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1.
Lung ; 198(6): 973-981, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33034720

RESUMO

BACKGROUND: Up to 50% of patients suffer short-term postoperative adverse events (AEs) and metastatic recurrence in the long-term following curative-intent lung cancer resection. The association between AEs, particularly infectious in nature, and disease recurrence is controversial. We sought to evaluate the association of postoperative AEs on risk of developing recurrence and recurrence-free survival (RFS) following curative-intent lung resection surgery. METHODS: All lung cancer resections at a single institution (January 2008-July 2015) were included, with prospective collection of AEs using the Thoracic Morbidity & Mortality System. Cox proportional hazards models were used to estimate the effect of AEs on recurrence, with results presented as hazard ratio (HR) with 95% confidence interval (CI). An a priori, clinically driven approach to predictor variable selection was used. Kaplan-Meier curves were used examine the relationship between AE and RFS. p < 0.05 was considered statistically significant. RESULTS: 892 patients underwent curative-intent resection. 342 (38.3%) patients experienced an AE; 69 (7.7%) patients developed infectious AEs. 17.6% (n = 157) of patients had disease recurrence after mean follow-up of 26.5 months. Severe (Grade IV) AEs were associated with increased risk of recurrence (3.40; 95% CI 1.56-7.41) and a trend to decreased RFS. Major infectious AEs were associated with increased risk of recurrence (HR 1.71; CI 1.05-2.8) and earlier time to recurrence (no infectious AE 66 months, minor infectious 41 months, major infectious 54 months; p = 0.02). CONCLUSION: For patients undergoing curative-intent lung cancer resection, postoperative AEs associated with critical illness or major infection were associated with increased risk of oncologic recurrence.


Assuntos
Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/cirurgia , Recidiva Local de Neoplasia/epidemiologia , Pneumonectomia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Canadá , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico , Complicações Pós-Operatórias/diagnóstico , Modelos de Riscos Proporcionais , Fatores de Risco , Taxa de Sobrevida , Resultado do Tratamento
2.
Lung ; 198(6): 983, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33191453

RESUMO

The original version of this article unfortunately contained a mistake in author names. The given and family names of all the authors was transposed. The author names are corrected with this correction. The original article has been corrected.

3.
Ann Surg ; 260(6): 1023-9, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24836142

RESUMO

OBJECTIVE: To clarify the biologic behavior of esophageal signet ring cell (SRC) carcinomas of the esophagus and gastroesophageal junction (GEJ). To evaluate the accuracy of pretreatment biopsies in diagnosing true SRC carcinoma. BACKGROUND: In contrast with gastric cancer, little is known about the biologic behavior and prognosis of SRC. METHODS: All adenocarcinomas (ADC) of the esophagus and GEJ-patients undergoing primary resection between 1990 and 2009 were included (n = 920). Specimens containing SRCs (n = 114) were classified according to World Health Organization criteria (>50% SRC or <50% SRC). RESULTS: Thirty-two patients showed more than 50% SRC and 71 patients showed less than 50% SRC. Overall cancer-specific 5-year survival was worse for SRC (22.4%, P < 0.0001) and for SRC > 50% (13.6%, P = 0.0001) compared with ADC. Complete resection was achieved in 86.5% of patients (n = 697) in ADC, 69.5% (n = 57) in SRC < 50%, and 78.1% (n = 25) in SRC > 50% (vs ADC, respectively, P < 0.0001 and P = 0.1801). In 379 pN + R0 patients, the median number of positive lymph nodes was comparable between ADC and SRC < 50% (4 vs 5, P = 0.207) or SRC > 50% (4 vs 8, P = 0.077). Compared with ADC, SRC > 50% showed more pN3's (30% vs 61%, P = 0.006), higher recurrence (56% vs 42% for ADC, P = 0.003), and local-regional recurrences (29% vs 16%, P = 0.002). Pretreatment biopsies were unreliable to define the presence of SRC > 50% (sensitivity = 56.3%, positive predictive value = 43.9%). CONCLUSIONS: SRCs are aggressive neoplasms associated with poorer prognosis than other ADCs after primary esophagectomy. Because our data suggest that pretreatment biopsies failed to reliably define presence of SRC > 50%, presence of SRCs in pretreatment biopsies seems to be of no use to define treatment strategy or prognosis.


