Controversies in orthopaedic oncology.

Chondrosarcoma is the second most common surgically treated primary bone sarcoma. Despite a large number of scientific papers in the literature, there is still significant controversy about diagnostics, treatment of the primary tumour, subtypes, and complications. Therefore, consensus on its day-to-day treatment decisions is needed. In January 2024, the Birmingham Orthopaedic Oncology Meeting (BOOM) attempted to gain global consensus from 300 delegates from over 50 countries. The meeting focused on these critical areas and aimed to generate consensus statements based on evidence amalgamation and expert opinion from diverse geographical regions. In parallel, periprosthetic joint infection (PJI) in oncological reconstructions poses unique challenges due to factors such as adjuvant treatments, large exposures, and the complexity of surgery. The meeting debated two-stage revisions, antibiotic prophylaxis, managing acute PJI in patients undergoing chemotherapy, and defining the best strategies for wound management and allograft reconstruction. The objectives of the meeting extended beyond resolving immediate controversies. It sought to foster global collaboration among specialists attending the meeting, and to encourage future research projects to address unsolved dilemmas. By highlighting areas of disagreement and promoting collaborative research endeavours, this initiative aims to enhance treatment standards and potentially improve outcomes for patients globally. This paper sets out some of the controversies and questions that were debated in the meeting.

Functional and oncological outcomes of patients with proximal humerus osteosarcoma managed by limb salvage.

BACKGROUND: Osteosarcoma is the most common primary bone malignancy in skeletally immature patients. The proximal humerus is the third most common site of osteosarcoma. The literature shows a paucity of published data concerning the outcome of proximal humerus osteosarcoma managed by limb salvage. The purpose of this study was to answer the following questions: (1) do patients with proximal humerus osteosarcoma managed by limb salvage and neoadjuvant chemotherapy show good functional and oncological outcomes, and (2) are there any prognostic factors that are associated with better oncological and functional outcomes? MATERIALS AND METHODS: The study was a retrospective case series study assessing the overall outcome of 34 patients with proximal humerus osteosarcoma. Eighteen patients were males (53%) while 16 were females. Biological reconstruction was done in 15 patients (44%), while nonbiological reconstruction was done in 19 patients. Resections were mainly intraarticular (82%). Functional outcome was assessed using the Musculoskeletal Tumor Society (MSTS) score, while oncological outcome was assessed based on local recurrence and development of chest metastasis. Comparisons between quantitative variables were done using the nonparametric Mann-Whitney test. To compare categorical data, the chi-square (χ2) test was performed. The exact test was used instead when the expected frequency was less than 5. Correlations between quantitative variables were examined using the Spearman correlation coefficient. RESULTS: The mean MSTS score was 25.5 (range 23-29). A younger age was statistically correlated with a poorer MSTS score (P = 0.0016). Six patients out of 34 (17.6%) had local recurrence and four of them (67%) were treated by forequarter amputation. 41% of patients developed chest metastasis, and the majority of them were treated by chemotherapy (71%). In comparison with patients with osteosarcoma at other sites who were also managed in our institution, proximal humerus osteosarcoma patients showed higher incidence rates of local recurrence and chest metastasis along with lower 5-year patient and limb survivorships compared to distal femur, proximal tibia and proximal femur osteosarcoma patients. CONCLUSION: Treatment of osteosarcoma of the proximal humerus by limb salvage and chemotherapy yields a good functional outcome. The method of reconstruction does not impact the resultant function. The 5-year survivorship of these patients is 65%. Younger patients have a better oncological outcome and an inferior functional outcome. LEVEL OF EVIDENCE: Level IV therapeutic study.

Outcomes of management of primary benign aggressive or malignant bone tumors around the elbow by limb-salvage surgery.

