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Introduction Bone metastases are frequent in patients with cancer. Electrochemotherapy (ECT) is a minimally invasive treatment. Preclinical and clinical studies supported the use of ECT in patients with metastatic bone disease (MBD). The purposes of this multicentre study are to confirm the safety and efficacy of ECT, and to identify appropriate operating procedures in different MBD conditions. Materials and methods 102 patients were treated in 11 Centres and recorded in the REINBONE registry (a shared database protected by security passwords): clinical and radiological information, ECT session, adverse events, response, quality of life indicators and duration of follow-up were registered. Results 105 ECT sessions were performed (one ECT session in 99 patients, two ECT sessions in 3 patients). 24 patients (23.5%) received a programmed intramedullary nail after ECT, during the same surgical procedure. Mean follow-up was 5.9 ± 5.1 months (range 1.5–52). The response to treatment by RECIST criteria was 40.4% objective responses, 50.6% stable disease and 9% progressive disease. According to PERCIST criteria the response was: 31.4% OR; 51.7% SD, 16.9% PD with no significant differences between the 2 criteria. Diagnosis of breast cancer and ECOG values 0–1 were significantly associated to objective response. A significant decrease in pain intensity and significant better quality of life was observed after ECT session at follow-up. Conclusion The results are encouraging on pain and tumour local control. ECT proved to be an effective and safe treatment for MBD and it should be considered as an alternative treatment as well as in combination with radiation therapy.

Background: Atlanta-Axial Rotatory Subluxation is an acquired condition, usually occurring in paediatric patients, because of either trauma or pharyngitis or ear-nose-throat (ENT) surgery or upper respiratory tract infection. Post-traumatic C1-C2 rotational subluxation in paediatric age is a very frequent event. It mimics benign torticollis but may result in permanent disability. The Atlanta-axial rotatory displacement, as defined initially by Fielding and Hawkins in 1977, is classified into four types: Type 1 is the most common form in children. It is a simple rotatory displacement without an anterior shift. Type 2 is potentially more dangerous. It is a rotatory displacement with an anterior shift of 5 mm or less. Type 3 is rotatory displacement with an anterior shift greater than 5 mm. Finally, type 4 is rotatory displacement with a posterior shift. Type 3 and 4 deformities are rare, but neurological involvement or even instant death may follow [Figure. 4] [18]. The condition requires prompt diagnosis by thorough examination to avoid any treatment delays. The difficulties for a timely and correct diagnosis and then the correct treatment is described. Case presentation: A 5-year-old girl comes to the emergency room with cervical pain and stiffness. This painful state, as mum reports, has been lasted for about ten days, after a mild trauma. The radiographic picture demonstrates a rotary subluxation C1-C2, type 1 according to Fielding and Hawkins classification. The treatment is head-halter traction with 2kg, and nonsteroidal anti-inflammatory drugs (NSAIDs). After 2 days the x-ray picture improves, but the painful symptoms persist. An in-depth diagnostic MRI of the cervical spine and brain revealed a medulloblastoma which made an immediate and effective neurosurgical intervention necessary. Conclusions: the C1-C2 rotatory dislocation must always be evaluated with extreme care, without neglecting any clinical and anamnestic information for a correct and timely differential diagnosis. Remember that children show very clearly what they feel, always. Keywords: AARS; Cervical spine dislocation; Rotatory subluxation; Differential diagnosis; Medulloblastoma

