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1.
Ann Surg ; 280(1): 91-97, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38568206

RESUMEN

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


Asunto(s)
Fuga Anastomótica , Neoplasias Esofágicas , Esofagectomía , Humanos , Masculino , Esofagectomía/efectos adversos , Femenino , Persona de Mediana Edad , Neoplasias Esofágicas/cirugía , Neoplasias Esofágicas/mortalidad , Estudios Retrospectivos , Anciano , Fuga Anastomótica/etiología , Fuga Anastomótica/cirugía , Quilo , Tiempo de Internación , Tasa de Supervivencia , Resultado del Tratamiento , Complicaciones Posoperatorias/mortalidad
2.
J Surg Oncol ; 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39257253

RESUMEN

INTRODUCTION: Minimally invasive surgery (MIS) reduces lengths of stay, complications, and potentially perioperative hospital costs. However, the impact of MIS on financial toxicity (FT), defined as the costs resulting from oncologic care and their negative effects on quality of life, in patients with lung cancer is unknown. Our objective was to investigate the association between surgical approach and FT in this population. METHODS: A single-institution study was performed evaluating resected lung cancer patients (2016-2021). FT was assessed using the Comprehensive Score for Financial Toxicity (COST) questionnaire. The relationship between surgical approach (MIS vs. thoracotomy) and FT was evaluated using propensity score-matched (PSM) regression analysis. A sensitivity analysis involving the entire cohort was also performed using an inverse probability-weighted generalized linear model. RESULTS: As reported previously, of 1477 patients surveyed, 463 responded (31.3%) with FT reported in 196 patients (42.3%). Resection was performed by thoracotomy in 53.3% (n = 247), and by MIS in the remainder (n = 216, 46.7%; video-assisted thoracoscopic surgery [VATS] = 115; robotic-assisted = 101). There was no difference in FT in patients who underwent VATS and robotic-assisted surgery (p = 0.515). In the PSM analysis, MIS was not associated with FT (odds ratio [OR]: 0.980, 95% confidence interval [CI]: 0.628-1.533, p = 0.929). Similar results were found on sensitivity analysis (OR: 1.488, CI: 0.931-2.378, p = 0.096). CONCLUSIONS: Compared to MIS, thoracotomy was not associated with FT in patients with resected lung cancer. Though there are several benefits from MIS, it does not appear to be a meaningful strategy to alleviate FT in this population.

3.
J Surg Oncol ; 129(2): 331-337, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37876311

RESUMEN

BACKGROUND AND OBJECTIVES: For patients with colorectal cancer (CRC), the lung is the most common extra-abdominal site of distant metastasis. However, practices for chest imaging after colorectal resection vary widely. We aimed to identify characteristics that may indicate a need for early follow-up imaging. METHODS: We retrospectively reviewed charts of patients who underwent CRC resection, collecting clinicopathologic details and oncologic outcomes. Patients were grouped by timing of pulmonary metastases (PM) development. Analyses were performed to investigate odds ratio (OR) of PM diagnosis within 3 months of CRC resection. RESULTS: Of 1600 patients with resected CRC, 233 (14.6%) developed PM, at a median of 15.4 months following CRC resection. Univariable analyses revealed age, receipt of systemic therapy, lymph node ratio (LNR), lymphovascular and perineural invasion, and KRAS mutation as risk factors for PM. Furthermore, multivariable regression showed neoadjuvant therapy (OR: 2.99, p < 0.001), adjuvant therapy (OR: 6.28, p < 0.001), LNR (OR: 28.91, p < 0.001), and KRAS alteration (OR: 5.19, p < 0.001) to predict PM within 3 months post-resection. CONCLUSIONS: We identified clinicopathologic characteristics that predict development of PM within 3 months after primary CRC resection. Early surveillance in such patients should be emphasized to ensure timely identification and treatment of PM.


Asunto(s)
Neoplasias Colorrectales , Neoplasias Pulmonares , Humanos , Neoplasias Colorrectales/patología , Estudios Retrospectivos , Proteínas Proto-Oncogénicas p21(ras) , Terapia Combinada , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/cirugía
4.
Dis Esophagus ; 37(6)2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38391198