PURPOSE: Bone tumors around the elbow are rare, with frequently delayed diagnosis. The current study aimed to assess the functional and oncological outcomes of limb salvage surgery for primary benign aggressive or malignant bone tumors around the elbow. METHODS: We conducted a retrospective review of patients with primary aggressive benign and malignant bone tumors around the elbow treated with limb salvage surgery between 1995 and 2020 at a single musculoskeletal oncology center. The minimum follow-up period was 24 months. Functional results were assessed using the Musculoskeletal Tumor Society (MSTS) scoring system at the last follow-up visit. Local recurrence, chest metastasis, and complications were recorded. RESULTS: This study included 30 patients, 19 males and 11 females, with a mean age of 25.4 ± 14.2 years. The tumor location was the distal humerus (n = 21), proximal radius (n = 5), and proximal ulna (n = 4). Reconstruction was done by elbow fusion using fibular graft (n = 10), mobile endoprosthesis (n = 9), excision arthroplasty (n = 7), and extracorporeal freezing and reimplantation (n = 4). The mean follow-up period was 36.2 ± 21.3 months. The median follow-up MSTS score was 27 [Interquartile range (IQR): 26-30]. Skeletally immature patients had a significantly higher MSTS score. The rate of postoperative complications was 26.7%. CONCLUSION: Limb salvage surgery with different reconstructive options for benign aggressive and malignant bone tumors around the elbow can achieve good functional and oncological outcomes. LEVEL OF EVIDENCE: Level IV.

Is Dissection and Preservation of Adherent Popliteal Vessels From a Posterior Soft Tissue Mass Associated With a Higher Proportion of Local Recurrence in Patients With a Distal Femoral Osteosarcoma?

BACKGROUND: In patients who have osteosarcoma of the distal femur, there is concern that when dissecting the popliteal vessels from the posterior soft tissue extent of the tumor, a less-than-wide margin of resection may be achieved depending on the extent of the posterior soft tissue mass. Surgeons have little information to guide them when deciding whether dissecting the popliteal vessels in a patient in whom the vessels are in direct contact with a posterior mass will result in an increased likelihood of local recurrence compared with patients in whom the popliteal vessels are not in contact with the tumor mass. QUESTIONS/PURPOSES: (1) Is dissecting the adherent popliteal artery and vein away from the posterior soft tissue extent of a distal femoral osteosarcoma by stripping them from their adventitia associated with an increased risk of local recurrence compared with patients in whom there is normal tissue between the tumor and vessels? (2) Is there an association with the type of tumor resection and the development of chest metastases and overall survivorship in this anatomic location? METHODS: We retrospectively studied our patient database. From August 1, 1994, until December 31, 2019, all patients with conventional distal femoral osteosarcomas treated with chemotherapy and surgery were identified. A minimum of 2 years of follow-up was required for patients who were alive. A total of 545 patients matched these criteria. We excluded 7% (37 patients) who did not have a posterior soft tissue mass, 9% (51 patients) who has metastases, 0.7% (four patients) who had osteosarcomas in multiple sites, 1% (five patients) who died of chemotherapy complications, and 6% (30 patients) who were lost to follow-up. A total of 418 patients (211 men and 207 women) were eligible for this study. The mean age of the patients was 17 ± 6.6 years. All patients underwent routine staging (plain radiographs, MRI, chest CT, and bone scan) and received preoperative chemotherapy. The patients were divided into two groups according to the relationship between the popliteal vessels and the posterior extent of the extraosseous tumor. Axial MRI slices (T1, T1 with contrast, T2, and short tau inversion recovery) were analyzed separately by the two senior authors. Disputes were settled by a senior musculoskeletal radiologist and confirmed by the patient's operative report. In Group 1, which included 229 patients, there was a clear plane between the popliteal vessels and tumor. All patients underwent limb salvage. In Group 2, which had 189 patients, the popliteal vessels adhered to the tumor. This group was further subdivided into Groups 2a (patients in whom the vessels were dissected and limb salvage was performed; dissection of the popliteal vessels from the tumor entailed stripping the vessels from its adventitia in some areas) and 2b (patients in whom no attempt was made to dissect the vessels, and amputation or rotationplasty was performed). When rotationplasty was performed, the vessels were resected and reanastomosed. The decision to perform limb salvage in Group 1 was not debatable; however, in patients in Group 2, who had adherent vessels, the decision was made by the tumor board. Tumors with complete encasement of the vessels or nerves, nonunited pathologic fractures, and fungating of the tumor through the skin were treated by amputation or rotationplasty. Patients with tumors with adherent vessels that were not encased were offered limb salvage. This was often a shared decision with the patient. We performed a pathologic evaluation of the resected specimens to evaluate margins and tumor necrosis in all specimens. RESULTS: Local recurrence-free survivorship was worse in patients with adherent tumors who underwent dissection of the vessels by stripping them from their adventitia (Group 2a; 68% at 5 years [95% CI 57% to 78%]) than in those without adherent tumors (Group 1: 96% [95% CI 93% to 99%]) and patients with adherent tumors who had amputation or rotationplasty (Group 2b: 99% [95% CI 96 to 100]; p < 0.01). Chest metastases developed in 142 patients. The proportion of chest metastases was higher in Group 2a (59% [60 of 101]) than in Group 1 (24% [55 of 229]) and Group 2b (31% [27 of 88]; p < 0.01). Five-year overall survivorship was worse in patients with adherent tumors who underwent dissection of the vessels by stripping them from their adventitia (Group 2a: 51% at 5 years [95% CI 40% to 63%]) than in those without adherent tumors (Group 1: 78% [95% CI 72% to 84%]) and patients with adherent tumors who had amputation or rotationplasty (Group 2b: 71% [95% CI 60% to 82%]; p < 0.01). CONCLUSION: In light of these findings, when performing limb salvage for distal femoral osteosarcoma with adherent vessels, leaving an adventitial margin is associated with an increase in the incidence of local recurrence and poorer overall survivorship. Surgeons should refrain from dissecting these adherent vessels or at minimum discuss the expected outcomes with the patient. Future studies could target the outcome of vascular resection and bypass graft in the management of osteosarcoma. LEVEL OF EVIDENCE: Level III, therapeutic study.

