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Background: Perinephric myxoid pseudotumor of fat (PMPF) is a rare benign pseudo-neoplastic proliferation of the perinephric and renal sinus adipose tissue. Its pathogenesis is thought to be a reactive process typically associated with neoplastic and non-neoplastic end-stage kidney disease. The distinctive histopathological feature of PMPF is a myxoid process comprising bland, spindled stromal cells interspersed with mature adipose tissue. Macroscopically, it is characterized by tumorous lipomatous remodeling of the kidney, which may raise concerns of malignancy on imaging. To date, only seven cases of PMPF have been documented in the context of kidney transplantation. Case presentation: This report describes three cases of PMPF in patients following renal transplantation, involving both native and grafted kidneys. Macroscopically, all cases consisted of shrunken kidneys with thinned and atrophic renal parenchyma surrounded by massively hypertrophic perirenal fat with mass-forming nodules, which was in concordance with cross sectional imaging findings acquired before surgery. Histology of the remaining renal parenchyma showed end stage renal disease in all four surgically removed kidneys, with diffuse interstitial fibrosis, tubular atrophy and sclerosed glomeruli. Perirenal adipose tissue consisted of mature fat with areas of significant myxoid and collagenous stromal component, interspersed with bland spindle and stellate-shaped cells. Immunohistochemistry for S100, smooth muscle actin, desmin and IgG4 were negative. No MDM2 gene amplification was identified by fluorescence in situ hybridization. Broad molecular profiling using the FoundationOne®Heme assay revealed no evidence of pathogenic alterations on DNA and RNA levels. Conclusion: PMPF is a rare benign condition typically associated with chronic kidney disease, occurring late in the course. The radiological findings may be mistaken for those of a malignant tumor, and histopathological examination is required to exclude a malignant neoplasm, in particular a well-differentiated or dedifferentiated liposarcoma of the retroperitoneum. Renal transplant recipients can be affected by PMPF, which can occur in both native and transplanted kidneys several years following renal transplantation. [ABSTRACT FROM AUTHOR]

Simple Summary: Sarcomas are rare tumors that can develop in bones or soft tissues. Recognizing them early is important because delays in diagnosis can lead to worse outcomes for patients. In our study, we looked at how different symptoms affect the time it takes for patients to be diagnosed with these tumors. We found that when patients experience pain, they tend to see a doctor sooner, leading to quicker diagnoses. However, symptoms like swelling or numbness often cause delays because patients or doctors may not realize they could be signs of a serious condition. Understanding which symptoms lead to delays can help improve education for both patients and healthcare providers, leading to earlier detection and better outcomes for people with sarcomas and similar tumors. Background/Objectives: The early diagnosis of mesenchymal tumors, including bone and soft tissue sarcoma and their benign counterparts, is crucial for improving patient outcomes. This study aims to analyze how different symptoms influence diagnostic timelines and identify factors contributing to delays in the diagnostic pathway. Methods: We conducted an analysis of 712 patients with mesenchymal tumors from the Swiss Sarcoma Network between January 2018 and December 2021. Symptoms were analyzed both individually, like pain and swelling, and by categories such as general, neurological and integumentary symptoms. Intervals of the total interval (TI) in the diagnostic pathway—including the patient interval (PI), primary care interval (PCI), secondary care interval (SCI) and tertiary care interval (TCI)—were assessed. Linear regression models estimated the impact of specific symptoms on these intervals. Results: Pain significantly reduced the PI and TI in patients with bone sarcomas (PI β = −1787.5; p = 0.001) and soft tissue sarcomas (TI β = −442.1; p = 0.04), prompting earlier medical consultation. In contrast, symptoms like growing swelling and sensory disturbances were associated with prolonged diagnostic intervals. Growing swelling lengthened the PI in benign bone tumors (β = 382.98; p = 0.04) and extended the TI in bone sarcomas (β = 1637.4; p = 0.02). Sensory disturbances delayed the PI and TI in superficial soft tissue sarcomas (PI β = 1705; p = 0.02; TI β = 2037.6; p = 0.03). Integumentary symptoms also led to significant delays in benign superficial soft tissue tumors. Conclusions: Pain accelerates the diagnostic process in mesenchymal tumors by prompting earlier consultation, while swelling and sensory disturbances contribute to delays across various diagnostic intervals. These findings highlight the need for increased awareness among patients and healthcare providers regarding the potential seriousness of these