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1.
Surg Endosc ; 38(6): 3470-3477, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38769187

RESUMEN

BACKGROUND: Soilage of the surgical endoscope occurs frequently during minimally invasive surgery. The resultant impairment of visualization of the surgical field compromises patient safety, prolongs operative times, and frustrates surgeons. The standard practice for cleaning the surgical camera involves a disruption in the conduct of surgery by completely removing the endoscope from the field, manually cleaning its lens, treating it with a surfactant, and reinserting it into the patient; after which the surgeon resumes the procedure. METHODS: We developed an automated solution for in vivo endoscope cleaning in minimally invasive surgery- a port that detects the position of the endoscope in its distal lumen, and precisely and automatically delivers a pressurized mist of cleaning solution to the lens of the camera. No additions to the scope and minimal user interaction with the port are required. We tested the efficacy of this troCarWash™ device in a porcine model of laparoscopy. Four board-certified general surgeons were instructed to soil and then clean the laparoscope using the device. Representative pre- and post-clean images were exported from the surgical video and clarity was graded (1) digitally by a canny edge detection algorithm, and (2) subjectively by 3 blinded, unbiased observers using a semi-quantitative scale. RESULTS: We observed statistically significant improvements in clarity by each method and for each surgeon, and we noted significant correlation between digital and subjective scores. CONCLUSION: Based on these data, we conclude that the troCarWash™ effectively restored impaired visualization in a large animal model of laparoscopy.


Asunto(s)
Laparoscopía , Laparoscopía/métodos , Laparoscopía/instrumentación , Animales , Porcinos , Laparoscopios , Contaminación de Equipos/prevención & control , Diseño de Equipo
2.
Ann Surg ; 277(6): e1215-e1216, 2023 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-34596078

RESUMEN

INTRODUCTION: Neurogenic thoracic outlet syndrome (TOS) is a musculoskeletal condition in which the brachial plexus is dynamically compressed within the scalene triangle, an anatomic space bordered by the anterior and middle scalene muscles and the first rib. In some cases, an offending cervical rib is present. Traditional surgical approaches to first rib resection and scalenectomy are limited by exposure, require retraction of neurovascular structures, and result in morbidity. METHODS: We describe a novel transthoracic robotic approach to first/cervical rib resection that overcomes these limitations, and we review its early clinical outcomes. RESULTS: Robotic first rib resection (FRR) is crystallized into 12 distinct steps, each with detailed video commentary, and nuances specific to neurogenic and venous TOS cases are provided. Published data supports decreased surgical morbidity of robotic FRR compared with open cases. CONCLUSIONS: Robotic FRR offers advantages over traditional operative approaches including improved exposure and elimination of retraction of neurovascular structures, which result in improved safety.


Asunto(s)
Costilla Cervical , Procedimientos Quirúrgicos Robotizados , Síndrome del Desfiladero Torácico , Humanos , Costilla Cervical/cirugía , Descompresión Quirúrgica , Síndrome del Desfiladero Torácico/cirugía , Costillas/cirugía , Resultado del Tratamiento
3.
Br J Cancer ; 127(9): 1691-1700, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-35999269

RESUMEN

BACKGROUND: Malignant pleural mesothelioma (MPM) is a lung pleural cancer with very poor disease outcome. With limited curative MPM treatment available, it is vital to study prognostic biomarkers to categorise different patient risk groups. METHODS: We defined gene signatures to separately characterise intrinsic and extrinsic features, and investigated their interactions in MPM tumour samples. Specifically, we calculated gene signature scores to capture the downstream pathways of major mutated driver genes (BAP1, NF2, SETD2 and TP53) as tumour-intrinsic features. Similarly, we inferred the infiltration levels for major immune cells in the tumour microenvironment to characterise tumour-extrinsic features. Lastly, we integrated these features with clinical factors to predict prognosis in MPM. RESULTS: The gene signature scores were more prognostic than the corresponding genomic mutations, mRNA and protein expression. High immune infiltration levels were associated with prolonged survival. The integrative model indicated that tumour features provided independent prognostic values than clinical factors and were complementary with each other in survival prediction. CONCLUSIONS: By using an integrative model that combines intrinsic and extrinsic features, we can more correctly predict the clinical outcomes of patients with MPM.