Assuntos
Carcinoma de Células em Anel de Sinete/secundário , Neoplasias Esofágicas/patologia , Junção Esofagogástrica/patologia , Estadiamento de Neoplasias , Bélgica/epidemiologia , Biópsia , Carcinoma de Células em Anel de Sinete/diagnóstico , Carcinoma de Células em Anel de Sinete/cirurgia , Progressão da Doença , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/cirurgia , Esofagectomia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Fatores de Tempo
4.
JTCVS Open ; 18: 360-368, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38690416

RESUMO

Objective: There is limited clinical evidence to support any specific parenchymal air leak resolution criteria when using digital pleural drainage devices following lung resection. The aim of this study is to determine an optimal air leak resolution criteria, where duration of chest tube drainage is minimized while avoiding complications from premature chest tube removal. Methods: Airflow data averaged at 10-minute intervals was collected prospectively using a digital pleural drainage device (Thopaz; Medela) in 400 patients from 2015 to 2019. All permutations of air leak resolution criteria from <10 to 100 mL/minute for 4 to 12 hours were applied retrospectively to the pleural drainage data to determine air leak duration, and air leak recurrence frequency and volume. Air leak recurrence indicates potential for rather than occurrence of adverse events. Descriptive statistics were used to identify the optimal criteria based on patient safety (low frequency and volume of air leak recurrences), and efficiency (shortest initial air leak duration). Results: The majority of the 400 patients underwent lobectomy (57% [227 out of 400]), wedge resections (29% [115 out of 400]), or segmentectomies (8% [32 out of 400]) for lung cancer (90% [360 out of 400]). An airflow threshold <50 mL/minute resulted in longer air leak duration before meeting the criteria for air leak resolution (P < .0001). Air leak recurrence frequency and volume were greater in patients with a monitoring period <8 consecutive hours (P < .0001). Conclusions: When using a digital pleural drainage device, a postoperative air leak resolution criteria <50 mL/minute for 8 consecutive hours was associated with the best safety and efficiency profile.

5.
J Chest Surg ; 56(6): 420-430, 2023 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-37817431

RESUMO

Background: This study provides an update to a landmark 2004 report describing demographics, training, and trends in adherence to thoracic surgery practice standards in Canada. Methods: An updated questionnaire was administered to all members of the Canadian Association of Thoracic Surgeons via email (n=142, compared to n=68 in 2004). Our report incorporates internal data from Ontario Health and the Canadian Partnership Against Cancer. Results: Forty-eight surgeons completed the survey (male, 70.8%; mean±standard deviation age, 50.3±9.3 years). This represents a 33.8% response rate, compared to 64.7% in 2004. Most surgeons (69%) served a patient population of over 1 million per center; 32%-34% reported an on-call ratio of 1:4-1:5 days, and the average weekly hours worked was 56.4±11.9. Greater access to dedicated geographic units per center (73% in 2021 vs. 53% in 2004) has improved thoracic-associated services and house staff, notably endoscopy units (100% vs. 91%), with 73% of respondents having access to both endobronchial and endoscopic ultrasound. Access to thoracic radiology has also improved, particularly regarding positron emission tomography scanners per center (76.9% vs. 13%). Annual case volumes for lung (255 vs. 128), esophageal (41 vs. 19), and mediastinal resections (30 vs. 13), along with hiatal hernia repair (45 vs. 20), have increased substantially despite reports of operating room availability and radiology as rate-limiting steps. Conclusion: This survey characterizes compliance with current practice standards, addressing the needs of thoracic surgeons across Canada. Over 85% of respondents were aware of the 2004 compliance paper, and 35% had applied for resources and equipment in response.

