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1.
J Nurs Care Qual ; 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38936412

ABSTRACT

BACKGROUND: Frailty is independently associated with adverse patient outcomes after surgery. The current standards of postoperative care rarely consider frailty status. LOCAL PROBLEM: There was no standardized protocol to optimize specialized postoperative care for frail patients at an academic medical center. METHODS: A quasi-experimental pre-/postimplementation study design, using the Reach, Effectiveness, Adoption, Implementation, Maintenance implementation framework, was utilized. INTERVENTIONS: A frailty-specific postoperative order set (FPOS) was developed, including tailored nursing care, activity levels, and nutritional goals. RESULTS: There were significant improvements in nurse's self-reported familiarity with frailty (P = .003) and FPOS awareness (P < .001). The number of orders for delirium prevention, elimination, nutrition, sleep promotion, and sensory support increased (P < .001). CONCLUSIONS: Implementing an FPOS showed improvements in nurse frailty knowledge, awareness, and order set utilization.

2.
Ann Thorac Surg ; 118(1): 275-281, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38574939

ABSTRACT

BACKGROUND: Chatbot use in medicine is growing, and concerns have been raised regarding their accuracy. This study assessed the performance of 4 different chatbots in managing thoracic surgical clinical scenarios. METHODS: Topic domains were identified and clinical scenarios were developed within each domain. Each scenario included 3 stems using Key Feature methods related to diagnosis, evaluation, and treatment. Twelve scenarios were presented to ChatGPT-4 (OpenAI), Bard (recently renamed Gemini; Google), Perplexity (Perplexity AI), and Claude 2 (Anthropic) in 3 separate runs. Up to 1 point was awarded for each stem, yielding a potential of 3 points per scenario. Critical failures were identified before scoring; if they occurred, the stem and overall scenario scores were adjusted to 0. We arbitrarily established a threshold of ≥2 points mean adjusted score per scenario as a passing grade and established a critical fail rate of ≥30% as failure to pass. RESULTS: The bot performances varied considerably within each run, and their overall performance was a fail on all runs (critical mean scenario fails of 83%, 71%, and 71%). The bots trended toward "learning" from the first to the second run, but without improvement in overall raw (1.24 ± 0.47 vs 1.63 ± 0.76 vs 1.51 ± 0.60; P = .29) and adjusted (0.44 ± 0.54 vs 0.80 ± 0.94 vs 0.76 ± 0.81; P = .48) scenario scores after all runs. CONCLUSIONS: Chatbot performance in managing clinical scenarios was insufficient to provide reliable assistance. This is a cautionary note against reliance on the current accuracy of chatbots in complex thoracic surgery medical decision making.


Subject(s)
Thoracic Surgical Procedures , Humans , Thoracic Surgical Procedures/methods , Reproducibility of Results
3.
J Clin Ethics ; 34(3): 270-272, 2023.
Article in English | MEDLINE | ID: mdl-37831650

ABSTRACT

AbstractInformed consent is a necessary component of the ethical practice of surgery. Ideally, consent is performed in a setting conducive to a robust patient-provider conversation, with careful consideration of risks, benefits, and outcomes. For patients with medical or surgical emergencies, navigating the consent process can be complicated and requires both careful and expedited assessment of decision-making capacity. We present a recent case in which a patient in need of emergency care refused intervention, requiring urgent capacity assessment and a modification to usual care.


Subject(s)
Emergency Treatment , Informed Consent , Surgical Procedures, Operative , Humans , Surgical Procedures, Operative/ethics , Emergency Treatment/ethics
4.
JAMA Netw Open ; 6(8): e2327351, 2023 08 01.
Article in English | MEDLINE | ID: mdl-37556141