Purpose: To assess the qualitative relationship between liquid biopsy and conventional tissue biopsy. As a secondary target, we evaluated the relationship between the liquid biopsy results and the T stage, N stage, M stage, and compared to grading. Methods: The Local Ethics Committee of the “Università degli Studi della Campania Luigi Vanvitelli”, with the internal resolution number 24997/2020 of 12.11.2020, approved this spontaneous prospective study. According to the approved protocol, patients with lung cancer who underwent Fine-Needle Aspiration Cytology (FNAC), CT-guided biopsy, and liquid biopsy were enrolled. A Yates chi-square test was employed to analyze differences in percentage values of categorical variables. A p-value < 0.05 was considered statistically significant. Data analysis was performed using the Matlab Statistic Toolbox (The MathWorks, Inc., Natick, MA, USA). Results: When a genetic mutation is present on the pathological examination, this was also detected on the liquid biopsy. ROS1 and PDL1 mutations were found in 2/29 patients, while EGFR Exon 21 was identified in a single patient. At liquid biopsy, 26 mutations were identified in the analyzed samples. The mutations with the highest prevalence rate in the study populations were: ALK (Ile1461Val), found in 28/29 patients (96.6%), EML4 (Lys398Arg), identified in 16/29 (55.2%) patients, ALK (Asp1529Glu), found in 14/29 (48.3%) patients, EGFR (Arg521Lys), found in 12/29 (41.4%) patients, ROS (Lys2228Gln), identified in 11/29 (37.9%) patients, ROS (Arg167Gln) and ROS (Ser2229Cys), identified in 10/29 (34.5%) patients, ALK (Lys1491Arg) and PIK3CA (Ile391Met), identified in 8/29 (27.6%) patients, ROS (Thr145Pro), identified in 6/29 (20.7%) patients, and ROS (Ser1109Leu), identified in 4/29 (13.8%) patients. No statistically significant differences can be observed in the mutation rate between the adenocarcinoma population and the squamous carcinoma population (p > 0.05, Yates chi-square test). Conclusions: We showed that, when a genetic mutation was detected in pathological examination, this was always detected by liquid biopsy, demonstrating a very high concordance rate of genomic testing between tissues and their corresponding mutations obtained by liquid biopsy, without cases of false-negative results. In addition, in our study, liquid biopsy highlighted 26 mutations, with the prevalence of ALK mutation in 96.6% of patients, supporting the idea that this approach could be an effective tool in cases with insufficient tumor tissue specimens or in cases where tissue specimens are not obtainable.

Background The ideal treatment for giant cell tumor of bone (GCTB) is still controversial. The purpose of this study was to evaluate whether curettage was successful in the treatment of GCTB. Intralesional curettage with adjuvant therapies, such as high-speed burring, polymethylmethacrylate, phenol, ethanol, and liquid nitrogen, may be used to reduce the local recurrence rate. However, there is no consensus on the optimal use of curettage, along with fillers and adjuvants, to limit the recurrence rate. Methods We performed a systematic review of articles using the terms long bones, GCTB, and treatment. Case reports, reviews, opinion articles, or technique notes were excluded based on the abstract. Twenty-six articles included in this review were then studied to establish the index in suggesting the surgical treatment of GCTB. Results The patient’s gender, their age, the Campanacci grade of their tumor, and the type of surgery they had were not significantly associated with the local recurrence rate. Local recurrences seemed to be associated with the site of the tumor, occurring more frequently in the proximal femur or distal radius. A pathological fracture was not a contraindication for intralesional curettage. Treatment with denosumab did not decrease the local recurrence rate in patients who had been treated with curettage. Conclusion The current literature seems to suggest that the ideal treatment for GCTB is to remove the tumor while preserving as much of the joint as possible. Local recurrent tumors can be treated with curettage to keep the re-recurrence rate within an acceptable limit. The choice for how to treat GCTB in the proximal femur or distal radius requires special attention.

Introduction: Studies focusing on enchondroma and atypical cartilaginous tumour (ACT) of the pelvis are lacking. The purpose of this study was to verify possible clinical and radiological findings with regard to distinguishing enchondromas from ACT of the pelvis. In addition, this study analysed functional and oncological outcomes in patients with enchondromas or ACT of the pelvis treated with curettage or resection. Materials and methods: We retrospectively reviewed the medical records of 21 patients with confirmed enchondroma or ACT of the pelvis treated by curettage or resection from 1985 to 2018. The minimum follow-up was 18months. The relationship between clinical and radiological factors and tumour type or local recurrence was assessed using Fisher exact test and Mann–Whitney U test. Results: Endosteal scalloping (p = 0.039), tumour size (0.005) and age (0.006) were shown to statistically favour ACT over enchondroma; by contrast, enchondroma and ACT patients had no difference in pain frequency (p = 0.5528). All patients with enchondroma had no local recurrence; in contrast, local recurrence occurred in one patient with ACT, initially treated with resection. The patient with local recurrence had a disease progression with a higher histological grade than the original tumour. Patients treated with curettage had better functional outcomes than patients treated with resection (p = 0.001). Discussion: Endosteal scalloping, tumour size and age could be helpful in the differential diagnosis between enchondroma and ACT of the pelvis. In addition, our study showed that ACT of the pelvis can be safely treated with curettage due to a low risk of local recurrence and better functional results compared with resection. In case of recurrence, we suggest to treat these patients with resection for the risk of disease progression.