6.
Int J Surg Pathol ; 30(2): 221-226, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34287076

RESUMO

Primary biphasic tumors of the lung are rare. Lung lesions with a biphasic pattern are far more commonly primary or metastatic soft tissue tumors with entrapped native respiratory epithelium, giving the false impression of a biphasic tumor. We report a case of bilateral benign metastasizing leiomyomas in a 69-year-old female where the tumor cells diffusely entrapped native respiratory glands in a phyllodes-like pattern. The radiographic characteristics and histologic appearance were not immediately diagnostic and covered a wide differential. Reaching the final diagnosis required the use of immunohistochemical studies as well as correlation with the patient's history and radiographic findings. To the best of our knowledge, this is the first report of pulmonary benign metastasizing leiomyoma presenting in a phyllodes-like pattern. This case illustrates the importance of considering entrapment of native lung epithelium in the differential diagnosis of biphasic-appearing lung tumors.


Assuntos
Leiomioma , Neoplasias Pulmonares , Neoplasias Uterinas , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Leiomioma/diagnóstico , Leiomioma/patologia , Pulmão/diagnóstico por imagem , Pulmão/patologia , Neoplasias Pulmonares/patologia , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/patologia
7.
Artigo em Inglês | MEDLINE | ID: mdl-35713491

RESUMO

OBJECTIVES: The prominence of "enhanced recovery after surgery" (ERAS) protocols being adopted in thoracic surgery requires a re-evaluation of mechanical venous thromboembolism (VTE) prophylaxis guidelines. The goal of this study was to assess the role of sequential compression devices (SCD) in the prevention of VTEs such as deep vein thrombosis and pulmonary embolism (PE) in thoracic surgical patients. METHODS: We identified 200 patients who underwent elective oncological thoracic surgery between December 2018 and December 2020 in 2 cohorts-1 with SCDs and 1 without (i.e. non-SCD). All patients followed a standardized enhanced recovery after surgery (ERAS) protocol. The quality of care provided by SCDs was evaluated by the incidence and severity of postoperative and follow-up VTEs. Cohorts were compared by the Caprini score (CS) and the Charlson Comorbidity Index (CCI) with a two one-sided t-test analysis. Secondary outcomes include perioperative characteristics and follow-up data. RESULTS: Only 2 patients within the SCD group developed a PE with average CS and CCI metrics, both after hospital discharge and treated with anticoagulants, raising concern over the prophylactic nature of SCDs. The CS (6.9 ± 1.3 and 6.9 ± 1.5; P = 0.96) and the CCI (3.8 ± 2.0 and 4.1 ± 2.6; P = 0.33) for non-SCD and SCD, respectively, did not differ. The two one-sided t-test analysis for CS (P < 0.001) and CCI (P < 0.001) demonstrated equivalence. CONCLUSIONS: Although larger studies are required to confirm these results, routine SCD use may not be required when implementing ERAS protocols because clinically significant VTE rates were minimal.


Assuntos
Embolia Pulmonar , Cirurgia Torácica , Procedimentos Cirúrgicos Torácicos , Tromboembolia Venosa , Anticoagulantes/uso terapêutico , Humanos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Embolia Pulmonar/complicações , Embolia Pulmonar/prevenção & controle , Procedimentos Cirúrgicos Torácicos/efeitos adversos , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle
8.
J Chest Surg ; 55(2): 118-125, 2022 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-35135904

RESUMO

BACKGROUND: A time course analysis was undertaken to evaluate how perioperative process-of-care and outcome measures evolved after implementation of an enhanced recovery after thoracic surgery (ERATS) program. METHODS: Outcome and process-of-care measures were compared between patients undergoing major elective thoracic surgery during a 9-month pre-ERATS implementation period to those at 1-3, 4-6, and 7-9 months post-ERATS implementation. Outcome measures included length of stay, the 30-day readmission rate, 30-day emergency department visits, and minor and major adverse events. Process measures included first time to activity, out-of-bed, ambulation, fluid diet, diet as tolerated, as well as removal of the first and last chest tube, epidural, patient-controlled analgesia, and Foley and intravenous catheters. RESULTS: In total, 704 patients (352 pre-ERATS, 352 post-ERATS) were included. Mobilization-related process measures, including time to first activity (16.5 vs. 6.8 hours, p<0.001), out-of-bed (17.6 vs. 8.9 hours, p<0.001), and ambulation (32.4 vs. 25.4 hours, p=0.04) saw statistically significant improvements by 1-3 months post-ERATS implementation compared to pre-ERATS. Time to Foley removal improved by 4-6 months post-ERATS (19.5 vs. 18.2 hours, p=0.003). Outcome measures, including the 30-day readmission rate and emergency department visits, steadily decreased post-ERATS. By 7-9 months post-ERATS, both minor (18.2% vs. 7.9%, p=0.009) and major (13.6% vs. 4.4%, p=0.007) adverse events demonstrated statistically significant improvements. Length of stay trended towards improvement from 6.2 days pre-ERATS to 4.8 days by 7-9 months post-ERATS (p=0.06). CONCLUSION: The adoption of ERATS led to improvements in multiple process-of-care measures, which may collectively and gradually achieve optimization of clinical outcomes.

