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OBJECTIVE: The impact of pancreaticoduodenectomy on absorption of drugs in the duodenum remains largely unknown. We aim to characterize the pharmacokinetics of apixaban in patients who had previously undergone pancreaticoduodenectomy. MATERIALS AND METHODS: A single 10-mg dose of apixaban was administered to 4 volunteers who underwent pancreaticoduodenectomy at least 6 months prior. The maximum plasma apixaban concentration (Cmax) and area under the plasma concentration time-curve (AUC0-24, AUC0-inf) were compared against healthy historical control subjects (N = 12). Geometric mean ratios (GMR) with 90% confidence interval (CI) were calculated for determination of comparative bioequivalence. RESULTS: In pancreaticoduodenectomy patients, AUC0-24 and AUC0-inf were 1,861 and 2,080 ng×h/mL, respectively. The GMRs of AUC0-24 and AUC0-inf between study subjects and healthy controls were 1.27 (90% CI 0.88 - 1.83) and 1.18 (90% CI 0.82 - 1.72). The mean Cmax of apixaban was 201 ng/mL (SD 15.6) occurring at a median tmax of 3.25 hours (range 2.5 - 4 hours). The GMR of Cmax between study subjects and healthy controls was 1.12 (90% CI 0.77 - 1.63). CONCLUSION: The pharmacokinetic characteristics of apixaban in subjects who had undergone pancreaticoduodenectomy are not significantly different from those of healthy controls. Though the sample size of this study is small, results suggest that no change to apixaban dose regimen is needed in patients who have had a pancreaticoduodenectomy.
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Área Sob a Curva , Inibidores do Fator Xa , Pancreaticoduodenectomia , Pirazóis , Piridonas , Humanos , Piridonas/farmacocinética , Piridonas/administração & dosagem , Pancreaticoduodenectomia/efeitos adversos , Pirazóis/farmacocinética , Pirazóis/administração & dosagem , Masculino , Pessoa de Meia-Idade , Feminino , Inibidores do Fator Xa/farmacocinética , Inibidores do Fator Xa/administração & dosagem , Idoso , Adulto , Equivalência TerapêuticaRESUMO
BACKGROUND: Minimally invasive pancreatic surgery (MIPS), when selectively utilized, has been shown to hasten recovery with outcomes comparable to open approaches, but access may not be equitable. This study explored variation in utilization of MIPS for pancreatic cancer. METHODS: The National Cancer Database was queried to identify patients diagnosed with a primary pancreatic neoplasm from 2010 to 2020. Study participants had diagnoses of clinical or pathologic stage 1-3 disease and received curative-intent surgery. Multivariable analyses assessed the association between surgical approach and patient and disease factors. RESULTS: Inclusion criteria identified 73,137 patients: 51,408 underwent open surgery and 21,729 received MIPS. In our multivariable analysis, Black race was associated with reduced odds of MIPS (AOR 0.88; p = 0.02), while older age (AOR 1.17; p = 0.01), later year of diagnosis (AOR 1.57; p < 0.001), and private insurance coverage (AOR 1.30; p = 0.05) were associated with increased odds. When patients with adenocarcinoma were analyzed in isolation, disparities in MIPS utilization persisted even when controlling for disease stage. CONCLUSION: Sociodemographic factors like age, race, and insurance coverage appear to vary in the utilization of MIPS technologies for the treatment of pancreatic malignancy. Addressing variation with robust mixed methods approaches in the future is proposed to incorporate prospective interventions with highly annotated outcomes for additional study.
