Active surveillance of atypical cartilaginous tumours of bone: short term quality of life measurements.

BACKGROUND: In the recent years active surveillance has been introduced for atypical cartilaginous tumours (ACT). This is the first study on the impact of this new treatment approach on patients' quality-of-life. We evaluated general health-related quality of life (HRQL) in patients diagnosed with enchondroma or ACT. METHODS: In this prospective study, patients recently diagnosed with enchondroma and ACT of the long bones were asked to participate. Health-related quality of life (HRQL) was assessed at diagnosis and at six month follow-up, using the 36-item Short Form Health Survey (SF-36) and Numeric Pain Rating Scale (NRS). HRQL of the active surveillance group was compared to the Dutch population and a Dutch sample with locoregional cancer. RESULTS: In total, 45 patients were included in the study, of which four patients underwent curettage and cryosurgery, 41 patients were under active surveillance. The HRQL of the active surveillance group seemed lower compared to the Dutch population, but similar to patients suffering locoregional cancers. No comparison between the surgery and the active surveillance group could be made. In the active surveillance group no statistical difference was found between baseline and six months follow-up regarding HRQL and pain during rest and activities. CONCLUSION: Patients diagnosed with non-malignant chondroid tumours have lower HRQL compared to the healthy population. Active surveillance had no adverse effect on patients well-being, after six months active surveillance the HRQL remained unchanged. Interestingly, in our study no impact on mental health was seen, implicating that diagnosed but untreated chondroid tumours do not seem to influence patients anxiety.

Midterm MRI Follow-Up of Untreated Enchondroma and Atypical Cartilaginous Tumors in the Long Bones.

Management of atypical cartilaginous tumors (ACTs) in the long bones is shifting towards active surveillance to avoid unnecessary surgeries. The frequency and duration of active surveillance for these tumors is unclear as there is little knowledge of its biological behavior. In this retrospective study, we examined the natural course of enchondroma and ACTs through active surveillance. A total of 128 central cartilaginous tumors, located in the long bones, with a minimum interval of 24 months between baseline and last MRI were included. MRI characteristics (e.g., size, scalloping, fat entrapment) were scored and tumors were classified according to the changes between MRIs. Mean follow-up of this study was 50 months, range = 25-138 months. The majority of the cartilaginous tumors (87%) remained stable (n = 65) or showed regression (n = 46) on MRI. A total of 87% of the cases that developed tumor regression presented with entrapped fat at diagnosis. Only 13% (n= 17) showed some progression on MRI, although none of the tumors developed characteristics of high-grade chondrosarcoma. Based on our results, active surveillance is considered safe for enchondroma and ACTs of the long bones. We propose active surveillance for all asymptomatic enchondroma or ACTs in the long bones irrespective of tumor size, and follow-up schemes should be tailored on natural course.

Curettage and cryosurgery for enchondroma and atypical cartilaginous tumors of the long bones: Oncological results of a large series.

BACKGROUND AND OBJECTIVES: Intralesional surgical treatment is the preferred therapy for atypical cartilaginous tumors (ACTs) of the long bones in many institutions. However, the literature is still controversial regarding intralesional treatment versus wide resection. Due to the relative rarity of these tumors, studies reporting on the results of intralesional treatment are often small sample studies. METHODS: We retrospectively analyzed the oncological results of 55 enchondromas, 119 ACTs, and 5 chondrosarcomas grade 2 (CS2) treated with curettage and cryosurgery between the years 2004 and 2017 at our institution. The median follow-up period was 53 months (range, 24-169 months). RESULTS: In total, seven cases (three ACT, four CS2) recurred. Residual tumor was detected in 20 cases. Three cases underwent secondary curettage and cryosurgery due to local recurrence. Four cases underwent wide resection and reconstruction due to local recurrence with aggressive imaging characteristics. In total, 20 postoperative complications were seen. CONCLUSION: Curettage and cryosurgery for enchondroma and ACT show very good oncological results with a low recurrence rate and acceptable complication rate. Curettage and cryosurgery is reliable as a surgical treatment for enchondroma and ACT. Further research should define the criteria for determining which specific cartilaginous tumors necessitate surgical treatment.