ABSTRACT

Importance: Patients with mesothelioma often have next-generation sequencing (NGS) of their tumor performed; tumor-only NGS may incidentally identify germline pathogenic or likely pathogenic (P/LP) variants despite not being designed for this purpose. It is unknown how frequently patients with mesothelioma have germline P/LP variants incidentally detected via tumor-only NGS. Objective: To determine the prevalence of incidental germline P/LP variants detected via tumor-only NGS of mesothelioma. Design, Setting, and Participants: A series of 161 unrelated patients with mesothelioma from a high-volume mesothelioma program had tumor-only and germline NGS performed during April 2016 to October 2021. Follow-up ranged from 18 months to 7 years. Tumor and germline assays were compared to determine which P/LP variants identified via tumor-only NGS were of germline origin. Data were analyzed from January to March 2023. Main Outcomes and Measures: The proportion of patients with mesothelioma who had P/LP germline variants incidentally detected via tumor-only NGS. Results: Of 161 patients with mesothelioma, 105 were male (65%), the mean (SD) age was 64.7 (11.2) years, and 156 patients (97%) self-identified as non-Hispanic White. Most (126 patients [78%]) had at least 1 potentially incidental P/LP germline variant. The positive predictive value of a potentially incidental germline P/LP variant on tumor-only NGS was 20%. Overall, 26 patients (16%) carried a P/LP germline variant. Germline P/LP variants were identified in ATM, ATR, BAP1, CHEK2, DDX41, FANCM, HAX1, MRE11A, MSH6, MUTYH, NF1, SAMD9L, and TMEM127. Conclusions and Relevance: In this case series of 161 patients with mesothelioma, 16% had confirmed germline P/LP variants. Given the implications of a hereditary cancer syndrome diagnosis for preventive care and familial counseling, clinical approaches for addressing incidental P/LP germline variants in tumor-only NGS are needed. Tumor-only sequencing should not replace dedicated germline testing. Universal germline testing is likely needed for patients with mesothelioma.


Subject(s)
Mesothelioma, Malignant , Mesothelioma , Humans , Male , Middle Aged , Female , Genetic Predisposition to Disease , Mesothelioma/diagnosis , Mesothelioma/genetics , High-Throughput Nucleotide Sequencing , Genomics , Adaptor Proteins, Signal Transducing/genetics , DNA Helicases/genetics
5.
Ann Thorac Surg ; 116(4): 712-719, 2023 10.
Article in English | MEDLINE | ID: mdl-37244601

ABSTRACT

BACKGROUND: Despite improved outcomes, minimally invasive esophagectomy (MIE) continues to be associated with anastomotic strictures. Most resolve after a single dilation; however, some become refractory. Little is known about strictures after MIE in North America. METHODS: We performed a single-institution retrospective review of MIEs from 2015 to 2019. Primary outcomes were the proportion of patients requiring anastomotic dilation and the dilation rate per year. Univariate analyses of patients undergoing dilation by various risk factors were performed with nonparametric tests, and multivariate analyses of the dilation rate were conducted using generalized linear models. RESULTS: Of 391 included patients, 431 dilations were performed on 135 patients (34.5%, 3.2 dilations per patient who required at least 1 per patient). One complication occurred after dilation. Comorbidities, tumor histology, and tumor stage were not significantly associated with stricture. Three-field MIE was associated with a higher percentage of patients undergoing dilation (48.9% vs 27.1%, P < .001) and a higher rate of dilations (0.944 vs 0.441 dilations per year, P = .007) than 2-field MIE, and this association remained significant after controlling for covariates. When accounting for surgeon variability, this difference was no longer significant. Among patients with 1 or more dilations, those receiving dilation within 100 days of surgery needed more subsequent dilations (2.0 vs 0.6 dilations per year, P < .001). CONCLUSIONS: After controlling for multiple variables, a 3-field MIE approach was associated with a higher rate of repeat dilations in patients undergoing MIE. A shorter interval between esophagectomy and initial dilation is strongly associated with the need for repeated dilations.


Subject(s)
Esophageal Neoplasms , Esophageal Stenosis , Humans , Constriction, Pathologic/surgery , Esophageal Stenosis/epidemiology , Esophageal Stenosis/etiology , Esophageal Stenosis/surgery , Esophagectomy/adverse effects , Treatment Outcome , Anastomosis, Surgical/adverse effects , Retrospective Studies , Minimally Invasive Surgical Procedures/adverse effects , Esophageal Neoplasms/complications
6.
Thorac Surg Clin ; 33(2): 189-196, 2023 May.
Article in English | MEDLINE | ID: mdl-37045488

ABSTRACT

There have been numerous recent advances in the treatmetn of stage IIIA non-small cell lung cancer. The most significant involve the addition of targeted therapies adn immune checkpoint inhibitors into perioperative care. These exciting advances are improving survival in this challenging patient population, but some-decade old controveries around the definition of resectability, prognositic importance of tumor response to induction therapy, and the role of pneumonectomy persist.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/therapy , Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/therapy , Lung Neoplasms/pathology , Neoplasm Staging , Immunotherapy , Pneumonectomy
7.
J Thorac Cardiovasc Surg ; 166(5): 1375-1384, 2023 Nov.
Article in English | MEDLINE | ID: mdl-36878749