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Pancreatectomia , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Estados Unidos , Pancreatectomia/tendências , Disparidades em Assistência à Saúde/tendências , Procedimentos Cirúrgicos Minimamente Invasivos/estatística & dados numéricos , Bases de Dados Factuais , Fatores Sociodemográficos , Estudos Retrospectivos , Fatores EtáriosRESUMO
Carbon capture represents a key pathway to meeting climate change mitigation goals. Powerful next-generation solvent-based capture processes are under development by many researchers, but optimization and testing would be significantly aided by integrating in situ monitoring capability. Further, real-time water analysis in water-lean solvents offers the potential to maintain their water balance in operation. To explore data acquisition techniques in depth for this purpose, Raman spectra of CO2, H2O, and a single-component water-lean solvent, N-(2-ethoxyethyl)-3-morpholinopropan-1-amine (2-EEMPA) were collected at different CO2 and H2O concentrations using an in situ Raman cell. The quantification of CO2 and H2O loadings in 2-EEMPA was done by principal component regression and partial least squares methods with analysis of uncertainties. We conclude with discussions on how this simultaneous online analysis method to quantify CO2 and H2O loadings can be an important tool to enable the optimal efficiency of water-lean CO2 solvents while also maintaining the critical water balance under operating conditions relevant to post-combustion CO2 capture.
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BACKGROUND: The impact of resecting positive margins during pancreaticoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDA) remains debated. Additionally, the survival benefit of resecting multiple positive margins is unknown. METHODS: We identified patients with PDA who underwent PD from 2006 to 2015. Pancreatic neck, bile duct, and uncinate frozen section margins were assessed before and after resection of positive margins. Survival curves were compared with log-rank tests. Multivariable Cox regression assessed the effect of margin status on overall survival. RESULTS: Of 501 patients identified, 17.3%, 5.3%, and 19.7% had an initially positive uncinate, bile duct, or neck margin, respectively. Among initially positive bile duct and neck margins, 77.8% and 67.0% were resected, respectively. Although median survival was decreased among patients with any positive margins (15.6 vs. 20.9 months; p = 0.006), it was similar among patients with positive bile duct or neck margins with or without R1 to R0 resection (17.0 vs. 15.6 months; p = 0.20). Median survival with and without positive uncinate margins was 13.8 vs. 19.7 months (p = 0.04). Uncinate margins were never resected. Resection of additional margins when the uncinate was concurrently positive was not associated with improved survival (p = 0.37). Patients with positive margins who received adjuvant therapy had improved survival, regardless of margin resection (p = 0.03). Adjuvant therapy was independently protective against death (hazard ratio 0.6, 95% CI 0.5-0.7). CONCLUSIONS: Positive PD margins at any position are associated with reduced overall survival; however, resection of additional margins may not improve survival, particularly with concurrently positive uncinate margins. Adjuvant chemotherapy improves survival with positive margins, regardless of resection.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Adenocarcinoma/cirurgia , Carcinoma Ductal Pancreático/cirurgia , Humanos , Pancreatectomia , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia , Estudos RetrospectivosRESUMO
BACKGROUND: Esophagectomy practices have evolved over time in response to new technologies and refinements in technique. Using the National Safety and Quality Improvement Program (NSQIP) database, we aimed to describe trends for esophagectomy in terms of approach, surgeon specialty, and associated outcomes. MATERIALS AND METHODS: Adult patients undergoing esophagectomy were identified within the 2007-2017 NSQIP database. The proportion of cases performed using different approaches was trended over time. Outcomes were compared with chi-squared and t-tests. Multivariate logistic regression was used to identify factors associated with outcomes and provide risk-adjusted measures. RESULTS: A total of 10,383 esophagectomies were included; 6347 (61.1%) were performed for cancer. The proportion of esophagectomies performed via the Ivor Lewis approach (ILE) increased between 2007 (37.0%) and 2017 (62.4%). Simultaneously, transhiatal esophagectomies (THEs) decreased from 41.1% to 21.5% (P < 0.001). THE was more frequently performed in patients with higher baseline probability of mortality (2.3% versus 2.0%, P < 0.001) and morbidity (32.2% versus. 28.7%, P < 0.001). The percentage performed with cardiothoracic surgeons increased from 0.8% in 2007 to 50.3% in 2017 (P < 0.001). The risk-adjusted complication rate was 45% for THE, 40% for ILE, and 50% for McKeown (MCK) esophagectomy (P < 0.001). The risk-adjusted rate of surgical site infection was 17.3% for THE, 13.1% for ILE, and 19% for MCK (P = 0.001). Within risk-adjusted analysis, surgical approach was not associated with complications. CONCLUSIONS: ILE has emerged as the predominant approach for esophagectomy nationwide among NSQIP-participating institutions and may be associated with lower complication rates than THE. The use of MCK esophagectomy has remained stable but is associated with increased complications.