Asunto(s)
Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurales , Humanos , Mesotelioma/patología , Pronóstico , Neoplasias Pulmonares/patología , ARN Mensajero , Biomarcadores , Biomarcadores de Tumor/genética , Microambiente Tumoral
4.
J Surg Res ; 279: 256-264, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-35797753

RESUMEN

INTRODUCTION: Selecting appropriate management for patients with esophageal adenocarcinoma (EA) is predicated on accurate clinical staging information. Inaccurate information could lead to inappropriate treatment and suboptimal survival. We investigated the relationship between staging accuracy, treatment, and survival. METHODS: This was a national cohort study of EA patients in the National Cancer Data Base (2006-2015) treated with upfront resection or neoadjuvant therapy (NAT). Clinical and pathological staging information was used to ascertain staging concordance for each patient. For NAT patients, Bayesian analysis was used to account for potential downstaging. We evaluated the association between staging concordance, receipt of NAT, and survival through hierarchical logistic regression and multivariable Cox regression. RESULTS: Among 7635 EA patients treated at 877 hospitals, 3038 had upfront resection and 4597 NAT followed by surgery. Relative to accurately staged patients, understaging was associated with a lower likelihood (odds ratio [OR] 0.04 95% confidence interval [CI] 0.02-0.05) while overstaging was associated with a greater likelihood of receiving NAT (OR 1.98 [1.53-2.56]). Relative to upfront surgery, treatment of cT1N0 patients with NAT was associated with a higher risk of death (HR 3.08 [2.36-4.02]). For accurately or overstaged cT3-T4 patients, NAT was associated with a lower risk of death whether downstaging occurred (ypN0 disease-HR 0.67 [0.49-0.92]; N+ disease-HR 0.55 [0.45-0.66]) or not (ypN + disease-HR 0.78 [95% CI 0.65-0.93]). CONCLUSIONS: Clinical understaging is associated with receipt of NAT which in turn may have a stage-specific impact on patients' survival regardless of treatment response. Guidelines should account for the possibility of inaccurate clinical staging.


Asunto(s)
Adenocarcinoma , Neoplasias Esofágicas , Teorema de Bayes , Estudios de Cohortes , Neoplasias Esofágicas/patología , Humanos , Terapia Neoadyuvante , Estadificación de Neoplasias , Estudios Retrospectivos , Tasa de Supervivencia
5.
Nature ; 521(7550): 99-104, 2015 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-25924063

RESUMEN

Whereas cancers grow within host tissues and evade host immunity through immune-editing and immunosuppression, tumours are rarely transmissible between individuals. Much like transplanted allogeneic organs, allogeneic tumours are reliably rejected by host T cells, even when the tumour and host share the same major histocompatibility complex alleles, the most potent determinants of transplant rejection. How such tumour-eradicating immunity is initiated remains unknown, although elucidating this process could provide the basis for inducing similar responses against naturally arising tumours. Here we find that allogeneic tumour rejection is initiated in mice by naturally occurring tumour-binding IgG antibodies, which enable dendritic cells (DCs) to internalize tumour antigens and subsequently activate tumour-reactive T cells. We exploited this mechanism to treat autologous and autochthonous tumours successfully. Either systemic administration of DCs loaded with allogeneic-IgG-coated tumour cells or intratumoral injection of allogeneic IgG in combination with DC stimuli induced potent T-cell-mediated antitumour immune responses, resulting in tumour eradication in mouse models of melanoma, pancreas, lung and breast cancer. Moreover, this strategy led to eradication of distant tumours and metastases, as well as the injected primary tumours. To assess the clinical relevance of these findings, we studied antibodies and cells from patients with lung cancer. T cells from these patients responded vigorously to autologous tumour antigens after culture with allogeneic-IgG-loaded DCs, recapitulating our findings in mice. These results reveal that tumour-binding allogeneic IgG can induce powerful antitumour immunity that can be exploited for cancer immunotherapy.


Asunto(s)
Anticuerpos Antineoplásicos/inmunología , Antígenos de Neoplasias/inmunología , Células Dendríticas/inmunología , Inmunoglobulina G/inmunología , Neoplasias/inmunología , Linfocitos T/inmunología , Animales , Anticuerpos Antineoplásicos/administración & dosificación , Antígenos CD40/metabolismo , Modelos Animales de Enfermedad , Femenino , Inmunoglobulina G/administración & dosificación , Isoanticuerpos/administración & dosificación , Isoanticuerpos/inmunología , Activación de Linfocitos/inmunología , Masculino , Ratones , Metástasis de la Neoplasia , Trasplante de Neoplasias/inmunología , Neoplasias/patología , Receptores de IgG/inmunología , Factor de Necrosis Tumoral alfa/inmunología
6.
Sensors (Basel) ; 21(22)2021 Nov 10.
Artículo en Inglés | MEDLINE | ID: mdl-34833540