Background: Atlanto-Axial Rotatory Subluxation is an acquired condition, usually occurring in pediatric patients, because of either trauma or pharyngitis or ear-nose-throat ( ENT) surgery or upper respiratory tract infection. Post-traumatic C1-C2 rotational subluxation in pediatric age is a very frequent event. It mimics benign torticollis but may result in permanent disability. The atlanto-axial rotatory displacement, as defined initially by Fielding and Hawkins in 1977, is classified into four types: Type 1 is the most common form in children. It is a simple rotatory displacement without an anterior shift. Type 2 is potentially more dangerous. It is a rotatory displacement with an anterior shift of 5 mm or less. Type 3 is rotatory displacement with an anterior shift greater than 5 mm. Finally, type 4 is rotatory displacement with a posterior shift. Type 3 and 4 deformities are rare, but neurological involvement or even instant death may follow [Fig. 4] (18). The condition requires prompt diagnosis by thorough examination to avoid any treatment delays. The difficulties for a timely and correct diagnosis and then the correct treatment are described. Case presentation: A 5 year old girl comes to the emergency room with cervical pain and stiffness.This painful state, as mum reports, has been lasted for about ten days, after a mild trauma. The radiographic picture demonstrates a rotary subluxation C1-C2, type 1 according to Fielding and Hawkins classificationThe treatment is head-halter traction with 2kg, and nonsteroidal anti-inflammatory drugs (NSAIDs) . After 2 days the x-ray picture improves, but the painful symptoms persist. An in-depth diagnostic MRI of the cervical spine and brain revealed a medulloblastoma which made an immediate and effective neurosurgical intervention necessary. Conclusions: the C1-C2 rotatory dislocation must always be evaluated with extreme care, without neglecting any clinical and anamnestic information for a correct and timely differential diagnosis. Remember that children show very clearly what they feel, always .

Purpose: Surgical options for long bone metastases include intramedullary nail fixation or prosthetic reconstruction. Patients with a short life expectancy may benefit from less invasive surgery such as intramedullary nail fixation, while patients with a long life expectancy could be treated with more invasive surgery such as prosthetic reconstruction. The purpose of our study was to analyze the survival of patients treated surgically for long bone metastases, determining the prognostic factors affecting survival and analyzing the surgical complications and reoperation rates. Based on our results, we developed a prognostic score that helps to choose the best treatment for these patients. In addition, we compared the performance of our prognostic score with other previous prognostic models. Method: We investigated prospectively potential clinical and laboratory prognostic factors in 159 patients with metastatic bone disease who underwent surgery with intramedullary nail fixation or prosthetic reconstruction. Clinical data were collected, recording the following data: age and sex of patients, primary tumour and time of diagnosis, number (single or multiple) and presentation (synchronous or metachronous) of bone metastases, presence of visceral metastases. The following laboratory data were analyzed: hemoglobin, leukocyte counts, lymphocyte counts, platelets count, alkaline phosphatase, and C-reactive protein. Results: Our study showed that pathological C-reactive protein and primary tumour diagnosis were significant negative independent prognostic factors at 12-month survival. Based on our results, we created a score using C-reactive protein and primary tumour diagnosis, creating three different prognostic groups: (A) good prognosis primary tumour and physiological CRP with probability of survival at 12 months of 88.9 [80.1–98.5]; (B) bad prognosis primary tumour and physiological CRP or good prognosis primary tumour and pathological CRP with a probability of survival at 12 months of 56.7 [45.4–70.7]; (C) bad prognosis primary tumour and pathological CRP with a probability of survival at 12 months of 12.5 [5.0–28.3]. Using ROC multiple analysis, our score (AUC = 0.816) was the most accurate in predicting a 12-month survival compared to previous prognostic models. Discussion: Patients treated surgically for long bone metastases with a life expectancy over 12 months should be treated with more durable reconstruction, while patients with a life expectancy less than 12 months should be treated with less invasive surgery. The diagnosis of primary cancer and C-reactive protein are two very simple data which every orthopaedic surgeon in any community hospital can easily rely on for any decision-making in the surgical treatment of a complex patient as with a patient with skeletal metastases. Conclusion: Our prognostic score based on only two simple variables (C-reactive protein and primary tumour diagnosis) was able to predict the 12-month survival of patients treated surgically for long bone metastases and could be helpful in choosing the best treatment for these patients.