RESUMEN

The use of octreotide in managing intrathoracic chyle leak following esophagectomy has gained popularity in the adult population. While the benefits of octreotide have been confirmed in the pediatric population, there remains limited evidence to support its use in the adults post-esophagectomy. Thus, we performed a single-institution cohort study to characterize its efficacy. The study was performed using a prospective, single-center database, from which clinicopathologic characteristics were extracted of patients who had post-esophagectomy chyle leaks. Kaplan-Meier and multivariable Cox regression analyses were performed to investigate the effect of octreotide use on chest tube duration (CTD), hospital length of stay (LOS), and overall survival (OS). In our cohort, 74 patients met inclusion criteria, among whom 27 (36.5%) received octreotide. Kaplan-Meier revealed no significant effect of octreotide on CTD (P = 0.890), LOS (P = 0.740), or OS (P = 0.570). Multivariable Cox regression analyses further corroborated that octreotide had no effect on CTD (HR = 0.62, 95% confidence interval [CI]: 0.32-1.20, P = 0.155), LOS (HR = 0.64, CI: 0.34-1.21, P = 0.168), or OS (1.08, CI: 0.53-2.19, P = 0.833). Octreotide use in adult patients with chyle leak following esophagectomy lacks evidence of association with meaningful clinical outcomes. Level 1 evidence is needed prior to further consideration in this population.


Asunto(s)
Quilotórax , Esofagectomía , Fármacos Gastrointestinales , Tiempo de Internación , Octreótido , Complicaciones Posoperatorias , Humanos , Octreótido/uso terapéutico , Esofagectomía/efectos adversos , Quilotórax/etiología , Quilotórax/tratamiento farmacológico , Masculino , Femenino , Persona de Mediana Edad , Tiempo de Internación/estadística & datos numéricos , Anciano , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/tratamiento farmacológico , Fármacos Gastrointestinales/uso terapéutico , Estimación de Kaplan-Meier , Estudios Prospectivos , Resultado del Tratamiento , Tubos Torácicos , Modelos de Riesgos Proporcionales , Adulto , Estudios Retrospectivos
5.
Ann Surg ; 278(6): 1038-1044, 2023 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-37249193

RESUMEN

OBJECTIVES: To describe financial toxicity (FT) in patients with resected lung cancer and identify risk factors in this population. BACKGROUND: FT describes the financial burden associated with cancer care and its impact on the quality of survivorship. Few prior studies have examined FT in patients with lung cancer. METHODS: Patients who underwent lung cancer resection at our institution between January 1, 2016 and December 31, 2021, were surveyed to gather demographic information and evaluate FT using a validated questionnaire. A multivariable model was built to identify risk factors for FT. RESULTS: Of the total, 1477 patients were contacted, of whom 463 responded (31.3%). Most patients were stage I (n = 349, 75.4%) and lobectomy was performed often (n = 290, 62.8%). There were 196 patients (42.3%) who experienced FT. Upon multivariable analyses, divorced marital status [odds ratio (OR) = 3.658, 95% CI: 1.180-11.337], household income <$40,000 (OR = 2.544, 95% CI: 1.003-6.455), credit score below 739 (OR = 2.744, 95% CI: 1.326-5.679), clinical stage >I (OR = 2.053, 95% CI: 1.088-3.877), and change in work hours or work cessation (all P < 0.05) were associated with FT. Coping mechanisms, such as decreased spending on food or clothing and increased use of savings or borrowing money, were more likely to be reported by patients experiencing FT than those who did not ( P < 0.001). CONCLUSIONS: Patients undergoing lung cancer resection often experienced significant financial stress with several identifiable risk factors. FT should be considered early in the care of these patients to alleviate detrimental coping mechanisms and enhance their quality of survivorship.


Asunto(s)
Neoplasias Pulmonares , Neoplasias , Humanos , Neoplasias Pulmonares/cirugía , Estrés Financiero , Costo de Enfermedad , Neoplasias/epidemiología , Renta , Encuestas y Cuestionarios , Calidad de Vida
6.
Ann Surg ; 277(5): 721-726, 2023 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-36052678

RESUMEN

OBJECTIVE: Clinical predictors of pathological complete response have not reliably identified patients for whom an organ-sparing approach following neoadjuvant chemoradiation be undertaken for esophageal cancer patients. We sought to identify high-risk predictors of residual carcinoma that may preclude patients from a selective surgical approach. BACKGROUND: Patients treated with neoadjuvant chemoradiation followed by esophagectomy for esophageal adenocarcinoma were identified. PATIENTS AND METHODS: Correlation between clinical and pathologic complete responses were examined. Regression models and recursive partitioning were utilized to identify features associated with residual carcinoma. External validation of these high-risk factors was performed on a data set from an independent institution. RESULTS: A total of 326 patients were identified, in whom clinical complete response was noted in 104/326 (32%). Pathologic complete response was noted in only 33/104 (32%) of these clinical complete responders. Multivariable analysis identified that the presence of stricture ( P =0.011), positive biopsy ( P =0.010), and signet ring cell histology ( P =0.019) were associated with residual cancer. Recursive partitioning corroborated a 94% probability of residual disease, or greater, for each of these features. The positive predictive value was >90% for these characteristics. A SUV max >5.4 at the esophageal primary in the absence of esophagitis was also a high-risk factor for residual carcinoma. External validation confirmed these high-risk factors to be implicated in the finding of residual carcinoma. CONCLUSIONS: Clinical parameters of response are poor predictors of complete pathologic response leading to challenges in selecting candidates for active surveillance. However, we characterize several high-risk features for residual carcinoma which indicate that esophagectomy should not be delayed.