ABSTRACT

OBJECTIVE: In recent years, the historically low proportion of women cardiothoracic surgeons and trainees has been a subject of intense focus. Publications remain a key metric of academic success and career advancement. We sought to identify trends in the gender of first and last author publications in cardiothoracic surgery. METHODS: We searched for publications between 2011 and 2020 in 2 US cardiothoracic surgery journals, identifying those with Medical Subject Heading publication types of clinical trials, observational studies, meta-analyses, commentary, reviews, and case reports. A commercially available, validated software (Gender-API) was used to associate gender with author names. Association of American Medical Colleges Physician Specialty Data Reports were used to identify concurrent changes in the proportion of active women in cardiothoracic surgery. RESULTS: We identified 6934 (57.1%) pieces of commentary; 3694 (30.4%) case reports; 1030 (8.5%) reviews, systematic analyses, meta-analyses, or observational studies; and 484 (4%) clinical trials. In total, 15,189 total names were included in analysis. Over the 10-year study period, first authorship by women rose from 8.5% to 16% (0.42% per year, on average), whereas the percentage of active US women cardiothoracic physicians rose from 4.6% to 8% (0.42% per year). Last authorship was generally flat over the decade, going from 8.9% in 2011% to 7.8% in 2020 and on average, increased at just 0.06% per year (P = .79). CONCLUSIONS: Over the past decade, authorship by women has steadily increased, more so at the first author position. Author-volunteered gender identification at the time of manuscript acceptance may be useful to more accurately follow trends in publication.

8.
Eur J Cardiothorac Surg ; 63(3)2023 03 01.
Article in English | MEDLINE | ID: mdl-36538926

ABSTRACT

OBJECTIVES: The STS Thoracic Surgery Practice and Access Task Force - 2019 Workforce Report noted gender-based differences in the income of cardiothoracic surgeons in the United States. We analysed the 2019 Medicare payment data for thoracic and cardiac surgeons to investigate the gender-based payment gap among cardiothoracic surgeons. METHODS: The 2019 Medicare Physician and Other Practitioners by Provider and Services data set merged with the Doctors and Clinicians National Downloadable File was utilized to conduct a cross-sectional analysis of gender differences in Medicare payments, numbers of services, unique billing codes, years in practice, Medicare beneficiary age, regional population density (rural-urban commuting area code) and patient panel complexity (hierarchical condition category) for providers. The providers' self-reported gender (women or men) and provider type (thoracic surgery or cardiac surgery) were binarily set according to the Center for Medicare and Medicaid Services standards. Independent analyses were performed with thoracic and cardiac surgeons. We also used the 2013 and 2016 Medicare Physician and Other Practitioners by Provider and Services data sets to analyse the trends in adjusted gender-based payment differences across 2013, 2016 and 2019. RESULTS: After controlling for the covariates, women thoracic surgeons received $25,183.50 [95% confidence interval (CI) $16,307.60, $34,059.40] less than the mean Medicare payment than men thoracic surgeons. Likewise, women cardiac surgeons received $20,960 [95% confidence interval (CI) $1,014.80, $40,902.80] less than the mean adjusted Medicare payment than their men counterparts. CONCLUSIONS: In 2019, women cardiothoracic surgeons received a significantly lower mean Medicare payment than men cardiothoracic surgeons after controlling for the number of services, unique billing codes, the complexity of the patient panel, years in practice and regional population density. The payment gap between women and men exhibited no statistically significant change over 2013, 2016 and 2019. Future studies are warranted to understand the association between gender representation and the pay gap.


