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The surgical-oncological treatment of pelvic and perineal malignancies is associated with a high complication rate and morbidity for patients. Modern multimodal treatment modalities, such as neoadjuvant radio-chemotherapy for anal or rectal cancer, increase the long-term survival rate while reducing the risk of local recurrence. Simultaneously, the increasing surgical radicality and higher oncological safety with wide resection margins is inevitably associated with larger and, due to radiation, more complex tissue defects in the perineal and sacral parts of the pelvic floor. Therefore, the plastic-surgical reconstruction of complex pelvic-perineal defects following oncological resection remains challenging. The reconstructive armamentarium, and thus the treatment of such defects, is broad and ranges from local, regional and muscle-based flaps to microvascular and perforator-based procedures. While the use of flaps is associated with a significant, well-documented reduction in postoperative complications compared to primary closure, there is still a lack of reliable data directly comparing the postoperative results of different reconstructive approaches. Additionaly, the current data shows that the quality of life of these patients is rarely recorded in a standardised manner. In a consensus workshop at the 44 th annual meeting of the German-speaking Association for Microsurgery on the topic of "Reconstruction of oncological defects in the pelvic-perineal area", the current literature was discussed and recommendations for the reconstruction of complex defects in this area were developed. The aim of this workshop was to identify knowledge gaps and establish an expert consensus to ensure and continuously improve the quality of reconstruction in this challenging area. In addition, the importance of the "patient-reported outcome measures" in pelvic reconstruction was highlighted, and the commitment to its widespread use in the era of value-based healthcare was affirmed., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Genomic rearrangements of the neurotrophic receptor tyrosine kinase genes (NTRK1, NTRK2, and NTRK3) are the most common mechanism of oncogenic activation for this family of receptors, resulting in sustained cancer cell proliferation. Several targeted therapies have been approved for tumours harbouring NTRK fusions and a new generation of TRK inhibitors has already been developed due to acquired resistance. We established a patient-derived LMNA::NTRK1-rearranged soft-tissue sarcoma cell model ex vivo with an acquired resistance to targeted TRK inhibition. Molecular profiling of the resistant clones revealed an acquired NF2 loss of function mutation that was absent in the parental cell model. Parental cells showed continuous sensitivity to TRK-targeted treatment, whereas the resistant clones were insensitive. Furthermore, resistant clones showed upregulation of the MAPK and mTOR/AKT pathways in the gene expression based on RNA sequencing data and increased sensitivity to MEK and mTOR inhibitor therapy. Drug synergy was seen using trametinib and rapamycin in combination with entrectinib. Medium-throughput drug screening further identified small compounds as potential drug candidates to overcome resistance as monotherapy or in combination with entrectinib. In summary, we developed a comprehensive model of drug resistance in an LMNA::NTRK1-rearranged soft-tissue sarcoma and have broadened the understanding of acquired drug resistance to targeted TRK therapy. Furthermore, we identified drug combinations and small compounds to overcome acquired drug resistance and potentially guide patient care in a functional precision oncology setting. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland., (© 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.)