Functional and Oncological Outcome of Patients with Distal Femoral Osteosarcoma Managed by Limb Salvage Using Modular Endoprosthesis.

BACKGROUND: The aim of the study was to assess the functional and oncological outcomes of patients with distal femoral osteosarcoma managed by limb salvage using modular endoprosthesis as well as to assess related complications. PATIENTS AND METHODS: A total of 82 patients were included in our study. Functional outcome was assessed using MSTS score and knee range of motion. Oncological outcome was assessed regarding local recurrence, chest metastasis, and patient survivorship. Complications were classified according to Henderson et al. RESULTS: The mean MSTS score was 26.21 (87.4%) (range 8-30 points) with 70.7% of patients having more than 90° of flexion. The incidence of local recurrence was 3.7% (3 patients), while the incidence of chest metastasis was 14.6% (12 patients). Aseptic loosening (type 2 failure) was the commonest complication (19.5%), followed by infection (15.9%). The 5- and 10-year survivorships of the limb were 98.8%, while the 5- and 10-year survivorships of the prosthesis were 67.7% and 52.4%, respectively. CONCLUSION: This study showed that patients with osteosarcoma distal femur who are treated by chemotherapy and limb salvage have an excellent long-term prognosis in terms of patient as well as limb survivorship. The use of modular endoprosthesis in these patients offer an acceptable function, with two-thirds of the patients retaining their prosthesis after 5 years and more than half retaining them after 10 years.

Functional and oncological outcome of patients with benign hindfoot tumors treated by curettage.

BACKGROUND: Only 3 % of osseous tumors occur in the foot. The metatarsals are the -most common site whereas the calcaneus and talus are less common sites. Because these tumors are rare, the aim of our study is to assess the functional and the oncological outcome of patients with benign hindfoot tumors managed by curettage. METHODS: The clinical and radiological data of 41 patients diagnosed with benign hindfoot tumors were retrospectively reviewed. The study included 31 males and 10 females. The average age was 23.68 (range, 5-49) years. The average follow-up period was 92.7 (range, 12-244) months. RESULTS: At the last follow-up visit, the average Musculoskeletal Tumor Society scoring system (MSTS) score was 28.12 (range, 21-30). MSTS scores were higher in patients with latent tumors (P = .028) and patients managed by simple curettage (P = .018). The recurrence rate in calcaneal tumors was higher than those in the talus. The overall complication rate was 12.2 % (5 of 41 patients). Infection and subtalar arthritis were the most common complications. CONCLUSION: Curettage of benign bone tumors of talus or calcaneus proved to be an effective method in the management of these patients. Their functional outcome is also excellent. All the complications are manageable without long term morbidity. LEVEL OF EVIDENCE: Level IV Therapeutic study.

Incidence and progression of osteoarthritis following curettage and cementation of giant cell tumor of bone around the knee: long-term follow-up.