Subject(s)
Surgeons , Thoracic Surgery , Male , Humans , Female , Aged , United States , Medicare , Sex Factors , Cross-Sectional Studies
9.
JTCVS Open ; 16: 1049-1062, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38204700

ABSTRACT

Objectives: The American Association for Thoracic Surgery recommends using frailty assessments to identify patients at higher risk of perioperative morbidity and mortality. We evaluated what patient factors are associated with frailty in a thoracic surgery patient population. Methods: New patients aged more than 50 years who were evaluated in a thoracic surgery clinic underwent routine frailty screening with a modified Fried's Frailty Phenotype. Differences in demographics and comorbid conditions among frailty status groups were assessed with chi-square and Student t tests. Logistic regressions performed with binomial distribution assessed the association of demographic and clinical characteristics with nonfrail, frail, prefrail, and any frailty (prefrail/frail) status. Results: The study population included 317 patients screened over 19 months. Of patients screened, 198 (62.5%) were frail or prefrail. Frail patients undergoing thoracic surgery were older, were more likely single or never married, had lower median income, and had lower percent predicted diffusion capacity of the lungs for carbon monoxide and forced expiratory volume during 1 second (all P < .05). More non-Hispanic Black patients were frail and prefrail compared with non-Hispanic White patients (P = .003) and were more likely to score at least 1 point on Fried's Frailty Phenotype (adjusted odds ratio, 3.77; P = .02) when controlling for age, sex, number of comorbidities, median income, diffusion capacity of the lungs for carbon monoxide, and forced expiratory volume during 1 second. Non-Hispanic Black patients were more likely than non-Hispanic White patients to score points for slow gait and low activity (both P < .05). Conclusions: Non-Hispanic Black patients undergoing thoracic surgery are more likely to score as frail or prefrail than non-Hispanic White patients. This disparity stems from differences in activity and gait speed. Frailty tools should be examined for factors contributing to this disparity, including bias.

10.
Eur J Cardiothorac Surg ; 62(2)2022 07 11.
Article in English | MEDLINE | ID: mdl-35211725

ABSTRACT

OBJECTIVES: Risk factors associated with intestinal ischaemia after heart surgery have been previously explored; however, a paucity of data exists with regard to extent of intestinal ischaemia in patients requiring surgical intervention. The purpose of this study is to assess predictors of abdominal exploration and extent of ischaemia following cardiac surgery. METHODS: A retrospective single-centre study was performed at a university hospital. The patient sample included consecutive patients between 2009 and 2020 who first received cardiac and then abdominal exploration during the same hospital stay. Control group patients were identified by 1:1 propensity matching. Logistic regression was performed to identify risk factors for laparotomy. Patients of the laparotomy group were further analysed for intraoperative findings from required abdominal operations. RESULTS: A total of 6832 patients were identified, of whom 70 (1%) underwent abdominal exploration. The median time to exploratory laparotomy was 6 days with no difference between intraoperatively confirmed ischaemia versus those who underwent negative exploration. Thirty-day mortality was 51%. Prior diagnosis of COPD or administration of 2 or more vaso-inotropes during the postoperative phase was independent risk factors for exploratory laparotomy. Vaso-inotrope use was a strong independent predictor of extent of intestinal ischaemia as well as for 30-day mortality. Degree of intestinal ischaemia was also an independent predictor of 30-day mortality. CONCLUSIONS: Intestinal ischaemia is a feared complication after cardiac surgery with high mortality, often necessitating multiple abdominal procedures. Administration of 2 or more vaso-inotropes in the postoperative phase of cardiac procedure is a strong predictor for the degree of ischaemia and 30-day mortality.


Subject(s)
Cardiac Surgical Procedures , Mesenteric Ischemia , Thoracic Injuries , Cardiac Surgical Procedures/adverse effects , Humans , Ischemia/diagnosis , Ischemia/etiology , Mesenteric Ischemia/diagnosis , Mesenteric Ischemia/etiology , Retrospective Studies , Risk Factors , Thoracic Injuries/complications
11.
Ann Surg ; 275(5): e708-e715, 2022 05 01.
Article in English | MEDLINE | ID: mdl-32773626