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Neoplasias Esofágicas/cirurgia , Esofagectomia/tendências , Complicações Pós-Operatórias/epidemiologia , Padrões de Prática Médica/tendências , Idoso , Bases de Dados Factuais/estatística & dados numéricos , Esofagectomia/efeitos adversos , Esofagectomia/métodos , Esofagectomia/estatística & dados numéricos , Feminino , Cirurgia Geral/estatística & dados numéricos , Cirurgia Geral/tendências , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Padrões de Prática Médica/estatística & dados numéricos , Estudos Prospectivos , Estudos Retrospectivos , Cirurgia Torácica/estatística & dados numéricos , Cirurgia Torácica/tendências , Estados UnidosRESUMO
BACKGROUND: Growing teratoma syndrome is a rare condition defined by the presence of enlarging metastatic lesions on serial imaging that arise after or during systemic chemotherapy for nonseminomatous germ cell tumors. Lesions commonly occur in the retroperitoneum, mediastinum, or lung and are notoriously unresponsive to conventional chemoradiotherapy. METHODS: In this study, we present a dynamic case of a 26-year-old male, who had undergone surgical resection and systemic bleomycin treatment for a metastatic nonseminomatous germ cell tumor, and later developed recurrent masses in his posterior mediastinum seen on surveillance imaging. Tumor markers remained normal. These lesions were resected via a right robot-assisted thoracoscopic approach with the da Vinci Xi®. RESULTS: The operation was completed successfully with an unremarkable postoperative hospital course. The robotic-assisted right thoracoscopic approach allowed for a minimally invasive dissection with good visualization and minimal morbidity when compared to previous cases of surgically resected mediastinal teratomas. Final pathology demonstrated mature teratomatous elements within a setting of inflammation and necrosis. CONCLUSIONS: Robot-assisted thoracoscopic management of metastatic mediastinal lesions in the setting of this rare condition is safe and feasible.
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Neoplasias do Mediastino/secundário , Neoplasias do Mediastino/cirurgia , Neoplasias Embrionárias de Células Germinativas/secundário , Neoplasias Embrionárias de Células Germinativas/cirurgia , Procedimentos Cirúrgicos Robóticos/métodos , Neoplasias Testiculares/secundário , Neoplasias Testiculares/cirurgia , Toracoscopia/métodos , Adulto , Antineoplásicos/uso terapêutico , Quimioterapia Adjuvante , Humanos , Excisão de Linfonodo , Masculino , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Embrionárias de Células Germinativas/patologia , Orquiectomia , Neoplasias Testiculares/tratamento farmacológico , Neoplasias Testiculares/patologiaRESUMO
BACKGROUND: Asymptomatic contralateral inguinal hernias are often present during initial inguinal hernia repair. Data on long-term results and progression to symptomaticity are sparse. The purpose of this study was to assess long-term rates and risk factors for contralateral inguinal hernia repair following unilateral inguinal hernia repair. METHODS: Using New York Statewide Planning and Research Collaborative administrative data, 32,384 adults who underwent initial inguinal hernia repair during 2002-2003 in New York State and achieved 10-year follow-up were identified. ICD-9 and CPT codes were used to identify patients. Patients were followed for 10 years subsequent to their operation to assess for contralateral repair. Those who did not achieve 10-year follow-up were excluded. Risk factors were compared using descriptive univariate statistics. Significant variables were then analyzed via multivariate regression models. RESULTS: For adult patients having primary unilateral hernia repair, 3364 patients (6.73 %) had contralateral repair during the follow-up period. After excluding "loss of follow-up" patients, the contralateral repair rate was 10.8 %. Contralateral hernia repairs first