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Sarcomas are rare tumors of mesenchymal origin and comprise only around 1% of adult cancers. The abundance of sarcoma histiotypes, with distinct imaging characteristics, biology, clinical behavior and treatment strategy, result in a complex disease presentation, requiring management by multidisciplinary specialized sarcoma centers. Oncologic and musculoskeletal radiology guidelines provide minimal guidance and only fragmentary information on the indications of 18F-FDG PET/CT in sarcoma. Therefore, knowledge of various phenotypes with preference for bone and lymph node metastases or higher incidence of local and distant recurrence is essential to select the appropriate diagnostic imaging tests and its interpretation. Benign and malignant soft tissue and bone tumors often share common radiographic and metabolic imaging characteristics. In addition, metastases of various histiotypes might exhibit a spectrum of atypical imaging appearances. Therefore, imaging specialists need to be aware of these variants and associated pitfalls of sarcoma imaging.

An ambiguous pathologic report can present a clinical dilemma to the treating surgeon. We describe lesions ranging from the potentially benign to the likely malignant. Correctly identifying features associated with higher-risk lesions has proven challenging given the overall good prognosis and low rate of events. An appropriate treatment plan generally requires discussion between the surgeon and an experienced dermatopathologist. When clinically indicated, additional testing may be used to further support or refute a diagnosis of melanoma. The indications for these techniques, the data to support their use, and the strengths and weakness of each are reviewed.

Purpose/Objective(s) Preoperative radiation therapy (RT) is an integral component of local control in soft tissue sarcoma (STS), but the conventional 5-week treatment course is burdensome for patients (pts). We conducted a single-institution phase 2 study of 5-day dose-equivalent preoperative RT for high-risk primary STS, which demonstrated acceptable rates of wound complications and 2-year toxicity. Here, we present results with longer follow-up, including additional pts from an expansion cohort. Materials/Methods The initial cohort accrued between April 2016 and May 2018 and included 52 pts with histologically confirmed extremity or trunk STS planning to undergo preoperative RT followed by surgery. The primary endpoint of the initial cohort was the rate of grade ≥2 radiation morbidity (fibrosis, lymphedema, or joint stiffness) at 2-years. An expansion cohort opened in October 2018 to compare wound complication rates between preoperative RT alone versus chemoRT and has enrolled an additional 47 pts. Patients received 30 Gy (RT alone) or 25 Gy (chemoRT) over 5 daily fractions to the primary tumor with standard margins. Here we report on pts with primary localized STS who completed preoperative RT and surgery in the initial and expansion cohorts (N = 79; chemoRT excluded). We assessed disease outcomes (local control, distant metastasis, and survival rates) and toxicity (grade ≥2 fibrosis, lymphedema, or joint stiffness) after minimum 2-year follow-up (N = 52). Fibrosis and joint stiffness were graded using RTOG/EORTC criteria, and lymphedema by Stern's scale. We also updated the major wound complication rate (defined per established criteria) after minimum 1-year follow up (N = 60). Results Of the 52 pts with minimum 2-year follow-up, predominant histologic subtypes included undifferentiated pleomorphic sarcoma, spindle cell sarcoma or sarcoma NOS (N = 24), myxofibrosarcoma (N = 8), and myxoid liposarcoma (N = 12). Median tumor size was 6.9 cm, and 15 pts had tumors ≥10 cm. At a median follow-up of 3 years, the local recurrence, distant metastasis and all-cause mortality rates were 6.5% (3 of 46 evaluable pts), 20.8% (10 of 48 evaluable pts), and 21.2% (11 of 52). Two of 3 pts (66%) with a local recurrence had undergone R1 resections, compared to 9 of 46 (19.5%) overall. The rate of overall grade ≥2 radiation morbidity in this same group was 13.0% (fibrosis: 5 pts, joint stiffness: 5 pts, lymphedema: 2 pts). Major wound complications were observed in 16 out of 60 (26.7%) evaluable pts. Conclusion Longer follow-up of a phase 2 study of 5-day pre-operative RT for pts with extremity/trunk STS demonstrates excellent local control. Rates of radiation fibrosis, joint stiffness and lymphedema, as well as wound complications, remain acceptable. We have also developed a web-based, interactive user interface for data visualization, which can help providers identify and understand relationships between baseline characteristics and clinical outcomes in our study.