ABSTRACT

OBJECTIVE: To investigate the impact of thoracic body composition on outcomes after lobectomy for lung cancer. SUMMARY AND BACKGROUND DATA: Preoperative identification of patients at risk for adverse outcomes permits treatment modification. The impact of body composition on lung resection outcomes has not been investigated in a multicenter setting. METHODS: A total of 958 consecutive patients undergoing lobectomy for lung cancer at 3 centers from 2014 to 2017 were retrospectively analyzed. Muscle and adipose tissue cross-sectional area at the fifth, eighth, and tenth thoracic vertebral body was quantified. Prospectively collected outcomes from a national database were abstracted to characterize the association between sums of muscle and adipose tissue and hospital length of stay (LOS), number of any postoperative complications, and number of respiratory postoperative complications using multivariate regression. A priori determined covariates were forced expiratory volume in 1 second and diffusion capacity of the lungs for carbon monoxide predicted, age, sex, body mass index, race, surgical approach, smoking status, Zubrod and American Society of Anesthesiologists scores. RESULTS: Mean patient age was 67 years, body mass index 27.4 kg/m2 and 65% had stage i disease. Sixty-three percent underwent minimally invasive lobectomy. Median LOS was 4 days and 34% of patients experienced complications. Muscle (using 30 cm2 increments) was an independent predictor of LOS (adjusted coefficient 0.972; P = 0.002), any postoperative complications (odds ratio 0.897; P = 0.007) and postoperative respiratory complications (odds ratio 0.860; P = 0.010). Sarcopenic obesity was also associated with LOS and adverse outcomes. CONCLUSIONS: Body composition on preoperative chest computed tomography is an independent predictor of LOS and postoperative complications after lobectomy for lung cancer.


Subject(s)
Lung Neoplasms , Pneumonectomy , Aged , Body Composition , Hospitals , Humans , Length of Stay , Lung Neoplasms/surgery , Pneumonectomy/adverse effects , Pneumonectomy/methods , Postoperative Complications/etiology , Retrospective Studies , Tomography, X-Ray Computed
12.
Ann Thorac Surg ; 113(2): 669-673, 2022 02.
Article in English | MEDLINE | ID: mdl-34391698

ABSTRACT

PURPOSE: Endoluminal vacuum (EVAC) therapy has gained popularity as a minimally invasive option for contained esophageal leaks. EVAC therapy may be useful for esophagogastric anastomotic leak fistulizing to the airway. DESCRIPTION: This report describes EVAC therapy of an esophagobronchial fistula with video depicting the procedure, including technical tips. Video and photographic evidence of progression and ultimate resolution is included. EVALUATION: Sponge exchanges were completed every 3 to 4 days. EVAC therapy was administered through a transnasal approach. In the presented case, a total of 11 exchanges over 6 weeks were required. EVAC sponge placement was transitioned from intracavitary to endoluminal for the final 4 treatments. All but 4 exchanges were able to be completed at the bedside in a monitored setting with sedation. CONCLUSIONS: An esophageal leak that has fistulized to a main airway is a rare and challenging clinical problem. Definitive EVAC therapy for esophageal anastomotic leak with esophagobronchial fistula is a feasible option in selected cases.


Subject(s)
Bronchial Fistula/therapy , Esophageal Fistula/therapy , Negative-Pressure Wound Therapy/methods , Aged , Bronchoscopy/methods , Humans , Male , Retrospective Studies , Treatment Outcome
13.
Ann Thorac Surg ; 112(2): 436-442, 2021 08.
Article in English | MEDLINE | ID: mdl-33127408

ABSTRACT

BACKGROUND: Simulation-based training is a valuable component of cardiothoracic surgical education. Effective curriculum development requires consensus on procedural components and focused attention on specific learning objectives. Through use of a Delphi process, we established consensus on the steps of video-assisted thoracoscopic surgery (VATS) left upper lobectomy and identified targets for simulation. METHODS: Experienced thoracic surgeons were randomly selected for participation. Surgeons voted and commented on the necessity of individual steps comprising VATS left upper lobectomy. Steps with greater than 80% of participants in agreement of their necessity were determined to have established "consensus." Participants voted on the physical or cognitive complexity of each, or both, and chose steps most amenable to focused simulation. RESULTS: Thirty thoracic surgeons responded and joined in the voting process. Twenty operative steps were identified, with surgeons reaching consensus on the necessity of 19. Components deemed most difficult and amenable to simulation included those related to dissection and division of the bronchus, artery, and vein. CONCLUSIONS: Through a Delphi process, surgeons with a variety of practice patterns can achieve consensus on the operative steps of left upper lobectomy and agreement on those most appropriate for simulation. This information can be implemented in the development of targeted simulation for VATS lobectomy.