occurred at a mean of 3.9 ± 3.5 years and a median of 2.5 years after the initial surgery. Risk factors included age >45 years (OR 1.7 [1.4-2.0], p < 0.001), male gender (OR 2.2 [1.9-2.6], p < 0.0001), and white race (OR 1.6 [1.1-2.4], p < 0.001). Factors associated with decreased likelihood for repair included: congestive heart failure (OR 0.6 [0.4-0.9], p = 0.01), diabetes (OR 0.7 [0.5-0.8], p = 0.02), neurological disorders (OR 0.6 [0.4-0.9], p = 0.02), obesity (OR 0.3 [0.1-0.8], p = 0.01), and alcohol abuse (OR 0.2 [0.03-0.8], p = 0.03). CONCLUSION: The 10-year probability of necessitating a contralateral inguinal hernia repair is significant. Elderly white males were more likely to undergo repair. Those less likely to undergo repair had significant comorbid conditions, possibly due to their poor suitability for intervention. These data highlight a key benefit of the laparoscopic approach over open repairs. Based on these data, an argument for laparoscopy with routine contralateral inspection in higher-risk patients can be made.
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Hérnia Inguinal/cirurgia , Herniorrafia/métodos , Adolescente , Adulto , Idoso , Alcoolismo/epidemiologia , Estudos de Coortes , Bases de Dados Factuais , Diabetes Mellitus/epidemiologia , Progressão da Doença , Etnicidade/estatística & dados numéricos , Feminino , Seguimentos , Insuficiência Cardíaca/epidemiologia , Hérnia Inguinal/epidemiologia , Herniorrafia/estatística & dados numéricos , Humanos , Incidência , Classificação Internacional de Doenças , Laparoscopia/métodos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Doenças do Sistema Nervoso/epidemiologia , New York/epidemiologia , Obesidade/epidemiologia , Fatores de Risco , Fatores Sexuais , População Branca/estatística & dados numéricos , Adulto JovemRESUMO
BACKGROUND: Bronchogenic cysts are rare foregut abnormalities that arise from aberrant budding of the tracheobronchial tree early in embryological development. These cysts predominantly appear in the mediastinum, where they may compress nearby structures. Intra-abdominal bronchogenic cysts are rare. We report an intra-abdominal bronchogenic cyst that was excised laparoscopically. METHODS: A 40-year old female with a history of gastritis presented for evaluation of recurrent abdominal pain. A previous ultrasound showed cholelithiasis and a presumed portal cyst. Physical examination and laboratory findings were unremarkable. A CT scan with pancreatic protocol was performed and an intra-abdominal mass adherent to the esophagus was visualized. A laparascopic enucleation of the mass was performed. A 3-cm myotomy was made after circumferential dissection of the cyst and the decision was made intraoperatively to reapproximate the muscularis layer. A PubMed literature search on surgical management of esophageal bronchogenic cysts was subsequently performed. RESULTS: The literature search performed on the subject of esophageal bronchogenic cysts found one review article focusing on intramural esophageal bronchogenic cysts in the mediastinum and five case reports of esophageal bronchogenic cysts. Of these, only one was both intraabdominal and managed laparascopically with simple closure of the resulting myotomy. The majority of the bronchogenic cysts mentioned in the literature were located mediastinally and were managed via open thoracotomy. Our findings confirm the rarity of this particular presentation and the unique means by which this cyst was surgically excised. CONCLUSION: This case highlights the management of a rare entity and advocates for enucleation of noncommunicating, extraluminal esophageal bronchogenic cysts and closure of the esophageal muscular layers over intact mucosa as a viable surgical approach to this unusual pathology. Other cases of laparascopic enucleation of bronchogenic cysts have shown similarly uneventful postoperative courses and rapid recovery with no apparent return of symptoms.
