Increased risk of pelvic fracture after radiotherapy in rectal cancer survivors: A propensity matched study.

To determine whether radiotherapy (RT) can increase pelvic fracture risk in rectal cancer survivors. Rectal cancer patients who underwent curative surgery between 1996 and 2011 in Taiwan were retrospectively studied using the National Health Insurance Research Database (NHIRD) of Taiwan. ICD-9 Codes 808, 805.4-805.7, 806.4-806.7, and 820 (including pelvic, sacrum, lumbar, and femoral neck fracture) were defined as pelvic fracture. Propensity scores for RT, age, and sex were used to perform one-to-one matches between the RT and non-RT group. Risks of pelvic and arm fractures were compared by multivariable Cox regression. Of the 32 689 patients, 7807 (23.9%) received RT, and 1616 suffered from a pelvic fracture (incidence rate: 1.17/100 person-years). The median time to pelvic fracture was 2.47 years. After matching, 6952 patients each in the RT and non-RT groups were analyzed. RT was associated with an increased risk of pelvic fractures in the multivariable Cox model (hazard ratio (HR): 1.246, 95% confidence interval (CI): 1.037-1.495, P = 0.019) but not with arm fractures (HR: 1.013, 95% CI: 0.814-1.259, P = 0.911). Subgroup analyses revealed that RT was associated with a higher pelvic fracture rate in women (HR: 1.431, 95% CI: 1.117-1.834) but not in men, and the interaction between sex and RT was significant (P = 0.03). The HR of pelvic fracture increased 2-4 years after RT (HR: 1.707, 95% CI: 1.150-2.534, P = 0.008). An increased risk of pelvic fracture is noted in rectal cancer survivors, especially women, who receive RT.

Outcome of conservative and surgical treatment of enchondromas and atypical cartilaginous tumors of the long bones: retrospective analysis of 228 patients.

BACKGROUND: Sufficient data on outcome of patients with clinically and radiologically aggressive enchondromas and atypical cartilaginous tumors (ACT) is lacking. We therefore analyzed both conservatively and surgically treated patients with lesions, which were not distinguishable between benign enchondroma and low-grade malignant ACT based upon clinical and radiologic appearance. METHODS: The series included 228 consecutive cases with a follow-up > 24 months to assess radiological, histological, and clinical outcome including recurrences and complications. Pain, satisfaction, functional limitations, and the musculoskeletal tumor society (MSTS) score were evaluated to judge both function and emotional acceptance at final follow-up. RESULTS: Follow-up took place at a mean of 82 (median 75) months. The 228 patients all had comparable clinical and radiological findings. Of these, 153 patients were treated conservatively, while the other 75 patients underwent intralesional curettage. Besides clinical and radiological aggressiveness, most lesions were histologically judged as benign enchondromas. 9 cases were determined to be ACT, while the remaining 7 cases had indeterminate histology. After surgery, three patients developed a recurrence, and a further seven had complications of which six were related to osteosynthesis. Both groups had excellent and almost equal MSTS scores of 96 and 97%, respectively, but significantly less functional limitations were found in the non-surgery group. Further sub-analyses were performed to reduce selection bias. Sub-analysis of histologically diagnosed enchondromas in the surgery group found more pain, less function, and worse MSTS score compared to the non-surgery group. Sub-analysis of smaller lesions (< 4.4 cm) did not show significant differences. In contrast, larger lesions displayed significantly worse results after surgery compared to conservative treatment (enchondromas > 4.4 cm: MSTS score: 94.0% versus 97.3%, p = 0.007; pain 2.3 versus 0.8, p = 0.001). The majority of lesions treated surgically was filled with polymethylmethacrylate bone-cement, while the remainder was filled with cancellous-bone, without significant difference in clinical outcome. CONCLUSION: Feasibility of intralesional curettage strategies for symptomatic benign to low-grade malignant chondrogenic tumors was supported. Surgery, however, did not prove superior compared to conservative clinical and radiological observation. Due to the low risk of transformation into higher-grade tumors and better functional results, more lesions might just be observed if continuous follow-up is assured.

Outcomes after extensive manual curettage and limited burring for atypical cartilaginous tumour of long bone.

