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Background: Reported advantages to robotic thoracic surgery include shorter length of stay (LOS), improved lymphadenectomy, and decreased complications. It is uncertain if these benefits occur when introducing robotics into a well-established video-assisted thoracoscopy (VATS) practice. We compared the two approaches to investigate these advantages. Materials and methods: IRB approval was obtained for this project. Patients who underwent segmentectomy or lobectomy from May 2016-December 2018 were propensity-matched 2: 1 (VATS: robotic) and compared using weighted logistic regression with age, gender, Charlson Comorbidity Index, surgery type, stage, Exparel, and epidural as covariates. Complication rates, operation times, number of sampled lymph nodes, pain level, disposition, and LOS were compared using Wilcoxon rank-sum and with Rao-Scott Chi-squared tests. Results: 213 patients (142 VATS and 71 robot) were matched. Duration of robotic cases was longer than VATS (median 186 min (IQR 78) vs. 164 min (IQR 78.75); p < 0.001). Significantly more lymph nodes (median 11 (IQR 7.50) vs. 8 (IQR 7.00); p = 0.004) and stations were sampled (median 4 (IQR 2.00) vs. 3 (IQR 1.00); p < 0.001) with the robot. Interestingly, robotic resections had higher 72-hour pain scores (median 3 (IQR 3.25) vs. 2 (IQR 3.50); p = 0.04) and 48-hour opioid usage (median 37.50 morphine milligram equivalents (MME) (IQR 45.50) vs. 22.50 MME (IQR 37.50); p = 0.01). Morbidity, LOS, and disposition were similar (all p > 0.05). Conclusions: The robotic approach facilitates better lymph node sampling, even in an established VATS practice.
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Background: Thoracic epidural analgesia (TEA) and liposomal bupivacaine (LB) are two methods used for postoperative pain control after thoracic surgery. Some studies have compared LB to standard bupivacaine. However, data comparing the outcomes of LB to TEA after minimally invasive lung resection is limited. Therefore, the objective of our study was to compare postoperative pain, opioid usage, and outcomes between patients who received TEA vs. LB. Methods: We conducted a retrospective chart review of patients who underwent minimally invasive lung resections over an 8-month period. Intraoperatively, patients received either LB under direct vision or a TEA. Pain scores were obtained in the post-anesthesia care unit (PACU) and at 12, 24, and 48 hours postoperatively. Morphine milligram equivalents (MMEs) were calculated at 24 and 48 hours postoperatively. Postoperative outcomes were then compared between groups. Results: In total, 391 patients underwent minimally invasive lung resection: 236 (60%) wedge resections, 51 (13%) segmentectomies, and 104 (27%) lobectomies. Of these, 326 (83%) received LB intraoperatively. Fewer patients in the LB group experienced postoperative complications (18% vs. 34%, P=0.004). LB patients also had lower median pain scores at 24 (P=0.03) and 48 hours (P=0.001) postoperatively. There was no difference in MMEs at 24 hours (P=0.49). However, at 48 hours, patients who received LB required less narcotics (P=0.02). Median hospital length of stay (LOS) was significantly shorter in patients who received LB (2 vs. 4 days, P<0.001). On multivariable analysis, increasing age, postoperative complications, and use of TEA were independently associated with a longer hospital LOS. Conclusions: Compared to TEA, LB intercostal block placed under direct vision reduced morphine use 48 hours after thoracic surgery. It was also associated with fewer postoperative complications and shorter median hospital LOS. LB is a good alternative to TEA for pain management after minimally invasive lung resection.
