ABSTRACT
Human cancers are biologically and morphologically heterogeneous. A variety of clonal populations emerge within these neoplasms and their interaction leads to complex spatiotemporal dynamics during tumor growth. We studied the reshaping of metabolic activity in human cancers by means of continuous and discrete mathematical models and matched the results to positron emission tomography (PET) imaging data. Our models revealed that the location of increasingly active proliferative cellular spots progressively drifted from the center of the tumor to the periphery, as a result of the competition between gradually more aggressive phenotypes. This computational finding led to the development of a metric, normalized distance from 18F-fluorodeoxyglucose (18F-FDG) hotspot to centroid (NHOC), based on the separation from the location of the activity (proliferation) hotspot to the tumor centroid. The NHOC metric can be computed for patients using 18F-FDG PET-computed tomography (PET/CT) images where the voxel of maximum uptake (standardized uptake value [SUV]max) is taken as the activity hotspot. Two datasets of 18F-FDG PET/CT images were collected, one from 61 breast cancer patients and another from 161 non-small-cell lung cancer patients. In both cohorts, survival analyses were carried out for the NHOC and for other classical PET/CT-based biomarkers, finding that the former had a high prognostic value, outperforming the latter. In summary, our work offers additional insights into the evolutionary mechanisms behind tumor progression, provides a different PET/CT-based biomarker, and reveals that an activity hotspot closer to the tumor periphery is associated to a worst patient outcome.
Subject(s)
Breast Neoplasms/diagnosis , Carcinogenesis/genetics , Carcinoma, Non-Small-Cell Lung/diagnosis , Models, Theoretical , Adult , Aged , Biomarkers, Tumor/genetics , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/pathology , Carcinoma, Non-Small-Cell Lung/diagnostic imaging , Carcinoma, Non-Small-Cell Lung/pathology , Cell Proliferation/genetics , Female , Fluorodeoxyglucose F18/pharmacology , Genetic Heterogeneity/drug effects , Humans , Male , Middle Aged , Positron-Emission Tomography/methods , PrognosisABSTRACT
Most physical and other natural systems are complex entities composed of a large number of interacting individual elements. It is a surprising fact that they often obey the so-called scaling laws relating an observable quantity with a measure of the size of the system. Here we describe the discovery of universal superlinear metabolic scaling laws in human cancers. This dependence underpins increasing tumour aggressiveness, due to evolutionary dynamics, which leads to an explosive growth as the disease progresses. We validated this dynamic using longitudinal volumetric data of different histologies from large cohorts of cancer patients. To explain our observations we put forward increasingly-complex biologically-inspired mathematical models that captured the key processes governing tumor growth. Our models predicted that the emergence of superlinear allometric scaling laws is an inherently three-dimensional phenomenon. Moreover, the scaling laws thereby identified allowed us to define a set of metabolic metrics with prognostic value, thus providing added clinical utility to the base findings.