BACKGROUND: Giant cell tumor of bone (GCTB) is a benign locally aggressive tumor frequently treated with intralesional curettage and cementation. The aim of this study was to investigate the long-term incidence of arthritic changes following curettage and cementation of GCTB around the knee. MATERIALS AND METHODS: This study was a retrospective review of patients with GCTB around the knee treated with curettage and cementation with a minimum follow-up of 10 years. The functional results were assessed using the Musculoskeletal Tumor Society (MSTS) score. The arthritic changes were classified using the Kellgren-Lawrence (KL) classification system of osteoarthritis. RESULTS: This study included 119 patients, 54 males and 65 females, with a mean age of 29.4 ± 9.2 years. There were 35 (29.4%) patients with pathological fractures. There were 84 (70.6%) patients with de novo lesions and 35 (29.4%) with recurrent lesions. The mean follow-up period was 13.2 ± 3.16 years. The mean MSTS score was 28.5 ± 1.9. Overall, 25 (21%) patients developed variable degrees of arthritis of KL grade 1 (n = 7), KL grade 2 (n = 11), KL grade 3 (n = 4), and KL grade 4 (n = 3). Ten patients showed progression of arthritis during the follow-up period. Age at presentation, gender, presence of pathological fracture, whether the tumor was de novo or recurrent, and tumor location were not associated with arthritis incidence. CONCLUSIONS: Curettage and cementation can be used safely to treat GCTB around the knee. Arthritis of the knee is a possible complication, but mild grades are expected in most cases. There was no association between arthritis incidence and age, gender, pathological fractures, tumor location, or recurrent tumors. LEVEL OF EVIDENCE: Level IV.

Functional Outcome Following Proximal Tibial Osteosarcoma Resection and Reconstruction by Modular Endoprosthesis.

PURPOSE: The proximal tibia is a common location for osteosarcoma. Modular endoprosthesis is a popular reconstructive option, yet it has been associated with many complications. Our study aimed to evaluate the functional outcome and complications of proximal tibial osteosarcoma patients treated by limb salvage using modular endoprosthesis. METHODS: A retrospective study of a prospective database was performed during the period between January 2000 and July 2017. Fifty-five patients with proximal tibial osteosarcoma underwent resection and modular endoprosthetic reconstruction. The functional outcome was evaluated using the Musculoskeletal tumor society scoring system and knee range of motion. Postoperative complications were classified according to Henderson classification; Type 1 (soft tissue failure), Type 2 (aseptic loosening), Type 3 (structural failure), Type 4 (infection) and Type 5 (local tumor progression). RESULTS: The mean follow-up period was 71.69 ± 49.76 months. The mean musculoskeletal tumor society score was 26.5 ± 2.22; the mean range of motion was 72.63 ± 25.07, and the mean extension lag was 15.09 ± 15.38. Type 1, type 2, type 3, type 4, and type 5 complications occurred in 7.3%, 14.5%, 21.8%, 23.6%, and 5.5%, respectively. Chest metastasis developed in 10 patients (18.2%). The estimated 5-year and 10-year survival rates for the treated patients were 83.6% and 79.9%. CONCLUSIONS: Proximal tibial osteosarcoma reconstruction with a modular endoprosthesis is a reliable treatment option for retaining limb function. Most complications are manageable.

Outcomes of modular endoprosthesis reconstruction versus cement spacer reconstruction following resection of proximal humeral tumors.

BACKGROUND: There is no agreement about the best reconstructive option following resection of proximal humerus tumors. The purpose of this study was to compare the functional outcomes of endoprosthesis reconstruction versus nail cement spacer reconstruction after wide resection of proximal humeral tumors. METHODS: This retrospective comparative study included 58 patients with proximal humerus tumors who had undergone tumor resection and reconstruction with modular endoprosthesis (humeral hemiarthroplasties) or cement spacer. Medical records were reviewed for the epidemiological, clinical, radiological, and operative data. Lung metastasis, local recurrence, and complication were also reviewed. The functional outcome was evaluated using the Musculoskeletal Tumor Society scoring (MSTS) system. RESULTS: Nineteen patients with a mean age of 33.4 ± 17.5 years underwent reconstruction by modular endoprosthesis, and 39 patients with a mean age of 24.6 ± 14.3 years underwent reconstruction by cement spacer. The mean MSTS score was 24.8 ± 1.1 in the endoprosthesis group and 23.9 ± 1.4 in the spacer group, P = 0.018. Complications were reported in 5 (26.3%) patients in the endoprosthesis group and 11 (28.2%) patients in the spacer group, P = 0.879. There were no statistically significant differences in the functional outcomes in both patient groups with or without axillary or deltoid resection. CONCLUSIONS: Both endoprostheses and cement spacers are durable reconstructions with almost equal functional outcomes with no added advantage of the expensive endoprosthesis.