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OBJECTIVES: To compare oncologic outcomes after segmentectomy with division of segmental bronchus, artery and vein (complete anatomic segmentectomy) versus segmentectomy with division of <3 segmental structures (incomplete anatomic segmentectomy). METHODS: We conducted a single-centre, retrospective analysis of patients undergoing segmentectomy from March 2005 to May 2020. Operative reports were audited to classify procedures as complete or incomplete anatomic segmentectomy. Patients who underwent neoadjuvant therapy or pulmonary resection beyond indicated segments were excluded. Survival was estimated with Kaplan-Meier models and compared using log-rank tests. Cox proportional hazards models were used to estimate hazard ratios (HRs) for death. Cumulative incidence functions for loco-regional recurrence were compared with Gray's test, with death considered a competing event. Cox and Fine-Gray models were used to estimate cause-specific and subdistribution HRs, respectively, for loco-regional recurrence. RESULTS: Of 390 cases, 266 (68.2%) were complete and 124 were incomplete anatomic segmentectomy. Demographics, pulmonary function, tumour size, stage and perioperative outcomes did not significantly differ between groups. Surgical margins were negative in all but 1 case. Complete anatomic segmentectomy was associated with improved lymph node dissection (5 vs 2 median nodes sampled; P < 0.001). Multivariable analysis revealed reduced incidence of loco-regional recurrence (cause-specific HR = 0.42; 95% confidence interval 0.22-0.80; subdistribution HR = 0.43; 95% confidence interval 0.23-0.81), and non-significant improvement in overall survival (HR = 0.66; 95% confidence interval: 0.43-1.00) after complete versus incomplete anatomic segmentectomy. CONCLUSIONS: This single-centre experience suggests complete anatomic segmentectomy provides superior loco-regional control and may improve survival relative to incomplete anatomic segmentectomy. We recommend surgeons perform complete anatomic segmentectomy and lymph node dissection whenever possible.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Pneumonectomia/métodos , Estudos Retrospectivos , Resultado do Tratamento , Recidiva Local de Neoplasia/cirurgia , Estadiamento de NeoplasiasRESUMO
OBJECTIVE: The advent of lung cancer screening and detection of smaller nodules amplifies the need to clarify the oncological quality of sublobar resections. Furthermore, studies comparing sublobar resections to lobectomies offer conflicting conclusions. We hypothesize that this is driven, in part, by inconsistency in reporting; that is, variable interpretation of what constitutes an operative segment. Without an established standard, 2 very different operations may be reported as segmental resections, leaving the data on sublobar approaches subject to interpretative variability. METHODS: A retrospective audit was performed on all segmental resections from May 2016 to December 2019 at Brigham and Women's Hospital. Pathology and operative reports were reviewed, with particular attention to the dissection of the component artery, vein, and bronchus. Resections with dissection and division of at least 1 major vascular structure (the segmental artery or vein), as well as the segmental bronchus, met operative criteria for anatomic segmentectomy. Surgical quality metrics were compared between the 2 groups. RESULTS: There were 271 segmental resections: 219 (80.8%) were anatomic segmentectomies and 52 (19.2%) were nonanatomic segmentectomies. For the entire cohort, nonanatomic segmentectomies had smaller margins (1.0 vs 1.5 cm; P = .02), fewer lymph nodes (2.0 vs 6.0; P < .001), and fewer mediastinal lymph node stations sampled (1.0 vs 2.0; P < .001). Similarly, there were smaller margins (1.5 vs 1.8 cm; P = .03), fewer lymph nodes (2.0 vs 6.0; P < .001), and fewer mediastinal lymph node stations sampled (1.0 vs 2.0; P < .001) in nonanatomic segmentectomies for non-small cell lung cancer. CONCLUSIONS: Nearly 20% of reported segmentectomies may not meet criteria for true segmental resection. Therefore, prior studies may need further scrutiny to clarify outcomes and results. Establishing a professional standard may help mitigate ambiguity in published data on this subject.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Feminino , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/patologia , Estudos Retrospectivos , Pneumonectomia/efeitos adversos , Pneumonectomia/métodos , Mastectomia Segmentar , Detecção Precoce de Câncer , Estadiamento de NeoplasiasRESUMO
Chylopericardium is a rare pathologic condition consisting of the accumulation of excess amounts of chylous fluid within the pericardial cavity. Most patients are asymptomatic at presentation; however, chest pressure, chest pain and lightheadedness have been reported, and the most common presenting symptom is shortness of breath. Patients are noted to have enlargement of the cardiac silhouette on routine chest radiograph, and evidence of a pericardial effusion on echocardiography. The diagnosis is only definitively confirmed with pericardiocentesis and fluid analysis. The fluid is typically turbid white or milky in appearance, with a triglyceride level in excess of 500 mg/dL. The mechanism by which chyle accumulates within the pericardium is believed to be secondary to abnormal or damaged lymphatics or due to elevated pressure within the thoracic duct that results in chyle reflux into the pericardium. Following drainage with a pericardiocentesis or pericardial drain, attempts at conservative therapy with nothing by mouth and parental nutrition can be made, but have a high rate of failure and subsequent reaccumulation of chyle. Surgical treatment provides the most definitive management and consists of ligation of the thoracic duct just above the level of the diaphragm and creation of a pericardial window. With this treatment, risk of recurrence is incredibly low (<5%).