Face transplantation is a viable reconstructive approach for severe craniofacial defects. Despite the evolution witnessed in the field, ethical aspects, clinical and psychosocial implications, public perception, and economic sustainability remain the subject of debate and unanswered questions. Furthermore, poor data reporting and sharing, the absence of standardized metrics for outcome evaluation, and the lack of consensus definitions of success and failure have hampered the development of a "transplantation culture" on a global scale. We completed a 2-round online modified Delphi process with 35 international face transplant stakeholders, including surgeons, clinicians, psychologists, psychiatrists, ethicists, policymakers, and researchers, with a representation of 10 of the 19 face transplant teams that had already performed the procedure and 73% of face transplants. Themes addressed included patient assessment and selection, indications, social support networks, clinical framework, surgical considerations, data on patient progress and outcomes, definitions of success and failure, public image and perception, and financial sustainability. The presented recommendations are the product of a shared commitment of face transplant teams to foster the development of face transplantation and are aimed at providing a gold standard of practice and policy., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Electrical injuries follow a specific pathophysiology and may progressively damage both skin and deeper tissues, frequently ending in amputations. Type and timing of soft tissue reconstruction after electrical burns is crucial for proper outcome. The aim of this study was to assess surgical management and outcome of patients with electrical injuries treated at the Zurich Burn Center over the last 15 years, with emphasis on risk factors for amputation and reconstructive strategy., Methods: Patient charts were reviewed retrospectively to identify cases admitted at the Zurich Burns Center (2005-2019). Patient characteristics and surgical management, with a special focus on amputations, reconstruction and outcome were analyzed and risk factors for amputation were assessed., Results: Eighty-nine patients were identified and a total of 522 operations were performed. Escharotomy and fasciotomies were performed in 40.5% and 24.7% of cases, respectively, mainly at admission. The total amputation rate was 13.5% (23 amputations, 12 patients). Development of compartment syndrome, rhabdomyolysis, high myoglobin and CK blood levels, kidney failure, sepsis and respiratory complications during the course were related to higher risk of amputation (p < 0.001). Sixty-six flap-based reconstructions were performed (25% cases): 49 loco-regional flaps, 3 distant pedicled flaps, 14 free flaps. Two flaps were lost (flap failure rate 14%). Both flap losses occurred in cases of early reconstruction (within 5-21 days)., Conclusions: Electrical injuries are still cause of elevated morbidity and mortality, with high amputation rate. Predictors for amputation can support physicians in the surgical care and decision-making. Reconstruction remains challenging in this type of injury: the surgical management with early decompression, serial necrectomies and delayed early reconstruction remains the procedure of choice at our unit., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Aim: Widespread clinical application of vascularized composite allotransplantation (VCA) has been limited by the need for lifelong systemic immunosuppression to prevent rejection. Our goal was to develop a site-specific immunosuppressive strategy that promotes VCA allograft survival and minimizes the risk of systemic side effects., Methods: Tacrolimus loaded polycaprolactone (TAC-PCL) disks were prepared and tested for their efficacy in sustaining VCA allograft survival via site-specific immunosuppression. Brown Norway-to-Lewis rat hind limb transplantations were performed; animals received one TAC disk either in the transplanted (DTx) or in the contralateral non-transplanted (DnonTx) limbs. In another group, animals received DTx and lymphadenectomy on Tx side. Blood and allograft levels of TAC were measured using LC-MS/MS. Systemic toxicity was evaluated., Results: Animals that received DTx achieved long-term allograft survival (> 200 days) without signs of metabolic and infectious complications. In these animals, TAC blood levels were low but stable between 2 to 5 ng/mL for nearly 100 days. High concentrations of TAC were achieved in the allografts and the draining lymph nodes (DLN). Animals that underwent lymphadenectomy rejected their allograft by 175 days. Animals that received DnonTx rejected their allografts by day 70., Conclusion: Controlled delivery of TAC directly within the allograft (with a single TAC disk) effectively inhibits rejection and prolongs VCA allograft survival, while mitigating the complications of systemic immunosuppression. There was a survival benefit of delivering TAC within the allograft as compared to a remote site. We believe this approach of local drug delivery has significant implications for drug administration in transplantation., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The urgent need to restructure healthcare delivery to address rising costs has been recognised. Value-based health care aims to deliver high and rising value for the patient by addressing unmet needs and controlling costs. Sarcoma is a rare disease and its care is therefore usually not organised as an institutional discipline. It comprises a set of various diagnostic entities and is highly transdisciplinary. A bottom-up approach to establishing sarcoma integrated practice units (IPUs) faces many challenges, but ultimately allows the scaling up of quality and outcomes of patient care, specific knowledge, experience and education. The key for value-based health care - besides defining the shared value of quality - is an integrated information technology platform that allows transparency by sharing values, brings all stakeholders together in real-time, and offers the opportunity to assess quality of care and outcomes, thereby ultimately saving costs. Sarcoma as a rare disease may serve as a model of how to establish IPUs through a supraregional network by increased connectivity, to advance patient care, to improve science and education, and to control costs in the future, thereby restructuring healthcare delivery. This article describes how the value-based health care delivery principles are being adopted and fine-tuned to the care of sarcoma patients, and already partially integrated in seven major referral hospitals in Switzerland.