9.
Ann Thorac Surg ; 111(5): 1717-1723, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-32891651

RESUMO

BACKGROUND: Achalasia is a primary esophageal motility disorder in which there is incomplete relaxation of the lower esophageal sphincter and absence of peristalsis in the lower two thirds of the esophagus. A favored treatment is laparoscopic modified Heller myotomy with Dor fundoplication (LHMDor) with more than 90% immediate beneficial effect. The short-term outcomes of LHMDor are well documented, but stability and durability of postoperative symptom control over time is less understood. METHODS: Between 2004 and 2016, 54 patients with achalasia underwent LHMDor (single center). Using validated questionnaires, patients rated their symptoms in five domains: pain, gastroesophageal reflux disease (GERD), dysphagia, regurgitation, and quality of life. Symptom ratings were done preoperatively, 4 weeks postoperatively, 6 months postoperatively, and yearly after the operation. RESULTS: As expected, patients reported marked improvement in dysphagia, odynophagia, regurgitation, GERD, and quality of life after the operation (P < .001). From then on, the symptom control remained durable with respect to absence of pain, regurgitation, and odynophagia; however, we observed a recurrence of GERD symptoms beginning 3 to 5 years postoperatively (P = .001 and P = .04, respectively), with associated increased antireflux medication use. After initial LHMDor, 5 patients required endoscopic dilatation an average of 1.5 years postoperatively, and no patient required reoperation. Patients reported preserved improved quality of life to 11 years after the operation (P = .001). CONCLUSIONS: These results demonstrate the durability of LHMDor in the definitive management of achalasia, offering consistent symptomatic relief and significant improvement in quality of life over the decade after surgery, despite some increase in GERD symptoms and antireflux medication use.


Assuntos
Acalasia Esofágica/cirurgia , Fundoplicatura , Miotomia de Heller , Adulto , Idoso , Feminino , Fundoplicatura/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
10.
Trials ; 22(1): 384, 2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34098992

RESUMO

BACKGROUND: Postoperative atrial fibrillation (POAF) is a frequent adverse event after thoracic surgery with associated morbidity, mortality, and healthcare costs. It has been shown to be preventable with prophylactic amiodarone, which is only recommended in high-risk individuals due to the potential associated side effects. Risk factors for POAF have been identified and incorporated into a prediction model to identify high-risk patients. Further evaluation in the form of a multicenter clinical trial is required to assess the effectiveness of prophylaxis specifically in this high-risk population. The feasibility of such a trial first needs to be assessed. METHODS: The PREP-AF trial is a double-blind randomized controlled feasibility trial. Individuals undergoing major thoracic surgery who are identified to be high-risk by the POAF prediction model will be randomized 1:1 to receive a short course of amiodarone vs. placebo in the immediate postoperative period. The primary outcome is feasibility, which will be measured by the number of eligible patients identified, consented, and randomized; intervention adherence; and measurement of future outcomes of a full trial. DISCUSSION: This study will determine the feasibility of a randomized controlled trial to assess the effectiveness of prophylactic amiodarone, in high-risk patients undergoing major thoracic surgery. This will inform the development of a multi-center trial to establish if prophylactic amiodarone is safe and effective at reducing the incidence of POAF. Preventing this adverse event will not only improve outcomes for patients but also reduce the associated health resource utilization and costs. TRIAL REGISTRATION: ClinicalTrials.gov NCT04392921 . Registered on 19 May 2020.