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BACKGROUND: Chest roentgenograms after chest tube removal are common practice in postoperative thoracic surgery patients. Whether these roentgenograms change clinical management is debatable. We investigated prevalence and management of post-pull pneumothoraces after lung resection. METHODS: Patients undergoing minimally invasive wedge resections, segmentectomies, and lobectomies between March 2018 and September 2018 were retrospectively reviewed. Baseline factors, operative technique, chest tube management, and outcomes after post-pull chest roentgenograms, and factors associated with post-pull pneumothoraces were analyzed. RESULTS: The study analyzed 200 consecutive patients comprising 117 wedge resections (59%), 24 segmentectomies (12%), and 59 lobectomies (30%). Wedge resections compared with segmentectomy or lobectomy had lower rates of chest tube use, drain duration, air leaks, and need for a clamp trial, with Blake drains most often removed last compared with segmentectomy or lobectomy (all P < .001). Post-pull pneumothoraces, which were largely small/tiny/trace (96%), occurred in 110 patients (55%). Five patients experienced symptoms, and no patients required intervention. Resection type was associated with the pneumothorax rate, need for additional imaging, and discharge timing (all P < .05). Those with pneumothoraces compared with those without differed in type of resection and chest drain, presence of air leak within 24 hours of removal, need for clamp trial, order of tube removal, and hospital length of stay (all P < .05). Multivariable regression showed only clamp trial was associated with post-pull pneumothorax development (odds ratio, 2.48; 95% CI, 1.13-5.45; P = .024). CONCLUSIONS: Although routine use of post-pull chest roentgenograms identified a high prevalence of pneumothorax, no intervention was required. Our study demonstrates post-pull imaging may not be indicated in asymptomatic patients without prior air leak or clamp trial.
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Tubos Torácicos , Pneumotórax , Humanos , Pneumotórax/diagnóstico por imagem , Pneumotórax/etiologia , Pneumotórax/cirurgia , Pneumonectomia/efeitos adversos , Pneumonectomia/métodos , Estudos Retrospectivos , Resultado do Tratamento , Pulmão , Tempo de InternaçãoRESUMO
Ectopic pancreas within the anterior mediastinum is a rare congenital anomaly. We present a case of a solid anterior mediastinal mass that presented with hemoptysis and ground glass parenchymal changes in the right upper lobe. Robotic surgical resection was completed, and final pathology was consistent with benign pancreatic tissue. The patient fully recovered with no recurrence of hemoptysis. Ectopic pancreas, although uncommon, should be included in the differential for solid and cystic anterior mediastinal masses; surgical resection is often curative and effectively manages symptoms.