RESUMEN

Neurogenic thoracic outlet syndrome (nTOS) is a musculoskeletal disorder in which compression of the brachial plexus between the scalene muscles of the neck and the first rib results in disabling upper extremity pain and paresthesia. Currently there are no objective metrics for assessing the disability of nTOS or for monitoring response to its therapy. We aimed to develop digital biomarkers of upper extremity motor capacity that could objectively measure the disability of nTOS using an upper arm inertial sensor and a 20-s upper extremity task that provokes nTOS symptoms. We found that digital biomarkers of slowness, power, and rigidity statistically differentiated the affected extremities of patients with nTOS from their contralateral extremities (n = 16) and from the extremities of healthy controls (n = 13); speed and power had the highest effect sizes. Digital biomarkers representing slowness, power, and rigidity correlated with patient-reported outcomes collected with the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire and the visual analog scale of pain (VAS); speed had the highest correlation. Digital biomarkers of exhaustion correlated with failure of physical therapy in treating nTOS; and digital biomarkers of slowness, power, and exhaustion correlated with favorable response to nTOS surgery. In conclusion, sensor-derived digital biomarkers can objectively assess the impairment of motor capacity resultant from nTOS, and correlate with patient-reported symptoms and response to therapy.


Asunto(s)
Síndrome del Desfiladero Torácico , Biomarcadores , Humanos , Dimensión del Dolor , Costillas , Síndrome del Desfiladero Torácico/diagnóstico , Resultado del Tratamiento
7.
J Vasc Surg ; 72(3): 790-798, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32497747

RESUMEN

The global SARS-CoV-2/COVID-19 pandemic has required a reduction in nonemergency treatment for a variety of disorders. This report summarizes conclusions of an international multidisciplinary consensus group assembled to address evaluation and treatment of patients with thoracic outlet syndrome (TOS), a group of conditions characterized by extrinsic compression of the neurovascular structures serving the upper extremity. The following recommendations were developed in relation to the three defined types of TOS (neurogenic, venous, and arterial) and three phases of pandemic response (preparatory, urgent with limited resources, and emergency with complete diversion of resources). • In-person evaluation and treatment for neurogenic TOS (interventional or surgical) are generally postponed during all pandemic phases, with telephone/telemedicine visits and at-home physical therapy exercises recommended when feasible. • Venous TOS presenting with acute upper extremity deep venous thrombosis (Paget-Schroetter syndrome) is managed primarily with anticoagulation, with percutaneous interventions for venous TOS (thrombolysis) considered in early phases (I and II) and surgical treatment delayed until pandemic conditions resolve. Catheter-based interventions may also be considered for selected patients with central subclavian vein obstruction and threatened hemodialysis access in all pandemic phases, with definitive surgical treatment postponed. • Evaluation and surgical treatment for arterial TOS should be reserved for limb-threatening situations, such as acute upper extremity ischemia or acute digital embolization, in all phases of pandemic response. In late pandemic phases, surgery should be restricted to thrombolysis or brachial artery thromboembolectomy, with more definitive treatment delayed until pandemic conditions resolve.


Asunto(s)
Betacoronavirus/patogenicidad , Infecciones por Coronavirus/prevención & control , Pandemias/prevención & control , Neumonía Viral/prevención & control , Guías de Práctica Clínica como Asunto , Síndrome del Desfiladero Torácico/diagnóstico , Triaje/normas , COVID-19 , Consenso , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/transmisión , Infecciones por Coronavirus/virología , Descompresión Quirúrgica/normas , Procedimientos Quirúrgicos Electivos/métodos , Procedimientos Quirúrgicos Electivos/normas , Tratamiento de Urgencia/métodos , Tratamiento de Urgencia/normas , Humanos , Control de Infecciones/normas , Comunicación Interdisciplinaria , Recuperación del Miembro/métodos , Recuperación del Miembro/normas , Selección de Paciente , Neumonía Viral/epidemiología , Neumonía Viral/transmisión , Neumonía Viral/virología , SARS-CoV-2 , Telemedicina/normas , Síndrome del Desfiladero Torácico/etiología , Síndrome del Desfiladero Torácico/terapia , Terapia Trombolítica/métodos , Terapia Trombolítica/normas , Tiempo de Tratamiento/normas
8.
Gut ; 66(2): 215-225, 2017 02.
Artículo en Inglés | MEDLINE | ID: mdl-27507904