symptoms. Educational initiatives and optimized referral protocols are essential to reducing diagnostic delays and improving patient outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: Soft tissue sarcomas are rare cancers that are often treated with a combination of surgery and preoperative radiotherapy to reduce the risk of cancer returning. Traditionally, this radiotherapy is delivered over five weeks, which can be challenging for patients due to the long treatment time and potential side effects. This study investigates a shorter, one-week radiotherapy option to determine if it provides similar results in terms of cancer control, survival and wound healing. By comparing these two treatment schedules, we aim to explore whether the shorter approach can offer a safe and effective alternative that might reduce the burden on patients and healthcare systems. If successful, this shorter treatment could improve patient convenience and resource efficiency, offering a new option in sarcoma care that aligns with modern goals for patient-centered, efficient cancer treatments. Background/Objectives: The historically most commonly used preoperative radiotherapy regimen for soft tissue sarcomas (STSs) consists of 50 Gray (Gy) delivered in 25 fractions over 5 weeks, achieving excellent local control, but with significant challenges due to prolonged treatment duration and early side effects. Reducing therapy duration while maintaining optimal local and distant control would be highly beneficial for patients. We aimed to investigate the outcome of an ultrahypofractionated radiotherapy (uhRT) regimen which may represent a shorter and more patient-friendly alternative. Methods: This multi-center, open-label, phase 2 clinical trial with a clustered cohort design was conducted within the Swiss Sarcoma Network (SSN). Adult patients (aged ≥ 18 years) with STS of the extremities or superficial trunk and an Eastern Cooperative Oncology Group (ECOG) performance status of 0–3 were included. Participants were assigned to either normofractionated radiotherapy (nRT) at 50 Gy in 25 fractions or uhRT at 25 Gy in 5 fractions. Data were collected prospectively in real-world-time clinical settings. The primary outcome was local recurrence-free survival (LRFS), with overall survival (OS) and wound complications as secondary outcomes. Results: Between March 2020 and October 2023, 138 patients were included in the study; 74 received nRT and 64 received uhRT. The median follow-up times were 2.2 years for uhRT and 3.6 years for nRT. The LRFS rates at 1 year were 97.0% for nRT and 94.8% for uhRT (p = 0.57). The two-year LRFS rates were 91.9% and 94.8%, respectively (p = 0.57). The one- and two-year OS rates were 97.1%/86.3% and 98.2%/88.8%, respectively (p = 0.72). The wound complication rate was comparable between the nRT (12.0%) and uhRT (12.5%) groups (p = 0.99). Conclusions: UhRT for STSs offers an effective and safe alternative to traditional nRT, with comparable early LRFS, OS and wound complication rates. Given the two-year median follow-up, which is critical for evaluating local recurrence, uhRT shows promise as a shorter and more convenient treatment regimen. UhRT may be a safe and effective alternative treatment option to traditional nRT. [ABSTRACT FROM AUTHOR]

Simple Summary: This study emphasizes the crucial role of effective communication to improve patients' understanding and satisfaction during biopsy procedures. It highlights the importance of managing patient anxiety and fear, which can directly impact pain experiences. The study also identifies areas where real-time pain management can be enhanced and underscores the need for clear and accurate patient education to address concerns after the procedure. Background/Objectives: This study evaluates the effectiveness of communication strategies and pain management protocols to enhance patients' experiences during sarcoma core biopsies. Recognizing the complexity and anxiety associated with sarcoma diagnoses, this research aims to assess the utility of the Invasive Procedure Assessment (IPA) tool, focusing on its ability to identify areas for improvement through Patient-Reported Outcome Measures (PROMs) and Patient-Reported Experience Measures (PREMs). Methods: Conducted at two Integrated Practice Units (IPUs) within the Swiss Sarcoma Network, this study involved 282 consecutive patients who underwent core biopsies. One week post-procedure, patients completed the IPA questionnaire, which included PROMs and PREMs. Statistical analyses explored correlations between physician communication, patient understanding, anxiety, pain, and overall satisfaction. Results: The IPA tool effectively captured patient perspectives on sarcoma core biopsies. A significant positive correlation (rho = 0.619, p < 0.0001) was found between effective physician communication and patient understanding, which was associated with reduced anxiety and pain. Higher anxiety levels strongly correlated with increased pain perception (rho = 0.653, p < 0.0001), emphasizing the need for anxiety