Asunto(s)
Adenocarcinoma , Neoplasias Esofágicas , Humanos , Terapia Neoadyuvante , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/patología , Adenocarcinoma/terapia , Adenocarcinoma/patología , Esofagectomía , Estudios Retrospectivos , Estadificación de Neoplasias
7.
J Surg Res ; 277: 125-130, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35489217

RESUMEN

INTRODUCTION: The lung represents a frequent site of spread for metastatic melanoma, which has historically been managed with surgical resection achieving promising outcomes. We hypothesized that the role of surgery in the management of melanoma pulmonary metastases (MPM) is evolving among the development of less invasive diagnostic and novel systemic therapeutic strategies. MATERIALS AND METHODS: A single-center thoracic surgery database was reviewed and patients who underwent surgical resection of MPM between 1998 and 2019 were identified. Demographic, clinicopathologic, and surgical data were collected and analyzed, as were the annual volumes and indications for surgical resection. A Cochran-Armitage test was used to assess the trend in surgical indication. RESULTS: Three hundred and seventy seven surgical procedures for MPM were performed during the years of study in the care of 347 patients. Patients were predominantly male, with a mean age of 59.3 y. The mean number of annual resections was 17 and while this number initially increased from six in 1998 to a peak of 39 cases in 2008, a decline was subsequently observed. Diagnostic resection decreased from 22% in 1998-1999 to 5% at the peak of procedures in 2008-2009 and to 0 in 2018-2019 (P = 0.02). Curative resection increased from 44% in 1998-1999 to 73% in 2008-2009 (P < 0.001) and remained the dominant reason for surgery in later years. CONCLUSIONS: Surgical indications in the management of MPM have transformed in conjunction with systemic modalities, and the volume of resections has decreased in the modern era. Despite innovations in systemic management and shifting goals of operative interventions, surgeons continue to play a vital role in caring for these patients with an advanced disease.


Asunto(s)
Neoplasias Pulmonares , Melanoma , Metastasectomía , Procedimientos Quirúrgicos Torácicos , Femenino , Humanos , Neoplasias Pulmonares/secundario , Neoplasias Pulmonares/cirugía , Masculino , Melanoma/patología , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia
8.
J Surg Oncol ; 124(4): 699-703, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34057733

RESUMEN

BACKGROUND AND OBJECTIVES: Adoptive T-cell therapies (ACTs) using expansion of tumor-infiltrating lymphocyte (TIL) populations are of great interest for advanced malignancies, with promising response rates in trial settings. However, postoperative outcomes following pulmonary TIL harvest have not been widely documented, and surgeons may be hesitant to operate in the setting of widespread disease. METHODS: Patients who underwent pulmonary TIL harvest were identified, and postoperative outcomes were studied, including pulmonary, cardiovascular, infectious, and wound complications. RESULTS: 83 patients met inclusion criteria. Pulmonary TIL harvest was undertaken primarily via a thoracoscopy with a median operative blood loss and duration of 30 ml and 65 min, respectively. The median length of stay was 2 days. Postoperative events were rare, occurring in only five (6%) patients, including two discharged with a chest tube, one discharged with oxygen, one episode of urinary retention, and one blood transfusion. No reoperations occurred. The median time from TIL harvest to ACT infusion was 37 days. CONCLUSIONS: Pulmonary TIL harvest is safe and feasible, without major postoperative events in our cohort. All patients were able to receive intended ACT infusion without delays. Therefore, thoracic surgeons should actively participate in ongoing ACT trials and aggressively seek to enroll patients on these protocols.