RESUMEN

OBJECTIVE: Oesophageal squamous cell carcinoma (ESCC) is a heterogeneous disease with variable outcomes that are challenging to predict. A better understanding of the biology of ESCC recurrence is needed to improve patient care. Our goal was to identify small non-coding RNAs (sncRNAs) that could predict the likelihood of recurrence after surgical resection and to uncover potential molecular mechanisms that dictate clinical heterogeneity. DESIGN: We developed a robust prediction model for recurrence based on the analysis of the expression profile data of sncRNAs from 108 fresh frozen ESCC specimens as a discovery set and assessment of the associations between sncRNAs and recurrence-free survival (RFS). We also evaluated the mechanistic and therapeutic implications of sncRNA obtained through integrated analysis from multiple datasets. RESULTS: We developed a risk assessment score (RAS) for recurrence with three sncRNAs (microRNA (miR)-223, miR-1269a and nc886) whose expression was significantly associated with RFS in the discovery cohort (n=108). RAS was validated in an independent cohort of 512 patients. In multivariable analysis, RAS was an independent predictor of recurrence (HR, 2.27; 95% CI, 1.26 to 4.09; p=0.007). This signature implies the expression of ΔNp63 and multiple alterations of driver genes like PIK3CA. We suggested therapeutic potentials of immune checkpoint inhibitors in low-risk patients, and Polo-like kinase inhibitors, mammalian target of rapamycin (mTOR) inhibitors, and histone deacetylase inhibitors in high-risk patients. CONCLUSION: We developed an easy-to-use prognostic model with three sncRNAs as robust prognostic markers for postoperative recurrence of ESCC. We anticipate that such a stratified and systematic, tumour-specific biological approach will potentially contribute to significant improvement in ESCC treatment.


Asunto(s)
Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , MicroARNs/análisis , Recurrencia Local de Neoplasia/genética , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/cirugía , Proteínas de Ciclo Celular/antagonistas & inhibidores , Línea Celular Tumoral/efectos de los fármacos , Fosfatidilinositol 3-Quinasa Clase I , Supervivencia sin Enfermedad , Ensayos de Selección de Medicamentos Antitumorales , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/cirugía , Femenino , Genómica , Inhibidores de Histona Desacetilasas/farmacología , Humanos , Masculino , MicroARNs/genética , Persona de Mediana Edad , Modelos Biológicos , Terapia Molecular Dirigida , Fosfatidilinositol 3-Quinasas/genética , Valor Predictivo de las Pruebas , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Proteínas Proto-Oncogénicas/antagonistas & inhibidores , Medición de Riesgo , Biología de Sistemas , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Factores de Transcripción/genética , Proteínas Supresoras de Tumor/genética , Quinasa Tipo Polo 1
9.
Ann Surg ; 266(2): 297-304, 2017 08.
Artículo en Inglés | MEDLINE | ID: mdl-27501170

RESUMEN

OBJECTIVE: To determine whether adjuvant chemotherapy (AC) after neoadjuvant chemoradiation and esophagectomy is associated with improved overall survival for patients with locally advanced esophageal cancer, and to evaluate how pathologic disease response to neoadjuvant treatment impacts this effect. BACKGROUND: Neoadjuvant chemoradiation is currently the preferred management approach for locoregional esophageal cancer. Although there is interest in the use of AC, the benefit of systemic therapy after neoadjuvant chemoradiation and esophagectomy is unclear. METHODS: Retrospective cohort study of patients with esophageal cancer treated with neoadjuvant chemoradiation and esophagectomy in the National Cancer Data Base (2006-2012). RESULTS: Among 3592 patients with esophageal cancer (84.7% adenocarcinoma, 15.2% squamous cell carcinoma), 335 (9.3%) were treated with AC. AC was not associated with a significantly lower risk of death among patients with no residual disease (ypT0N0) or residual non-nodal disease (ypT+N0). Among patients with residual nodal disease (ypTanyN+), AC was associated with a 30% lower risk of death in the overall cohort [hazard ratio (HR) 0.70, (0.57-0.85)] and among those with adenocarcinoma [HR 0.69 (0.57-0.85)]. Using a 90-day postoperative landmark, findings were similar. Among patients with postoperative length of stay ≤10 days and no unplanned readmission, AC was associated with approximately 40% lower risk of death among patients with residual nodal disease [overall cohort, HR 0.63 (0.48-0.84); adenocarcinoma, HR 0.66 (0.49-0.88)]. CONCLUSIONS: AC after neoadjuvant chemoradiation and esophagectomy is associated with improved survival in patients with residual nodal disease. Our findings suggest AC may provide additional benefit for esophageal cancer patients, and merits further investigation.