Long-term outcome of patients with primary or secondary tumors of the proximal femur treated by bipolar modular tumor prosthesis.

PURPOSE: The proximal femur is a common area for primary and also metastatic bone tumors. The objective of this study was to assess the long-term functional and oncological outcomes of patients with malignant primary or secondary tumors of the proximal femur, who underwent proximal femoral resection then reconstruction using bipolar modular tumor prosthesis. METHODS: Sixty patients with proximal femoral malignant tumors underwent resection and bipolar modular prosthesis between 2000 and 2016, were retrospectively reviewed. Based on diagnosis and presence or absence of pathological fracture, patients were divided into groups. The functional outcome of the patients was evaluated using the Musculoskeletal Tumor Society (MSTS) functional scoring system for the lower extremities. RESULTS: The mean age was 38 (9-80) years at the time of primary surgery. Pathological fracture was the presentation in 28 patients. The study included 44 patients with primary bone tumor and 16 patients with a secondary bone tumor. The mean MSTS functional score of the patients was 24.3 (range, 18-30) points with no significant difference in patients with primary or secondary tumors. The rate of complications in the present series was 45%. The most frequent complication was an infection in 10 patients (16.7%), followed by aseptic loosening in 7 patients (11.7%). Local recurrence of primary bone tumors occurred in three out of 44 patients (6.8%). CONCLUSION: Modular bipolar tumor prosthesis has a good long-term functional result in both primary and secondary tumors of the proximal femur, with no significant effect of age, presence or absence of pathological fracture or femoral resection length on the functional outcome. It was found that the only statistically significant variable regarding the risk of infection is previous surgeries. LEVEL OF EVIDENCE: Level IV, retrospective case series.

Outcome of Surgical Resection of Primary Malignant and Aggressive Benign Metacarpal Bone Tumors.

Primary bone tumors of the hand are relatively rare. Different treatment options have been described in case reports. In this study, the authors present the diagnostic methods and treatment strategies that they used. The goal of this study is to present the oncologic and functional outcomes of surgical resection of primary malignant and aggressive benign metacarpal bone tumors. This retrospective study included 7 patients with primary malignant and aggressive benign bone tumors of the metacarpals who underwent surgical resection with or without metacarpal reconstruction between 2000 and 2017, with a minimum follow-up of 2 years. Clinical and radiologic evaluations were reviewed, and functional evaluation was performed with the Musculoskeletal Tumor Society scoring system. Seven patients (6 female; 1 male), with a mean age of 30.9±11.3 years, were included in the study. Six tumors were de novo, whereas 1 was recurrent. After resection, 5 patients had metacarpal reconstruction. Nonvascularized fibula was used for 3 patients, extracorporeal freezing of the metacarpal using liquid nitrogen was used for 1 patient, and metacarpal shift was used for 1 patient. Mean follow-up was 52.6±26.7 months. At the final follow-up, mean Musculoskeletal Tumor Society score was 27.4±1.6, and no local recurrence was documented. One patient had chest metastasis after 8 years of follow-up. The results show that surgical resection of primary malignant and aggressive benign tumors of the metacarpal bones can achieve satisfactory functional and oncologic outcomes. [Orthopedics. 2021;44(5):e633-e638.].

Risk factors and oncological outcomes of pulmonary metastasis in patients with giant cell tumor of bone.

BACKGROUND: Giant cell tumor (GCT) of bone has a rare potential for metastatic spread. This study aimed at evaluating the incidence of chest metastases in GCT and their oncological outcome and identifying possible risk factors. METHODS: Medical records of 466 (313 de novo and 153 recurrent) patients with primary GCT of bone were retrospectively reviewed. Fifteen (3.2%) patients developed chest metastasis. Time from diagnosis of the primary bone lesion to the diagnosis of metastasis, treatment modalities of metastasis, and the course of treatment were revised. The functional outcome was evaluated using the Musculoskeletal Tumor Society (MSTS) scoring system, and postoperative complications were recorded. RESULTS: This study included 7 males and 8 females with a mean age of 27.3 ± 7.9 years. The most common site of the primary tumor was the distal femur. All fifteen patients were recurrent cases. The mean follow-up period was 67.7 ± 33.2 months. Chest metastasis was diagnosed after a mean time of 28.1 ± 28.9 months from the initial diagnosis of the bone lesion. One patient died of disease (DOD) 18 months after the surgical intervention. The incidence of chest metastasis in recurrent cases was 9.8%, while de novo cases did not develop chest metastasis, P < 0.001. Previous curettage was associated with a higher incidence of chest metastasis (14.6%) compared to previous resection (4.2%), P = 0.03. CONCLUSIONS: Chest metastasis following GCT of bone is rare. Risk factors include recurrent cases, especially following previous curettage. Patients have a good prognosis and a low mortality rate. LEVEL OF EVIDENCE: Level IV, retrospective.

