Orgânicos/química , Catálise , Técnicas de Química Sintética , Solventes
16.
Beilstein J Org Chem ; 17: 1952-1980, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34386105

RESUMO

Coumarin derivatives are essential scaffolds in medicinal and synthetic chemistry. Compounds of this class have shown important activities, such as anticancer and antiparasitic, besides the commercially available drugs. These properties led to the development of efficient and greener synthetic methods to achieve the 2H-chromen-2-one core. In this context, the advances in asymmetric organocatalyzed synthesis of coumarin derivatives are discussed in this review, according to the mode of activation of the catalyst.

17.
J Thorac Oncol ; 16(8): 1289-1297, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33857666

RESUMO

INTRODUCTION: Major pathologic response (MPR), defined as residual viable tumor of less than or equal to 10%, currently serves as a surrogate end point for survival for patients with resectable NSCLC after neoadjuvant chemotherapy. However, the significance of pathologic response in lymph nodes harboring metastatic tumors in such patients remains uncertain. Therefore, we studied the effect of neoadjuvant chemotherapy on resected positive lymph nodes and determined if the degree of pathologic response in the lymph nodes alone (LN-MPR) or in combination with that of the primary tumor (PT-MPR) was able to predict the outcome. METHODS: A total of 75 patients with NSCLC who underwent neoadjuvant chemotherapy and completed surgical resection were included in this study. Tissue specimens were retrospectively evaluated by two pathologists blinded to the patients' treatments and outcomes. Specimens were reviewed for the degree of pathologic response in the primary tumor and in any involved lymph nodes. The prognostic performance of LN-MPR alone or in combination with PT-MPR with respect to overall survival (OS) was evaluated using the Kaplan-Meier method and Cox regression model. RESULTS: LN-MPR was significantly predictive of long-term OS after neoadjuvant chemotherapy. A combination of PT-MPR with LN-MPR was significantly associated with outcome and allowed stratification of patients into three prognostic groups (p = 0.001). CONCLUSIONS: LN-MPR in isolation is a reliable predictor of OS in patients with NSCLC receiving neoadjuvant chemotherapy. A combination of LN-MPR with PT-MPR seems to correlate well with the outcome and can be used to predict prognosis in this patient population.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Linfonodos , Terapia Neoadjuvante , Prognóstico , Estudos Retrospectivos
18.
Gut ; 70(12): 2238-2248, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33487592

RESUMO

OBJECTIVE: Gastro-oesophageal cancers (GEC) are resistant to therapy and lead to poor prognosis. The cancer stem cells (CSCs) and antiapoptotic pathways often confer therapy resistance. We sought to elucidate the antitumour action of a BCL-2 inhibitor, AT101 in GEC in vitro, in vivo and in a clinical trial. METHODS: Extensive preclinical studies in vitro and in vivo were carried out to establish the mechanism action of AT101 on targeting CSCs and antiapoptotic proteins. A pilot clinical trial in patients with GEC was completed with AT-101 added to standard chemoradiation. RESULTS: Overexpression of BCL-2 and MCL-1 was noted in gastric cancer tissues (GC). AT-101 induced apoptosis, reduced proliferation and tumour sphere formation in MCL-1/BCL-2 high GC cells. Interestingly, AT101 dramatically downregulated genes (YAP-1/Sox9) that control CSCs in GEC cell lines regardless of BCL-2/MCL-1 expression. Addition of docetaxel to AT-101 amplified its antiproliferation and induced apoptosis effects. In vivo studies confirmed the combination of AT101 and docetaxel demonstrated stronger antitumour activity accompanied with significant decrease of CSCs biomarkers (YAP1/SOX9). In a pilot clinical trial, 13 patients with oesophageal cancer (EC) received AT101 orally concurrently with chemoradiation. We observed dramatic clinical complete responses and encouraging overall survival in these patients. Clinical specimen analyses revealed that AT-101 dramatically reduced the expression of CSCs genes in treated EC specimens indicating antitumour activity of AT101 relies more on its anti-CSCs activity. CONCLUSIONS: Our preclinical and clinical data suggest that AT-101 overcomes resistance by targeting CSCs pathways suggesting a novel mechanism of action of AT101 in patients with GEC.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Neoplasias Esofágicas/tratamento farmacológico , Gossipol/análogos & derivados , Células-Tronco Neoplásicas/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/antagonistas & inibidores , Neoplasias Gástricas/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Modelos Animais de Doenças , Docetaxel/farmacologia , Neoplasias Esofágicas/genética , Feminino , Gossipol/farmacologia , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Projetos Piloto , Proteínas Proto-Oncogênicas c-bcl-2/genética , Neoplasias Gástricas/genética
19.
Ann Surg ; 274(6): 1099-1106, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-32229762