Asunto(s)
Adenocarcinoma/terapia , Carcinoma de Células Escamosas/terapia , Quimioradioterapia , Quimioterapia Adyuvante , Neoplasias Esofágicas/terapia , Esofagectomía , Terapia Neoadyuvante , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Anciano , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/patología , Femenino , Humanos , Ganglios Linfáticos/patología , Metástasis Linfática , Masculino , Persona de Mediana Edad , Neoplasia Residual/patología , Neoplasia Residual/terapia , Estudios Retrospectivos , Análisis de Supervivencia
10.
Ann Surg Oncol ; 22 Suppl 3: S1318-23, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26228108

RESUMEN

PURPOSE: The computed tomographic (CT) appearance of so-called ground glass components within lung adenocarcinomas correlate with noninvasive tumor histology, and solid radiographic components correlate with invasive histology. We hypothesized that T stage might be more accurately applied by considering the solid component nodule diameter rather than total nodule diameter. METHODS: We identified 74 patients with a solitary lung adenocarcinoma who underwent resection without receiving neoadjuvant therapy. Maximum total diameter and solid diameter of the nodules were measured on CT scans performed within 3 months of surgery. Cox proportional hazard modeling and Kaplan-Meier analyses were performed to determine whether total nodule diameter or solid component diameter was more predictive of overall survival. RESULTS: Thirty-three patients (45 %) had a solid nodule and 41 patients (55 %) had a part-solid nodule. Most patients were white (59 %) and female (69 %), and 42 % had never smoked. Seventy-four percent underwent lobectomy and 23 % sublobar resection. Sixty-six percent had pathologic stage I disease, 22 % stage II, and 12 % stage IIIA. Mean ± SD total and solid nodule diameters were 32.1 ± 17.5 and 24.8 ± 18.0 mm, respectively (p = 0.01). Among patients with part-solid nodules, multivariate modeling incorporating significant univariate predictors of survival (age, gender, procedure, N descriptor) revealed that maximum solid diameter was associated with overall survival (hazard ratio 1.4, p = 0.01), while maximum total diameter was not. CONCLUSIONS: In a largely non-Asian cohort undergoing resection for adenocarcinoma, radiographic diameter of the solid component of a part-solid lesion on CT predicts overall survival better than total lesion diameter. These data provide further evidence to support altering the T descriptor for lung adenocarcinoma for part-solid nodules.


Asunto(s)
Neoplasias Pulmonares/patología , Neumonectomía , Carga Tumoral , Anciano , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Tasa de Supervivencia
11.
NPJ Precis Oncol ; 8(1): 47, 2024 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-38396241

RESUMEN

Malignant pleural mesothelioma (MPM) is a rare but lethal pleural cancer with high intratumor heterogeneity (ITH). A recent study in lung adenocarcinoma has developed a clonal gene signature (ORACLE) from multiregional transcriptomic data and demonstrated high prognostic values and reproducibility. However, such a strategy has not been tested in other types of cancer with high ITH. We aimed to identify biomarkers from multi-regional data to prognostically stratify MPM patients. We generated a multiregional RNA-seq dataset for 78 tumor samples obtained from 26 MPM patients, each with one sample collected from a superior, lateral, and inferior region of the tumor. By integrating this dataset with the Cancer Genome Atlas MPM RNA-seq data, we selected 29 prognostic genes displaying high variability across different tumors but low ITH, which named PRACME (Prognostic Risk Associated Clonal Mesothelioma Expression). We evaluated PRACME in two independent MPM datasets and demonstrated its prognostic values. Patients with high signature scores are associated with poor prognosis after adjusting established clinical factors. Interestingly, the PRACME and the ORACLE signatures defined respectively from MPM and lung adenocarcinoma cross-predict prognosis between the two cancer types. Further investigation indicated that the cross-prediction ability might be explained by the high similarity between the two cancer types in their genomic regions with copy number variation, which host many clonal genes. Overall, our clonal signature PRACME provided prognostic stratification in MPM and this study emphasized the importance of multi-regional transcriptomic data for prognostic stratification based on clonal genes.

12.
Cancer Cell ; 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38906155

RESUMEN

Tumor-specific CD8+ T cells are frequently dysfunctional and unable to halt tumor growth. We investigated whether tumor-specific CD4+ T cells can be enlisted to overcome CD8+ T cell dysfunction within tumors. We find that the spatial positioning and interactions of CD8+ and CD4+ T cells, but not their numbers, dictate anti-tumor responses in the context of adoptive T cell therapy as well as immune checkpoint blockade (ICB): CD4+ T cells must engage with CD8+ T cells on the same dendritic cell during the effector phase, forming a three-cell-type cluster (triad) to license CD8+ T cell cytotoxicity and cancer cell elimination. When intratumoral triad formation is disrupted, tumors progress despite equal numbers of tumor-specific CD8+ and CD4+ T cells. In patients with pleural mesothelioma treated with ICB, triads are associated with clinical responses. Thus, CD4+ T cells and triads are required for CD8+ T cell cytotoxicity during the effector phase and tumor elimination.