Functional and oncological outcomes of limb-salvage surgery for foot and ankle tumors.

BACKGROUND: Limb-salvage surgery has become the backbone treatment for musculoskeletal tumors in the last decades. However, limb-salvage with safe margins for tumors of the foot and ankle is challenging, due to the complex anatomy of this region. This study aimed to evaluate functional and oncological outcomes, complications, and local recurrence of limb-salvage procedures for tumors of the foot and ankle. METHODS: This study was a retrospective review of 18 patients with primary tumors of the foot and ankle who underwent limb-salvage surgery between 1996 and 2015, with a minimum follow-up of 2 years. Clinical presentations, radiological and histopathological investigations, surgical procedures, functional and oncological outcomes, complications and local recurrences were analyzed. The Musculoskeletal Tumor Society (MSTS) scoring system was utilized for evaluation of the functional outcome. RESULTS: With a mean follow-up period of 44.2 months, 7 males and 11 females with a mean age of 29.2 years were included. Nine patients were presented as recurrent cases. The most common location was forefoot in 7 patients. Synovial sarcoma was the histopathologic diagnosis in 7 patients. The final surgical margins were wide in 15 patients, wide-contaminated in one patient, and marginal in two patients. After resection, soft tissue reconstruction and wound coverage were done by soft tissue flaps in 4 patients. The mean MSTS score was 27.5. Four patients developed local recurrence, all of them were recurrent cases. CONCLUSION: Limb-salvage surgery for foot and ankle tumors is an effective treatment option with good functional outcome. LEVEL OF EVIDENCE: Level IV, retrospective case series.

Functional and Oncological Outcome After Treatment of Chondroblastoma With Intralesional Curettage.

BACKGROUND: Chondroblastoma is a rare cartilaginous benign bone tumor that commonly arises in long bones of young people. Surgical management is the primary treatment of choice for chondroblastoma and it entails adequate intralesional curettage alone or in combination with adjuvants. This study was performed to describe the epidemiological characteristics and clinical and radiologic results of intralesional curettage of chondroblastoma. METHODS: This was a retrospective study which included an analysis of 91 patients with chondroblastoma who were treated with intralesional curettage and were followed up between 1994 and 2014 for at least 3 years. Epidemiological data, clinical symptoms, radiologic and histologic investigations, surgery, functional outcomes, complications, and local recurrence rate were analyzed. RESULTS: There were 60 males (65.9%) and 31 females (34.1%) with a mean age of 16.4 years. The most commonly involved bone was the proximal tibia in 24 patients (26.4%), followed by distal femur in 20 patients (22%), proximal humerus in 17 patients (18.7%) and proximal femur in 15 patients (16.6%). All patients underwent intralesional curettage. High-speed burr was used in 66 patients (72.5%). The resultant cavity was filled with autogenous bone graft, bone substitute, bone cement or a combination of bone graft and cement. Four patients (4.4%) had complications. Three patients (3.3%) developed local recurrence. Age, site, history of previous intervention or pathologic fracture had no impact on the rate of recurrence. The mean Musculoskeletal Tumor Society (MSTS) score was 28.88 (range, 24 to 30) points. CONCLUSIONS: Thorough curettage using high-speed burr and bone-grafting or bone cement in the treatment of chondroblastoma has good local control, low recurrence rate and excellent functional long-term outcome. LEVEL OF EVIDENCE: Level IV, retrospective case series.

All-endoscopic management of benign bone lesions; a case series of 26 cases with minimum of 2 years follow-up.

