Soft tissue sarcomas (STS) are rare malignant tumors often associated with poor outcomes and high local recurrence rates. Current tools for intraoperative and definitive margin assessment include intraoperative frozen section and permanent pathology, respectively. Indocyanine green dye (ICG) is a historically safe fluorophore dye that has demonstrated efficacy for intraoperative margin assessment in the surgical management of both breast and gastrointestinal cancers. The utility of ICG in the surgical management of sarcoma surgery has primarily been studied in pre-clinical mouse models and warrants further investigation as a potential adjunct to achieving negative margins. This study is a prospective, non-randomized clinical study conducted on patients with confirmed or suspected STS. Patients younger than 18 years, with a prior adverse reaction to iodine or fluorescein, or with renal disease were excluded from the study. Intravenous ICG was infused approximately three hours prior to surgery at a dosage of 2.0–2.5 mg/kg, and following tumor resection, the excised tumor and tumor bed were imaged for fluorescence intensity. When scanning the tumor bed, a threshold of 77% calibrated to the region of maximum intensity in the resected tumor was defined as a positive ICG margin, according to published protocols from the breast cancer literature. ICG results were then compared with the surgeon’s clinical impression of margin status and permanent pathology results. Out of 26 subjects recruited for the original study, 18 soft tissue sarcomas (STS) were included for analysis. Three subjects were excluded for having bone sarcomas, and five subjects were excluded due to final pathology, which was ultimately inconsistent with sarcoma. The average age of patients was 64.1 years old (range: 28–83), with an average ICG dose of 201.8 mg. In 56% (10/18) of patients, ICG margins were consistent with the permanent pathology margins, with 89% specificity. The use of ICG as an intraoperative adjunct to obtaining negative margins in soft tissue sarcoma surgery is promising. However, studies with larger sample sizes are warranted to further delineate the accuracy, optimal dosage, timing, and types of sarcoma in which this diagnostic tool may be most useful.

Background: Osteosarcoma (OS) and chondrosarcoma (CS) are primary bone malignancies whose prognoses have stagnated despite advancements in surgical management, chemotherapy, radiation therapy, and immunotherapy. The role of the immune system in generating anti-cancer physiologic responses is critical to prognosis. Prior studies have explored if immune system activation via infection enhances survival in bone sarcomas without a clear consensus. Methods: This study sought to (I) retrospectively examine the effect of postoperative infection on survival in OS and CS and (II) systematically review the effect of postoperative infection on survival in primary bone malignancies. We performed a retrospective case-control study of 192 patients treated between 1/2000–12/2015 at a single academic sarcoma referral center. Patients with OS or CS undergoing operative resection were included. Eligible patients were grouped by presence of metastasis, and survival was compared between patients with or without postoperative infection. Furthermore, we performed a systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines investigating the effect of infection on primary bone malignancy survival. Risk of bias assessment was performed utilizing the ROBINS-I (Risk of Bias in Non-randomized Studies-of Interventions) assessment tool. All presented studies included author information, study population, and overall or disease-free survival results. Results: One hundred and four patients were included, with 85 without infection (26 metastatic, 59 non-metastatic) and 19 with infection (10 metastatic, 9 non-metastatic). Five-year survival was greatest in patients without metastasis with a postoperative infection (100%), followed by patients without metastasis who were infection-free (80%). Five-year survival was comparatively lower in patients with metastasis who were infection-free (35%) and lowest in patients with metastasis with a postoperative infection (20%). No significant differences were present (P=0.17) on log-rank analysis. Our systematic review collected six studies exploring the impact of infection on primary bone malignancy survival, with two studies reporting significant findings of infection improving survival. Limitations of this review included risk of bias due to confounding, inconsistency comparing outcomes, and differences in patient populations. Conclusions: This retrospective study and systematic review suggests postoperative infection may play a role in modulating immune response to malignancy. Understanding the synergy between anti-pathogen and anti-cancer responses warrants further investigation as an alternative method of targeted cancer treatment.

