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Purpose: Hyperthermic isolated limb perfusion (HILP) with TNF-αα and melphalan has high response rates in patients with soft tissue sarcomas (STS) or melanomas of the limbs. Its effectiveness is based on the destructive effect of TNF-αα on the blood supply of the tumours. Shedding of soluble TNF-receptor (sTNF-R) negatively modulates the effects of TNF-αα, whereas hyperthermia (HT) induces shedding. Here, we investigated whether sTNF-R shedding in response to HT occurs during HILP. Material and methods: The serum levels of sTNFR-1 were measured in 23 patients with HILP by obtaining serum from the extracorporeal and central circuits. The samples were taken from the patients under normothermic (37°°C) and hyperthermic (39°°C) conditions. Additionally, cell cultures of HUVEC, human fibrosarcoma cells and peripheral blood cells were used to confirm the effects of HT on sTNF-R1 shedding by ELISA and western blot. Results: Under HT, levels of sTNF-R1 increased 23.5%% in the extracorporeal circuit, but this increase was not observed in the systemic circuit. However, we could not confirm this effect using the cell culture model, where cellular TNF-R1 and sTNF-R1 of culture supernatants, respectively, were not significantly different between NT and HT conditions. Conclusions: HT is associated with an increase of sTNF-R1 in the extracorporeal circuit of perfused limbs. Interestingly, HT does not exhibit the same effect on cells cultured in  vitro. Additional studies will be aimed at determining whether our findings have an impact in the clinic by analysing the relationship between TNF-R1 shedding and tumour response to HILP. [ABSTRACT FROM AUTHOR]

Custom-made, three-dimensionally-printed (3D) bone prostheses gain increasing importance in the reconstruction of bone defects after musculoskeletal tumor resections. They may allow preservation of little remaining bone stock and ensure joint or limb salvage. However, we believe that by constructing anatomy-imitating implants with highly cancellous titanium alloy (TiAl6V4) surfaces using 3D printing technology, further benefits such as functional enhancement and reduction of complications may be achieved. We present a case series of four patients reconstructed using custom-made, 3D-printed intercalary monobloc tibia prostheses treated between 2016 and 2020. The mean patient age at operation was 30 years. Tumor resections were performed for Ewing sarcoma (n = 2), high-grade undifferentiated pleomorphic bone sarcoma (n = 1) and adamantinoma (n = 1). Mean resection length was 17.5 cm and mean operation time 147 min. All patients achieved full weight-bearing and limb salvage at a mean follow-up of 21.25 months. One patient developed a non-union at the proximal bone-implant interface. Alteration of implant design prevented non-union in later patients. Mean MSTS and TESS scores were 23.5 and 88. 3D-printed, custom-made intercalary tibia prostheses achieved joint and limb salvage in this case series despite high, published complication rates for biological and endoprosthetic reconstructions of the diaphyseal and distal tibia. Ingrowth of soft tissues into the highly cancellous implant surface structure reduces dead space, enhances function, and appears promising in reducing complication rates. [ABSTRACT FROM AUTHOR]