Analysis of Drug Metabolizing Gene Panel in Osteosarcoma Patients Identifies Association Between Variants in SULT1E1, CYP2B6 and CYP4F8 and Methotrexate Levels and Toxicities.

High-dose methotrexate is a cornerstone agent in the chemotherapeutic treatment of patients with osteosarcoma. However, patients often develop methotrexate-induced toxicities. We aim to identify determinants of methotrexate-induced toxicities in osteosarcoma patients by investigating the relation between drug plasma levels, methotrexate-induced toxicities, and germline variants in genes related to drug absorption, distribution, metabolism, and elimination. A cohort of 114 osteosarcoma patients was genotyped for 1,931 variants in 231 genes using the Drug Metabolism Enzymes and Transporters Plus array. Methotrexate plasma levels and laboratory measurements during and after high-dose methotrexate treatment concerning renal function, liver damage, and myelopoiesis to reflect toxicity outcomes were obtained. One hundred and thirteen patients and a subset of 545 variants in 176 genes passed quality control checks. Methotrexate plasma levels showed associations with creatinine, alanine aminotransferase, and hemoglobin. Genetic variant rs3736599 in the 5'-untranslated region of SULT1E1 was associated with lower 48 hour methotrexate plasma levels [coef -0.313 (95% CI -0.459 - -0.167); p = 2.60 × 10-5]. Association with methotrexate-induced decreased thrombocyte counts was found for two intronic variants in CYP2B6 {rs4803418 [coef -0.187 (95% CI -0.275 - -0.099); p = 3.04 × 10-5] and rs4803419 [coef -0.186 (95% CI -0.278 - -0.093); p = 8.80 × 10-5]}. An association with increased thrombocyte counts was identified for the intronic variant rs4808326 in CYP4F8 [coef 0.193 (95% CI 0.099 - 0.287); p = 6.02 × 10-5]. Moreover, a secondary analysis with a binary approach using CTCAE toxicity criteria resulted in a nominal significant associations (p < 0.05) for two out of three variants (rs4803418 and rs4808326). This is the first study to identify genetic variants in SULT1E1, CYP2B6, and CYP4F8 to be associated with methotrexate pharmacokinetics and toxicities. Validation of these variants in an independent cohort and further functional investigation of variants in the identified genes is needed to determine if and how they affect methotrexate plasma levels and the development of methotrexate-induced toxicities.

Can MRI differentiate between atypical cartilaginous tumors and high-grade chondrosarcoma? A systematic review.

Background and purpose - Adequate staging of chondroid tumors at diagnosis is important as it determines both treatment and outcome. This systematic review provides an overview of MRI criteria used to differentiate between atypical cartilaginous tumors (ACT) and high-grade chondrosarcoma (HGCS).Patients and methods - For this systematic review PubMed and Embase were searched, from inception of the databases to July 12, 2018. All original articles describing MRI characteristics of pathologically proven primary central chondrosarcoma and ACT were included. A quality appraisal of the included papers was performed. Data on MRI characteristics and histological grade were extracted by 2 reviewers. Meta-analysis was performed if possible. The study is registered with PROSPERO, CRD42018067959.Results - Our search identified 2,132 unique records, of which 14 studies were included. 239 ACT and 140 HGCS were identified. The quality assessment showed great variability in consensus criteria used for both pathologic and radiologic diagnosis. Due to substantial heterogeneity we refrained from pooling the results in a meta-analysis and reported non-statistical syntheses. Loss of entrapped fatty marrow, cortical breakthrough, and extraosseous soft tissue expansion appeared to be present more often in HGCS compared with ACT.Interpretation - This systematic review provides an overview of MRI characteristics used to differentiate between ACT and HGCS. Future studies are needed to develop and assess more reliable imaging methods and/or features to differentiate ACT from HGCS.

Tenosynovial Giant Cell Tumors in Children: A Similar Entity Compared With Adults.