Assuntos
Amiodarona , Fibrilação Atrial , Amiodarona/efeitos adversos , Antiarrítmicos/uso terapêutico , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/etiologia , Fibrilação Atrial/prevenção & controle , Estudos de Viabilidade , Humanos , Estudos Multicêntricos como Assunto , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Período Pós-Operatório , Ensaios Clínicos Controlados Aleatórios como Assunto
11.
Eur J Cardiothorac Surg ; 57(5): 874-880, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-31845993

RESUMO

OBJECTIVES: A prediction model developed by Passman et al. stratifies patients' risk of postoperative atrial fibrillation (POAF) after major non-cardiac thoracic surgery using 3 simple factors (sex, age and preoperative resting heart rate). The model has neither undergone external validation nor proven to be relevant in current thoracic surgery practice. METHODS: A retrospective single-centre analysis of all patients who underwent major non-cardiac thoracic surgery (2008-2017) with prospective documentation of incidence and severity of POAF was used for external validation of Passman's derivation sample (published in 2005 with 856 patients). The model calibration was assessed by evaluating the incidence of POAF and patients' risk scores (0-6). RESULTS: A total of 2054 patients were included. Among them, POAF occurred in 164 (7.9%), compared to 147 (17.2%) in Passman's study. Differences in our sample compared to Passman's sample included mean heart rate (75.7 vs 73.7 bpm, P < 0.001), proportion of patients with hypertension (46.1 vs 29.4%, P < 0.001), proportion of extensive lung resections, particularly pneumonectomy (6.1 vs 21%, P < 0.001) and proportion of minimally invasive surgeries (56.6% vs 0%). The model demonstrated a positive correlation between risk scores and POAF incidence (risk score 1.2% vs 6.16%). CONCLUSIONS: The POAF model demonstrated good calibration in our population, despite a lower overall incidence of POAF compared to the derivation study. POAF rates were higher among patients with a higher risk score and undergoing procedures with greater intrathoracic dissection. This tool may be useful in identifying patients who are at risk of POAF when undergoing major thoracic surgery and may, therefore, benefit from targeted prophylactic therapy.


Assuntos
Fibrilação Atrial , Cirurgia Torácica , Procedimentos Cirúrgicos Torácicos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/etiologia , Humanos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , Procedimentos Cirúrgicos Torácicos/efeitos adversos
13.
Semin Thorac Cardiovasc Surg ; 31(4): 861-867, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30797904

RESUMO

Improving evidence-based chest tube removal may reduce the length of stay following surgery. Presently, most chest tube removal protocols include a fluid output threshold based on a 24-hour observation period. The purpose of this study was to evaluate if, within a 24-hour time period, fluid output measurements at 6, 8, and 12 hours could predict if the total 24-hour fluid output would comply with a predetermined volume threshold considered acceptable for safe chest tube removal. Following lung resection, pleural fluid output data were prospectively recorded by a digital drainage system and analyzed retrospectively. Twenty-four-hour fluid output was calculated from every available 6-, 8-, and 12-hour measurement and compared to set 24-hour output criteria for chest tube removal (ie, 400 mL, 250 mL, and 20% of whole-body lymphatic flow). Performance of interim fluid outputs in predicting whether 24-hour fluid output criteria were satisfied was measured. From 2015 to 2018, 150 patients had digital pleural fluid drainage data suitable for analysis. Performance of interim fluid output data in identifying which patients would satisfy 24-hour output criteria ranged from 85% (95% confidence interval [CI] = 83-86) to 94% (95% CI = 93-94) for specificity, 75% (95% CI = 73-76) to 92% (95% CI = 90-93) for positive predictive value, and 6% (95% CI = 6-7) to 15% (95% CI = 14-17) for false-positive rate. Potential time saved in duration of drainage using interim fluid output data ranged from 10 to 16 hours. Pleural fluid output measured for 6-, 8-, and 12-hour durations can accurately identify patients who will meet 24-hour fluid output threshold for safe chest tube removal.