RESUMO

OBJECTIVE: The aim of this study was to assess the effect of an enhanced recovery after surgery (ERAS) pathway on pain and opioid use following lung resection. SUMMARY BACKGROUND DATA: A major component ERAS pathways is opioid-sparing analgesia; however, the effect on postoperative pain and opioid use in patients undergoing lung resection is unknown. METHODS: Following implementation of an ERAS pathway for lung resection, 123 consecutive patients were identified. Patients were propensity-matched 1:1 with a group of consecutive patients (n = 907) undergoing lung resection before ERAS. Differences regarding in-hospital opioid consumption, discharge prescribing of opioids, and postoperative pain scores were examined. Morphine milligram equivalents were separately calculated including and excluding tramadol as an opioid medication. RESULTS: There were no significant differences between matched patients regarding age, sex, performance status, receipt of preoperative treatment, extent of lung resection, or operative approach. Epidural analgesia was used in 66% of controls and in none of the ERAS group (P < 0.001). The number of adjunct analgesics used postoperatively was greater in the ERAS group (median 3 vs 2, P < 0.001). There was a major reduction in morphine milligram equivalents in the ERAS group whether tramadol was included (median 14.2 vs 57.8, P < 0.001) or excluded (median 2.7 vs 57.8, P < 0.001) and regardless of surgical approach. Average daily pain scores were lower in the ERAS group (median 1.3 vs 1.8, P = 0.004); however, this difference was present only among patients undergoing thoracotomy. The proportion of patients who were prescribed discharge opioids varied whether tramadol was included (96% each group, P = 1.00) or excluded (39% vs 80%, P < 0.001) in the analysis. CONCLUSIONS: Implementation of an ERAS pathway was associated with effective post-operative analgesia, major reductions in in-hospital consumption of opioids, and reduced pain, compared to conventional management.


Assuntos
Analgésicos Opioides/uso terapêutico , Recuperação Pós-Cirúrgica Melhorada , Pneumopatias/cirurgia , Manejo da Dor/métodos , Dor Pós-Operatória/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Análise por Pareamento , Pessoa de Meia-Idade , Pontuação de Propensão , Estudos Retrospectivos
20.
J Thorac Cardiovasc Surg ; 162(1): 296-305, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-32713636

RESUMO

OBJECTIVES: Although colorectal cancer bowel segment location has been shown to independently predict the outcomes in early stage disease, it has not been previously studied in the setting of pulmonary metastases. We sought to determine whether colorectal cancer location affects survival after pulmonary metastasectomy. METHODS: Patients who had undergone pulmonary metastasectomy for colorectal cancer at a single institution from 2011 to 2018 were reviewed. Univariable and multivariable Cox regression analyses were performed to identify predictors of overall survival and disease-free survival. The Kaplan-Meier survival method was used to determine differences between groups. RESULTS: A total of 194 patients were evaluated. The median follow-up, survival time, and 5-year survival rate were 36.8 months, 75.8 months, and 57%, respectively, and 122 patients (63%) had experienced disease recurrence at any location. On univariable analysis, age, primary tumor location, pulmonary nodule size, ≥3 pulmonary nodules, and intrathoracic nodal disease were associated with overall survival. On multivariable analysis, patients with left-sided tumors experienced a survival benefit (hazard ratio, 0.31; P = .036). Kaplan-Meier analysis revealed a median survival time of 90 months (95% confidence interval, 82 months to not reached) compared with 55 months (95% confidence interval, 49 months to not reached) for patients with left-sided and rectal tumors, respectively, after metastasectomy (P = .078). Location was not associated with disease-free survival on Cox multivariable regression. CONCLUSIONS: We found that left-sided colorectal cancer is associated with prolonged survival after pulmonary metastasectomy. Future investigations are required to determine the validity of such findings, including the effect of location in the prognostication for patients who are candidates for pulmonary metastasectomy.


Assuntos
Neoplasias Colorretais , Neoplasias Pulmonares , Pneumonectomia/mortalidade , Idoso , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
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