PURPOSE: Assessment of the functional and oncologic outcomes regarding endoscopic curettage of different benign bone tumor types within variable anatomic locations. PATIENTS AND METHODS: During the period between February 2012 and December 2016, 26 patients with symptomatic intra-osseous benign bony lesions were included. The age ranged from 3 up to 49 years (mean 20), of 14 females and 12 males. The follow-up duration ranged from 26 up to 58 months (mean 41). Functional scoring was done according to the Revised Musculoskeletal Tumour Society Rating Scale. Anatomic locations of the lesions included: 6 cases in the proximal tibia, 6 cases in the distal femur, 4 cases in the calcaneus, 3 cases in the proximal humerus, 3 cases in the distal tibia, 2 cases in the talus, 1 case in the proximal femur, and 1 case in the distal fibula. The procedure used 4 mm 30° scope for endoscopy, and high speed burrs 3.5-5 mm for extended curettage. Autogenous bone grafting was done in 5 cases, and adjuvant material (polymethylmethacrylate) was needed in 7 cases. RESULTS: After exclusion of one case that was lost in the follow-up, the remaining 25 cases showed full functional recovery at a period of 8-12 weeks, and improved mean functional scores from 20.2 to 28.6/30 post-operatively, with p value <0.001 which was considered as a statistically significant result. The oncologic outcome showed 24 cases with adequate healing, while 1 case developed recurrence (aneurysmal bone cyst in the proximal tibia) for which, an open revision surgery was performed. Intra-operative fracture occurred in another case with aneurysmal bone cyst of the proximal femur, which was fixed by flexible nails with complete healing. CONCLUSION: Endoscopic curettage of different types of intra-osseous benign bony lesions proved to be an effective treatment modality with promising oncologic outcome, improved functional scores, and fast functional recovery.

Management of Fibrous Dysplasia of Proximal Femur by Internal Fixation Without Grafting: A Retrospective Study of 19 Patients.

INTRODUCTION: This paper assesses whether treating patients with fibrous dysplasia of proximal femur by internal fixation with correction of the deformity, if present, without grafting is enough or not. METHODS: This study is a retrospective study using patient's medical records, including analysis of 19 patients with fibrous dysplasia of proximal femur treated by internal fixation only and followed up between 2000 and 2017 for at least 2 years. Epidemiologic data, clinical manifestations, radiologic and histologic investigations, surgery, functional outcomes, and complications in these patients were analyzed. RESULTS: The study included 12 male patients and 7 female patients, with a mean age of 20.74 years. Of these, two patients presented with pathologic fractures, two presented with shepherd's crook deformity, and the remaining presented with hip pain and limping. Implants used for internal fixation were intramedullary nail in four patients, dynamic hip screw in eight patients, cannulated screws in four patients, broad dynamic compression plate in two patients, and narrow dynamic compression plate in one patient. The mean follow-up period was 53.58 months. Four patients had postoperative complications. The mean Musculoskeletal Tumor Society score was 27.63 points. DISCUSSION: The optimal management option for fibrous dysplasia of proximal femur is debatable. We suggest that internal fixation without grafting has a good local control and satisfactory functional long-term outcome.

Simultaneous Determination of Aliskiren Hemifumarate, Amlodipine Besylate and Hydrochlorothiazide in Spiked Human Plasma Using UPLC-MS/MS.

A sensitive UPLC-MS/MS method was developed and validated for simultaneous estimation of aliskiren hemifumarate (ALS), amlodipine besylate (AML) and hydrochlorothiazide (HCZ) in spiked human plasma using valsartan as an internal standard (IS). Liquid-liquid extraction was used for purification and pre-concentration of analytes. The mobile phase consisted of 0.1% formic acid in ammonium acetate buffer (0.02 M, pH 3.5) and methanol (25:75, v/v), flowing through XBridge BEH (50 × 2.1 mm ID, 5 µm) C18 column, at a flow rate of 0.6 mL min(-1). Multiple reaction monitoring (MRM) transitions were measured using an electrospray source in the positive ion mode for ALS and AML, whereas HCZ and IS were measured in negative ion mode. Validation of the method was performed as per US-FDA guidelines with linearity in the range of 2.0-400.0, 0.3-25.0 and 5.0-400.0 ng mL(-1) for ALS, AML and HCZ, respectively. In human plasma, ALS, AML and HCZ were stable for at least 1 month at -70 ± 5°C and for at least 6 h at ambient temperature. After extraction from plasma, the reconstituted samples of ALS, AML and HCZ were stable in the autosampler at ambient temperature for 6 h. The LC-MS/MS method is suitable for bioequivalence and pharmacokinetic studies of this combination.

Stability-indicating RP-LC method for determination of azilsartan medoxomil and chlorthalidone in pharmaceutical dosage forms: application to degradation kinetics.