Background Inguinodynia, defined as pain lasting >3 months after inguinal hernia repair, remains the major complication of hernia operation. We sought to determine the effect of direct perineural infiltration on acute pain and inguinodynia after open inguinal hernia repair. Methods Patients who presented with an inguinal hernia at a university teaching hospital were evaluated prospectively and randomized to either (1) percutaneous ilioinguinal nerve block or (2) percutaneous ilioinguinal nerve block with additional perineural infiltration of the ilioinguinal, iliohypogastric, genitofemoral nerves. All patients in each group received a total of 12 mL of 0.5% bupivacaine. Self-reported faces of pain level (1–10), minutes to discharge from the recovery room, narcotic quantity consumed (oxycodone 5 mg/paracetamol 325 mg), days on narcotics, and incidence of inguinodynia at 3 months were all recorded. Results Ninety-two patients were randomized in the study. Patients who received perineural bupivacaine infiltration of nerves had less recovery room pain (1.3 vs 3.9, P P = .047) and consumed fewer narcotics (9.7 vs 15.1 doses, P = .010). The incidence of inguinodynia at 3 months was less in the treatment group (8.2% vs 27.9%, P = .013). Conclusion We have implemented a novel and inexpensive method of local nerve blockade that decreases pain immediately after operation and at 3 months postoperatively. Furthermore, our method leads to shorter recovery room stay and fewer narcotics after operation.

Long-term survival and antitumor immunity of adoptively transferred CD8(+) T cells is dependent on their metabolic fitness, but approaches to isolate therapeutic T cells based on metabolic features are not well established. Here we utilized a lipophilic cationic dye tetramethylrhodamine methyl ester (TMRM) to identify and isolate metabolically robust T cells based on their mitochondrial membrane potential (ΔΨm). Comprehensive metabolomic and gene expression profiling demonstrated global features of improved metabolic fitness in low-ΔΨm-sorted CD8(+) T cells. Transfer of these low-ΔΨm T cells was associated with superior long-term in vivo persistence and an enhanced capacity to eradicate established tumors compared with high-ΔΨm cells. Use of ΔΨm-based sorting to enrich for cells with superior metabolic features was observed in CD8(+), CD4(+) T cell subsets, and long-term hematopoietic stem cells. This metabolism-based approach to cell selection may be broadly applicable to therapies involving the transfer of HSC or lymphocytes for the treatment of viral-associated illnesses and cancer.

Although immunosuppression has been a key component to the success of solid-organ transplantation, the morbidity associated with long-term immunosuppression remains a substantial burden, particularly as recipients of transplants live longer. Indeed, malignancy is one of the most common reasons for mortality following transplantation and the most common of these cancers are cutaneous in origin. Recently, the incidence of these malignancies has been on the rise, partly due to the fact that recipients of these transplants are living longer as a result of improvements in surgical technique, immunosuppression and perioperative management. Although there have been initiatives to increase awareness of cutaneous malignancies following transplantation, such programs are not standardized and there continues to be gaps in skin cancer education and post-operative surveillance. This review provides an update on the epidemiology, risk factors, clinical management, prevention and surveillance of cutaneous malignancies.

BACKGROUND: Here we describe the Systematically Tabulated Outcomes Research Matrix (STORM) method to generate research questions from pre-existing databases with the aim of improving patient outcomes. MATERIALS AND METHODS: STORM can be applied to a database by tabulating its variables into a matrix of independent variables (y-axis) and dependent variables (x-axis) and then applying each unique pairing of an independent and dependent variable to a patient population to generate potentially meaningful research questions. RESULTS: To demonstrate this methodology and establish proof-of-principle, STORM was applied on a small scale to the National Trauma Data Bank and generated at least seven clinically meaningful research questions. CONCLUSION: When coupled with rigorous clinical judgment, the STORM approach complements the traditional method of hypothesis formation and can be generalized to outcomes research using registry databases across different medical specialties. Language: en

Engineering CD8⁺ T cells to deliver interleukin 12 (IL-12) to the tumor site can lead to striking improvements in the ability of adoptively transferred T cells to induce the regression of established murine cancers. We have recently shown that IL-12 triggers an acute inflammatory environment that reverses dysfunctional antigen presentation by myeloid-derived cells within tumors and leads to an increase in the infiltration of adoptively transferred antigen-specific CD8⁺ T cells. Here, we find that local delivery of IL-12 increased the expression of Fas within tumor-infiltrating macrophages, dendritic cells, and myeloid-derived suppressor cells (MDSC), and that these changes were abrogated in mice deficient in IL-12-receptor signaling. Importantly, upregulation of Fas in host mice played a critical role in the proliferation and antitumor activity of adoptively transferred IL-12-modified CD8⁺ T cells. We also observed higher percentages of myeloid-derived cell populations within tumors in Fas-deficient mice, indicating that tumor stromal destruction was dependent on the Fas death receptor. Taken together, these results describe the likely requirement for costimulatory reverse signaling through Fasl on T cells that successfully infiltrate tumors, a mechanism triggered by the induction of Fas expression on myeloid-derived cells by IL-12 and the subsequent collapse of the tumor stroma.