Asunto(s)
Inmunoterapia Adoptiva/métodos , Neoplasias Pulmonares/terapia , Linfocitos Infiltrantes de Tumor/inmunología , Melanoma/terapia , Procedimientos Quirúrgicos Pulmonares/métodos , Adulto , Estudios de Factibilidad , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/secundario , Masculino , Melanoma/inmunología , Melanoma/patología , Persona de Mediana Edad , Cuidados Posoperatorios , Pronóstico , Estudios Prospectivos
9.
Cancer Immunol Immunother ; 69(8): 1519-1534, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32300858

RESUMEN

Enhanced tumor glycolytic activity is a mechanism by which tumors induce an immunosuppressive environment to resist adoptive T cell therapy; therefore, methods of assessing intratumoral glycolytic activity are of considerable clinical interest. In this study, we characterized the relationships among tumor 18F-fluorodeoxyglucose (FDG) retention, tumor metabolic and immune phenotypes, and survival in patients with resected non-small cell lung cancer (NSCLC). We retrospectively analyzed tumor preoperative positron emission tomography (PET) 18F-FDG uptake in 59 resected NSCLCs and investigated correlations between PET parameters (SUVMax, SUVTotal, SUVMean, TLG), tumor expression of glycolysis- and immune-related genes, and tumor-associated immune cell densities that were quantified by immunohistochemistry. Tumor glycolysis-associated immune gene signatures were analyzed for associations with survival outcomes. We found that each 18F-FDG PET parameter was positively correlated with tumor expression of glycolysis-related genes. Elevated 18F-FDG SUVMax was more discriminatory of glycolysis-associated changes in tumor immune phenotypes than other 18F-FDG PET parameters. Increased SUVMax was associated with multiple immune factors characteristic of an immunosuppressive and poorly immune infiltrated tumor microenvironment, including elevated PD-L1 expression, reduced CD57+ cell density, and increased T cell exhaustion gene signature. Elevated SUVMax identified immune-related transcriptomic signatures that were associated with enhanced tumor glycolytic gene expression and poor clinical outcomes. Our results suggest that 18F-FDG SUVMax has potential value as a noninvasive, clinical indicator of tumor immunometabolic phenotypes in patients with resectable NSCLC and warrants investigation as a potential predictor of therapeutic response to immune-based treatment strategies.


Asunto(s)
Biomarcadores de Tumor/análisis , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Fluorodesoxiglucosa F18/metabolismo , Linfocitos Infiltrantes de Tumor/inmunología , Tomografía de Emisión de Positrones/métodos , Microambiente Tumoral/inmunología , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Glucólisis , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/cirugía , Pronóstico , Radiofármacos/metabolismo , Estudios Retrospectivos , Tasa de Supervivencia , Transcriptoma
10.
J Surg Oncol ; 122(3): 495-505, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32356321

RESUMEN

BACKGROUND: The improvement in the management of lung cancer have the potential to improve survival in patients undergoing resection for early-stage (stage I and II) non-small cell lung cancer (NSCLC), but few studies have evaluated time trends and identified predictors of overall survival (OS). METHODS: We identified surgically resected early-stage NSCLC between 1998 and 2016. The 3-year OS (1998-2014) and 5-year OS (1998-2012) rates were calculated for each year. Joinpoint regression was used to calculate annual percentage changes (APC) and to test time trends in OS. Multivariable Cox regression was used to identify predictors of OS. RESULTS: There was a significant upward trend in the 3-year (1998, 56%; 2014, 83%; APC = 1.8) and 5-year (1998, 47%; 2012, 76%; APC = 3.1) OS. Older age; male sex; history of diabetes, coronary artery disease, and chronic obstructive pulmonary disease; high ASA score; smoking pack-years; high-grade tumor; pneumonectomy; thoracotomy; neoadjuvant therapy; nodal disease; and positive tumor margin were predictors of poor OS. CONCLUSION: The upward time trend in OS suggests that improved staging, patient selection, and management have conferred a survival benefit in early-stage NSCLC patients. The prediction model of OS could be used to refine selection criteria for resection and improve survival outcomes.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/cirugía , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Humanos , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Nomogramas , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores Sexuales , Tasa de Supervivencia/tendencias , Adulto Joven
11.
J Surg Oncol ; 121(6): 984-989, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32077113

RESUMEN

BACKGROUND AND OBJECTIVES: Precision medicine has altered the management of colorectal cancer (CRC). However, the concordance of mutational findings between primary CRC tumors and associated pulmonary metastases (PM) is not well-described. This study aims to determine the concordance of genomic profiles between primary CRC and PM. METHODS: Patients treated for colorectal PM at a single institution from 2000 to 2017 were identified. Mutational concordance was defined as either both wild-type or both mutant alleles in lung and colorectal lesion; genes with opposing mutational profiles were reported as discordant. RESULTS: Thirty-eight patients met inclusion criteria, among whom KRAS, BRAF, NRAS, MET, RET, and PIK3CA were examined for concordance. High concordance was demonstrated among all evaluated genes, ranging from 86% (KRAS) to 100% concordance (NRAS, RET, and MET). De novo KRAS mutations were detected in the PM of 4 from 35 (11%) patients, 3 of whom had previously received anti-epidermal growth factor receptor (EGFR) therapy. Evaluation of Cohen's κ statistic demonstrated moderate to perfect correlation among evaluated genes. CONCLUSIONS: Because high intertumoral genomic homogeneity exists, it may be reasonable to use primary CRC mutational profiles to guide prognostication and targeted therapy for PM. However, the possibility of de novo KRAS-mutant PM should be considered, particularly among patients previously treated with anti-EGFR therapy.