13.
Thorac Surg Clin ; 33(3): 265-271, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37414482

RESUMEN

Robot-assisted thoracoscopic surgery for the treatment of thoracic outlet syndrome is a novel approach that continues to increase in popularity due to advantages compared with traditional open first rib resection. Following publication of the Society of Vascular Surgeons expert statement in 2016, the diagnosis and management of thoracic outlet syndrome is favorably evolving. Technical mastery of the operation requires precise knowledge of anatomy, comfort with robotic surgical platforms, and understanding of the disease.


Asunto(s)
Procedimientos Quirúrgicos Robotizados , Robótica , Síndrome del Desfiladero Torácico , Procedimientos Quirúrgicos Torácicos , Humanos , Resultado del Tratamiento , Costillas/cirugía , Síndrome del Desfiladero Torácico/cirugía
14.
Thorac Surg Clin ; 33(1): 71-79, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36372535

RESUMEN

Robot-assisted thoracoscopic surgery for the treatment of thoracic outlet syndrome and chest wall lesions are burgeoning topics on thoracic surgery. Following publication of the Society of Vascular Surgeons expert statement in 2016, the diagnosis and management of thoracic outlet syndrome is favorably evolving. Robot-assisted first rib resection is a novel approach to the surgical management of thoracic outlet syndrome that may have advantages compared with traditional open surgical approaches. Robot-assisted chest wall resection is technically feasible for a variety of chest wall conditions and may also have advantages compared with thoracotomy approaches.


Asunto(s)
Procedimientos Quirúrgicos Robotizados , Robótica , Síndrome del Desfiladero Torácico , Pared Torácica , Humanos , Pared Torácica/cirugía , Costillas/cirugía , Síndrome del Desfiladero Torácico/cirugía , Cirugía Torácica Asistida por Video , Resultado del Tratamiento
15.
J Thorac Cardiovasc Surg ; 165(5): 1722-1730, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36740497

RESUMEN

OBJECTIVES: Mesothelioma is a nearly uniformly fatal tumor. Multimodality therapy including cytoreductive surgery and chemotherapy is associated with long-term survival in some patients. Cytoreductive surgery for thoracic disease includes a lung-sparing operation called an "extended pleurectomy/decortication" or a lung-sacrificing surgery called an "extrapleural pneumonectomy." The benefit of cytoreductive surgery for bicavitary disease (chest and abdomen) is poorly understood. Our objective was to evaluate the long-term survivals for patients undergoing cytoreductive surgery for bicavitary disease and to determine whether any prognostic factors were associated with outcome. METHODS: We reviewed our Institutional Review Board-approved, institutional, International Association for the Study of Lung Cancer Mesothelioma Staging Project database. Inclusion criteria were all patients who underwent cytoreductive surgery for bicavitary disease. Overall survival was calculated by Kaplan-Meier methodology. All International Association for the Study of Lung Cancer database elements were evaluated by univariable analysis. RESULTS: From February 2014 to August 2021, 440 patients with mesothelioma were evaluated. Fourteen patients (3%) underwent cytoreductive surgery of both chest and abdomen as a planned 2-stage operation. Most patients (13/14; 93%) underwent chest surgery before abdomen surgery. For the entire cohort, the median overall survival was 33.6 months with a 5-year survival of 20%. Extended pleurectomy/decortication was associated with a better outcome compared with extrapleural pneumonectomy, with median overall survivals of 58.2 versus 13.5 months, respectively. CONCLUSIONS: For a highly selected group of patients with bicavitary mesothelioma, long-term survival can be achieved with an aggressive, staged surgical approach. The patients who undergo extended pleurectomy/decortication with preservation of the lung appear to have more favorable outcomes compared with patients undergoing extrapleural pneumonectomy.


Asunto(s)
Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurales , Humanos , Neumonectomía/efectos adversos , Neumonectomía/métodos , Procedimientos Quirúrgicos de Citorreducción/efectos adversos , Resultado del Tratamiento , Estudios Retrospectivos , Neoplasias Pulmonares/cirugía
16.
bioRxiv ; 2023 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-37461721