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Coristoma , Doenças do Mediastino , Coristoma/complicações , Coristoma/diagnóstico , Coristoma/cirurgia , Hemoptise/diagnóstico , Hemoptise/etiologia , Humanos , Doenças do Mediastino/complicações , Doenças do Mediastino/diagnóstico , Doenças do Mediastino/cirurgia , Mediastino/patologia , Pâncreas/patologiaRESUMO
OBJECTIVES: Prolonged air leak (PAL; >5 days) following lung resection is associated with postoperative morbidity. We investigated factors associated with PAL and PAL requiring intervention. METHODS: Retrospective review of all patients undergoing lobectomy, segmentectomy or wedge resection from 2016 to 2019 at our institution. Bronchoplastic reconstructions and lung-volume reduction surgeries were excluded. Incidence and risk factors for PAL and PAL requiring intervention were evaluated. RESULTS: In total, 2384 patients were included. PAL incidence was 5.4% (129/2384); 22.5% (29/129) required intervention. PAL patients were more commonly male (56.6% vs 39.7%), older (mean age 69 vs 65 years) and underwent lobectomy or thoracotomy (all P < 0.001). Patients with PAL had longer length of stay (9 vs 3 days), more discharge needs and increased odds of complication (all P < 0.050).Twenty-nine patients required intervention (9 chest tubes; 4 percutaneous drains; 16 operations). In 50% of operative interventions, an air leak source was identified; however, the median time from intervention to resolution was 13 days. Patients requiring intervention had increased steroid use, lower diffusion capacity for carbon monoxide and twice the length of stay versus PAL patients (all P < 0.050).On univariable analysis, forced expiratory volume in 1 s (FEV1) <40%, diffusion capacity for carbon monoxide <50%, steroid use and albumin <3 had increased odds of intervention (P < 0.050). CONCLUSIONS: Age, gender and operative technique were related to PAL development. Patients with worse forced expiratory volume in 1 s or diffusion capacity for carbon monoxide, steroid use or poor nutrition were less likely to heal on their own, indicating a population that could benefit from earlier intervention.
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Pneumonectomia , Complicações Pós-Operatórias , Idoso , Feminino , Humanos , Pulmão/cirurgia , Masculino , Pneumonectomia/efeitos adversos , Complicações Pós-Operatórias/cirurgia , Complicações Pós-Operatórias/terapia , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: The Surveillance, Epidemiology and End Results (SEER) and the National Cancer Database (NCDB) are databases for cancer analysis that may be subject to error in data reporting. This study examined the rates and impact of discordant data for non-small cell lung cancer. METHODS: NCDB and SEER were queried for non-small cell lung cancer pathologic tumor, node, metastasis data (NCDB) or "derived" data (SEER). Discordancy between descriptors with stage and impact of outlier data were analyzed. RESULTS: Incomplete staging was noted in 71.5% of the NCDB and 10.3% of SEER patients. A total of 174 829 patients from the NCDB and 117 114 from SEER were analyzed. The NCDB had 97 cases with ≥20 positive lymph nodes recorded vs 27 in SEER (P < .001). Mean and median sampled lymph nodes were skewed with inclusion of these data points (P < .001). The NCDB misclassified 0.99% tumors >5 cm as stage I vs 0.04% in SEER (P < .001). The NCDB misstaged positive lymph nodes as pathologic N0 (0.59%) or stage 0 or stage I (0.65%). The NCDB misclassified pathologic N1 as lower than stage II (0.91%) or N2 as lower than stage III (0.36%). The NCDB misclassified stage I with documentation of pathologic N1 or N3 disease (0.24%) or stage II with evidence of N2 or N3 disease (0.50%). The NCDB misclassified pathologic M1 as pathologic stage Assuntos
Carcinoma Pulmonar de Células não Pequenas
, Neoplasias Pulmonares
, Linfoma
, Carcinoma Pulmonar de Células não Pequenas/patologia
, Humanos
, Neoplasias Pulmonares/patologia
, Linfonodos/patologia
, Linfoma/patologia
, Estadiamento de Neoplasias
, Prognóstico
, Programa de SEER
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BACKGROUND: There is limited information on the frequency of complications among older adults after oncological thoracic surgery in the modern era. We hypothesized that morbidity and mortality in older adults with lung cancer undergoing lobectomy is low and different than that of younger patients undergoing thoracic surgery. METHODS: All patients undergoing lobectomy at a large volume academic center between May 2016 and May 2019 were included. Patients were prospectively monitored to grade postoperative morbidity by organ system, based on the Clavien-Dindo classification. Patients were divided into two groups: Group 1 included patients 65-91â¯years of age, and Group 2 included those <65â¯years. RESULTS: Of 680 lobectomies in 673 patients, 414(61%) were older than 65â¯years of age (group 1). Median age at surgery was 68â¯years (20-91). Median hospital stay was 4â¯days (1-38) and longer in older adults. Older adults experienced higher rates of grade II and IV complications, mostly driven by an increased incidence of delirium, atrial fibrillation, prolonged air leak, respiratory failure and urinary retention. In this modern cohort, there was only 1 stroke (0.1%), and delirium was reduced to 7%. Patients undergoing minimally invasive (MI) surgery had a lower rate of Grade IV life-threatening complications. Older adults were more likely to be discharged to a rehabilitation facility, however this difference also disappeared with MI surgical procedures. CONCLUSIONS: Current morbidity of older adults undergoing lobectomy for cancer is low and is different than that of younger patients. Thoracotomy may be associated with postoperative complications in these patients. Our findings suggest the need to consider MI approaches and broad-based, geriatric-focused perioperative management of older adults undergoing lobectomy.