Asunto(s)
Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/secundario , Cetuximab/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Análisis Mutacional de ADN , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Terapia Molecular Dirigida , Medicina de Precisión , Proteínas Proto-Oncogénicas p21(ras)/genética
12.
J Surg Oncol ; 122(3): 515-522, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32468580

RESUMEN

BACKGROUND AND OBJECTIVES: It is unclear if a specific strategy for simultaneous treatment of primary thymic neoplasms and pleural metastases confers benefit for Masaoka stage IVA disease. We reviewed our experience with thymic neoplasms with concurrent pleural metastases to identify factors influencing outcomes. METHODS: Records of patients who presented with stage IVA thymic neoplasms from 2000 to 2018 were assessed. Multivariate Cox proportional hazards analyses were completed to determine predictors of progression-free and overall survival. RESULTS: Forty-eight patients were identified, including 34 (71%) who underwent surgery. Median overall and progression-free survival were 123 and 21 months, respectively. The extent of resection varied, and was most commonly thymectomy plus partial pleurectomy (22, 65%). Median progression-free survival for patients who underwent surgical resection versus those who had not was 24 versus 12 months (P = .018). Following surgical resection, mediastinal recurrence was uncommon (2, 6%, vs 7, 50% nonoperatively). Five-year survival rates in these groups were suggestive of possible benefit to surgery (87% vs 68%). CONCLUSIONS: Thymic neoplasms with pleural dissemination represents a treatment challenge. As part of a multidisciplinary approach, surgery appears to be associated with more favorable long-term results, although selection bias may account for some of the survival differences observed.


Asunto(s)
Neoplasias Pleurales/secundario , Neoplasias Pleurales/cirugía , Neoplasias del Timo/patología , Neoplasias del Timo/cirugía , Adulto , Anciano , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Modelos de Riesgos Proporcionales , Procedimientos Quirúrgicos Torácicos , Timectomía
13.
Cancer ; 125(21): 3738-3748, 2019 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-31287557

RESUMEN

BACKGROUND: Patient-derived xenograft (PDX) models increasingly are used in translational research. However, the engraftment rates of patient tumor samples in immunodeficient mice to PDX models vary greatly. METHODS: Tumor tissue samples from 308 patients with non-small cell lung cancer were implanted in immunodeficient mice. The patients were followed for 1.5 to approximately 6 years. The authors performed histological analysis of PDXs and some residual tumor tissues in mice with failed PDX growth at 1 year after implantation. Quantitative polymerase chain reaction and enzyme-linked immunoadsorbent assay were performed to measure the levels of Epstein-Barr virus genes and human immunoglobulin G in PDX samples. Patient characteristics were compared for PDX growth and overall survival as outcomes using Cox regression analyses. Disease staging was based on the 7th TNM staging system. RESULTS: The overall engraftment rate for PDXs from patients with non-small cell lung cancer was 34%. Squamous cell carcinomas had a higher engraftment rate (53%) compared with adenocarcinomas. Tumor samples from patients with stage II and stage III disease and from larger tumors were found to have relatively high engraftment rates. Patients whose tumors successfully engrafted had worse overall survival, particularly those individuals with adenocarcinoma, stage III or stage IV disease, and moderately differentiated tumors. Lymphoma formation was one of the factors associated with engraftment failure. Human CD8-positive and CD20-positive cells were detected in residual samples of tumor tissue that failed to generate a PDX at 1 year after implantation. Human immunoglobulin G was detected in the plasma of mice that did not have PDX growth at 14 months after implantation. CONCLUSIONS: The results of the current study indicate that the characteristics of cancer cells and the tumor immune microenvironment in primary tumors both can affect engraftment of a primary tumor sample.