Functional dissatisfaction following total knee replacement (TKR) is recorded as high as 20%. The majority of these patients report anterior knee pain (AKP) as the main source of dissatisfaction. Elevated patellofemoral compression forces and soft tissue extensor hood strain have been implicated in the generation of significant AKP. A novel method of assessing and measuring patellofemoral compression forces dynamically in the native and resurfaced patella for TKR in four different quadrants of the patella is described. Results are reported from an in vitro model and cadaveric studies in the native and resurfaced knee. Patellofemoral compression forces are shown to be characteristic and consistent over repeated assessments in the native knee. Placement of a TKR significantly alters this pattern. Furthermore, over-stuffing or under-stuffing the resurfaced patella also significantly alters the nature and magnitude of patellofemoral compression forces. These studies may lead to an improved understanding of the nature of AKP following TKR, and using this assessment tool presents an opportunity to more effectively balance the third space, reproduce the native patellofemoral forces, and subsequently reduce AKP following TKR.

Introduction: Sarcomas are rare malignancies that affect both adults and children. Surgical removal with negative histopathological margins is the foundation of sarcoma treatment. Failure to achieve negative margins puts patients at risk of local recurrence (LR). LR rates range between 10% and 30%. Intraoperative margin assessment is largely subjective and based on surgeon experience. Indocyanine green (ICG) dye has been used for decades for many medical and surgical applications. We previously demonstrated its capacity to guide intraoperative margin assessment in a mouse sarcoma model and described its use in human patients. Here we describe our experience in a larger cohort of 51 patients that enabled us to develop sarcoma‐specific ICG parameters. Methods: After IRB approval, we performed an observational study on sarcoma patients at our institution. Intraoperative ICG measurements were compared with surgeons’ impressions of margin adequacy and final histopathological margin evaluations. The incidence of LR was compared with these three data points (ICG, surgeon impression, final pathology). Statistical modeling was applied to develop sarcoma‐specific ICG parameters. Results: 67 patients were recruited and 16 were excluded, leaving 51 patients. Pathology identified 15 (29.4%) positive margins while surgeons predicted 8 (15.7%) positive margins. Compared with pathology, surgeons correctly identified only 4 out of 15 positive margins (sensitivity: 26.7%) and 32 out of 36 negative margins (specificity: 88.9%). To determine sarcoma‐specific ICG parameters, we inspected an ROC curve. ROC curve analysis with signal‐to‐background ratio (SBR) as predictor showed AUC of 0.6704. Youden index was 0.35 and the corresponding optimal ICG‐SBR cut point was 1.67. With margins classified as positive if SBR ≥ 1.67, the corresponding sensitivity was 93.3%, specificity 41.7%, PPV 40.0%, NPV 93.8% and accuracy 56.9%. Sensitivity was higher with the SBR method with greater identification of positive margins intraoperatively. NPV was also higher with this method. Conclusions: Here we describe sarcoma‐specific parameters for intraoperative ICG. While ICG is extremely sensitive for detecting positive sarcoma margins, it cannot replace surgeons’ clinical expertise. This study suggests that a prospective randomized clinical trial might discern how the sensitivity of ICG and the specificity of surgeon experience could be combined to decrease the incidence of LR.

Knee range of motion (ROM) is an important indicator of knee function. Outside the clinical setting, patients may not be able to accurately assess knee ROM, which may impair recovery following trauma or surgery. This study aims to validate a smartphone mobile application developed to measure knee ROM compared to visual and goniometer ROM measurements. A knee ROM Android mobile application was developed to measure knee ROM. Patients ≥ 18 years old presenting to an orthopaedic clinic with native knee complaints were approached to participate. Knee ROM was measured bilaterally by an arthroplasty-trained surgeon using (1) vision, (2) goniometer, and (3) the mobile application. Measurements were compared in flexion and extension using a one-way analysis of variance with post hoc Tukey test (alpha = 0.05). Eighty-four knee ROM measurements (40 left, 44 right) were obtained in 47 patients. Median Kellgren–Lawrence grade from available radiographs was grade 3. In flexion, mobile application (117.6 ± 14.7 degrees) measurements were not significantly different from visual (116.1 ± 13.6 degrees) or goniometer (116.2 ± 13.6 degrees) measurements. In extension, mobile application (4.8 ± 7.3 degrees) measurements were significantly different from visual (1.9 ± 4.1 degrees) measurements on post hoc analysis (p < 0.01), while no differences were present compared to goniometer (3.1 ± 5.8 degrees) measurements. Our study found that a mobile application for evaluating knee ROM was noninferior to goniometer-based measurements performed by an arthroplasty-trained surgeon. Future studies will investigate this application's utility in (1) remote patient care, (2) accelerating recovery during rehabilitation, (3) detecting early postoperative complications including arthrofibrosis, and (4) adding additional functionalities to the application to provide more detail-oriented descriptive analyses of patient knee function.