RESUMEN

Tumor-reactive CD8 T cells found in cancer patients are frequently dysfunctional, unable to halt tumor growth. Adoptive T cell transfer (ACT), the administration of large numbers of in vitro-generated cytolytic tumor-reactive CD8 T cells, is an important cancer immune therapy being pursued. However, a limitation of ACT is that transferred CD8 T cells often rapidly lose effector function, and despite exciting results in certain malignancies, few ACT clinical trials have shown responses in solid tumors. Here, we developed preclinical cancer mouse models to investigate if and how tumor-specific CD4 T cells can be enlisted to overcome CD8 T cell dysfunction in the setting of ACT. In situ confocal microscopy of color-coded cancer cells, tumor-specific CD8 and CD4 T cells, and antigen presenting cells (APC), combined with functional studies, revealed that the spatial positioning and interactions of CD8 and CD4 T cells, but not their numbers, dictates ACT efficacy and anti-tumor responses. We uncover a new role of antigen-specific CD4 T cells in addition to the known requirement for CD4 T cells during priming/activation of naïve CD8 T cells. CD4 T cells must co-engage with CD8 T cells and APC cross-presenting CD8- and CD4-tumor antigens during the effector phase, forming a three-cell-cluster (triad), to license CD8 T cell cytotoxicity and mediate cancer cell elimination. Triad formation transcriptionally and epigenetically reprogram CD8 T cells, prevent T cell dysfunction/exhaustion, and ultimately lead to the elimination of large established tumors and confer long-term protection from recurrence. When intratumoral triad formation was disrupted, adoptively transferred CD8 T cells could not be reprogrammed, and tumors progressed despite equal numbers of tumor-infiltrating CD8 and CD4 T cells. Strikingly, the formation of CD4 T cell::CD8 T cell::APC triads in tumors of patients with lung cancers treated with immune checkpoint blockade was associated with clinical responses, but not CD4::APC dyads or overall numbers of CD8 or CD4 T cells, demonstrating the importance of triads in non-ACT settings in humans. Our work uncovers intratumoral triads as a key requirement for anti-tumor immunity and a new role for CD4 T cells in CD8 T cell cytotoxicity and cancer cell eradication.

17.
Clin Cancer Res ; 29(3): 548-559, 2023 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-36469573

RESUMEN

PURPOSE: We report the results of a phase II, randomized, window-of-opportunity trial of neoadjuvant durvalumab versus durvalumab plus tremelimumab followed by surgery in patients with resectable malignant pleural mesothelioma (MPM; NCT02592551). PATIENTS AND METHODS: The primary objective was alteration of the intratumoral CD8/regulatory T cell (Treg) ratio after combination immune checkpoint blockade (ICB) therapy. Secondary and exploratory objectives included other changes in the tumor microenvironment, survival, safety, tumor pathologic response (PR), and systemic immune responses. RESULTS: Nine patients received monotherapy and 11 received combination therapy. Seventeen of the 20 patients (85%) receiving ICB underwent planned thoracotomy. Both ICB regimens induced CD8 T-cell infiltration into MPM tumors but did not alter CD8/Treg ratios. At 34.1 months follow-up, patients receiving combination ICB had longer median overall survival (not reached) compared with those receiving monotherapy (14.0 months). Grade ≥3 immunotoxicity occurred in 8% of patients in the monotherapy group and 27% of patients in the combination group. Tumor PR occurred in 6 of 17 patients receiving ICB and thoracotomy (35.3%), among which major PR (>90% tumor regression) occurred in 2 (11.8%). Single-cell profiling of tumor, blood, and bone marrow revealed that combination ICB remodeled the immune contexture of MPM tumors; mobilized CD57+ effector memory T cells from the bone marrow to the circulation; and increased the formation of tertiary lymphoid structures in MPM tumors that were rich in CD57+ T cells. CONCLUSIONS: These data indicate that neoadjuvant durvalumab plus tremelimumab orchestrates de novo systemic immune responses that extend to the tumor microenvironment and correlate with favorable clinical outcomes.


Asunto(s)
Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurales , Humanos , Antígeno B7-H1 , Antígeno CTLA-4 , Neoplasias Pulmonares/patología , Mesotelioma/patología , Terapia Neoadyuvante , Neoplasias Pleurales/patología , Microambiente Tumoral
18.
J Clin Med ; 11(18)2022 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-36142958

RESUMEN

Background: Over the last 100 years, the original three-bottle chest drainage system has been variously engineered into compact disposables and electronic units. Clinicians are now surrounded by a plethora of different types of systems, but little is known about the way that they work and perform. Thus, we sought to test the performance of the most commonly used chest drainage units under conditions that are relevant to clinical practice. Methods: A pleural space environment simulator was built. Thirty-two units were tested under four clinical scenarios: air leak interpretation during quiet breathing and after obstructed inspiration (−5 to −150 cmH2O), a buildup of negative pressure (−100 cmH2O), a bronchopleural fistula (10 L/min) and the need for effective external suction in the presence of air leakage. Twenty-five units were "traditional" thoracic drainages, five were "digital" low-flow/low-vacuum pumps and two were hybrids (a combination of the two). According to the design of the seal and of the suction control, the units were classified as wet-wet, wet-dry and dry-dry. Results: All wet units showed reverse air flow, with the potential to mimic an air leak when there was none. Ten wet units showed no automatic negative pressure relief features, while five dry-dry did but were slow to react. Ten wet and five dry-dry units showed no capability to handle a 10 L/min leak, as they were restrictive to flow (peak pressure up to 55 cmH2O). Only seven dry-suction units were able to maintain the set suction at high airflow rates (>20 L/min). Conclusions: Different chest drainage unit designs lead to different performances, some of which may negatively impact patient outcomes. This sounds the call to tailor our clinical practice for the individual patient. A paradigm shift to better understand all components of pleural physiology post-surgical intervention on this relatively neglected topic is needed to improve our daily practice.