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Cisto Broncogênico/cirurgia , Cisto Esofágico/cirurgia , Laparoscopia , Dor Abdominal/etiologia , Dor Abdominal/cirurgia , Adulto , Cisto Broncogênico/diagnóstico por imagem , Cisto Esofágico/diagnóstico por imagem , Feminino , Humanos , RadiografiaRESUMO
OBJECTIVES: There are significant variations in both perioperative and long-term outcomes after lung cancer resection. While perioperative outcomes are often used as comparative measures of quality, they are unreliable, and their association with long-term outcomes remain unclear. In this context, we evaluated whether historical perioperative mortality after lung cancer resection is associated with 5-year survival. PATIENTS AND METHODS: The National Cancer Database (NCDB) was queried to identify patients diagnosed with non-small cell lung cancer (NSCLC) in 2010-2016 who underwent surgical resection (n = 234200). Hospital-level reliability-adjusted 90-day mortality rate quartiles for 2010-2013 was used as the independent variable to analyze 5-year survival for patients diagnosed in 2014-2016 (n = 85396). RESULTS: There were 85,396 patients in the 2014-2016 cohort across 1,086 hospitals. Overall observed 90-day mortality rate was 3.2% (SD 17.6%) with 2.6% (SD 16.0%) for the historically best performing quartile vs. 3.9% (SD 19.4%) for the worst performing quartile (p < 0.0001). Patients who underwent resection at hospitals with the best historical mortality rate had significantly better 5-year survival across all stages compared to those treated at hospitals in the worst performing quartile in multivariate Cox regression analysis (all stages - HR 1.21 [95% CI 1.15-1.26]; stage I - HR 1.19 [95% CI 1.12-1.25]; stage II - HR 1.20 [95% CI 1.09-1.32]; stage III - HR 1.36 [95% CI 1.20-1.54]) and Kaplan-Meier survival estimates (all stages - p < 0.0001, stage I - p < 0.0001; stage II - p = 0.0004; stage III - p < 0.0001). CONCLUSION: With expanded lung cancer screening criteria and likely increase in early-stage detection, profiling performance is paramount to ensuring mortality benefits. We found that episodes surrounding surgical resection may be used to profile long-term outcomes that likely reflect quality across a broader context of care. Evaluating lung cancer care quality using perioperative outcomes may be useful in profiling provider performance and guiding value-based payment policies.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/patologia , Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Detecção Precoce de Câncer , Reprodutibilidade dos Testes , Estudos Retrospectivos , Estadiamento de Neoplasias , PneumonectomiaRESUMO
BACKGROUND: Parenchymal-sparing approaches to pancreatectomy are technically challenging procedures but allow for preserving a normal pancreas and decreasing the rate of postoperative pancreatic insufficiency. The robotic platform is increasingly being used for these procedures. We sought to evaluate robotic parenchymal-sparing pancreatectomy and assess its complication profile and efficacy. METHODS: This systematic review consisted of all studies on robotic parenchymal-sparing pancreatectomy (central pancreatectomy, duodenum-preserving partial pancreatic head resection, enucleation, and uncinate resection) published between January 2001 and December 2022 in PubMed and Embase. RESULTS: A total of 23 studies were included in this review (n = 788). Robotic parenchymal-sparing pancreatectomy is being performed worldwide for benign or indolent pancreatic lesions. When compared to the open approach, robotic parenchymal-sparing pancreatectomies led to a longer average operative time, shorter length of stay, and higher estimated intraoperative blood loss. Postoperative pancreatic fistula is common, but severe complications requiring intervention are exceedingly rare. Long-term complications such as endocrine and exocrine insufficiency are nearly nonexistent. CONCLUSIONS: Robotic parenchymal-sparing pancreatectomy appears to have a higher risk of postoperative pancreatic fistula but is rarely associated with severe or long-term complications. Careful patient selection is required to maximize benefits and minimize morbidity.