Asunto(s)
Adenocarcinoma/patología , Carcinoma de Pulmón de Células no Pequeñas/patología , Modelos Animales de Enfermedad , Neoplasias Pulmonares/patología , Adenocarcinoma/genética , Adenocarcinoma/inmunología , Animales , Antígenos CD20/inmunología , Antígenos CD20/metabolismo , Linfocitos B/inmunología , Linfocitos B/metabolismo , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Xenoinjertos , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/inmunología , Ratones Endogámicos NOD , Ratones Noqueados , Ratones SCID , Estadificación de Neoplasias , Ensayos Antitumor por Modelo de Xenoinjerto/métodos
14.
J Surg Oncol ; 120(4): 729-735, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31290159

RESUMEN

BACKGROUND AND OBJECTIVES: While knowledge has grown extensively regarding the impact of mutations on colorectal cancer prognosis, their role in outcomes after pulmonary metastasectomy (PM) remains minimally understood. We sought to determine the prognostic role of mutant disease on survival and recurrence after metastasectomy. METHODS: Patients with available tumor sequencing profiles who underwent PM for colorectal cancer at a single institution from 2011 to 2017 were reviewed. Various demographic and clinicopathologic factors, as well as mutational status, were tested in the Cox regression analyses to identify predictors of survival and disease-free survival (DFS). RESULTS: A total of 130 patients met inclusion criteria, among whom 78 (60%) were male and the mean age was 57 years. The median survival time and 5-year survival rate were 58.2 months and 47%, respectively. A single pulmonary nodule was present in 54%. Disease recurrence occurred for 87 (67%) patients, including 75 (58%) who had at least one lung recurrence after metastasectomy at a median time to recurrence of 19.4 months. Upon multivariable analysis, RAS and TP53 mutations were associated with shorter survival DFS, while APC is associated with prolonged survival. CONCLUSIONS: After metastasectomy for colorectal cancer, mutations in RAS, TP53, and APC play an important role in survival and recurrence.


Asunto(s)
Biomarcadores de Tumor/genética , Neoplasias Colorrectales/mortalidad , Neoplasias Pulmonares/mortalidad , Metastasectomía/mortalidad , Mutación , Recurrencia Local de Neoplasia/mortalidad , Neumonectomía/mortalidad , Adulto , Anciano , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/secundario , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia
15.
Dis Esophagus ; 32(10): 1-6, 2019 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-30888418

RESUMEN

Endoscopic mucosal resection (EMR) can be an effective therapy for superficial esophageal cancer. Many patients with cT2 invasion by endoscopic ultrasound (EUS) receive surgery but are subsequently found to have superficial disease. The purpose of this study was to investigate the safety profile and the added value of attempting EMR for EUS-staged cT2N0 esophageal cancer. A retrospective review was performed at a single institution from 2008 to 2017. Patients who were staged cT2N0 by EUS were identified from a prospectively maintained surgical database. Among 75 patients identified for analysis, 30 underwent an attempt at EMR. No perforations or other immediate complications occurred. EMR was more likely to be attempted among older patients (P = 0.001) with smaller tumor size (P < 0.001) and diminished SUVmax (P = 0.001). At the time of treatment, EMR was successful in clearing all known disease among 17/30 patients, with 12 representing pT1a or less and 5 representing pT1b with negative margins. Among the 17 patients for whom EMR was able to clear all known disease, there were no recurrences or cancer-related deaths. Although all the patients were staged as cT2N0 by EUS, many patients were identified by EMR to have superficial disease. There were no perforations or other adverse events related to EMR. Furthermore, EMR cleared all known disease among 17 patients with no known recurrences or cancer-related deaths. The results indicate that EMR for cT2N0 esophageal cancer is a safe diagnostic option that is therapeutic for some.


Asunto(s)
Resección Endoscópica de la Mucosa/estadística & datos numéricos , Neoplasias Esofágicas/cirugía , Esofagectomía/estadística & datos numéricos , Selección de Paciente , Anciano , Anciano de 80 o más Años , Bases de Datos Factuales , Resección Endoscópica de la Mucosa/métodos , Neoplasias Esofágicas/diagnóstico por imagen , Neoplasias Esofágicas/patología , Esofagectomía/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Prospectivos , Estudios Retrospectivos , Resultado del Tratamiento , Ultrasonografía
16.
Cancer ; 124(5): 1061-1069, 2018 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-29178133