BACKGROUND: Tenosynovial giant cell tumor (TGCT) is a rare, benign, monoarticular entity. Many case-series in adults are described, whereas TGCT is only incidentally reported in children. Therefore, its incidence rate and natural history in children are unknown. QUESTIONS/PURPOSES: (1) How many cases have been reported of this condition, and what were their characteristics? (2) What is the standardized pediatric incidence rate for TGCT? (3) Is there a clinical difference in TGCT between children and adults? (4) What is the risk of recurrence after open resection in children compared with adults? METHODS: Data were derived from three sources: (1) a systematic review on TGCT in children, seeking sources published between 1990 and 2016, included 17 heterogeneous, small case-series; (2) the nationwide TGCT incidence study: the Dutch pediatric incidence rate was extracted from this nationwide study by including patients younger than 18 years of age. This registry-based study, in which eligible patients with TGCT were clinically verified, calculated Dutch incidence rates for localized and diffuse-type TGCT in a 5-year timeframe. Standardized pediatric incidence rates were obtained by using the direct method; (3) from our nationwide bone and soft tissue tumor data registry, a clinical data set was derived. Fifty-seven children with histologically proven TGCT of large joints, diagnosed and treated between 1995 and 2015, in all four tertiary sarcoma centers in The Netherlands, were included. These clinically collected data were compared with a retrospective database of 423 adults with TGCT. Chi-square test and independent t-test were used to compare children and adults for TGCT type, sex, localization, symptoms before diagnosis, first treatment, recurrent disease, followup status, duration of symptoms, and time to followup. The Kaplan-Meier method was used to evaluate recurrence-free survival at 2.5 years. RESULTS: TGCT is seldom reported because only 76 pediatric patients (39 female), 29 localized, 38 diffuse, and nine unknown type, were identified from our systematic review. The standardized pediatric TGCT incidence rate of large joints was 2.42 and 1.09 per million person-years in localized and diffuse types, respectively. From our clinical data set, symptoms both in children and adults were swelling, pain, and limited ROM with a median time before diagnosis of 12 months (range, 1-72 months). With the numbers available, we did not observe differences in presentation between children and adults in terms of sex, symptoms before diagnosis, first treatment, recurrent disease, followup status, or median time to followup. The 2.5-year recurrence-free TGCT survival rate after open resection was not different with the numbers available between children and adults: 85% (95% confidence interval [CI], 67%-100%) versus 89% (95% CI, 83%-96%) in localized, respectively (p = 0.527) and 53% (95% CI, 35%-79%) versus 56% (95% CI, 49%-64%) in diffuse type, respectively (p = 0.691). CONCLUSIONS: Although the incidence of pediatric TGCT is low, it should be considered in the differential diagnosis in children with chronic monoarticular joint effusions. Recurrent disease after surgical treatment of this orphan disease seems comparable between children and adults. With targeted therapies being developed, future research should define the most effective treatment strategies for this heterogeneous disease. LEVEL OF EVIDENCE: Level III, therapeutic study.

Higher incidence rates than previously known in tenosynovial giant cell tumors.

Background and purpose - Tenosynovial giant cell tumors (TGCT) are rare, benign tumors, arising in synovial lining of joints, tendon sheaths, or bursae. 2 types are distinguished: localized, either digits or extremity, and diffuse lesions. Current TGCT incidence is based on 1 single US-county study in 1980, with an incidence of 9 and 2 per million person-years in localized (including digits) and diffuse TGCT, respectively. We aim to determine nationwide and worldwide incidence rates (IR) in TGCT affecting digits, localized-extremity TGCT and diffuse-type TGCT. Material and methods - Over a 5-year period, the Dutch Pathology Registry (PALGA) identified 4,503 pathology reports on TGCT. Reports affecting digits were solely used for IR calculations. Reports affecting extremities were clinically evaluated. Dutch IRs were converted to world population IRs. Results - 2,815 (68%) digits, 933 (23%) localized-extremity and 390 (9%) diffuse-type TGCT were identified. Dutch IR in digits, localized-extremity, and diffuse-type TGCT was 34, 11 and 5 per million person-years, respectively. All 3 groups showed a female predilection and highest number of new cases in age category 40-59 years. The knee joint was most often affected: localized-extremity (46%) and diffuse-type (64%) TGCT, mostly treated with open resection: localized (65%) and diffuse (49%). Reoperation rate due to local recurrence for localized-extremity was 9%, and diffuse TGCT 23%. Interpretation - This first nationwide study and detailed analyses of IRs in TGCT estimated a worldwide IR in digits, localized-extremity and diffuse TGCT of 29, 10, and 4 per million person-years, respectively. Recurrence rate in diffuse type is 2.6 times higher, compared with localized extremity. TGCT is still considered a rare disease; however, it is more common than previously understood.

