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.

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.

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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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Prolonged mechanical ventilation (MV) prior to the initiation of extracorporeal membrane oxygenation (ECMO) is associated with decreased survival. Pediatric burn patients without inhalational injury are a unique population as they may be intubated for longer durations due to frequent interventions such as dressing changes and burn excisions. This study utilized the Extracorporeal Life Support Organization (ELSO) registry and evaluated patients 0-18 years old placed on ECMO and with a burn injury from January 2010-December 2020. Inhalation injury was excluded. Descriptive statistics and bivariate analyses were performed. Multivariable logistic regression was used to assess the association between mortality and precannulation MV duration prior to ECMO cannulation, and odds ratios and predicted probabilities of mortality were estimated. Our cohort of 47 patients had a median age of 2.7 years old. Mortality occurred in 48.9% of the cohort. The overall median number of days on ECMO was 6.3 days, with no difference between survivors and non-survivors (6.8 days vs. 6.3 days; p=0.67). Survivors were ventilated for 4.1 days and non-survivors for 4.8 days prior to cannulation (p=0.25). Regression modeling demonstrated that with each additional day on MV prior to ECMO cannulation, the odds of mortality increases by 12% (p=0.03). Our study suggests that, similar to pediatric patients without thermal injury, increasing precannulation MV duration is associated with an increasing risk of mortality in pediatric burn patients without inhalational injury. Though the pediatric burn population is unique, evaluation of burn patients with respiratory failure for ECMO should be similar to the general population.

In recent years, studies have demonstrated non-operative management with antibiotics alone to be a safe and effective treatment option for children with uncomplicated acute appendicitis. Shared decision-making is critical in the treatment of uncomplicated appendicitis due to the markedly different risks and benefits associated with surgery and non-operative management. In this report, we discuss the importance of shared decision-making in surgery using a case of uncomplicated appendicitis as an example. We present both the patient-family and provider perspectives on evaluating and deciding between operative and non-operative management and discuss the value of shared decision-making in the unique setting of an acute pathologic process with surgical and medical treatment options.