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BACKGROUND: The National Lung Screening Trial (NLST) established a role for lung cancer screening. Mortality benefits with screening are predicated on successful treatment with low surgical mortality. Given variations observed in perioperative outcomes after lung cancer resection, it remains unknown whether benefits observed in the NLST are generalizable to a broader population. We sought to determine whether NLST perioperative outcomes are reflective of contemporary practice in a national cohort. METHODS: We identified patients diagnosed with non-small cell lung cancer who underwent lung resection in the 2014 to 2015 National Cancer Database (NCDB) and the NLST. We compared demographic and cancer characteristics in both datasets. We used hierarchical logistic regression to compare 30-day and 90-day postoperative mortality across facilities in both datasets. RESULTS: In all, 65054 patients in NCDB and 1003 patients in the NLST treated across 1119 NCDB hospitals and 33 NLST hospitals were included. After risk and reliability adjustment, mean 30-day and 90-day mortality were significantly higher among NCDB hospitals (mean 30-day, 2.2 [95% confidence interval (CI), 2.2 to 2.2] vs 1.8 [95% CI, 1.8 to 1.8], P < .001; mean 90-day, 4.2 [95% CI, 4.2 to 4.3] vs 2.9 [95% CI, 2.9 to 2.9], P < .001). Variation in risk- and reliability-adjusted 30-day mortality (95% CI, 1.1% to 4.9%) and 90-day mortality (95% CI, 2.6% to 9.7%) was observed among NCDB hospitals. Adjusted mortality was similar among NLST facilities (30 days, 1.8% to 1.8%; 90 days, 2.9% to 2.9%). CONCLUSIONS: Risk- and reliability-adjusted postoperative mortality varies widely in a national cohort compared with outcomes observed in the NLST. Efforts to minimize this variation are needed to ensure that benefits of lung cancer screening are fully realized in the United States.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Detecção Precoce de Câncer , Pulmão , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/cirurgia , Programas de Rastreamento , Reprodutibilidade dos Testes , Resultado do Tratamento , Estados Unidos/epidemiologiaRESUMO
The utilization of endoscopic ultrasound-guided gastrojejunostomy (EUS-GJ) in the setting of an obstructed (ingrown) duodenal stent as a bridge to pancreaticoduodenectomy (PD) remains undescribed. Herein, we report a case study of a 51-year-old patient who underwent EUS-GJ using lumen apposing metal stent (LAMS) for an obstructed duodenal stent during neoadjuvant treatment for duodenal adenocarcinoma. The patient ultimately underwent surgical resection by a classic PD 14 weeks after LAMS placement. EUS-GJ using LAMS represents a potential option as a salvage bridge to surgery for duodenal obstruction in the setting of an obstructed duodenal stent.
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Adenocarcinoma , Neoplasias Duodenais , Obstrução Duodenal , Derivação Gástrica , Humanos , Pessoa de Meia-Idade , Obstrução Duodenal/diagnóstico por imagem , Obstrução Duodenal/etiologia , Obstrução Duodenal/cirurgia , Stents , Neoplasias Duodenais/complicações , Neoplasias Duodenais/diagnóstico por imagem , Neoplasias Duodenais/cirurgia , Ultrassonografia de Intervenção , Adenocarcinoma/complicações , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/cirurgiaRESUMO
BACKGROUND: Measuring variation in perioperative outcomes to accurately discriminate performance between surgical providers may be limited by reliability. We aimed to evaluate reliability estimates of metrics associated with lung cancer resection. METHODS: We performed a retrospective cohort study utilizing the 2015 National Cancer Database to identify patients undergoing lung cancer resection. Primary outcomes were reliability estimates for perioperative outcomes and for measures of adherence to clinical benchmarks, generated through hierarchical multilevel modeling techniques. RESULTS: We identified 27,300 patients undergoing resection. Overall risk-adjusted and reliability-adjusted 30-day and 90-day mortality rates were 1.7% and 3.3%, respectively; 61.0% and 41.1% of eligible patients received stage-appropriate adjuvant and neoadjuvant therapy. Video-assisted thoracoscopic surgery was performed in 59.6% of cases with clinical stage I disease. The mean reliability of 30-day and 90-day mortality was 0.11 ± 0.09 and 0.22 ± 0.15, respectively; for performing video-assisted