Citations

Concentration of extracellular vesicles (EVs) from biological fluids in a scalable and reproducible manner represents a major challenge. This study reports the use of tangential flow filtration (TFF) for the highly efficient isolation of EVs from large volumes of samples. When compared to ultracentrifugation (UC), which is the most widely used method to concentrate EVs, TFF is a more efficient, scalable, and gentler method. Comparative assessment of TFF and UC of conditioned cell culture media revealed that the former concentrates EVs of comparable physicochemical characteristics, but with higher yield, less single macromolecules and aggregates (<15 nm in size), and improved batch-to-batch consistency in half the processing time (1 h). The TFF protocol was then successfully implemented on fluids derived from patient lipoaspirate. EVs from adipose tissue are of high clinical relevance, as they are expected to mirror the regenerative properties of the parent cells.

PurposeFree flap reconstruction in head and neck cancer patients with prior tumor resection, neck dissection, and irradiation is clinically challenging. The purpose of this study was to investigate the reliability and outcome of using the anterolateral thigh (ALT) flap and transverse cervical recipient vessels for microvascular reconstruction in patients with depleted vessels in the head and neck region caused by previous surgery and irradiation.MethodsBetween January 2015 and December 2017, microsurgical head and neck reconstruction was performed using the ALT flap and transverse cervical artery (TCA) as the recipient vessel in 15 patients who had undergone previous neck dissections and irradiation for cancer treatment. All patients had a “vessel-depleted neck” resulting from severe scarring and radiation fibrosis. Clinical data of each patient were recorded.ResultsAll ipsilateral TCAs were found to be damage free. Subsequently, free ALT flaps were revascularized using the TCAs. One patient developed venous thrombosis, and another patient developed arterial thrombosis. They were both salvaged within 6 hours postoperatively. No flap failure or mortalities were reported within the 30-day postoperative period. Two patients developed orocutaneous fistula and were further managed with wound care. The mean follow-up time was 11.9 ± 6.0 months (range, 5–23 months). Five patients died during the follow-up period from cancer progression.ConclusionsThe use of the free ALT flap and TCA as the recipient vessel provides favorable microsurgical outcomes in patients with depleted recipient vessels in the head and neck region caused by previous neck dissections and radiation therapy.

Pancreatic cancer is the eleventh most common cancer, yet it is the third leading cause of mortality. It is also largely a disease of older adults, with the median age of 71 at diagnosis in the US, with <1% of diagnoses occurring prior to age 50. Current NCCN guidelines recommend surgery for localized disease, followed by adjuvant therapy and/or consideration of enrollment in a clinical trial. For metastatic disease, current guidelines recommend clinical trial enrollment or systemic chemotherapy based on results from the landmark ACCORD-11 and MPACT trials. However, these trials focused heavily on younger, more fit patients, with the ACCORD-11 trial excluding patients over age 75 and the MPACT trial having 92% of its patients with a Karnofsky performance score >80. This article summarizes the available evidence in current literature in regards to the best treatment options for older adults, who represent the majority of pancreatic cancer diagnoses.

Abstract The clinical success of immune checkpoint inhibitors in treating metastatic and refractory cancers has generated significant interest in investigating their role in treating locally advanced diseases, thus requiring them to be combined with standard treatments in the hope of producing synergistic antitumor responses. Radiotherapy, in particular, has long been hypothesized to have actions complementary to those of immune checkpoint blockade, and a growing body of evidence indicates that cancer immunotherapy may also have radiosensitizing effects, which would provide unique benefit for locoregional treatments. Recent studies have demonstrated that when immune cells are activated by immunotherapeutics, they can reprogram the tumor microenvironment in ways that may potentially increase the radiosensitivity of the tumor. In this review, we highlight the evidence that supports reciprocal interactions between cancer immunotherapy and radiotherapy, where in addition to the traditional notion that radiation serves to enhance the activation of antitumor immunity, an alternative scenario also exists in which T-cell activation by cancer immunotherapy may sensitize tumors to radiation treatment through mechanisms that include normalization of the tumor vasculature and tissue hypoxia. We describe the empirical observations from preclinical models that support such effects and discuss their implications for future research and trial design.