Arthroplasty for tenosynovial giant cell tumors.

Background and purpose - Tenosynovial giant cell tumors (t-GCTs) can behave aggressively locally and affect joint function and quality of life. The role of arthroplasty in the treatment of t-GCT is uncertain. We report the results of arthroplasty in t-GCT patients. Patients and methods - t-GCT patients (12 knee, 5 hip) received an arthroplasty between 1985 and 2015. Indication for arthroplasty, recurrences, complications, quality of life, and functional scores were evaluated after a mean follow-up time of 5.5 (0.2-15) years. Results - 2 patients had recurrent disease. 2 other patients had implant loosening. Functional scores showed poor results in almost half of the knee patients. 4 of the hip patients scored excellent and 1 scored fair. Quality of life was reduced in 1 or more subscales for 2 hip patients and for 5 knee patients. Interpretation - In t-GCT patients with extensive disease or osteoarthritis, joint arthroplasty is an additional treatment option. However, recurrences, implant loosening, and other complications do occur, even after several years.

A First Step toward Personalized Medicine in Osteosarcoma: Pharmacogenetics as Predictive Marker of Outcome after Chemotherapy-Based Treatment.

PURPOSE: Overall survival in patients with osteosarcoma is only 60%. Poor response to chemotherapy is the dominant risk factor for poor survival. Pharmacogenetic research can offer possibilities to optimize treatment and improve outcome. We applied a pathway-based approach to evaluate the cumulative effect of genes involved in the metabolism of cisplatin and doxorubicin in relationship to clinical outcome. EXPERIMENTAL DESIGN: We included 126 patients with osteosarcoma. To comprehensively assess common genetic variation in the 54 genes selected, linkage disequilibrium (LD; r(2) = 0.8)-based tag-single nucleotide polymorphisms (SNP) strategy was used. A final set of 384 SNPs was typed using Illumina Beadarray platform. SNPs significantly associated with 5-year progression-free survival (PFS) were replicated in another 64 patients with osteosarcoma. RESULTS: We identified five variants in FasL, MSH2, ABCC5, CASP3, and CYP3A4 that were associated with 5-year PFS. Risk stratification based on the combined effects of the risk alleles showed a significant improvement of 5-year PFS. Patients that carried no or only one risk allele had a 5-year PFS of 100% compared with a 5-year PFS of 84.4% for carriers of two or three risk alleles, 66.7% PFS if a patient carried four to five alleles, and a 5-year PFS of 41.8% for patients with >5 risk alleles (P < 0.001). CONCLUSIONS: We identified several genes that showed association with PFS in patients with osteosarcoma. These pharmacogenetic risk factors might be useful to predict treatment outcome and to stratify patients immediately after diagnosis and offer the possibility to improve treatment and outcome.

Long-term follow-up results of primary and recurrent pigmented villonodular synovitis.

OBJECTIVE: Adequate documentation of the outcome of treatment of pigmented villonodular synovitis (PVNS) is sparse. Available case series show relatively short follow-up times and often combine locations or subtypes to increase patient numbers. This article describes the long-term follow-up of a single institution's large consecutive series of PVNS. METHODS: Retrospectively, 107 PVNS patients were identified between 1985 and 2011 by searching pathology and radiology records. Treatment complications, recurrences and quality of life were evaluated. Most patients (85.2%) were primarily or secondarily treated at our institution. RESULTS: Both subtypes, localized PVNS [29 (27%)] and diffuse PVNS [75 (70%)] were represented. The knee was affected in 88% of patients. Treatments received were surgery, external beam radiotherapy, radiosynovectomy, targeted therapy, immunotherapy or combinations of these. Forty-nine (46%) patients had prior treatment elsewhere. The mean follow-up from diagnosis until last contact was 7.0 years (range 0.3-27.4) for localized PVNS and 14.5 years (range 1.1-48.7) for diffuse PVNS. The 1- and 5-year recurrence-free survival rates for diffuse PVNS were 69% and 32%, respectively. Quality of life, estimated by 36-item Short Form Health Survey (SF-36) scores, were not significantly different between localized and diffuse PVNS. However, both patient groups scored lower than the general population norms on the general health component (59.2 and 56.3, respectively, P < 0.05). CONCLUSION: Recurrence rates of PVNS increase with time. Long-term follow-up shows, particularly in diffuse PVNS, it is a continually recurring problem, and over time it becomes increasingly difficult to cure. The quality of life is decreased in patients with PVNS compared with the general population.