thoracoscopic surgery for stage I disease, reliability was 0.97 ± 0.04. When stratified by hospital volume quartile, the mean reliability of 30-day mortality was 0.04 ± 0.03 in the lowest quartile and 0.20 ± 0.10 in the highest quartile. Only 14% of hospitals met an established 0.7 reliability benchmark for 30-day and 90-day mortality, but over 97% of hospitals exceeded these benchmarks for providing stage-appropriate systemic therapy and performing VATS for stage I disease. CONCLUSIONS: Metrics used to compare lung cancer surgical performance between providers have varying levels of reliability. Reliability should be considered when profiling providers, which will become particularly important as lung cancer treatment under screening programs continues to expand.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Benchmarking , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Humanos , Pneumonectomia/métodos , Reprodutibilidade dos Testes , Estudos Retrospectivos , Cirurgia Torácica Vídeoassistida/métodos , Resultado do TratamentoRESUMO
Cellular plasticity contributes to intra-tumoral heterogeneity and phenotype switching, which enable adaptation to metastatic microenvironments and resistance to therapies. Mechanisms underlying tumor cell plasticity remain poorly understood. SOX10, a neural crest lineage transcription factor, is heterogeneously expressed in melanomas. Loss of SOX10 reduces proliferation, leads to invasive properties, including the expression of mesenchymal genes and extracellular matrix, and promotes tolerance to BRAF and/or MEK inhibitors. We identify the class of cellular inhibitor of apoptosis protein-1/2 (cIAP1/2) inhibitors as inducing cell death selectively in SOX10-deficient cells. Targeted therapy selects for SOX10 knockout cells underscoring their drug tolerant properties. Combining cIAP1/2 inhibitor with BRAF/MEK inhibitors delays the onset of acquired resistance in melanomas in vivo. These data suggest that SOX10 mediates phenotypic switching in cutaneous melanoma to produce a targeted inhibitor tolerant state that is likely a prelude to the acquisition of resistance. Furthermore, we provide a therapeutic strategy to selectively eliminate SOX10-deficient cells.
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Melanoma , Neoplasias Cutâneas , Linhagem Celular Tumoral , Humanos , Melanoma/tratamento farmacológico , Melanoma/genética , Melanoma/patologia , Fenótipo , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas B-raf/metabolismo , Fatores de Transcrição SOXE/genética , Fatores de Transcrição SOXE/metabolismo , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/metabolismo , Microambiente TumoralRESUMO
BACKGROUND: Intraoperative frozen section (IFS) is routinely utilized by many surgeons during pancreaticoduodenectomy. However, its utility has not been rigorously studied. METHODS: Patients who underwent pancreaticoduodenectomy between 2006 and 2015 were identified from institutional data. Measures of diagnostic accuracy of frozen section and multivariate logistic regression are reported. RESULTS: The cohort included 1076 patients. Of resected specimens, 73.3% were malignant. IFS and final pathologic review (the gold standard) were discrepant for (1) pathologic diagnosis or (2) resection margin status in 5.3% and 3.3% of cases. The sensitivity, specificity, and accuracy of IFS for histologic determination of malignancy were 97.2%, 95.3%, and 96.7% respectively. For resection margins, they were 92.3%, 99.3%, and 96.8%, respectively. Positive bile duct and neck margins were revised intraoperatively 62% and 65% of the time, respectively; positive uncinate margins were never resected but led surgeons to avoid revision of a second positive margin in 13% of cases (4.2% of all PDA). Operative changes were rarely noted in the presence of benign disease (n = 11, 1.0%); conversion to total pancreatectomy based on positive margins was performed in just 13 cases (1.2%). Upon multivariable analysis, a positive neck margin proved to be the greatest predictor for a revised resection margin (AOR 16.9 [4.8-59.8]), whereas a positive uncinate margin or a diagnosis of chronic pancreatitis was protective against IFS-driven operative changes (AOR 0.25 [0.09-0.73]; AOR 0.16 [0.13-0.19]). CONCLUSIONS: IFS is highly accurate and guides reresection of margins. However, selective omission of IFS may be justified for cases where benign disease is suspected.