AIMS: Adjuvant treatment after intralesional curettage for atypical cartilaginous tumours (ACTs) of long bones is widely accepted for extending surgical margins. However, evaluating the isolated effect of adjuvant treatment is difficult, and it is unclear whether not using such adjuvants provides poor oncological outcomes. Hence, we analyzed whether intralesional curettage without cryosurgery or chemical adjuvants provides poor oncological outcomes in patients with an ACT. PATIENTS AND METHODS: A total of 24 patients (nine men, 15 women) (mean age 45 years; 18 to 62) were treated for ACTs of long bones and followed up for a median of 66 months (interquartile range 50 to 84). All patients were treated with extensive manual curettage and limited burring. Bone cement and grafts were used to fill bone defects in 16 and eight patients, respectively. No chemical adjuvants or cryosurgery were used. RESULTS: No local recurrence was detectable on plain radiographs and MRI or CT images. At the last follow-up, there were no distant metastases or disease-specific deaths. No procedure-related complications or postoperative fractures developed. CONCLUSION: Intralesional curettage without cryosurgery or chemical adjuvants may provide excellent oncological outcomes for patients with ACTs of long bones, without the risk of complications related to adjuvant use. Our investigation suggests thorough curettage alone is a reasonable treatment option for ACT. However, we acknowledge the limited size of our investigation warrants a multicentre collaborative study to confirm our findings. Cite this article: Bone Joint J 2018;100-B:256-61.

Does a less intensive surveillance protocol affect the survival of patients after treatment of a sarcoma of the limb? updated results of the randomized TOSS study.

AIMS: A single-centre prospective randomized trial was conducted to investigate whether a less intensive follow-up protocol would not be inferior to a conventional follow-up protocol, in terms of overall survival, in patients who have undergone surgery for sarcoma of the limb. Initial short-term results were published in 2014. PATIENTS AND METHODS: The primary objective was to show non-inferiority of a chest radiograph (CXR) group compared with a CT scan group, and of a less frequent (six-monthly) group than a more frequent (three-monthly) group, in two-by-two comparison. The primary outcome was overall survival and the secondary outcome was a recurrence-free survival. Five-year survival was compared between the CXR and CT scan groups and between the three-monthly and six-monthly groups. Of 500 patients who were enrolled, 476 were available for follow-up. Survival analyses were performed on a per-protocol basis (n = 412). RESULTS: The updated results recorded 12 (2.4%) local recurrences, 182 (36.8%) metastases, and 56 (11.3%) combined (local + metastases) recurrence at a median follow-up of 81 months (60 to 118). Of 68 local recurrences, 60 (88%) were identified by the patients themselves. The six-monthly regime (overall survival (OS) 54%, recurrence-free survival (RFS) 46%) did not lead to a worse survival and was not inferior to the three-monthly regime (OS 55%, RFS 47%) in terms of detecting recurrence. Although CT scans (OS 53%, RFS 54%) detected pulmonary metastasis earlier, it did not lead to a better survival compared with CXR (OS 56%, RFS 59%). CONCLUSION: The overall survival of patients who are treated for a sarcoma of the limb is not inferior to those followed up with a less intensive regimen than a more intensive protocol, in terms of frequency of visits and mode of imaging. CXR at six-monthly intervals and patient education about examination of the site of the surgery will detect most recurrences without deleterious effects on the eventual outcome. Cite this article: Bone Joint J 2018;100-B:262-8.

Low-grade chondrosarcoma of long bones treated with intralesional curettage followed by application of phenol, ethanol, and bone-grafting.