ABSTRACT
La plicatura diafragmática es el tratamiento más aceptado para la eventración diafragmática sintomática en adultos. La infrecuencia de esta dolencia y la escasa difusión de este procedimiento hacen que esta técnica sea excepcional en nuestro medio. Para estimar la difusión en la literatura, realizamos una revisión estructurada en lenguas inglesa y castellana a la que sumamos nuestra casuística: encontramos solo 6 series que aportan un total de 59 plicaturas diafragmáticas en adultos asistidas por toracoscopia. Ninguna en castellano. Nuestra serie sería la segunda mayor: 18 casos, con resultados satisfactorios similares a los publicados. Finalmente efectuamos una encuesta a todos los servicios españoles de cirugía torácica: ninguno tiene más de 10 casos operados por toracoscopia en los últimos 8 años (a excepción del nuestro) y la mayoría continúa utilizando la toracotomía como abordaje. En nuestra opinión muchos pacientes con eventración diafragmática sintomática podrían beneficiarse con la difusión de estas técnicas
Diaphragmatic plication is the most accepted treatment for symptomatic diaphragmatic hernia in adults. The fact that this pathology is infrequent and this procedure not been widespread means that this is an exceptional technique in our field. To estimate its use in the literature, we carried out a review in English and Spanish, to which we added our series. We found only 6 series that contribute 59 video-assisted mini-thoractomy for diaphragmatic plications in adults, and none in Spanish. Our series will be the second largest with 18 cases. Finally, we conducted a survey in all the Spanish Thoracic Surgery units in Spain: none reported more than 10 cases operated by thoracoscopy in the last 8 years (except our series) and most continue employing thoracotomy as the main approach. We believe that many patients with symptomatic diaphragmatic hernia could benefit from the use of such techniques
Subject(s)
Humans , Male , Female , Adult , Diaphragmatic Eventration/surgery , Thoracic Surgery, Video-Assisted , Respiratory Paralysis/surgery , Hernia, Diaphragmatic/diagnosis , Diagnosis, Differential , /statistics & numerical dataABSTRACT
Diaphragmatic plication is the most accepted treatment for symptomatic diaphragmatic hernia in adults. The fact that this pathology is infrequent and this procedure not been widespread means that this is an exceptional technique in our field. To estimate its use in the literature, we carried out a review in English and Spanish, to which we added our series. We found only six series that contribute 59 video-assisted mini-thoractomy for diaphragmatic plications in adults, and none in Spanish. Our series will be the second largest with 18 cases. Finally, we conducted a survey in all the Spanish Thoracic Surgery units in Spain: none reported more than 10 cases operated by thoracoscopy in the last 8 years (except our series) and most continue employing thoracotomy as the main approach. We believe that many patients with symptomatic diaphragmatic hernia could benefit from the use of such techniques.
Subject(s)
Diaphragm/surgery , Hernia, Diaphragmatic/surgery , Thoracic Surgery, Video-Assisted , Adult , Humans , Spain , Surveys and QuestionnairesSubject(s)
Horner Syndrome/etiology , Pleura/surgery , Postoperative Complications , Suction , Adult , Female , Humans , ThoracoscopyABSTRACT
No disponible
No disponible
Subject(s)
Humans , Female , Adult , Horner Syndrome/etiology , Drainage/adverse effects , Pneumothorax/therapy , Horner Syndrome/diagnosis , Postoperative Care/adverse effects , Pleural Cavity , ThoracoscopyABSTRACT
Bilateral chylothorax after delivery is a highly infrequent entity. We present the case of a 28-year-old woman who developed progressive dyspnea due to bilateral milky pleural effusion several months after delivery. The effusion was found to contain chylomicrons in the biochemical analysis. Initial conservative treatment failed twice and the chylothorax was successfully treated through sequential bilateral videothoracoscopy with an interval of 6 days between the two interventions and pleurodesis with spray talc.
Subject(s)
Chylothorax/surgery , Pleural Effusion/therapy , Pleurodesis/methods , Puerperal Disorders , Talc/administration & dosage , Thoracic Surgery, Video-Assisted , Adult , Chylothorax/diagnostic imaging , Chylothorax/therapy , Female , Follow-Up Studies , Humans , Pleural Effusion/diagnostic imaging , Time Factors , Tomography, X-Ray Computed , Treatment OutcomeABSTRACT
El quilotórax bilateral posparto es una entidad muy poco frecuente. Presentamos el caso de una mujer de 28 años que varios meses después de dar a luz presentó disnea progresiva por derrame pleural bilateral de aspecto lechoso y con presencia de quilomicrones en su análisis bioquímico. El tratamiento inicialmente conservador fracasó en 2 ocasiones. El quilotórax fue tratado eficazmente con videotoracoscopia bilateral secuencial con un intervalo de 6 días entre ambas intervenciones y pleurodesis con talco en aerosol (AU)
Bilateral chylothorax after delivery is a highly infrequent entity. We present the case of a 28-year-old woman who developed progressive dyspnea due to bilateral milky pleural effusion several months after delivery. The effusion was found to contain chylomicrons in the biochemical analysis. Initial conservative treatment failed twice and the chylothorax was successfully treated through sequential bilateral videothoracoscopy with an interval of 6 days between the two interventions and pleurodesis with spray talc (AU)
