Essential versus accessory aspects of cell death: recommendations of the NCCD 2015

Cells exposed to extreme physicochemical or mechanical stimuli die in an uncontrollable manner, as a result of their immediate structural breakdown. Such an unavoidable variant of cellular demise is generally referred to as ‘accidental cell death’ (ACD). In most settings, however, cell death is initiated by a genetically encoded apparatus, correlating with the fact that its course can be altered by pharmacologic or genetic interventions. ‘Regulated cell death’ (RCD) can occur as part of physiologic programs or can be activated once adaptive responses to perturbations of the extracellular or intracellular microenvironment fail. The biochemical phenomena that accompany RCD may be harnessed to classify it into a few subtypes, which often (but not always) exhibit stereotyped morphologic features. Nonetheless, efficiently inhibiting the processes that are commonly thought to cause RCD, such as the activation of executioner caspases in the course of apoptosis, does not exert true cytoprotective effects in the mammalian system, but simply alters the kinetics of cellular demise as it shifts its morphologic and biochemical correlates. Conversely, bona fide cytoprotection can be achieved by inhibiting the transduction of lethal signals in the early phases of the process, when adaptive responses are still operational. Thus, the mechanisms that truly execute RCD may be less understood, less inhibitable and perhaps more homogeneous than previously thought. Here, the Nomenclature Committee on Cell Death formulates a set of recommendations to help scientists and researchers to discriminate between essential and accessory aspects of cell death

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Extremity Soft Tissue Sarcoma in Adults

When treating soft tissue sarcomas (STSs) of the extremities, the major therapeutic goals are survival, local tumor control, optimal function, and minimal morbidity. Surgical resection of the primary tumor is the essential component of treatment for virtually all patients. A wide surgical margin is necessary for local tumor control when surgery is used without radiation, i.e., the cut should traverse normal tissue outside the reactive tumor zone. This is because sarcomas tend to infiltrate normal tissue adjacent to the evident lesion. Thus, removal of the gross lesion by a simple excision alone (only a narrow margin) is followed by relatively high rates of local recurrence. Radical resections are associated with a reduction in the local recurrence rate, but they may compromise limb function. The combination of function-sparing surgery and radiation achieves better rates of local control than either treatment alone, for nearly all patients with STSs, although combined treatment can be associated with acute wound complications in some patients and late normal tissue complications in others. Because both surgical and radiation techniques are both critically important for optimizing local control of tumor and functional outcome, it is important to manage these patients in dedicated multispecialty clinics comprised of physicians with expertise in sarcomas, including orthopedic and general oncology surgeons, radiation oncologists, medical oncologists, sarcoma pathologists, and bone and soft tissue diagnostic radiologists. Radiation therapy can be given by external beam radiation (EBRT) or brachytherapy or combination thereof. EBRT can be given either pre-operatively or post-operatively