Liquid nitrogen or phenolization for giant cell tumor of bone?: a comparative cohort study of various standard treatments at two tertiary referral centers.

BACKGROUND: The rate of recurrence of giant cell tumor of bone is decreased by use of adjuvant treatments such as phenol, liquid nitrogen, or polymethylmethacrylate (PMMA) during curettage. We assessed recurrence and complication rates and functional outcome after curettage with use of phenol and PMMA, liquid nitrogen and PMMA, and liquid nitrogen and bone grafts. METHODS: We retrospectively compared the relative effectiveness of treatment of giant cell tumors of bone at two tertiary centers with a regional function from 1990 to 2010. The 132 (of 201) patients who met the inclusion criteria had a mean age of thirty-three years (range, eleven to sixty-nine years). Treatment assignment depended purely on the center, with primary treatment consisting of curettage with use of phenol and PMMA (n = 82) at one center and with use of either liquid nitrogen and PMMA (n = 26) or liquid nitrogen and bone grafts (n = 24) at the other center. Recurrence and complication rates were determined, and functional outcome was assessed on the basis of the Musculoskeletal Tumor Society (MSTS) score. RESULTS: The mean duration of follow-up was eight years (range, two to twenty-two years). Recurrence rates were comparable among the groups (28% for phenol and PMMA, 31% for liquid nitrogen and PMMA, and 38% for liquid nitrogen and bone grafts; p = 0.52). Soft-tissue extension increased the recurrence risk (hazard ratio [HR] = 2.1, 95% confidence interval [CI] = 1.1 to 4.0, p = 0.024). The complication rate was 33% after use of liquid nitrogen and bone grafts, 27% after liquid nitrogen and PMMA, and 11% after phenol and PMMA (p = 0.019); complications included osteoarthritis, infection, postoperative fracture, nonunion, transient nerve palsy, and PMMA leakage. The complication risk was increased by the presence of a pathologic fracture (HR = 4.1, 95% CI = 1.7 to 9.5, p = 0.001) and use of liquid nitrogen (HR = 3.9, 95% CI = 1.5 to 10, p = 0.006 for liquid nitrogen and bone grafts; HR = 3.1, 95% CI = 1.1 to 8.6, p = 0.028 for liquid nitrogen and PMMA). The mean MSTS score was 26 (range, 8 to 30) and was comparable among all three groups (p = 0.52). CONCLUSIONS: Recurrence rates were comparable for treatment with phenol and PMMA, liquid nitrogen and PMMA, and liquid nitrogen and bone grafts. Complication rates were higher after use of liquid nitrogen. The functional outcome was excellent in all three cohorts.

Pigmented villonodular synovitis: current concepts about diagnosis and management.

At present, the treatment strategies in patients with localized and diffuse forms of pigmented villonodular synovitis have more or less been standardized. However, these strategies are not optimal because high recurrence rates persist and studies with a sufficient level of evidence are lacking. This systematic review article describes all known treatment options for intra-articular pigmented villonodular synovitis and their clinical results. Based on this research, we provide guidelines to support physicians in making the optimal treatment decisions. Given the rarity of the disease, randomized studies are not to be expected, but an international registry through existing networks would offer the benefit of getting a better insight into the outcome of this disease. Therefore, we propose a basic set of data to be investigated and ideally to be reported on in such a registry.

High fatigue scores before and after surgical treatment of bone and soft tissue tumors.

