Targeted irradiation in an autochthonous mouse model of pancreatic cancer.

The value of radiotherapy in the treatment of pancreatic cancer has been the subject of much debate but limited preclinical research. We hypothesise that the poor translation of radiation research into clinical trials of radiotherapy in pancreatic cancer is due, in part, to inadequate preclinical study models. Here, we developed and refined methods for targeted irradiation in autochthonous mouse models of pancreatic cancer, using a small animal radiotherapy research platform. We tested and optimised strategies for administration of contrast agents, iohexol and the liver imaging agent Fenestra LC, to enable the use of computed tomography imaging in tumour localisation. We demonstrate accurate tumour targeting, negligible off-target effects and therapeutic efficacy, depending on dose, number of fractions and tumour size, and provide a proof of concept that precise radiation can be delivered effectively to mouse pancreatic tumours with a clinically relevant microenvironment. This advance will allow investigation of the radiation response in murine pancreatic cancer, discovery of mechanisms and biomarkers of radiosensitivity or resistance, and development of radiosensitising strategies to inform clinical trials for precision radiotherapy in this disease.

Gravity- vs Wall Suction-Driven Large-Volume Thoracentesis: A Randomized Controlled Study.

BACKGROUND: Prior studies have found no differences in procedural chest discomfort for patients undergoing manual syringe aspiration or drainage with gravity after thoracentesis. However, whether gravity drainage could protect against chest pain due to the larger negative-pressure gradient generated by wall suction has not been investigated. RESEARCH QUESTION: Does wall suction drainage result in more chest discomfort compared with gravity drainage in patients undergoing large-volume thoracentesis? STUDY DESIGN AND METHODS: In this multicenter, single-blinded, randomized controlled trial, patients with large free-flowing effusions of ≥ 500 mL were assigned at a 1:1 ratio to wall suction or gravity drainage. Wall suction was performed with a suction system attached to the suction tubing and with vacuum pressure adjusted to full vacuum. Gravity drainage was performed with a drainage bag placed 100 cm below the catheter insertion site and connected via straight tubing. Patients rated chest discomfort on a 100-mm visual analog scale before, during, and after drainage. The primary outcome was postprocedural chest discomfort at 5 min. Secondary outcomes included measures of postprocedure chest discomfort, breathlessness, procedure time, volume of fluid drained, and complication rates. RESULTS: Of the 228 patients initially randomized, 221 were included in the final analysis. The primary outcome of procedural chest discomfort did not differ significantly between the groups (P = .08), nor did the secondary outcomes of postprocedural discomfort and dyspnea. Similar volumes were drained in both groups, but the procedure duration was longer in the gravity arm by approximately 3 min. No differences in rate of pneumothorax or reexpansion pulmonary edema were noted between the two groups. INTERPRETATION: Thoracentesis via wall suction and gravity drainage results in similar levels of procedural discomfort and dyspnea improvement. CLINICAL TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT05131945; URL: www. CLINICALTRIALS: gov.

Lung cancer in the emergency department.

Background: Though decreasing in incidence and mortality in the USA, lung cancer remains the deadliest of all cancers. For a significant number of patients, the emergency department (ED) provides the first pivotal step in lung cancer prevention, diagnosis, and management. As screening recommendations and treatments advance, ED providers must stay up-to-date with the latest lung cancer recommendations. The purpose of this review is to identify the many ways that emergency providers may intersect with the disease spectrum of lung cancer and provide an updated array of knowledge regarding detection, management, complications, and interdisciplinary care. Findings: Lung cancer, encompassing 10-12% of cancer-related emergency department visits and a 66% admission rate, is the most fatal malignancy in both men and women. Most patients presenting to the ED have not seen a primary care provider or undergone screening. Ultimately, half of those with a new lung cancer diagnosis in the ED die within 1 year. Incidental findings on computed tomography are mostly benign, but emergency staff must be aware of the factors that make them high risk. Radiologic presentations range from asymptomatic nodules to diffuse metastatic lesions with predominately pulmonary symptoms, and some may present with extra-thoracic manifestations including neurologic. The short-term prognosis for ED lung cancer patients is worse than that of other malignancies. Screening offers new hope through earlier diagnosis but is underutilized which may be due to racial and socioeconomic disparities. New treatments provide optimism but lead to new complications, some long-term. Multidisciplinary care is essential, and emergency medicine is responsible for the disposition of patients to the appropriate specialists at inpatient and outpatient centers. Conclusion: ED providers are intimately involved in all aspects of lung cancer care. Risk factor modification and referral for lung cancer screening are opportunities to further enhance patient care. In addition, with the advent of newer cancer therapies, ED providers must stay vigilant and up-to-date with all aspects of lung cancer including disparities, staging, symptoms of disease, prognosis, treatment, and therapy-related complications.

Loss of Cxcr2 in Myeloid Cells Promotes Tumour Progression and T Cell Infiltration in Invasive Bladder Cancer.

BACKGROUND: CXCR2 is a chemokine receptor expressed in myeloid cells, including neutrophils and macrophages. Pharmacological inhibition of CXCR2 has been shown to sensitize tumours to immune checkpoint inhibitor immunotherapies in some cancer types. OBJECTIVE: To investigate the effects of CXCR2 loss in regulation of tumour-infiltrating myeloid cells and their relationship to lymphocytes during bladder tumorigenesis. METHODS: Urothelial pathogenesis and immune contexture was investigated in an OH-BBN model of invasive bladder cancer with Cxcr2 deleted in myeloid cells (LysMCre Cxcr2 flox/flox ). CXCR2 gene alterations and expression in human muscle invasive bladder cancer were analysed in The Cancer Genome Atlas. RESULTS: Urothelial tumour pathogenesis was significantly increased upon Cxcr2 deletion compared to wildtype mice. This was associated with a suppression of myeloid cell infiltration in Cxcr2-deleted bladders shortly after the carcinogen induction. Interestingly, following a transient increase of macrophages at the outset of tumour formation, an increase in T cell infiltration was observed in Cxcr2-deleted tumours. The increased tumour burden in the Cxcr2-deleted bladder was largely independent of T cells and the status of immune suppression. The Cxcr2-deleted mouse model reflected the low CXCR2 mRNA range in human bladder cancer, which showed poor overall survival. CONCLUSIONS: In contrast to previous reports of increased CXCR2 signalling associated with disease progression and poor prognosis, CXCR2 was protective against bladder cancer during tumour initiation. This is likely due to a suppression of acute inflammation. The strategy for sensitizing checkpoint immunotherapy by CXCR2 inhibition in bladder cancer may benefit from an examination of immune suppressive status.

Ruptura del bronquio fuente en los traumatismos cerrados del torax. / Bronchial rupture in thoracic traumatisms

Se presentan 4 pacientes con ruptura traumatica en bronquios fuentes. Uno fallecio dentro de las 36 hs de producida luego de una incompleta correccion quirurgica. Los 3 restantes sobrevivieron el episodio agudo sin que se efectuara el diagnostico; se operaron al mes y medio, 2 y 10 meses en forma exitosa. Se discute el mecanismo de produccion: de acuerdo a datos de laboratorio y clinicos, se acepta que el tironeamiento lateral y la hipertension en la via aerea simultanea, son las causas de la efraccion bronquial. Esta situacion es mas factible en pacientes lucidos y con torax elastico. En cuanto a la evolucion se destaca la diferencia neta entre la que sufre la lesion parcial, seguida de estenosis e infeccion y la total, seguida habitualmente de cierre de ambos cabos. Esto evita la infeccion y permite la restauracion mediante una plastica, con recuperacion del parenquima atelectasiado