BACKGROUND: A common treatment of low-grade cartilaginous lesions of bone is intralesional curettage with local adjuvant therapy. Because of the wide variety of different diagnoses and treatments, there is still a lack of knowledge about the effectiveness of the use of phenol as local adjuvant therapy in patients with grade-I central chondrosarcoma of a long bone. METHODS: A retrospective study was done to assess the clinical and oncological outcomes after intralesional curettage, application of phenol and ethanol, and bone-grafting in eighty-five patients treated between 1994 and 2005. Inclusion criteria were histologically proven grade-I central chondrosarcoma and location of the lesion in a long bone. The average age at surgery was 47.5 years (range, 15.6 to 72.3 years). The average duration of follow-up was 6.8 years (range, 0.2 to 14.1 years). Patients were evaluated periodically with conventional radiographs and gadolinium-enhanced magnetic resonance imaging (Gd-MRI) scans. When a lesion was suspected on the basis of the MRI, the patient underwent repeat intervention. Depending on the size of the recurrent lesion, biopsy followed by radiofrequency ablation (for lesions of <10 mm) or repeat curettage (for those of ≥10 mm) was performed. RESULTS: Of the eighty-five patients, eleven underwent repeat surgery because a lesion was suspected on the basis of the Gd-MRI studies during follow-up. Of these eleven, five had a histologically proven local recurrence (a recurrence rate of 5.9% [95% confidence interval, 0.9% to 10.9%]), and all were grade-I chondrosarcomas. General complications consisted of one superficial infection, and two femoral fractures within six weeks after surgery. CONCLUSIONS: This retrospective case series without controls has limitations, but the use of phenol as an adjuvant after intralesional curettage of low-grade chondrosarcoma of a long bone was safe and effective, with a recurrence rate of <6% at a mean of 6.8 years after treatment.

Survival from high-grade localised extremity osteosarcoma: combined results and prognostic factors from three European Osteosarcoma Intergroup randomised controlled trials.

BACKGROUND: Neoadjuvant chemotherapy improves outcome in osteosarcoma. Determination of optimum regimens for survival, toxicity and prognostic factors requires randomised controlled trials to be conducted. PATIENTS AND METHODS: Between 1983 and 2002, the European Osteosarcoma Intergroup recruited 1067 patients with localised extremity osteosarcoma to three randomised controlled trials. Standard treatment in each was doxorubicin 75 mg/m(2) and cisplatin 100 mg/m(2). Comparators were addition of methotrexate (BO02/80831), a multidrug regimen (BO03/80861) and a dose-intense schedule (BO06/80931). Standard survival analysis methods were used to identify prognostic factors, temporal and other influences on outcome. RESULTS: Five- and 10-year survival were 56% (95% confidence interval 53% to 59%) and 52%, respectively (49% to 55%), with no difference between trials or treatment arms. Median follow-up was 9.4 years. Age range was 3-40 years (median 15). Limb salvage was achieved in 69%. Five hundred and thirty-three patients received the standard arm, 79% completing treatment. Good histological response to preoperative chemotherapy, distal tumour location (all sites other than proximal humerus/femur) and female gender were associated with improved survival. CONCLUSIONS: Localised osteosarcoma will be cured in 50% of patients with cisplatin and doxorubicin. Large randomised trials can be conducted in this rare cancer. Failure to improve survival over 20 years argues for concerted collaborative international efforts to identify and rapidly test new treatments.

Multicystic bone disease (Gorham-Stout syndrome) in a spider monkey (Ateles geoffroyi ).

BACKGROUND: In April 2000, a 2.5-year-old pet female Geoffroyi's spider monkey presented for reduced activity, a subdued demeanor, and boney enlargement involving both radii. METHODS: On further examination, polyostotic bone cysts were identified involving many of the tubular bones and were identified radiographically. Microscopic examination of a bone biopsy revealed hemorrhage and other characteristics typical of an aneurysmal bone cyst. In addition, excessive osteoclasia was noted, in association with fibrotic areas rather than with Howship's lacunae as expected from a growing animal. RESULTS: These findings were consistent with Gorham-Stout syndrome, a rare condition reported previously in ∼175 human cases and in a dog at necropsy. The diet history and further testing suggested a negative calcium balance. Treatment included the administration of bis-phosphonates, which appeared to bring about marked improvement. Almost 8 years later (November 2008), radiographs were again taken and suggested some resolution of bone cysts, primarily those in the legs. CONCLUSIONS: This represents the first reported case and a potential therapy for this rare condition in a non-human primate.

Camptomelia in a rhesus macaque (Macaca mulatta).