management. Patients with malignant tumors reported lower overall satisfaction compared to those with benign tumors (p = 0.0003), highlighting the need for tailored communication and pain management strategies. The data also suggested that clear communication might mitigate overly negative subjective impressions, such as concerns about wound complications. Conclusions: Effective communication and anxiety management are essential for improving patient satisfaction during sarcoma core biopsies. The study emphasizes the need for personalized care strategies tailored to tumor characteristics and patient demographics. Future research should validate these findings in diverse healthcare settings and explore the broader application of the IPA tool across different cultural and demographic contexts. [ABSTRACT FROM AUTHOR]

Simple Summary: This study examines how care pathways impact local recurrence (LR) rates in patients with soft tissue sarcomas (STS). It compares outcomes between those managed entirely within a comprehensive care pathway (CCP) at the Swiss Sarcoma Network (SSN) and those with a fragmented care pathway (FCP) where initial treatment occurred outside specialized centers. Patients in FCPs had higher LR rates, unplanned "whoops" resections, and positive surgical margins, highlighting the critical role of referral patterns and early, coordinated care. The findings underscore the need for better education and standardized early referrals to improve outcomes and establish quality benchmarks in specialized sarcoma care. This study evaluated the impact of care pathways on the incidence of local recurrence (LR) in patients with soft tissue sarcomas (STS) and identified factors predictive of LR. It compared outcomes between patients managed entirely within a comprehensive care pathway (CCP) at the Swiss Sarcoma Network (SSN) and those who experienced fragmented care pathways (FCPs), where initial treatment occurred outside specialized centers. This prospective study utilized real-world-time data from the SSN-Sarconnector, capturing quality indicators through weekly Multidisciplinary Team/Sarcoma-Board (MDT/SB) meetings. The overall incidence of LR was 17.6% (n = 68/386), higher than rates typically reported in sarcoma center-based studies due to the inclusion of patients with prior inadequate management from real-world referrals. In a univariable logistic regression analysis, the FCP was significantly associated with higher LR rates, unplanned "whoops" resections (25.4%, n = 96), and positive surgical margins, emphasizing the detrimental impact of suboptimal initial management outside of specialized centers. Multivariable analysis confirmed that the FCP (aOR 2.7, 95% CI [1.41, 5.12], p = 0.003), tumor size (aOR 1.49, 95% CI [1.1, 2.02], p = 0.01), and biological behavior (aOR 5.84 95% CI [1.8, 18.86], p = 0.0003) are independent predictors of LR. Notably, patients referred to sarcoma centers after an initial FCP presented with inadequately managed disease, such as incomplete resections and unplanned surgeries, leading to increased complexity of subsequent treatments. These findings underscore the critical role of referral patterns on sarcoma center outcomes, highlighting the significant disparity in LR rates between institutions. The need for improved education and standardized early referral strategies at the spoke level is paramount to optimize patient outcomes and reduce the burden of LR. Enhanced spoke-level education and standardized referral protocols are critical to ensuring effective initial management and optimizing patient outcomes within specialized sarcoma networks like the SSN. [ABSTRACT FROM AUTHOR]

Simple Summary: Sarcomas are rare and diverse tumors that develop in various tissues like bone, muscle, and fat. This study examines the outcomes of two types of surgical removal of these tumors: planned resections (PEs), where the tumor is diagnosed a-priori and surgically removed with a plan, and unplanned resections (UEs), where the tumor is removed without prior diagnosis. We found that planned surgeries, while better at completely removing the tumor initially, are associated with more advanced tumors that have a higher chance of spreading and leading to cancer-related deaths. On the other hand, unplanned surgeries tend to have higher chances of the tumor coming back locally but do not significantly affect long-term survival. These findings highlight the importance of early detection and timely treatment at specialized centers to improve patient outcomes. Our research aims to help develop better tools for predicting and managing sarcomas to enhance patient care. Background: Sarcomas, a diverse group of malignant tumors arising from mesenchymal tissues, pose significant diagnostic and therapeutic challenges. This study compares the outcomes of planned resections (PEs) and unplanned resections (UEs) to inform better clinical practices. Methods: Data were analyzed from the Swiss Sarcoma Network (SSN), including patients with soft tissue and bone sarcomas treated at two major hospitals. This