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Neoplasias Pulmonares , Melhoria de Qualidade , Idoso , Humanos , Tempo de Internação , Neoplasias Pulmonares/cirurgia , Morbidade , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Cirurgia Torácica Vídeoassistida , ToracotomiaRESUMO
OBJECTIVE: To develop a team-based institutional infrastructure for navigating management of a novel disease, to determine a safe and effective approach for performing tracheostomies in patients with COVID-19 respiratory failure, and to review outcomes of patients and health care personnel following implementation of this approach. METHODS: An interdisciplinary Task Force was constructed to develop innovative strategies for management of a novel disease. A single-institution, prospective, nonrandomized cohort study was then conducted on patients with coronavirus disease 2019 (COVID-19) respiratory failure who underwent tracheostomy using an induced bedside apneic technique at a tertiary care academic institution between April 27, 2020, and June 30, 2020. RESULTS: In total, 28 patients underwent tracheostomy with induced apnea. The median lowest procedural oxygen saturation was 95%. The median number of ventilated days following tracheostomy was 11. There were 3 mortalities (11%) due to sepsis and multiorgan failure; of 25 surviving patients, 100% were successfully discharged from the hospital and 76% are decannulated, with a median time of 26 days from tracheostomy to decannulation (range 12-57). There was no symptomatic disease transmission to health care personnel on the COVID-19 Tracheostomy Team. CONCLUSIONS: Patients with respiratory failure from COVID-19 disease may benefit from tracheostomy. This can be completed effectively and safely without viral transmission to health care personnel. Performing tracheostomies earlier in the course of disease may expedite patient recovery and improve intensive care unit resource use. The creation of a collaborative Task Force is an effective strategic approach for management of novel disease.
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Analyze "number of nodes" as an integer-valued variable to identify possible minimum lymph node (LN) number to sample during lung cancer resection. The National Cancer Database (NCDB) queried 2004-14 for surgically treated clinical stage I/II non-small-cell lung cancer (NSCLC). Overall survival (OS) by number of LN sampled was examined for the complete dataset, by adenocarcinoma, and by degree of resection using number of sampled LN both as integer-valued (0-30 nodes) variable and collapsed into classes. A total of 102,225 patients were analyzed. Median sampled LNs were 7. Median overall survival was 59 months if no LNs were sampled (95% confidence interval [CI]: 57.0-62.4), 74.7 months for 1 sampled LN (95% CI: 69.6-78.1), 80.2 (95% CI: 74.2-85.6) for 2 sampled LN, up to 81.5 mos. for 29 sampled LN. A Cox regression model using "0 LN" as baseline level, showed association with increased overall survival starting at 1 LN (hazard ratio [HR] 0.81, 95% CI 0.76-0.87; P <0.001). A "moving baseline" Cox regression model, showed no additional benefit when sampling additional nodes. We noticed a decreasing, linear association between OS and a number of 0-5 sampled LNs, most pronounced between 0 and 1 LN sampled, using a martingale residual plot from a null Cox model; no association was observed for more sampled LNs. For patients undergoing lobectomy, difference in OS was noted between 0 and 1LN sampled but not between 2 and 30 LN. These differences were not statistically significant until the number of 4 removed LN (respectively 3 for wedge-resections). For segmentectomies, median survival was not statistically associated with number of LN sampled. Based on NCDB data, LN sampling for lung cancer resections is recommended. Lobectomy survival is positively associated with 4 LN sampled, but ideal sampling may lie at 5LN in most cases. NCDB data does not seem to justify the quality metric of minimum 10 LNs.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Excisão de Linfonodo , Linfonodos/patologia , Linfonodos/cirurgia , Estadiamento de Neoplasias , Prognóstico , Estudos RetrospectivosRESUMO