The first objective of the present study was to investigate fatigue severity in patients diagnosed with bone and soft tissue tumors prior to the surgical treatment of the tumor and 6 months post-operatively. The second objective was to determine which variables are associated with severe fatigue. Patients diagnosed with benign or low-grade malignant bone and soft tissue tumors, undergoing surgical therapy for the tumor only, were included in this study. The control group contained patients scheduled for knee arthroscopy for suspected meniscus tears. Fatigue, pain, anxiety and self-efficacy were measured pre-operatively and after 6 months and each patient wore an actometer to quantify physical activity. In the tumor group of 43 patients, 35% were severely fatigued pre-operatively and 33% post-operatively. The tumor group reported a significantly higher level of anxiety. No differences were observed in pain, physical limitations, self-efficacy or actometer scores. Multiple regression analysis of the tumor group revealed that higher pain scores, higher state anxiety and lower self-efficacy were asssociated with fatigue severity. In the control group of 24 knee arthroscopy patients, the percentage of severely fatigued patients decreased from 38% (n=9) prior to treatment to 29% (n=7) 6 months later. A substantial number of patients were severely fatigued in both the tumor group and the knee arthroscopy group. Self-efficacy, pain and anxiety appear to be the most important variables associated with fatigue severity in tumor patients prior to surgery.

Age as prognostic factor in patients with osteosarcoma.

Age at diagnosis is a well known prognostic factor in many different malignancies; its significance for patients with osteosarcoma is however controversial. To gain more insight in the prognostic role of age, we performed a retrospective study at our institute. We included 102 patients with de-novo osteosarcoma and formed three age groups to evaluate age specific survival rates: ≤ 14 years, 15-19 years and 20-40 years. Differences in outcome between patients aged 15-19 years treated at either the pediatric department or the adult department of oncology were evaluated. The 5-year overall survival rate (OSR) of the whole population was 53.5%±1.5%. OSR of 70.6%±0.8% was seen in patients ≤ 14 years old, 52.5%±1.1% in patients 15-19 years old and 33.3%±0.9% in the patients aged 20-40 years (p=0.01). Significant differences were observed with regard to stage at presentation (higher in older age groups), size of the tumor (larger in younger age groups) and histological response (more good responders in younger age groups). No significant difference was seen between outcomes of patients aged 15-19 years treated at the pediatric or adult oncology department. In conclusion, younger patients have a significantly better outcome than older patients.

Percutaneous radiofrequency ablation of osteoid osteomas with use of real-time needle guidance for accurate needle placement: a pilot study.

PURPOSE: To evaluate the accuracy and technical success of positioning a radiofrequency ablation (RFA) electrode in osteoid osteomas by use of a new real-time needle guidance technology combining cone-beam computed tomography (CT) and fluoroscopy. MATERIALS AND METHODS: Percutaneous RFA of osteoid osteomas was performed in five patients (median age 18 years), under general anesthesia, with the use of cone-beam CT and fluoroscopic guidance for electrode positioning. The outcome parameters were technical success, meaning correct needle placement in the nidus; accuracy defined as the deviation (in mm) from the center of the nidus; and clinical outcome at follow-up. RESULTS: In all five cases, positioning was possible within 3 mm of the determined target location (median nidus size 6.8 mm; range 5-10.2 mm). All procedures were technically successful. All patients were free of pain at clinical follow-up. No complications were observed. CONCLUSION: Real-time fluoroscopy needle guidance based on cone-beam CT is a useful tool to accurately position radiofrequency needles for minimally invasive treatment of osteoid osteomas.

Taqman genotyping assays can be used on decalcified and paraffin-embedded tissue from patients with osteosarcoma.

BACKGROUND: In cancers like osteosarcoma with a 5-year overall survival of 50-60%, archived histological specimens can be a useful source of biological material. However, this material generally has been decalcified and formalin-fixed for many years. In our study, we investigated whether DNA obtained from these tissues can be used for reliable single nucleotide polymorphism (SNP) genotyping. PROCEDURE: We studied two SNPs in the drug transporter MDR1 using Taqman® SNP genotyping assays. Genotypes of the germ line DNA derived from freshly isolated DNA of 20 surviving patients with osteosarcoma were compared with genotypes obtained from archived material from decalcified formalin-fixed, paraffin-embedded (FFPE) blocks of the same patients. RESULTS: Decalcified FFPE-derived DNA yielded smaller PCR fragments compared to DNA extracted from peripheral blood cells, with a reliable size of ∼200 bp. However, we were able to evaluate each SNP in 19 of 20 cases included in this study. All successfully genotyped samples showed 100% concordance between genotypes obtained from DNA of FFPE tissue and the genotypes obtained from DNA of blood from the same patients. CONCLUSIONS: In conclusion, we have demonstrated that decalcified FFPE tissue can be used for genetic polymorphism analysis using Taqman® allelic discrimination assays. This forms a unique opportunity to combine new insights in genetic research with historical patient cohorts.