study utilized logistic regression and Cox regression models to examine the odds of UEs and their impact on local recurrence-free survival. Results: Among 429 patients registered by SSN members, 323 (75%) underwent PEs and 106 (25%) experienced UEs. PEs were associated with significantly larger tumors (94 mm vs. 47 mm, p < 0.001) and higher-grade tumors (Grade 3: 50.5% vs. 37.4%, p = 0.03). Despite achieving superior resection margins (R0: 78.8% vs. 12.6%, p < 0.001), PEs showed higher metastasis rates at follow-up (31.0% vs. 10.4%, p < 0.001) and greater cancer-specific mortality (16.7% vs. 6.6%, p = 0.01). UEs, while linked to higher local recurrence, did not significantly affect metastasis-free survival (MFS) or overall survival (OS). Conclusions: PEs achieve superior immediate surgical outcomes but are linked to higher metastasis and cancer-specific mortality due to the advanced stage of tumors. UEs, while associated with higher local recurrence rates, do not significantly impact MFS or OS. Early detection, comprehensive diagnostics, and timely referrals to specialized sarcoma hubs are essential to avoid UEs and reduce metastatic risk. Future research should focus on developing diagnostic tools using individual tumor and patient characteristics to improve sarcoma management. [ABSTRACT FROM AUTHOR]

Simple Summary: In this study, we aimed to understand the association between two types of surgeries on sarcoma outcomes: surgeries that were planned with a clear understanding of the cancer (planned resections) and those that were performed unexpectedly, without prior knowledge that the tumor was cancerous (unplanned resections). Using the novel Target Trial Emulation framework, we assessed how these surgeries impact local recurrence-free survival, metastasis-free survival, cancer-specific survival, and overall survival. Our study found that patients who had unplanned surgeries were more likely to experience their cancer recur at the surgery site. However, there was not a substantial difference in how long patients survived after either type of surgery. Our findings highlight the importance of immediately referring patients to specialized sarcoma treatment centers where unplanned resections are less likely to occur to improve treatment outcomes and provide evidence to guide better management strategies for sarcoma. This study follows the Target Trial Emulation (TTE) framework to assess the impact of unplanned resections (UEs) and planned resections (PEs) of sarcomas on local recurrence-free survival (LRFS), metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS). Sarcomas, malignant tumors with mesenchymal differentiation, present a significant clinical challenge due to their rarity, complexity, and the frequent occurrence of UEs, which complicates effective management. Our analysis utilized real-world-time data from the Swiss Sarcoma Network, encompassing 429 patients, to compare the impact of UEs and PEs, adjusting for known prognostic factors through a multivariable Cox regression model and propensity score weighting. Our findings reveal a significantly higher risk of local recurrence for UEs and a short-term follow-up period that showed no marked differences in MFS, CSS, and OS between the UE and PE groups, underlining the importance of optimal initial surgical management. Furthermore, tumor grade was validated as a critical prognostic factor, influencing outcomes irrespective of surgical strategy. This study illuminates the need for improved referral systems to specialized sarcoma networks to prevent UEs and advocates for the integration of TTE in sarcoma research to enhance clinical guidelines and decision-making in sarcoma care. Future research should focus on the prospective validations of these findings and the exploration of integrated care models to reduce the incidence of UEs and improve patient outcomes. [ABSTRACT FROM AUTHOR]

The landscape of sarcoma care is on the cusp of a transformative era, spurred by the convergence of digital health and artificial intelligence (AI). This perspectives article explores the multifaceted opportunities and challenges in leveraging these technologies for value-based, precision sarcoma care. We delineate the current state-of-the-art methodologies and technologies in sarcoma care and outline their practical implications for healthcare providers, administrators, and policymakers. The article also addresses the limitations of AI and digital health platforms, emphasizing the need for high-quality data and ethical considerations. We delineate the promise held by the synergy of digital health platforms and AI algorithms in enhancing data-driven decision-making, outcome analytics, and personalized treatment planning. The concept of a sarcoma digital twin serves as an illustrative paradigm for this integration, offering a comprehensive, patient-centric view of the healthcare journey. The paper concludes with proposals for future research aimed at advancing the field, including the need for randomized controlled trials or target trial emulations and studies focusing on ethical and economic aspects. While the road to this transformative care is laden with ethical, regulatory, and practical challenges, we believe that the potential benefits far outweigh the obstacles. We conclude with a call to action for multidisciplinary collaboration and systemic adoption of these technologies, underscoring the urgency to act now for the future betterment of sarcoma care and healthcare at large. [ABSTRACT FROM AUTHOR]