BACKGROUND: We analyzed the association between neoadjuvant chemoradiation in patients undergoing bronchial sleeve resection with the incidence of postoperative pulmonary and airway complications. METHODS: After instructional review board approval we performed a retrospective review of a prospectively maintained database of 136 patients who underwent sleeve resection in our institution between January 1998 and December 2016. Administration of neoadjuvant chemoradiation treatment was the studied exposure. Outcomes of interest were rates of postoperative pulmonary and airway complications. Nonparametric testing of demographic, surgical, and pathologic characteristics and morbidity was performed. Logistic regression models evaluated postoperative pulmonary complications and airway complications. Analysis was performed using Stata/IC 15. RESULTS: We analyzed 136 patients (18 underwent neoadjuvant chemoradiation), 77 (57%) of whom had non-small cell lung cancer. Postoperative pulmonary complications were observed in 44 of 136 patients (32%). Incidences of pulmonary complications were higher in the neoadjuvant chemoradiation group compared with the non-neoadjuvant radiation group (15/18 patients [83%] vs 29/118 patients [25%], respectively; P < .001). Likewise, rates of pneumonia, atelectasis, respiratory insufficiency, bronchial stenosis, prolonged air leak, bronchopleural fistula, and completion pneumonectomy (2/18 [11%]) were higher in the neoadjuvant chemoradiation group, reaching statistical significance in all cases except bronchial stenosis and prolonged air leak. Only neoadjuvant chemoradiation therapy remained significant for postoperative pulmonary and airway complications on logistic regression (both P < .05) CONCLUSIONS: Patients who undergo neoadjuvant chemoradiation before sleeve resection are at an increased risk of pulmonary and airway complications.
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Brônquios/cirurgia , Neoplasias Pulmonares/cirurgia , Pneumonectomia/efeitos adversos , Pneumonectomia/métodos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estudos Retrospectivos , Adulto JovemRESUMO
To understand the potential and limitations of circulating tumor cell (CTC) sequencing for molecular diagnostics, we investigated the feasibility of identifying the ubiquitous KRAS mutation in single CTCs from pancreatic cancer (PC) patients. We used the NanoVelcro/laser capture microdissection CTC platform, combined with whole genome amplification and KRAS Sanger sequencing. We assessed both KRAS codon-12 coverage and the degree that allele dropout during whole genome amplification affected the detection of KRAS mutations from single CTCs. We isolated 385 single cells, 163 from PC cell lines and 222 from the blood of 12 PC patients, and obtained KRAS sequence coverage in 218 of 385 single cells (56.6%). For PC cell lines with known KRAS mutations, single mutations were detected in 67% of homozygous cells but only 37.4% of heterozygous single cells, demonstrating that both coverage and allele dropout are important causes of mutation detection failure from single cells. We could detect KRAS mutations in CTCs from 11 of 12 patients (92%) and 33 of 119 single CTCs sequenced, resulting in a KRAS mutation detection rate of 27.7%. Importantly, KRAS mutations were never found in the 103 white blood cells sequenced. Sequencing of groups of cells containing between 1 and 100 cells determined that at least 10 CTCs are likely required to reliably assess KRAS mutation status from CTCs.