Assuntos
Tubos Torácicos , Remoção de Dispositivo , Drenagem/instrumentação , Derrame Pleural/terapia , Pneumonectomia , Idoso , Diagnóstico Precoce , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Derrame Pleural/diagnóstico , Derrame Pleural/etiologia , Pneumonectomia/efeitos adversos , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
14.
J Thorac Dis ; 10(Suppl 32): S3781-S3788, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30505565

RESUMO

Surgical resection of lung cancer is the preferred treatment for early-stage disease in medically fit patients. The rates of postoperative pulmonary complications (PPCs) such as pneumonia, empyema and atelectasis are as high as 10% in contemporary series. A review of the literature was performed to identify the best evidence supporting interventions to identify, prevent and treat PPCs. The use of patient risk scores, appropriate choice of antibiotic prophylaxis, intraoperative ventilatory strategies, chest physiotherapy, sputum management and non-invasive ventilatory support were specifically discussed, as was the relevant supporting data. Recommendations to guide best practice and inform future research questions are outlined.

15.
Transl Oncol ; 11(4): 988-998, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29940414

RESUMO

Anthracyclines, such as doxorubicin, are used as first-line chemotherapeutics, usually in combination therapies, for the treatment of advanced breast cancer. While these drugs have been successful therapeutic options, their use is limited due to serious drug related toxicities and acquired tumor resistance. Uncovering the molecular mechanisms that mediate doxorubicin's cytotoxic effect will lead to the identification of novel more efficacious combination therapies and allow for reduced doses of doxorubicin to be administered while maintaining efficacy. In our study, we demonstrate that activating transcription factor (ATF) 3 expression was upregulated by doxorubicin treatment in a representative panel of human breast cancer cell lines MCF7 and MDA-MB-231. We have also shown that doxorubicin treatment can induce ATF3 expression in ex vivo human breast and ovarian tumor samples. The upregulation of ATF3 in the cell lines was regulated by multiple cellular mechanisms including the activation of JNK and ATM signaling pathways. Importantly, loss of ATF3 expression resulted in reduced sensitivity to doxorubicin treatment in mouse embryonic fibroblasts. Through a 1200 FDA-approved compound library screen, we identified a number of agents whose cytotoxicity is dependent on ATF3 expression that also enhanced doxorubicin induced cytotoxicity. For example, the combination of the HDAC inhibitor vorinostat or the nucleoside analogue trifluridine could synergistically enhance doxorubicin cytotoxicity in the MCF7 cell line. Synergy in cell lines with the combination of ATF3 inducers and patients with elevated basal levels of ATF3 shows enhanced response to chemotherapy. Taken together, our results demonstrate a role for ATF3 in mediating doxorubicin cytotoxicity and provide rationale for the combination of ATF3-inducing agents with doxorubicin as a novel therapeutic approach.

16.
J Thorac Dis ; 10(Suppl 32): S3747-S3754, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30505561

RESUMO

BACKGROUND: Prolonged air leak (PAL) is often the limiting factor for hospital discharge after lung surgery. Our goal was to develop a statistical model that reliably predicts pulmonary air leak resolution by applying statistical time series modeling and forecasting techniques to digital drainage data. METHODS: Autoregressive Integrated Moving Average (ARIMA) modeling was used to forecast air leak flow from transplural air flow data. The results from ARIMA were retrospectively internally validated with a group of 100 patients who underwent lung resection between December 2012 and March 2017, for whom digital pleural drainage data was available for analysis and a persistent air leak was the limiting factor for chest tube removal. RESULTS: The ARIMA model correctly identified 82% (82/100) of patients as to whether or not the last chest tube removal was appropriate. The performance characteristics of the model in properly identifying patients whose air leak would resolve and who would therefore be candidates for safe chest tube removal were: sensitivity 80% (95% CI, 69-88%), specificity 88% (95% CI, 68-97%), positive predictive value 95% (95% CI, 86-99%), and negative predictive value 59% (95% CI, 42-79%). The false positive and false negative rate was 12% (95% CI, 12-31%) and 20% (95% CI, 12-31%). CONCLUSIONS: We were able to validate a statistical model that that reliably predicted resolution of pulmonary air leak resolution over a 24-hour period. This information may improve the care of patients with chest tube by optimizing duration of pleural drainage.