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Secções Congeladas , Pancreaticoduodenectomia , Humanos , Margens de Excisão , Pâncreas/cirurgia , Pancreatectomia , Estudos RetrospectivosRESUMO
BACKGROUND: Early cholecystectomy (E-CCY; 8 weeks or less) after percutaneous cholecystostomy tube (PCT) placement has been associated with increased postoperative complications, but this finding has not been validated at a national level and PCT-related complications and interventions (PCT-RCIs) were not evaluated. STUDY DESIGN: Adults with PCT for acute cholecystitis subsequently undergoing CCY were identified within the Nationwide Readmission Database (2010-2015) and our institution (2017-2019). Adjusted relative risks (aRRs) of postoperative complications were estimated using Poisson regression comparing E-CCY with delayed cholecystectomy (D-CCY; more than 8 weeks) within the nationwide cohort. Institutional PCT-RCIs, operative data, and postoperative outcomes were compared between E-CCY and D-CCY using chi-square and Kruskal-Wallis tests. RESULTS: Of 6,145 patients from the Nationwide Readmission Database, 32.9% were D-CCY. Risk-adjusted analysis identified no differences between E-CCY and D-CCY in complications (aRR 0.98; 95% CI, 0.89 to 1.07), mortality (aRR 0.88; 95% CI, 0.43 to 1.81), or 30-day readmissions (aRR 1.04; 95% CI, 0.85 to 1.27). Risk-adjusted analyses assessing the association of time to interval cholecystectomy (IC) with morbidity indicated an increased risk of surgical complications in the first month after PCT placement (aRR 1.17; 95% CI, 1.08 to 1.33). In the institutional cohort (E-CCY, n = 23; D-CCY, n = 45), there were no statistically significant differences found in estimated blood loss, length of stay, and postoperative complications. There were increased PCT-RCIs in the D-CCY group (26.9% E-CCY vs 69% D-CCY; p < 0.01) based on our unadjusted analysis. CONCLUSIONS: Increased operative complications when IC is performed within 1 month of PCT placement and increased PCT-RCIs when IC is performed 8 weeks after PCT placement suggest that the most favorable timing for IC is between 4 and 8 weeks after PCT placement.
Assuntos
Colecistectomia/métodos , Colecistite Aguda/cirurgia , Colecistostomia/métodos , Idoso , Colecistectomia/efeitos adversos , Colecistite Aguda/terapia , Colecistostomia/instrumentação , Bases de Dados como Assunto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Estados UnidosRESUMO
BACKGROUND: Patients undergoing esophagectomy often receive jejunostomy tubes (j-tubes) for nutritional supplementation. We hypothesized that j-tubes are associated with increased post-esophagectomy readmissions. STUDY DESIGN: We identified esophagectomies for malignancy with (EWJ) or without (EWOJ) j-tubes using the 2010-2015 Nationwide Readmissions Database. Outcomes include readmission, inpatient mortality, and complications. Outcomes were compared before and after propensity score matching (PSM). RESULTS: Of 22,429 patients undergoing esophagectomy, 16,829 (75.0%) received j-tubes. Patients were similar in age and gender but EWJ were more likely to receive chemotherapy (24.2% vs. 15.1%, p < 0.01). EWJ was associated with decreased 180-day inpatient mortality (HR 0.72 [0.52-0.99]) but not with higher readmissions at 30- (15.2% vs. 14.0%, p = 0.16; HR 0.9 [0.77-1.05]) or 180 days (25.2% vs. 24.3%, p = 0.37; HR 0.94 [0.79-1.10]) or increased complications (p = 0.37). These results were confirmed in the PSM cohort. CONCLUSION: J-tubes placed in the setting of esophagectomy do not increase inpatient readmissions or mortality.