Introduction: A need exists to improve the efficiency of clinical trials in burn care. The objective of this study was to validate "Persistent Organ Dysfunction" plus death as endpoint in burn patients and to demonstrate its statistical efficiency., Methods: This secondary outcome analysis of a dataset from a prospective international multicenter RCT (RE-ENERGIZE) included patients with burned total body surface area >20% and a 6-month follow-up. Persistent organ dysfunction was defined as persistence of organ dysfunction with life-supportiing technologies and ICU care., Results: In the 539 included patients, the prevalence of 0p p+ pdeath was 40% at day 14 and of 27% at day 28. At both timepoints, survivors with POD (vs. survivors without POD) had a higher mortality rate, longer ICU- and hospital-stays, and a reduced quality of life. POD + death as an endpoint could result in reduced sample size requirements for clinical trials. Detecting a 25% relative risk reduction in 28-day mortality would require a sample size of 4492 patients, whereas 1236 patients would be required were 28-day POD + death used., Conclusions: POD + death represents a promising composite outcome measure that may reduce the sample size requirements of clinical trials in severe burns patients. Further validation in larger clinical trials is warranted., Study Type: Prospective cohort study, level of evidence: II., (Copyright © 2020 Elsevier Ltd and ISBI. All rights reserved.)

Introduction: The burn comb model is a well-established model for studying secondary burn progression. It creates four rectangular burn surfaces intercalated by three unburned zones prone to secondary burn progression. While burn progression is a tri-dimensional phenomenon, of which the vertical extension from the superficial to deeper tissue layer is clinically most relevant, the models initial focus was mainly on the horizontal surface extension within interspaces. The aim of this study is to evaluate the correlation between horizontal surface and vertical depth burn progression., Methods: 24 large (400-450 g) Wistar male rats underwent standardized burn injuries using a burn comb. Laser Doppler flowmetry to assess perfusion, planimetric evaluation of burn progression within interspaces and histological analyses assessing burn depth were performed before burn induction (baseline; BL) and after 1 h, as well as after 1, 4, and 7 days. Histological burn depth was graded from superficial (1) to the subcutaneous layer (5). Furthermore, final scarring time and contracture rate were also assessed., Results: The burn comb resulted in consistent and uniform superficial burns (mean ± SEM burn depth score: 2 ± 0; hour 1) separated by intact but critically perfused interspaces (63 ± 1% of BL; p < 0.05 vs. BL). Tissue damage significantly progressed to the deep dermis within the first day (burn depth score 4.3 ± 0.2; p < 0.05 vs. hour 1), while significant interspace necrosis at the surface did not develop within this time period (4 ± 3% of interspace necrosis; p n.s vs. hour 1). However, interspace necrosis was observed at day 4 (83 ± 3%; p < 0.05 vs. hour 1) and further progressed until day 7 (94 ± 2%; p < 0.05 vs. hour 1)., Conclusion: This study shows the limits of the burn comb model originally described with a discrepancy between horizontal surface and vertical depth progression of the burn injury. We herein propose a necessary refinement of this model to adequately evaluate vertical depth progression using a histological score. This revisited approach focusing on assessment of depth progression of the burn will allow a better evaluation of experimental burn treatments in future., (Copyright © 2019 Elsevier Ltd and ISBI. All rights reserved.)

Reconstruction of the burned hand requires detailed knowledge and surgical skills to develop a therapeutic concept for optimal functional outcomes through predictive planning. The key to success is to use a broad spectrum of plastic surgery and hand surgery techniques, individually applied to the patient's situation.In this overview article, we describe basic principles, timing of reconstruction, classification of deformities, and the corresponding techniques for surgical correction., Competing Interests: M. Calcagni– Beratungsverträge mit Medartis, Arthrex, Silk Biomaterials– bezahlter Redner SOBI– Scientific Advisory Board für DyCareJ. Plock– Beratervertrag mit Mediwound, KCI/Acelity, Polymedics– Vortragshonorare mit Careum ZH, Integra, (© Georg Thieme Verlag KG Stuttgart · New York.)

Complex Hernia Repair Abstract. Treatment of complex hernia is underestimated and remains a challenge. Often tailored surgical techniques are required. The anatomy of the abdominal wall is reconstructed and reinforced by the placement of a mesh. In this article current surgical techniques of abdominal wall reconstruction are discussed.