Despite advances in systemic therapies, surgery is crucial for the management of solid malignancy. There is increasing evidence suggesting that the body’s response to surgical stress resulting from tumor resection has direct effects on tumor cells or can alter the tumor microenvironment. Surgery can lead to the activation of early and key components of the innate and adaptative immune systems. Platelet activation and the subsequent pro-coagulation state can accelerate the growth of micrometastases. Neutrophil extracellular traps (NETs), an extracellular network of DNA released by neutrophils in response to inflammation, promote the adhesion of circulating tumor cells and the growth of existing micrometastatic disease. In addition, the immune response following cancer surgery can modulate the tumor immune microenvironment by promoting an immunosuppressive state leading to impaired recruitment of natural killer (NK) cells and regulatory T cells (Tregs). In this review, we will summarize the current understanding of mechanisms of tumor progression secondary to surgical stress. Furthermore, we will describe emerging and novel peri-operative solutions to decrease pro-tumorigenic effects from surgery.

ImportanceThe management of pilonidal disease continues to be a challenge due to high rates of recurrence and treatment-associated morbidity.ObservationsThere is a heterogeneous repertoire of treatment modalities used in the management of pilonidal disease and wide practice variation among clinicians. Available treatment options vary considerably in their level of invasiveness, associated morbidity and disability, risks of complications, and effectiveness at preventing disease recurrence. Conservative nonoperative management strategies, including persistent improved hygiene, depilation, and lifestyle modification, focus on disease prevention and minimization of disease activity. Epilation techniques using both laser and intense pulse light therapy are also used as primary and adjunct treatment modalities. Other nonoperative treatment modalities include phenol and fibrin injection to promote closure of pilonidal sinuses. The traditional operative management strategy for pilonidal disease involves excision of affected tissue paired with a variety of closure types including primary midline closure, primary off-midline closure techniques (ie, Karydakis flap, Limberg flap, Bascom cleft lift), and healing by secondary intention. There has been a recent shift toward more minimally invasive operative approaches including sinusectomy (ie, trephination or Gips procedure) and endoscopic approaches. Overall, the current evidence supporting the different treatment options is limited by study quality with inconsistent characterization of disease severity and use of variable definitions and reporting of treatment-associated outcomes across studies.Conclusions and RelevancePilonidal disease is associated with significant physical and psychosocial morbidity. Optimal treatments will minimize disease and treatment-associated morbidity. There is a need for standardization of definitions used to characterize pilonidal disease and its outcomes to develop evidence-based treatment algorithms.

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The proteasome inhibitor carfilzomib is highly effective in the treatment of multiple myeloma. It irreversibly binds the chymotrypsin-like active site in the β5 subunit of the 20S proteasome. Despite impressive response rates when carfilzomib is used in combination with immunomodulatory agents in newly diagnosed multiple myeloma patients; no biomarker exists to accurately predict response and clinical outcomes. We prospectively assessed the activity in peripheral blood of the chymotrypsin-like (CHYM), caspase-like (CASP) and trypsin-like (TRYP) proteolytic sites in 45 newly diagnosed multiple myeloma patients treated with eight cycles of carfilzomib, lenalidomide and dexamethasone (CRd) (NCT01402284). Samples were collected per protocol and proteasome activity measured through a fluorogenic assay. Median CHYM levels after one dose of carfilzomib decreased by >70%. CHYM and CASP activity decreased throughout treatment reaching a minimum after eight cycles of treatment. Higher levels of proteasome activity associated with higher disease burden (r > 0.30; p < 0.05) and higher disease stage (0.10 < p <0.20). No association was found with the probability of achieving a complete response, minimal residual disease negativity or time to best response. Further studies evaluating proteasome activity in malignant plasma cells may help elucidate how proteasome activity can be used as a biomarker in multiple myeloma.