17.
J Thorac Dis ; 10(Suppl 32): S3799-S3808, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30505567

RESUMO

Atrial fibrillation (AF) is the most common sustained arrhythmia after non-cardiac thoracic surgery and is associated with a significant increase in perioperative morbidity, intensive care unit (ICU) admission, and mortality. Practical guidance is needed to assist clinicians in managing this critical issue and direct further research. Here we aim to provide a synoptic review and analysis of the literature to distil practical recommendations for prediction, prevention and management of post-operative atrial fibrillation (POAF) suitable for clinical application and further evaluation. To predict POAF, risk factors including age, gender, elevated pre-operative heart rate and extent of surgical resection have been reproducibly identified and integrated into scoring systems. To prevent POAF, prophylactic therapy with beta-blockers, amiodarone, or magnesium have demonstrated to be effective, but need further trials in high-risk populations. To manage unstable POAF that precipitates hypotension and hypoperfusion, although rare, requires immediate electrocardioversion to restore cardiac output and adequate oxygen delivery. For hemodynamically stable patients, rate control and prevention of adverse events are the objectives. We propose an individualized approach aimed at rate control using initial incremental low dose beta-blocker or calcium channel blocker (CCB) therapy with close monitoring of a patient's response, and continuation of the drug that they respond to, along with simultaneous identification and reduction of triggers of AF, in order for spontaneous return to sinus rhythm. For patients who persistently fail to respond to rate control therapy, rhythm control may be considered using an agent selected based on the patient's comorbidities and the medications' side effect profile. While controversial and requiring further study, anticoagulation therapy is recommended in patients with risk factors for thromboembolic events after 48 hours of persistent AF. We recommend continuous prospective monitoring of incidence and severity of POAF to track the impact of protocols to predict, prevent and manage POAF.

18.
J Healthc Qual ; 40(4): e62-e70, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29315152

RESUMO

As an innovative approach to improve quality of surgical care, we combined surgeon self-assessment and anonymized peer comparison with continuous quality improvement seminars using positive deviance (CQI/PD) to identify surgeon(s) with the lowest rates of adverse events (AEs) to guide group practice recommendations. Our objective was to quantify the impact these interventions on postoperative AEs rates after major non-cardiac chest operations. All postoperative AEs after all thoracic operations (n = 1,084, March, 2013 to February, 2016, single-center) were prospectively collected using the thoracic morbidity and mortality system, based on Clavien-Dindo schema. Online software provided surgeons (n = 6) with self-evaluation and peer comparison at all times. In addition, quarterly CQI/PD seminars (n = 8, September, 2013 to December, 2015) focused on common impactful AEs: atrial fibrillation (AFIB), prolonged alveolar air leak (PAAL), and anastomotic leak (AL). Impact was analyzed using univariate statistics 6, 9, and 12 months before and after implementation. We observed reductions of postoperative AEs after CQI/PD: a decrease (all time periods) in AFIB, greatest at 6 months (10.1% vs. 6.7%; p = .36); a decrease (all time periods) in PAAL, greatest at 12 months (18.9% vs. 11.7%; p < .05); and decrease (6 and 9 months) in AL, greatest at 6 months (11.1% vs. 8.3%; p = .82). Improvements in AE rates after individual surgeon self-evaluation and CQI/PD seminars provide encouraging results that merit further investigation.


Assuntos
Avaliação de Resultados em Cuidados de Saúde , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/psicologia , Melhoria de Qualidade/organização & administração , Cirurgiões/psicologia , Procedimentos Cirúrgicos Torácicos/psicologia , Procedimentos Cirúrgicos Torácicos/normas , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Autoavaliação (Psicologia)
19.
J Thorac Cardiovasc Surg ; 155(2): 798-807, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29103816