BACKGROUND/PURPOSE: The mechanism of injury (MOI) may serve as a useful adjunct to injury scoring systems in pediatric trauma outcomes research. The objective is to determine the independent effect of MOI on case fatality and functional outcomes in pediatric trauma patients. METHODS: Retrospective review of pediatric patients ages 2 to 18 years in the National Trauma Data Bank from 2002 through 2006 was done. Mechanism of injury was classified by the International Classification of Diseases, Ninth Revision, E codes. The main outcome measures were mortality, discharge disposition (home vs rehabilitation setting), and functional impairment at hospital discharge. Multiple logistic regression was used to adjust for injury severity (using the Injury Severity Score and the presence of shock upon admission in the emergency department), age, sex, and severe head or extremity injury. RESULTS: Thirty-five thousand ninety-seven pediatric patients in the National Trauma Data Bank met inclusion criteria. Each MOI had differences in the adjusted odds of death or functional disabilities as compared with the reference group (fall). The MOI with the greatest risk of death was gunshot wounds (odds ratio [OR], 3.52; 95% confidence interval [CI], 2.23-5.54 95). Pediatric pedestrians struck by a motor vehicle have the highest risk of locomotion (OR, 3.30; 95% CI, 2.89-3.77) and expression (OR, 1.65; 95% CI, 1.22-2.23) disabilities. CONCLUSION: Mechanism of injury is a significant predictor of clinical and functional outcomes at discharge for equivalently injured patients. These findings have implications for injury prevention, staging, and prognosis of traumatic injury and posttreatment planning. Language: en

Background The Revised Trauma Score (RTS) is commonly used to assess physiologic injury; however its use is limited by missing data. This study compares different parameters of physiologic injury assessment in their ability to predict mortality after trauma. Methods Adult patients in the National Trauma Data Bank (NTDB version 7.0) were analyzed, and the following physiologic injury parameters were compared: RTS, systolic blood pressure (SBP), shock (SBP ≤ 90 mm Hg), Glasgow coma scale-total (GCS-T), and GCS-motor (GCS-M). Areas under the receiver-operating characteristic curves (AUROC) were calculated for unadjusted and multivariate regression models to predict mortality after trauma. Results There were 1,484,648 patients who met inclusion criteria. In unadjusted analyses, RTS had the highest proportion of missing data (21%) and was highly predictive of mortality (AUROC = 0.85). SBP and shock had a much lower AUROC of 0.67 and 0.66, respectively, but had many fewer missing cases. The combination parameters of GCS-M with SBP or GCS-M with shock showed AUROC comparable to RTS (0.85) with approximately 80,000 fewer missing cases. Conclusion The discriminatory power of RTS is significantly better than SBP, shock, or GCS alone. Given the limitation of missing data associated with RTS, the combination of SBP and GCS-M is a more reliable and equally effective method of assessing physiologic injury severity in studying trauma outcomes.

Background Studies of sexual dimorphism in trauma outcomes suggest that women have a survival advantage compared to equivalently injured men. It is unknown if this gender disparity is mediated by potentially life-threatening complications. Objective To determine (1) if there is a sex-based differences in the odds of developing inpatient complications after trauma, and (2) if are these complications associated with death among trauma patients. Methods Review of adult trauma patients admitted to hospitals in the National Trauma Data Bank that report complications. Patient and injury severity covariates were adjusted using multiple logistic regression and the independent effect of sex on developing complications and associated mortality was determined. Results A total of 681,730 adult patients met the inclusion criteria of hospital admission ≥3 days. Women demonstrated a 21% lower adjusted risk of death compared to males (OR 0.79, 95% CI 0.76–0.83). Females had decreased adjusted odds of developing life-threatening complications including pneumonia, acute respiratory distress syndrome, acute renal failure and pulmonary embolism. However, when compared to males with life-threatening complications, females with complications were found to be at greater risk of dying. Conclusion This study demonstrates that women are less likely than men to develop inpatient complications, suggesting that the survival advantage among women after traumatic injury may involve a reduced susceptibility to developing life-threatening complications.

In two studies published in this issue of Cell Stem Cell, Nishimura et al. (2013) and Vizcardo et al. (2013) reprogram mature, antigen-specific cytotoxic T cells into induced pluripotent stem cells (iPSCs). The antigen-specific iPSCs can be redifferentiated into "rejuvenated" proliferative T cells and have broad applications for adoptive immunotherapy.