[Diagnosis and treatment of bone metastasis]. / Diagnostiek en behandeling van botmetastasen.

The improved prognosis of cancer patients has led to an increased incidence of both bone metastases and (impending) pathological fractures. A solitary bone lesion seen on radiography should never be assumed to be a metastasis. Preoperative biopsy is necessary in patients with a known malignancy and a solitary lytic bone lesion as well as in patients in whom the primary tumor is unknown, in order to prevent an incorrect operation (also known as 'whoops surgery'). If the patient has an (impending) pathological fracture, normal bone healing is not to be expected, not even after stable fixation. Surgical fixation of an impending pathologic fracture is recommended when radiography indicates that a length of more than 3 cm of the cortex of a long bone has been destroyed. If surgical treatment is necessary, it should support the whole long bone in order to enable full weight bearing. When the diagnosis of a bone lesion is uncertain, referral to an experienced treatment centre is recommended.

Quality of life in young patients after bone tumor surgery around the knee joint and comparison with healthy controls.

BACKGROUND: This study aimed to compare the health related quality of life (HRQoL) of children and adolescents after malignant bone tumor surgery of the leg with healthy controls. PROCEDURE: Patients between 8 and 25 years old were cross-sectional recruited. Patients under 16 years of age received the TNO (Netherlands Organization for Applied Scientific Research) and AZL (Leiden University Medical Center) Children's Quality of Life Questionnaire (TACQOL), patients aged 16 years and older received the TNO-AZL Questionnaire for Adult's Quality of Life (TAAQOL) and the Short Form-36 (SF-36). Three age- and sex-matched normative random samples, drawn from large, nationwide studies, were used for the comparison with healthy controls. Patients were interviewed regarding their most important problems related to the disease and its treatment. RESULTS: Eighty-one patients with a mean age of 16.9 years (SD 4.2) were included (41 female). Limb sparing surgery was executed in 38 patients, ablative surgery in 43 patients. In comparison with healthy controls, patients had significantly poorer HRQoL within the domains autonomy and motor function of the TACQOL, gross motor function, cognitive functioning, daily functioning and sexuality of the TAAQOL, and physical functioning, role physical, general health, and the physical and mental component summary scales of the SF-36. Patients reported limitations in physical activities, participation in sports, and cosmetic aspects as the most detrimental consequences of their disease and its treatment. CONCLUSION: In children and adolescents who underwent surgery for a malignant tumor of the leg physical, functioning was significantly impaired as compared to healthy controls.

The presence of periosteum is essential for the healing of large diaphyseal segmental bone defects reconstructed with trabecular metal: a study in the femur of goats.

Large segmental diaphyseal bone defects can be reconstructed with massive structural allografts, but this technique is associated with high complication rates. Tantalum tabecular metal implants have been successfully used to restore bone defects associated with revision total knee or hip arthroplasties. The aim of this study was to investigate if tantalum cylinders could be used to reconstruct large load bearing segmental diaphyseal bone defects in the presence or absence of a periosteum coverage. Segmental bone defects were reconstructed with tantalum cylinders with or without preservation of the periosteum and stabilized by an intramedullary nail. Radiological analysis was performed postop and at 26 weeks follow-up. New bone was labeled with fluorochromes at 13 and 26 weeks follow-up. Reconstructions were tested mechanically and subsequently investigated histologically. Contra-lateral femurs were used as controls. Clinically all goats returned to normal functional loading after 2 weeks allowing unlimited weight bearing. Radiologically, all tantalum cylinders with periosteum coverage united with the host bone. Reconstructions with cylinders without periosteum coverage lead to radiological nonunion in five out of six cases. The strengths of the reconstruction with and without periosteum preservation were respectively 102.1% and 24.5% compared to controls. In the periosteum covered implants, bone contact was found at all levels of the tantalum cylinder and more and deeper bone ingrowth was found in this group. Tantalum cylinders seem a safe and reliable alternative for a massive cortical graft to reconstruct large diaphyseal bone defects in a goat model if healthy periosteum is present.