RESUMO

OBJECTIVE: To determine whether all grades of severity of postoperative adverse events are associated with prolonged length of stay in patients undergoing pulmonary cancer resection. METHODS: This was a retrospective cohort study of all patients who underwent pulmonary resection with curative intent for malignancy at The Ottawa Hospital, Division of Thoracic Surgery (January 2008 to July 2015). Postoperative adverse events were collected prospectively with the Thoracic Morbidity & Mortality System, based on the Clavien-Dindo severity classification. Patient demographics, comorbidities, preoperative investigations, cardiopulmonary assessment, pathologic staging, operative characteristics, and length of stay were retrospectively reviewed. Prolonged hospital stay was defined as >75th percentile for each procedure performed (wedge resection 6 days, segmentectomy 6 days, lobectomy 7 days, extended lobectomy 8 days, pneumonectomy 10 days). Univariable and multivariable logistic regression analyses were conducted to identify factors associated with prolonged hospital stay. RESULTS: Of 1041 patients, 579 (55.6%) were female, 610 (58.1%) were >65 years old, 232 (22.3%) experienced prolonged hospital stay, and 416 (40.0%) patients had ≥1 postoperative adverse event. Multivariable analyses identified significant (P < .05) factors associated with prolonged hospital stay to be (odds ratio; 95% confidence interval): lower diffusion capacity of the lung for carbon monoxide (0.99; 0.98-0.99), surgical approach: open thoracotomy (1.8; 1.3-2.5), and presence of any postoperative adverse event: Grade I (5.8; 3.3-10.2), Grade II (6.0; 4.0-8.9), Grade III (11.4; 7.0-18.7), and Grade IV (19.40; 7.1-55.18). CONCLUSIONS: Lower diffusion capacity of the lung for carbon monoxide, open thoracotomy approach, and the development of any postoperative adverse event, including minor events that required no additional therapy, were factors associated with prolonged hospital stay.


Assuntos
Tempo de Internação , Neoplasias Pulmonares/cirurgia , Pulmão/cirurgia , Pneumonectomia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Idoso , Feminino , Volume Expiratório Forçado , Humanos , Pulmão/fisiopatologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/fisiopatologia , Masculino , Pessoa de Meia-Idade , Ontário , Pneumonectomia/mortalidade , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/fisiopatologia , Complicações Pós-Operatórias/terapia , Capacidade de Difusão Pulmonar , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Toracotomia/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
20.
Ann Thorac Surg ; 104(2): 382-388, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28669503

RESUMO

BACKGROUND: Postoperative adverse events (AEs), prolonged length of stay (PLOS), and patient experience are common quality measures after thoracic surgical procedures. Our objective was to investigate the relationship of postoperative AEs on patient experience and hospital length of stay (LOS) after lung cancer resection. METHODS: AEs (using Thoracic Morbidity and Mortality system based on Clavien-Dindo schema) and LOS were prospectively collected for all patients undergoing lung cancer resection. A 21-item questionnaire, retrospectively asking about patient experience, was mailed to patients twice (October 2015 and January 2016). The impact of AEs on experience was investigated and stratified by hospital LOS, with PLOS defined as the 75th percentile. Univariate analysis used parametric (t test) and nonparametric (Mann-Whitney) tests according to test conditions. RESULTS: Of 288 patients who responded to the survey (70% response rate), 175 (61%) had no AEs, 113 (39%) had experienced at least one AE, and 52 (18%) had experienced PLOS. Lung cancer patients who experienced PLOS showed significantly decreased experience on several questionnaire items, including their impression of comprehensiveness of surgeons information provision during inpatient period (p = 0.008), inpatient recovery from operation (p = 0.001), quality of life 30 days after operation (p = 0.032), follow-up care, (p = 0.022), and satisfaction with outcome 1 year after operation during follow-up care (p = 0.022). The presence of postoperative AEs led only to reduced impression about inpatient recovery from the operation (p = 0.01). CONCLUSIONS: In this cohort, postoperative AEs were minimally associated with negative patient experience. However, patients who experienced PLOS demonstrated a marked reduction in experience after thoracic surgical procedures.


Assuntos
Tempo de Internação/tendências , Neoplasias Pulmonares/cirurgia , Pneumonectomia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Incidência , Masculino , Ontário/epidemiologia , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Fatores de Tempo
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