RESUMEN

BACKGROUND: Next-generation sequencing of cell-free DNA (cfDNA) has been shown to be a useful noninvasive test for detecting mutations in solid tumors. METHODS: Targeted gene sequencing was performed with a panel of 263 cancer-related genes for cfDNA and genomic DNA of peripheral blood mononuclear cells (PBMCs) obtained from presurgical specimens of 6 lung cancer patients, and mutation calls in these samples were compared with those of primary tumors and corresponding patient-derived xenografts (PDXs). RESULTS: Approximately 67% of the mutations detected in the tumor samples (primary tumors and/or PDXs) were also detected in genomic DNA from PBMCs as background mutations. These background mutations consisted of germline polymorphisms and a group of mutations with low allele frequencies, mostly <10%. These variants with a low allele frequency were repeatedly detected in all types of samples from the same patients and at similarly low allele frequency levels in PBMCs from different patients; this indicated that their detection might be derived from common causes, such as homologous sequences in the human genome. Allele frequencies of mutations detected in both primary tumors and cfDNA showed 2 patterns: 1) low allele frequencies (approximately 1%-10%) in cfDNA but high allele frequencies (usually >10% or >3-fold increase) in primary tumors and further enrichment in PDXs and 2) similar allele frequencies across samples. CONCLUSIONS: Because only a small fraction of total cfDNA might be derived from tumor cells, only mutations with the first allele frequency pattern may be regarded as tumor-specific mutations in cfDNA. Effective filtering of background mutations will be required to improve the accuracy of mutation calls in cfDNA. Cancer 2018;124:1061-9. © 2017 American Cancer Society.


Asunto(s)
ADN Tumoral Circulante/genética , ADN de Neoplasias/genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Leucocitos Mononucleares/metabolismo , Neoplasias Pulmonares/genética , Mutación , Femenino , Frecuencia de los Genes , Genómica/métodos , Humanos , Neoplasias Pulmonares/patología , Masculino , Estadificación de Neoplasias
17.
J Surg Oncol ; 118(3): 518-524, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-30109699

RESUMEN

BACKGROUND AND OBJECTIVES: Chest wall sarcomas are rare and may demonstrate heterogeneous features. Surgery remains the mainstay of treatment with chemotherapy and radiotherapy used as adjuncts. Herein, we report outcomes of a large cohort of patients with primary chest wall sarcoma who underwent resection. METHODS: Records of 121 patients who underwent resection for primary chest wall sarcoma between 1998 and 2013 were reviewed. A thoracic pathologist reexamined all tumors and categorized them according to grade. Univariable and multivariable Cox analyses were conducted to identify predictors of overall survival (OS). RESULTS: The median age was 45.0 (range, 11-81) years, and most tumors (63.6%, 77) were high grade. The median tumor size was 7 cm (range, 1-21 cm). Fifty-nine (48.8%) patients received neoadjuvant chemotherapy and 12 (9.9%) received neoadjuvant radiotherapy. A complete resection was achieved in 103 (85.1%) patients. Neoadjuvant chemotherapy (P = 0.532) and radiation ( P = 1.000) were not associated with a complete resection. Five-year OS among patients undergoing R0 and R1 resections was 61.9% and 27.8%, respectively. Multivariable analysis identified high grade (HR, 15.21; CI, 3.57-64.87; P < 0.001), R1 (HR, 3.10; CI, 1.40-6.86; P = 0.005), R2 resection (HR, 5.18; CI, 1.91-14.01; P = 0.001), and age (HR, 1.02; CI, 1.01-1.03; P = 0.002) as predictors of OS. CONCLUSIONS: In this series of resected chest wall sarcomas, complete resection and tumor grade remain the most important survival predictors. Individual decisions are required for the utilization of neoadjuvant therapy.


Asunto(s)
Sarcoma/mortalidad , Neoplasias Torácicas/mortalidad , Procedimientos Quirúrgicos Torácicos/mortalidad , Pared Torácica/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Estudios Retrospectivos , Sarcoma/patología , Sarcoma/cirugía , Tasa de Supervivencia , Neoplasias Torácicas/patología , Neoplasias Torácicas/cirugía , Pared Torácica/cirugía , Adulto Joven
18.
Cancer ; 123(21): 4106-4113, 2017 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-28885712