19.
Ann Thorac Surg ; 113(1): 279-285, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33484675

RESUMEN

BACKGROUND: Treatment selection for patients with esophageal adenocarcinoma is predicated on clinical staging information, which is inaccurate in 20% to 30% of cases and could impact the delivery of guideline-concordant treatment. We aimed to evaluate the association between staging concordance at the patient and hospital levels with the delivery of guideline-concordant treatment among esophageal adenocarcinoma patients. METHODS: This was a national cohort study of resected esophageal adenocarcinoma patients in the National Cancer Data Base (2006 to 2015) treated either with upfront resection or neoadjuvant therapy followed by surgery. Patient- and hospital-level clinical and pathologic staging concordance and deviations from treatment guidelines were ascertained. For neoadjuvant therapy patients, staging concordance was predicted through Bayesian analysis. Reliability adjustment was used when evaluating hospital-level concordance. RESULTS: Among 9393 esophageal adenocarcinoma patients treated at 927 hospitals, 41% had upfront surgery. Among upfront surgery patients, staging concordance was 85.1% for T1N0 and 86.9% for T3-T4N+ disease, but less than 50% for all others. Among patients treated with neoadjuvant therapy, treatment downstaging was observed in 33.9%. Deviations from treatment guidelines were identified in 38.5% of upfront surgery patients and 3.3% of neoadjuvant therapy patients. The proportion of concordantly staged patients ranged from 60.1% to 87.9%, and deviations from treatment guidelines were observed among 14.9% to 22.7% of the patients. Patient staging concordance increased, and deviations from guidelines decreased, as hospital-level concordance increased (trend test, P values less than .001 for all). CONCLUSIONS: Deviations from treatment guidelines in esophageal adenocarcinoma patients appear to be a function of inaccurate clinical staging information, which should be a new focus for quality improvement efforts.


Asunto(s)
Adenocarcinoma/patología , Adenocarcinoma/terapia , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/terapia , Estudios de Cohortes , Terapia Combinada , Humanos , Estadificación de Neoplasias , Guías de Práctica Clínica como Asunto
20.
Ann Thorac Surg ; 114(3): 919-925, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-34419432

RESUMEN

BACKGROUND: Robotic transthoracic first rib resection (R-FRR) has advantages over traditional approaches; however, its impact on postoperative neurogenic thoracic outlet syndrome (nTOS) outcomes is unknown. Our primary objective was to determine improvement of patient-reported outcome measures (PROMs) of pain and disability after R-FRR in nTOS. Our secondary objective was to compare improvement of patient-reported pain between R-FRR and supraclavicular FRR (SC-FRR) in nTOS. METHODS: We queried a prospectively maintained, single-surgeon, single-institution database for patients with nTOS undergoing R-FRR or SC-FRR with available preoperative and postoperative PROMs. PROMs included the Disability of the Arm, Hand, and Shoulder (DASH) questionnaire and visual analog scale (VAS) for pain. RESULTS: Cohort 1 included 37 patients (32 women) undergoing 40 R-FRRs, with an average age of 36 years. Preoperative VAS and DASH (6.0 and 64.2, respectively) improved significantly at the first (2.8 and 35.0; P < .001 for both) and second postoperative visits (1.4 and 30.2; P < .01 for both) which occurred at 2.6 and 15.3 weeks, respectively. Cohort 2 included 57 R-FRRs performed in 53 patients and 35 SC-FRRs performed in 34 patients. The R-FRR and SC-FRR groups did not significantly differ in sex, age, hand dominance, TOS laterality, or preoperative VAS. At the first postoperative visit (2.4 weeks), R-FRR was associated with lower VAS scores (P = .023) and greater VAS improvement than SC-FRR (53% and 27% decrease, respectively; P = .008). CONCLUSIONS: R-FRR results in significant improvement in disability and pain in nTOS and may have a greater impact on patient-reported pain than SC-FRR in the early postoperative period.


Asunto(s)
Procedimientos Quirúrgicos Robotizados , Síndrome del Desfiladero Torácico , Adulto , Descompresión Quirúrgica/métodos , Femenino , Humanos , Dolor/cirugía , Estudios Retrospectivos , Costillas/cirugía , Síndrome del Desfiladero Torácico/cirugía , Resultado del Tratamiento
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