Introduction In the study of many biological processes, it is often desirable to be able to genetically manipulate multiple genes simultaneously. A prime example is tumor modeling in mice. The [...], Here, we describe the multiple lentiviral expression (MuLE) system that allows multiple genetic alterations to be introduced simultaneously into mammalian cells. We created a toolbox of MuLE vectors that constitute a flexible, modular system for the rapid engineering of complex polycistronic lentiviruses, allowing combinatorial gene overexpression, gene knockdown, Cre-mediated gene deletion, or CRISPR/Cas9-mediated (where CRISPR indicates clustered regularly interspaced short palindromic repeats) gene mutation, together with expression of fluorescent or enzymatic reporters for cellular assays and animal imaging. Examples of tumor engineering were used to illustrate the speed and versatility of performing combinatorial genetics using the MuLE system. By transducing cultured primary mouse cells with single MuLE lentiviruses, we engineered tumors containing up to 5 different genetic alterations, identified genetic dependencies of molecularly defined tumors, conducted genetic interaction screens, and induced the simultaneous CRISPR/Cas9-mediated knockout of 3 tumor-suppressor genes. Intramuscular injection of MuLE viruses expressing oncogenic [H-Ras.sup.G12V] together with combinations of knockdowns of the tumor suppressors cyclin-dependent kinase inhibitor 2A (Cdkn2a), transformation-related protein 53 (Trp53), and phosphatase and tensin homolog (Pten) allowed the generation of 3 murine sarcoma models, demonstrating that genetically defined autochthonous tumors can be rapidly generated and quantitatively monitored via direct injection of polycistronic MuLE lentiviruses into mouse tissues. Together, our results demonstrate that the MuLE system provides genetic power for the systematic investigation of the molecular mechanisms that underlie human diseases.

Simple Summary: Benchmarking is a crucial tool for healthcare providers to improve quality and efficiency, especially for complex conditions like sarcomas. Sarcomas are a type of cancer that require a multidisciplinary approach to treatment. However, despite adherence to international guidelines, differences in the processes used by these boards can affect patient outcomes and treatment costs. This study compared two multidisciplinary teams/sarcoma tumor boards and established an interoperable digital platform, Sarconnector®, for real-world time (RWT) data assessment and automated analysis. Differences were obtained in various areas, such as first-time presentations, follow-up presentations, primary sarcomas, biopsies and chemotherapy indications. By identifying areas of improvement and making data-driven decisions on the meta-level, healthcare providers can optimize resources and improve patient outcomes. Benchmarking with the RWT harmonized data approach provided by the Sarconnector® can help healthcare providers achieve better outcomes for their patients and improve the overall effectiveness of the healthcare system. Benchmarking is crucial for healthcare providers to enhance quality and efficiency, notably for complex conditions like sarcomas. Multidisciplinary teams/sarcoma boards (MDT/SBs) are vital in sarcoma management, but differences in their processes can affect patient outcomes and treatment costs, despite adherence to international guidelines. To address this issue, this study aimed to compare two MDT/SBs and establish an interoperable digital platform, Sarconnector®, for real-time-world data assessment and automated analysis. The study included 983 patients, 46.0% of whom female, with a median age of 58 years, and 4.5% of patients presented with metastasis at diagnosis. Differences were observed in the number of first-time presentations, follow-up presentations, primary sarcomas, biopsies and chemotherapy indications between the two MDT/SB. The results highlight the importance of benchmarking and utilizing a harmonized data approach, such as the RWT approach provided by the Sarconnector®, to standardize and evaluate quality and cost metrics. By identifying areas of improvement and making data-driven decisions on the meta-level, healthcare providers can optimize resources and improve patient outcomes. In conclusion, benchmarking with the RWT harmonized data approach provided by the Sarconnector® can help healthcare providers improve the overall effectiveness of the healthcare system and achieve better outcomes for their patients in terms of both outcomes and costs. [ABSTRACT FROM AUTHOR]