Objectives: To evaluate the diagnostic yield and concordance of upper tract urothelial carcinoma (UTUC) grading between ureterorenoscopic biopsies and surgical resections. Methods: The nationwide Dutch Pathology Registry (PALGA) was searched for UTUC-positive renal units with histopathology excerpts from ureterorenoscopic biopsies and surgical resections, matched for laterality and localization of the tumor, from 2011 until 2018. The positive predictive value (concordance) of the biopsy grade with regard to the final grade according to the WHO 2004 classification were calculated. Results: 1002 UTUC-positive rental units were included, of which 776 UTUC-positive renal units were graded according to the WHO 2004 classification in either the ureterorenoscopic biopsy, the localization-matched surgical resection or in both. The diagnostic yield of biopsies for a classifying diagnosis was 89% with a sensitivity for UTUC of 84%. In case of UTUC, the diagnostic yield for biopsy-based grading and staging was 97% and 72%, respectively. The concordance of high-grade biopsies with regard to the final histopathology was 97% and 62% for low-grade biopsies. Upgrading to final high grade occurred in 33% of the low-grade biopsies. Downgrading to final low grade occurred in 2% of high-grade biopsies. Conclusions: This is the first study to portray the limitations of ureterorenoscopic biopsies for UTUC in a nationwide cohort. The diagnostic yield of ureterorenoscopic biopsies for a classifying diagnosis is suboptimal but the diagnostic yield for grading according to the WHO 2004 classification is high. Yet, a worrisome amount of ureterorenoscopic biopsies are upgraded with regard to the surgical resection. Consequently, one third of patients, who qualify for kidney-sparing treatment according to one of the criteria recommended for risk-stratification, might be stratified incorrectly. These findings stress the importance of a timely and stringent ureterorenoscopic follow-up after kidney sparing surgery and highlight the need for improvements in the diagnostic approach to optimize the risk-stratification.

Rotationplasty is a surgical procedure primarily performed in patients with malignancies around the knee. Altered gait mechanics after surgery, such as reduced flexion of the (pseudo)knee and ipsilateral hip and changes in ground reaction forces, may predispose patients to osteoarthritis (OA) in the lower extremities. This study evaluated the long-term prevalence of OA and its association with pain and daily functioning. Rotationplasty survivors who underwent surgery between 1980 and 2002 in Amsterdam received radiographic assessment of the (pseudo)knee, contralateral ankle, and both hips (weight-bearing mortise, lateral and AP views). OA was graded using the Kellgren-Lawrence scale. Functional outcomes, pain, quality of life, and sports participation were evaluated with the FAOS, AOFAS, and Harris Hip Score questionnaires. Statistical analyses included t-tests, Mann-Whitney U, chi-square, and Fisher's exact tests. Thirty patients (mean age 49.4 ​± ​9.2 years; mean follow-up 32.4 ​± ​4.6 years) participated. Moderate-to-severe OA was found in 43 ​% of ipsilateral (pseudo)knees, 10 ​% of contralateral ankles, 33 ​% of ipsilateral hips, and 11 ​% of contralateral hips. Osteophytes were most common in the anterior tibial and subtalar regions (20 ​%), and joint space narrowing was most frequent in the subtalar (20 ​%) and medial tibiotalar (13 ​%) regions. Functional scores were generally favorable. The presence of osteoarthritis in the pseudo-knee was significantly associated with longer follow-up time. Functional outcomes after rotationplasty are well preserved over time, despite a higher prevalence of osteoarthritis in the (pseudo)knee compared to the contralateral ankle as a long-term consequence of the procedure.

Giant cell tumor of bone (GCTB) is a rare, locally aggressive, intermediate-grade neoplasm. While typically benign, GCTB can exhibit atypical behavior, including indolent pulmonary metastases and malignant transformation. This study characterizes malignant and metastatic GCTB, distinguishing primary malignant GCTB (PM-GCTB), secondary malignant GCTB (SM-GCTB), and secondary osteosarcoma, and evaluates their outcomes. A retrospectively review of 520 patients with suspected GCTB treated between 1985–2021 was performed, with malignant cases followed through 2025. Diagnosis was confirmed histologically and, where available, by H3F3A/H3F3B mutation testing. PM-GCTB was defined as a de novo high-grade sarcoma. SM-GCTB and secondary osteosarcoma were defined as malignant transformations of previously benign, histologically proven GCTB. Benign pulmonary metastases were analyzed separately. Outcomes were descriptively assessed. Twelve patients (2.4 %) had malignant GCTB: five PM-GCTB (1.0 %), five SM-GCTB (1.0 %), and two secondary osteosarcoma (0.4 %). Three patients (0.6 %) developed histologically benign pulmonary metastases with indolent behavior. Three SM-GCTB patients transformed within one year despite benign baseline pathology, indicating true rapid malignant progression rather than diagnostic error. Median latency to malignant transformation was 7.5 years for SM-GCTB and up to 35 years for secondary osteosarcoma. SM-GCTB showed the highest disease-specific mortality (80 %), compared to PM-GCTB (20 %) and secondary osteosarcoma (0 %). None malignant transformations occurred following denosumab or radiotherapy. Three aggressive GCTB variants were identified: benign pulmonary metastatic GCTB, PM-GCTB, and secondary malignant transformation. SM-GCTB and osteosarcoma arise from benign GCTB but differ in morphology and prognosis. Because malignant transformation is exceptionally rare and symptomatic, a patient-centered, symptom-driven follow-up strategy is preferred over routine lifelong radiologic surveillance.