Subject(s)
Computer Simulation , Consensus , Education, Medical, Graduate/methods , Pneumonectomy/education , Simulation Training/methods , Surgeons/education , Thoracic Surgery, Video-Assisted/education , Clinical Competence , Humans , Lung Neoplasms/surgery
14.
Proc Natl Acad Sci U S A ; 117(36): 22423-22429, 2020 09 08.
Article in English | MEDLINE | ID: mdl-32848073

ABSTRACT

Metastases are the cause of the vast majority of cancer deaths. In the metastatic process, cells migrate to the vasculature, intravasate, extravasate, and establish metastatic colonies. This pattern of spread requires the cancer cells to change shape and to navigate tissue barriers. Approaches that block this mechanical program represent new therapeutic avenues. We show that 4-hydroxyacetophenone (4-HAP) inhibits colon cancer cell adhesion, invasion, and migration in vitro and reduces the metastatic burden in an in vivo model of colon cancer metastasis to the liver. Treatment with 4-HAP activates nonmuscle myosin-2C (NM2C) (MYH14) to alter actin organization, inhibiting the mechanical program of metastasis. We identify NM2C as a specific therapeutic target. Pharmacological control of myosin isoforms is a promising approach to address metastatic disease, one that may be readily combined with other therapeutic strategies.


Subject(s)
Acetophenones/pharmacology , Actomyosin/metabolism , Cytoskeleton , Neoplasm Metastasis/physiopathology , Actins/metabolism , Animals , Cell Adhesion/drug effects , Cell Movement/drug effects , Colorectal Neoplasms/metabolism , Cytoskeleton/drug effects , Cytoskeleton/metabolism , Female , HCT116 Cells , Humans , Mice , Mice, Nude
16.
J Surg Educ ; 77(3): 534-539, 2020.
Article in English | MEDLINE | ID: mdl-32201142

ABSTRACT

BACKGROUND: Progressive autonomy leading to conditional independence is necessary to achieve competence in surgical skills and decision making. Trust and transparency are ethical imperatives, but practices vary regarding the extent of disclosure of specific resident roles. We tested whether a standardized preoperative script would improve patient acceptance of resident involvement in perioperative care. METHODS: Patients admitted to a resident-run acute care general surgery service between October 2017 and October 2018 were enrolled in an IRB-approved study. During the first half of the rotation (control), operative consent was obtained according to individual practice without specified explanation of resident roles. During the second half (intervention), the senior resident read a short semistructured script specifically explaining team roles and responsibilities, including the degree of resident independence and supervision by attendings. On postoperative day 3, patients completed a survey assessing understanding of their surgical care. RESULTS: Sixty-two patients under the care of 10 rotating chief residents were enrolled; 46 patients completed the survey, 23 in each arm (74% response rate). Ten patients in the control arm (43%) compared to only 3 (13%) in the intervention arm indicated that residents should not be allowed to perform portions of operations (odds ratio 4.94, p = 0.047). Patients in the intervention arm felt that care team roles were more adequately explained to them before their operation (p = 0.002). There was no difference in the number of patients naming a resident as "their doctor." CONCLUSIONS: Use of a short script specifying resident roles improves patient acceptance of trainee participation in perioperative care.


Subject(s)
General Surgery , Internship and Residency , Clinical Competence , Critical Care , General Surgery/education , Humans , Professional Autonomy , Surveys and Questionnaires
17.
Biomaterials ; 210: 94-104, 2019 07.
Article in English | MEDLINE | ID: mdl-31060867

ABSTRACT

Though early detection and treatment of primary tumors has significantly improved in recent years, metastatic disease remains among the most significant challenges in cancer therapy. Cancer cells can disseminate before the primary tumor is detected to form micro or gross metastases, requiring toxic systemic therapies. To prevent and suppress metastases, we have developed a nontoxic, long-circulating nanoscale coordination polymer (NCP) protecting microRNA (miRNA) in circulation and releasing it in tumors. PtIV(en)2 [en = ethylenediamine] containing NCPs (PtEN) can release a nontoxic, kinetically inert PtII(en)2 compound and carbon dioxide which aids the endosomal escape of its miRNA cargo, miR-655-3p. Without the presence of the PtEN core, the miRNA showed cellular uptake but no effect. When transfected into human colorectal HCT116 cells by NCPs, this oligometastatic miRNA limited proliferation and epithelial-to-mesenchymal transition by preventing ß-catenin nuclear translocation and tumor cell invasion. Systemic administrations of PtEN/miR-655-3p sustained effective transfection to reduce liver colonization and tumor burden in a xenogenic hepatic metastatic model of HCT116 without any observable toxicity.