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Procedimentos Analíticos em Microchip/métodos , Células Neoplásicas Circulantes/metabolismo , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética , Análise de Célula Única/métodos , Biomarcadores Tumorais , Linhagem Celular Tumoral , Análise Mutacional de DNA , Genótipo , Humanos , Técnicas de Diagnóstico Molecular , Células Neoplásicas Circulantes/patologia , Reação em Cadeia da Polimerase , Proteínas Proto-Oncogênicas p21(ras)/genética , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Análise de Sequência de DNARESUMO
BACKGROUND: Long-term survival (LTS) is uncommon for patients with pancreatic ductal adenocarcinoma (PDAC). We sought to identify factors that predict 10-year, LTS after resection of PDAC. METHODS: We identified all patients with PDAC who underwent resection at UCLA after 1990 and included all patients eligible for observed LTS (1/1/1990-12/31/2004). An independent pathologist reconfirmed the diagnosis of PDAC in patients with LTS. Logistic regression was used to predict LTS on the basis of patient and tumor characteristics. RESULTS: Of 173 included patients, 53% were male, median age at diagnosis was 66 years, and median survival was 23 months. The rate of observed LTS was 12.1% (n = 21). Age, sex, number of lymph nodes evaluated, margin status, lymphovascular invasion, and adjuvant chemotherapy and radiation were not associated with LTS. The following were associated with LTS on bivariate analysis: low AJCC stage (Ia, Ib, IIa) (P = .034), negative lymph node status (P = .034), low grade (well-, moderately-differentiated) (P = .001), and absence of perineural invasion (P = .019). Only low grade (odds ratio 7.17, P = .012) and absent perineural invasion (odds ratio 3.28, P = .036) were independently associated with increased odds of LTS. Our multivariate model demonstrated good discriminatory power for LTS, as indicated by a c-statistic of 0.7856. CONCLUSION: Absence of perineural invasion and low tumor grade were associated with greater likelihood of LTS. Understanding the tumor biology of LTS may provide critical insight into a disease that is typically marked by aggressive behavior and limited survival.
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Carcinoma Ductal Pancreático/mortalidade , Neoplasias Pancreáticas/mortalidade , Idoso , Idoso de 80 Anos ou mais , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/terapia , Quimioterapia Adjuvante , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica , Estadiamento de Neoplasias , Pancreatectomia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/terapia , Radioterapia Adjuvante , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
PURPOSE: Prostate stem cell antigen (PSCA) is highly expressed in local prostate cancers and prostate cancer bone metastases and its expression correlates with androgen receptor activation and a poor prognosis. In this study, we investigate the potential clinical applications of immunoPET with the anti-PSCA A11 minibody, an antibody fragment optimized for use as an imaging agent. We compare A11 minibody immunoPET to (18)F-Fluoride PET bone scans for detecting prostate cancer bone tumors and evaluate the ability of the A11 minibody to image tumor response to androgen deprivation. EXPERIMENTAL DESIGN: Osteoblastic, PSCA-expressing, LAPC-9 intratibial xenografts were imaged with serial (124)I-anti-PSCA A11 minibody immunoPET and (18)F-Fluoride bone scans. Mice bearing LAPC-9 subcutaneous xenografts were treated with either vehicle or MDV-3100 and imaged with A11 minibody immunoPET/CT scans pre- and posttreatment. Ex vivo flow cytometry measured the change in PSCA expression in response to androgen deprivation. RESULTS: A11 minibody demonstrated improved sensitivity and specificity over (18)F-Fluoride bone scans for detecting LAPC-9 intratibial xenografts at all time points. LAPC-9 subcutaneous xenografts showed downregulation of PSCA when treated with MDV-3100 which A11 minibody immunoPET was able to detect in vivo. CONCLUSIONS: A11 minibody immunoPET has the potential to improve the sensitivity and specificity of clinical prostate cancer metastasis detection over bone scans, which are the current clinical standard-of-care. A11 minibody immunoPET additionally has the potential to image the activity of the androgen signaling axis in vivo which may help evaluate the clinical response to androgen deprivation and the development of castration resistance.