Giant Cell Tumours of Bone (GCTB) are locally aggressive, benign bone tumours. Denosumab was initially introduced as a neoadjuvant therapy to facilitate curettage but is now also used prior to en-bloc resection, as definitive treatment for unresectable disease, and as long-term treatment for recurrent or metastatic disease. Evidence regarding indication-specific outcomes remains limited. This study evaluated contemporary Denosumab use according to treatment intent, focusing on treatment duration, recurrence patterns, and long-term administration. A retrospective review was conducted of all GCTB patients treated with Denosumab at the Royal Orthopaedic Hospital, Birmingham, between 2010 and 2023. Patients were categorized according to treatment intent: 1) Short-course Neoadjuvant Denosumab (SCND), 2) Long-course Neoadjuvant Denosumab (LCND), 3) Definitive Denosumab for unresectable disease, and 4) Long-term Denosumab following local or distant recurrence. The study included 155 patients. Twenty-eight patients (18%) received SCND for median 15 weeks (IQR 11-20), local recurrence occurring in 13 patients (46%). Fifty-two patients (34%) received LCND for median 22 weeks (IQR 13-54), local recurrence occurring in 6 patients (12%). Forty-two patients (27%) received definitive Denosumab for median 123 weeks (IQR 83-182), while 33 patients (21%) received long-term Denosumab following recurrence for median 123 weeks (IQR 29-247). Dose de-escalation was frequently feasible in patients with sustained disease control, whereas adverse events were primarily associated with prolonged treatment exposure. This study demonstrates that Denosumab is used across several distinct clinical indications in GCTB. High recurrence rates were observed following short-course neoadjuvant treatment prior to curettage, whereas prolonged disease control was frequently achieved in selected patients receiving definitive or long-term Denosumab. A preliminary clinical framework for indication-specific Denosumab use is proposed and warrants prospective validation.

Denosumab, a RANKL inhibitor, has transformed the management of giant cell tumor of bone (GCTB). This study evaluates evolving patterns of Denosumab therapy, associated outcomes, and adverse events in a large cohort. A retrospective review was conducted on all GCTB patients who were treated at the Royal Orthopaedic Hospital, Birmingham, UK, between 2000 and 2023. Patients who received Denosumab as part of their management were included. Data was stratified by tumour location (axial skeleton vs. extremities) and treatment period (before or after 2018). Among 155 eligible patients (median age 34 years, IQR 25-47; 52% female), Denosumab treatment patterns changed markedly over time. Prior to 2018, short-course neoadjuvant Denosumab before intralesional curettage was common but was associated with high local recurrence rates (37% in extremities, 10% in axial skeleton). After 2018, Denosumab was used more selectively for long-term disease control, especially in complex or inoperable cases. Adverse events occurred in 18% of patients, and were categorized as serious (14/155, 9%), moderate (7/155, 5%), or mild (7/155, 5%). Respectively they occurred after median 45 weeks (IQR 8-100), 45 weeks (IQR 22-94) and 130 weeks (IQR 89-220). The adverse events occurred more frequently on a monthly Denosumab regime(16%, 25/155) when compared to 2-monthly(3%, 2/59) and 3-monthly (3%, 1/31). These findings reveal a change in Denosumab use for GCTB, moving away from short-course neoadjuvant therapy due to high recurrence risk, and towards long-term treatment in select patients. A standardized Denosumab dosing regimen is recommended to achieve consistent international treatment outcomes, safely reduce dosage, and potentially lower the risk of adverse events. Our results support a tailored, multidisciplinary approach with careful monitoring for adverse events and ongoing research studies to refine treatment protocols.

Although rotationplasty patients typically regain good mobility, the altered anatomy, reduced muscle volume, and impaired proprioception may compromise gait stability. This study evaluated long-term gait stability in rotationplasty patients compared with a control group without lower limb pathology. In this cross-sectional study, 3D-gait analysis using a 12-camera Vicon system was performed at self-selected walking speed. Gait stability was quantified using temporal-spatial variability and the margin of stability (MoS) in mediolateral (ML) and anterior-posterior (AP) directions. Parameters were compared between the rotationplasty and contralateral limbs with a control group of eleven participants. Perceived balance and walking ability were assessed with the Prosthesis Evaluation Questionnaire. Associations between stability metrics and perceived outcomes were explored using Spearman correlations. Twenty-nine survivors (mean follow-up 32.3 years) were included. Compared with the control group, patients demonstrated greater step width (mean difference(MD) = 31.1 mm; p = 0.007) and step-width variability (MD = 7.8 mm; p < 0.001) and shorter stance time on the rotationplasty limb but longer on the contralateral limb (both p < 0.001). AP MoS were lower (MD = -68.6 and - 65.9 mm; both p < 0.001), whereas ML MoS were higher in people with rotationplasty (MD = 29.0 and 9.2 mm; both p = 0.049) compared with the control group. No significant correlations were found between gait stability measures and balance or ambulation questionnaire scores. Three decades after surgery, rotationplasty survivors exhibit reduced gait stability characterized by higher step width variability, and reduced AP MoS versus the control group. Higher ML MoS likely reflects a compensatory balance strategy.