Subject(s)
Colorectal Neoplasms/secondary , Epithelial-Mesenchymal Transition , Gene Transfer Techniques , Liver Neoplasms/pathology , MicroRNAs/administration & dosage , Nanoparticles/chemistry , Polymers/chemistry , Animals , Cell Adhesion , Cell Proliferation , Endosomes/metabolism , HCT116 Cells , Humans , Mice, Inbred BALB C , MicroRNAs/genetics , Neoplasm Invasiveness , Neoplasm Metastasis , PTEN Phosphohydrolase/metabolism , beta Catenin/metabolism
18.
Curr Treat Options Oncol ; 20(4): 27, 2019 03 14.
Article in English | MEDLINE | ID: mdl-30874964

ABSTRACT

OPINION STATEMENT: Patients with locally advanced non-small cell lung cancer (NSCLC) are treated for cure, but treatment decisions are not straightforward. Chemotherapy is essential due to the high risk of systemic relapse, but local therapy is also required for cure. In the small subset of stage III patients with N0 or N1 disease, surgery is typically the initial therapy and extended resections are frequent. The majority of IIIA patients present with N2 disease and treatment paradigms for these patients are controversial, particularly concerning the role of resection. Surgery has a limited role in bulky IIIA, IIIB, and IIIC disease, which is typically treated with combined systemic therapy and radiation. The authors believe that in resectable IIIA disease, the addition of surgery to multimodality treatment appears to improve local control and overall survival. Induction therapy is essential, and the use of chemotherapy alone or chemoradiotherapy remains an area of debate. Pneumonectomy should be used with caution in IIIA disease, as numerous prospective trials have noted excessive perioperative mortality. The introduction of immunotherapies in this stage may quickly transform treatment decisions.


Subject(s)
Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/surgery , Lung Neoplasms/pathology , Lung Neoplasms/surgery , Pneumonectomy , Carcinoma, Non-Small-Cell Lung/mortality , Clinical Decision-Making , Combined Modality Therapy , Disease Management , Humans , Lung Neoplasms/mortality , Neoplasm Metastasis , Neoplasm Staging , Pneumonectomy/adverse effects , Pneumonectomy/methods , Treatment Outcome
19.
20.
Surgery ; 163(5): 1047-1052, 2018 05.
Article in English | MEDLINE | ID: mdl-29336810

ABSTRACT

BACKGROUND: The benefit of adding external beam radiation to adjuvant chemotherapy in patients that have undergone a margin positive resection for early stage, pancreatic ductal adenocarcinoma has not been determined definitively. METHODS: The National Cancer Data Base was queried to evaluate the utility of adjuvant radiation in patients with pathologic stage I-II pancreatic ductal adenocarcinoma who underwent upfront pancreatoduodenectomy with a positive margin (margin positive resection) between 2004 and 2013. RESULTS: In the study, 1,392 patients met inclusion criteria, of whom 263 (18.9%) were lymph node-negative (pathologic stages IA, IB, IIA) and 1,129 (81.1%) were node-positive (pathologic stage IIB); 938 (67.4%) patients received adjuvant radiation and chemotherapy, while 454 (32.6%) received adjuvant chemotherapy alone. Cox modeling stratified by nodal status demonstrated the benefit of radiation to be statistically significant only in node positive patients (hazard ratio 0.81, 95% confidence interval, 0.71-0.93). Node-positive patients receiving adjuvant radiation and chemotherapy had an adjusted median survival of 17.5 months vs 15.2 months for those receiving adjuvant chemotherapy alone (P=.003). In patients who had negative nodes, there was no difference in overall survival with radiation (22.5 vs 23.6 months, P=.511). CONCLUSION: Addition of radiation to adjuvant chemotherapy after a margin positive resection confers a survival benefit albeit limited (about 2 months) in patients with node-positive pancreatic head cancer. (Surgery 2017;160:XXX-XXX.).


Subject(s)
Carcinoma, Pancreatic Ductal/radiotherapy , Pancreatic Neoplasms/radiotherapy , Adult , Aged , Aged, 80 and over , Carcinoma, Pancreatic Ductal/mortality , Carcinoma, Pancreatic Ductal/surgery , Chemoradiotherapy, Adjuvant , Humans , Middle Aged , Pancreatic Neoplasms/mortality , Pancreatic Neoplasms/surgery , Radiotherapy, Adjuvant , Retrospective Studies , United States/epidemiology
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