RESUMEN

BACKGROUND: Reports are limited regarding clinical and pretreatment features that might predict a pathological complete response (pathCR) after treatment in patients with esophageal cancer (EC). This might allow patient selection for different strategies. This study examines the association of a pathCR with pretreatment variables, overall survival (OS), recurrence-free survival (RFS), and patterns of recurrence in a large cohort from a single institution. METHODS: The baseline clinical features of 911 consecutive patients with EC who were treated with trimodality therapy from January 2000 to November 2013 were analyzed. A pathCR was defined as a surgical specimen with no residual carcinoma (primary or nodes). Logistic regressions were used to identify independent baseline features associated with a pathCR. We applied log-rank testing and Cox models to determine the association between a pathCR and the time-to-event outcomes (OS and RFS). RESULTS: Of 911 patients, 218 (23.9%) achieved a pathCR. The pathCR rate was 23.1% for adenocarcinoma and 32.2% for squamous cell carcinoma. A lower pathCR rate was observed for 1) older patients (>60 years), 2) patients with poorly differentiated tumors, 3) patients with signet ring cells (SRCs), and 4) patients with a higher T stage. Patients with a pathCR had longer OS and RFS than those without a pathCR (P = .0021 and P = .0011, respectively). Recurrences occurred more in non-pathCR patients. Distant metastases were the most common type of recurrence. PathCR patients developed brain metastases at a marginally higher rate than non-pathCR patients (P = .051). CONCLUSIONS: In this large cohort study, a pathCR is confirmed to be associated with better OS and RFS. The presence of a poorly differentiated tumor or SRCs reduces the likelihood of a pathCR. Future research should focus on molecular classifiers. Cancer 2017;123:4106-4113. © 2017 American Cancer Society.


Asunto(s)
Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/patología , Adenocarcinoma/secundario , Adenocarcinoma/terapia , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Encefálicas/secundario , Instituciones Oncológicas , Carcinoma de Células Escamosas/secundario , Carcinoma de Células Escamosas/terapia , Quimioradioterapia/métodos , Terapia Combinada/métodos , Supervivencia sin Enfermedad , Neoplasias Esofágicas/terapia , Femenino , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Inducción de Remisión , Texas
19.
Support Care Cancer ; 22(2): 527-35, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24141699

RESUMEN

PURPOSE: Unlike infections related to chemotherapy-induced neutropenia, postoperative infections occurring in patients with solid malignancy remain largely understudied. Our aim is to evaluate the outcomes and the volume-outcomes relationship associated with postoperative infections following resection of common solid tumors. METHODS: We used Texas Discharge Data to study patients undergoing resection of cancer of the lung, esophagus, stomach, pancreas, colon, or rectum from 01/2002 to 11/2006. From their billing records, we identified ICD-9 codes indicating a diagnosis of serious postoperative infection (SPI), i.e., bacteremia/sepsis, pneumonia, and wound infection, occurring during surgical admission or leading to readmission within 30 days of surgery. Using regression-based techniques, we estimated the impact of SPI on mortality, resource utilization, and costs, as well as the relationship between hospital volume and SPI, after adjusting for confounders and data clustering. RESULTS: SPI occurred following 9.4 % of the 37,582 eligible tumor resections and was independently associated with nearly 12-fold increased odds of in-hospital mortality [95 % confidence interval (95 % CI), 7.2-19.5, P < 0.001]. Patients with SPI required six additional hospital days (95 % CI, 5.9-6.2) at an incremental cost of $16,991 (95 % CI, $16,495-$17,497). Patients who underwent resection at high-volume hospitals had a 16 % decreased odds of developing SPI than those at low-volume hospitals (P = 0.03). CONCLUSIONS: Due to the substantial burden associated with SPI following common solid tumor resections, hospitals must identify more effective prophylactic measures to avert these potentially preventable infections. Additional volume-outcomes research is needed to identify infection prevention processes that can be transferred from high- to lower-volume providers.


Asunto(s)
Neoplasias/cirugía , Complicaciones Posoperatorias/microbiología , Sepsis/etiología , Procedimientos Quirúrgicos Operativos/estadística & datos numéricos , Infección de la Herida Quirúrgica/etiología , Adulto , Anciano , Centros de Día , Femenino , Mortalidad Hospitalaria , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/economía , Neoplasias/epidemiología , Evaluación de Resultado en la Atención de Salud , Neumonía/economía , Neumonía/etiología , Neumonía/mortalidad , Complicaciones Posoperatorias/economía , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/mortalidad , Análisis de Regresión , Sepsis/economía , Sepsis/mortalidad , Procedimientos Quirúrgicos Operativos/efectos adversos , Infección de la Herida Quirúrgica/microbiología , Infección de la Herida Quirúrgica/mortalidad , Texas/epidemiología
20.
Semin Diagn Pathol ; 31(4): 289-92, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25239273

RESUMEN

Ground glass opacities, also known as GGOs, are detected on computed tomography (CT) scans as hazy areas if increased attenuation in the lung, and my represent a variety of pulmonary processes. Natural history of GGOs and their clinical implications are not yet fully understood. Controversies associated with the management of GGOs surround their histological classification, malignant potential, indications, timing, and type of intervention. Herein we discuss the principles and role of surgical therapy for ground glass opacities.


Asunto(s)
Enfermedades Pulmonares/cirugía , Humanos , Enfermedades Pulmonares/diagnóstico por imagen , Radiografía
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