An 8.5-mo-old female rhesus macaque was examined for an apparent lump on the right arm, below the elbow. The macaque showed no signs of pain or discomfort. Examination revealed that the lump was actually a bend in the forearm. Radiography demonstrated that some of the long bones of the animal were bowed. Differential diagnoses included rickets, hyperparathyroidism, pseudohyperparathyroidism, and a growth dysplasia. No other similar abnormalities in animals from that cage or any other enclosure in our large colony were observed. Blood chemistries and a complete hemogram were within normal limits for a macaque of this age. Serum was submitted for a vitamin D profile that included assays for parathyroid hormone, 25-hydroxyvitamin D, and ionized calcium. Serum samples from sex- and age-matched normal controls were sent for comparison and to establish a baseline profile. The affected animal had vitamin D levels comparable to unaffected controls. Bone biopsies appeared normal for a macaque of this age. Fluorine levels in the drinking water supply were within acceptable limits. Consistent with the information available, a diagnosis of idiopathic camptomelia, or bowing of the long bones, was made. In humans, developmental camptomelia is associated with several bone dysplasias in infants and children. These conditions are thought to be caused by genetic mutations in enzymes or transcription factors that control development of the epiphyses and are almost always associated with other lethal and nonlethal developmental abnormalities.

Long bone defect models for tissue engineering applications: criteria for choice.

The replacement and repair of bone lost due to trauma, cancer, or congenital defects is a major clinical challenge. Skeletal tissue engineering is a potentially powerful strategy in modern regenerative medicine, and research in this field has increased greatly in recent years. Tissue engineering strategies seek to translate research findings in the fields of materials science, stem cell biology, and biomineralization into clinical applications, demanding the use of appropriate in vivo models to investigate bone regeneration of the long bone. However, identification of the optimal in vivo segmental bone defect model from the literature is difficult due to the use of different animal species (large and small mammals), different bones (weight-bearing and nonweight bearing), and multiple protocols, including the use of various scaffolds, cells, and bioactives. The aim of this review is to summarize the available animal models for evaluating long bone regeneration in vivo. We highlight the differences not only in species and sites but also in defect size, means of defect creation, duration of study, and fixation method. A critical evaluation of the most clinically relevant models is addressed to guide the researcher in his/her choice of the most appropriate model to use in future hypothesis-driven investigations.

Recurring gnathodiaphyseal dysplasia in two Russian brothers.

Two Russian brothers presented with recurring benign facial bone tumors and progressive limb bowing. The association of fibro-osseous jawbone lesions and long-bone bowing with cortical thickening suggested the diagnosis of gnathodiaphyseal dysplasia, in the absence of arguments in favor of fibrous dysplasia. Gnathodiaphyseal dysplasia is a rare autonomic dominant syndrome due to a mutation of the TMEM16E gene. The extreme and recurring phenotype of these two patients illustrates the variable expressivity of this disease. Differential diagnosis with other benign facial bone tumors is discussed.

Evolving concepts in the management of the bone gap in the upper limb. Long and small defects.

Vascularised bone graft is a well accepted technique when dealing with long defects. Its role in refractory nonunion, in small defects and in the growing patient is rarely discussed. In this paper the authors review the different alternatives to deal with bone defects in the upper extremity. The indications of vascularised corticoperiosteal graft for solving small defects harbouring refractory nonunion, and the use of vascularised bone phalanx and metatarsal for complex - but small - defects in the fingers is presented. The ability of the bone to grow and remodel when a living epiphysis is included, and to maintain the cartilage viability when a composite osteochondral graft is transferred are also discussed.

Imaging of pseudoneoplastic masses associated with allografts.

OBJECTIVE: The objective of this study is to describe the imaging features of non-neoplastic masses suspected of being tumor recurrences adjacent to allografts. The allografts were utilized for the treatment of various musculoskeletal tumors. MATERIALS AND METHODS: We reviewed the medical records and imaging studies of 56 patients who were suspected of having recurrent tumors following surgical resection and allograft replacement treatment for a variety of musculoskeletal neoplasms. The imaging modalities included radiographs, CT, and MRI. RESULTS: There were 47 cases of recurrent tumors. All tumor recurrences were in the soft tissues of the surgical bed (41 patients), or in the native bone adjacent to the host/allograft junction (6 patients). None of the recurrences originated in the allografts. Nine patients suspected of having recurrences were discovered to have non-neoplastic masses. Five of these were very closely related to the allograft, wrapping around parts of the allograft, and the other 4 were in the surgical bed, 2 of which were abscesses and two were seromas. CONCLUSION: Most masses arising in the vicinity of allografts implanted following resection of musculoskeletal tumors represent recurrent neoplasms. A minority are reactive processes or abscesses or fluid collections. These "pseudoneoplasms," specifically those closely related to the allografts, have specific imaging characteristics that help distinguish them from recurrent tumors.