Minimally invasive adrenalectomy: a cohort study of surgical approach and outcomes.

BACKGROUND: In the context of minimally invasive adrenal surgery, there remains debate about whether the transperitoneal adrenalectomy (TPA) and posterior retroperitoneoscopic adrenalectomy (PRA) approach have equivalent indications. This study aims to examine complication and conversion rates associated with three surgical approaches for adrenal tumours over the last 17 years in a specialized endocrine surgical unit. METHODS: All adrenalectomy cases performed in the period 2005-2021 were identified within a prospectively maintained surgical database. A retrospective cohort study was undertaken with patients divided into two cohorts (2005-2013 and 2014-2021). Surgical approach (open adrenalectomy (OA), TPA, PRA), tumour size, histopathology, complication and conversion rates were compared. RESULTS: During the study period, 596 patients underwent adrenalectomy with 31 and 40 cases each year per cohort. The dominant surgical approach per cohort significantly changed from TPA (79% versus 17%) to PRA (8% versus 69%, P < 0.001), whilst the frequency of OA remained stable (13% versus 15%). TPA removed larger tumours (3.0 ± 2.9 cm) than PRA (2.8 ± 2.2 cm, P = 0.02), with the median size increasing from 3.0 ± 2.5 to 4.5 ± 3.5 cm per cohort (P < 0.001). The maximum tumour sizes treated by TPA and PRA were 15 and 12 cm, respectively. Adrenocortical adenoma was the commonest pathology treated by either laparoscopic technique. Complication rates were greatest for OA (30.1%) with no significant difference between minimally invasive approaches (TPA 7.3%, PRA 8.3%, P = 0.7). Both laparoscopic techniques had equivalent conversion rates (3.6%). PRA was preferably converted to TPA (2.8%) over OA (0.8%). CONCLUSION: This study demonstrates the transition from TPA to PRA, offering similarly low complication and conversion rates.

Mesenchymal Stem Cell-Derived Extracellular Vesicles to the Rescue of Renal Injury.

Acute kidney injury (AKI) and chronic kidney disease (CKD) are rising in global prevalence and cause significant morbidity for patients. Current treatments are limited to slowing instead of stabilising or reversing disease progression. In this review, we describe mesenchymal stem cells (MSCs) and their constituents, extracellular vesicles (EVs) as being a novel therapeutic for CKD. MSC-derived EVs (MSC-EVs) are membrane-enclosed particles, including exosomes, which carry genetic information that mimics the phenotype of their cell of origin. MSC-EVs deliver their cargo of mRNA, miRNA, cytokines, and growth factors to target cells as a form of paracrine communication. This genetically reprograms pathophysiological pathways, which are upregulated in renal failure. Since the method of exosome preparation significantly affects the quality and function of MSC-exosomes, this review compares the methodologies for isolating exosomes from MSCs and their role in tissue regeneration. More specifically, it summarises the therapeutic efficacy of MSC-EVs in 60 preclinical animal models of AKI and CKD and the cargo of biomolecules they deliver. MSC-EVs promote tubular proliferation and angiogenesis, and inhibit apoptosis, oxidative stress, inflammation, the epithelial-to-mesenchymal transition, and fibrosis, to alleviate AKI and CKD. By reprogramming these pathophysiological pathways, MSC-EVs can slow or even reverse the progression of AKI to CKD, and therefore offer potential to transform clinical practice.

Manipulating the tumor microenvironment by adoptive cell transfer of CAR T-cells.

T-cells expressing synthetic chimeric antigen receptors (CARs) have revolutionized immuno-oncology and highlighted the use of adoptive cell transfer, for the treatment of cancer. The phenomenal clinical success obtained in the treatment of hematological malignancies with CAR T-cells has not been reproduced in the treatment of solid tumors, mainly due to the suppressive and hostile tumor microenvironment (TME). This review will address the immunosuppressive features of the TME, which include the stroma, cytokine and chemokine milieu, suppressive regulatory cells and hypoxic conditions, which can all pose formidable barriers for the effective anti-tumor function of CAR T-cells. Some of the novel next generation CARs that have been developed and tested against the TME, will be discussed, to highlight the status of current research in CAR T-cell therapy for solid tumors.