A RP-LC method was developed and validated for simultaneous determination of the active components, azilsartan medoxomil (AZL) and chlorthalidone (CLT), in their novel antihypertensive combined recipe. The chromatographic separation was achieved on an Eclipse XDB-C18 (4.6 × 150 mm, 5 µm) column using a mobile phase consisting of methanol/potassium hydrogen phosphate buffer (pH 8, 0.05 M) (40:60, v/v) in isocratic mode. The flow rate was maintained at 0.8 mL min(-1) at ambient temperature. Detection was carried out at 210 nm. The method was validated according to the ICH guidelines. Linearity, accuracy, and precision were satisfactory over the concentration range of 5.0-50.0 and 2.5-25.0 µg mL(-1) for AZL and CLT, respectively (r (2) = 0.9999). LODs for AZL and CLT were 0.90 and 0.32 µg mL(-1), whereas LOQs were 2.72 and 0.98 µg mL(-1), respectively. Both drugs were subjected to forced degradation studies under hydrolysis (neutral, acidic, and alkaline), oxidative, and photolytic extensive stress conditions. The proposed method is stability indicating by the resolution of the investigated drugs from their degradation products. Moreover, the kinetics of the acidic degradation of AZL as well as the kinetics of the alkaline degradation of CLT were investigated. Arrhenius plots were constructed and the apparent first-order rate constants, half-life times, shelf-life times, and the activation energies of the degradation processes were calculated. The method was successfully applied for the determination of the studied drugs simultaneously in their coformulated tablet. The developed method is specific and stability indicating for the quality control and routine analysis of the cited medications in their pharmaceutical preparations.

Spectrophotometric and spectrofluorimetric studies on azilsartan medoxomil and chlorthalidone to be utilized in their determination in pharmaceuticals.

The recently approved angiotensin II receptor blocker, azilsartan medoxomil (AZL), was determined spectrophotometrically and spectrofluorimetrically in its combination with chlorthalidone (CLT) in their combined dosage form. The UV-spectrophotometric technique depends on simultaneous measurement of the first derivative spectra for AZL and CLT at 286 and 257 nm, respectively, in methanol. The spectrofluorimetric technique depends on measurement of the fourth derivative of the synchronous spectra intensities of AZL in presence of CLT at 298 nm in methanol. The effects of different solvents on spectrophotometric and spectrofluorimetric responses were studied. For, the spectrofluorimetric study, the effect of pH and micelle-assisted fluorescence enhancement were also studied. Linearity, accuracy, and precision were found to be satisfactory over the concentration ranges of 8-50 µg mL(-1) and 2-20 µg mL(-1) for AZL and CLT, respectively, in the spectrophotometric method as well as 0.01-0.08 µg mL(-1) for AZL in the spectrofluorimetric method. The methods were successfully applied for the determination of the studied drugs in their co-formulated tablets. The developed methods are inexpensive and simple for the quality control and routine analysis of the cited drugs in bulk and in pharmaceuticals.

Steady-state and synchronous spectrofluorimetric methods for simultaneous determination of aliskiren hemifumarate and amlodipine besylate in dosage forms.

Aliskiren hemifumarate (ALS) and amlodipine besylate (AML) were simultaneously determined by two different spectrofluorimetric techniques. The first technique depends on direct measurement of the steady-state fluorescence intensities of ALS and AML at 313 nm and 452 nm upon excitation at 290 and 375 nm, respectively, in a solvent composed of methanol and water (10: 90, v/v). The second technique utilizes synchronous fluorimetric quantitative screening of the emission spectra of ALS and AML at 272 and 366 nm, respectively using Δλ of 97 nm. Effects of different solvents and surfactants on relative fluorescence intensity were studied. The method was validated according to ICH guidelines. Linearity, accuracy and precision were found to be satisfactory in both techniques over the concentration ranges of 1-15 and 0.4-4 µg/mL for ALS and AML, respectively. In the first technique, limit of detection and limit of quantification were estimated and found to be 0.256 and 0.776 µg/mL for ALS as well as 0.067 and 0.204 µg/mL for AML, respectively. Also, limit of detection and limit of quantification were calculated in the synchronous method and found to be 0.293 and 0.887 µg/mL for ALS as well as 0.034 and 0.103 µg/mL for AML, respectively. The methods were successfully applied for the determination of the two drugs in their co-formulated tablets. The results were compared statistically with reference methods and no significant difference was found. The developed methods are rapid, sensitive, inexpensive and accurate for the quality control and routine analysis of the cited drugs in bulk and in pharmaceutical preparations without pre-separation.