BackgroundThe outcomes of patients with lung metastases from giant cell tumor of bone (GCTB) vary from spontaneous regression to uncontrolled growth. To investigate whether observation is an appropriate first-line management approach for patients with lung metastases from GCTB, we evaluated the outcomes of patients who were initially managed by observation.MethodsWe retrospectively reviewed the data of 22 patients with lung metastases from histologically confirmed GCTB who received observation as a first-line treatment approach. The median follow-up period was 116 months.ResultsDisease progression occurred in 12 patients (54.5%). The median interval between the discovery of lung metastases and progression was 8 months. Eight patients underwent metastasectomy following initial observation. The median interval between the discovery of lung metastases and treatment by metastasectomy was 13.5 months. None of the patients experienced spontaneous regression. Of the 22 patients, 36.4% needed a metastasectomy, and 9.1% required denosumab treatment during the course of the follow-up period. Disease progression occurred in 45.5% of the 11 patients with lung nodules ≤ 5 mm, while all five of the patients with lung nodules > 5 mm experienced disease progression. Progression-free survival was significantly worse in the group with lung nodules > 5 mm compared to the group with lung nodules ≤ 5 mm (p= 0.022).ConclusionsObservation is a safe first-line method of managing patients with lung metastases from GCTB. According to radiological imaging, approximately half of the patients progressed, and approximately half required a metastasectomy or denosumab treatment. However, patients with lung nodules > 5 mm should receive careful observation because of the high rate of disease progression in this group.

Background: The outcome of lung metastases in patients with giant cell tumor of bone (GCTB) varies from spontaneous regression to uncontrolled growth. To investigate whether observation is an appropriate first-line management for patients with lung metastases from GCTB, we compared the outcomes of patients initially treated with observation with those treated with metastasectomy.Methods: We retrospectively reviewed the data of 29 patients with lung metastases from histologically confirmed GCTB. The median follow-up period was 114 months. We evaluated progression-free survival, which was defined as the time from the date of occurrence of lung metastases to the date of disease progression in the observation or incomplete metastasectomy group, disease recurrence in the complete metastasectomy group, or the last follow-up.Results: Disease progression or recurrence occurred in 14 patients (48.3%). Progression-free survival did not vary significantly between the observation and metastasectomy groups (p=0.373). The total number of metastasectomies was significantly higher in the initial metastasectomy group than in the observation group (p=0.017).Conclusions: The number of patients included in this study is small, however the data suggests that observation can be used safely as first-line management for patients with lung metastases from GCTB with an outcome similar to that of metastasectomy. It is necessary to confirm our result in multi-institutional study with sufficient number of patients.

Introduction: The purpose of our study is to verify possible clinical and radiological findings with regard to distinguishing enchondroma from atypical cartilaginous tumour (ACT). In addition, this study determined risk factors that are associated with local recurrence of enchondroma or ACT treated with curettage. Materials and methods: We retrospectively reviewed the records of 54 patients with enchondroma and 35 patients with ACT of the long bones treated by curettage between 1986 and 2015. The minimum follow-up was 18 months. The relationship between clinical and radiological factors and the tumour type or local recurrence was assessed using Chi-square test or Fischer exact test. Results: Endosteal scalloping (p = 0.004) and soft tissue extension (p = 0.017) were shown to statistically favour ACT over enchondroma; by contrast, pain (p = 0.034) was more frequent in enchondroma compared to ACT. All patients with enchondroma had no local recurrence; in contrast, local recurrence occurred in four patients with ACT (11%). Soft tissue extension (p = 0.049) and the diagnosis of ACT (p = 0.021) were associated with an increased risk of local recurrence. We had a disease progression in three of four patients with local recurrence, and these had higher histological grade than the original tumour. Discussion: Our data show that endosteal scalloping and soft tissue extension could be helpful in the differential diagnosis between enchondroma and ACT. We suggest following only those patients with ACT after surgery to identify any possible recurrence and, in case of recurrence, treat these patients with resection for the risk of disease progression.

There are conflicting reports regarding the outcome and effect of denosumab for distal radius giant cell tumor of bone (GCTB). The authors performed this study to evaluate the behavior of distal radius GCTB in relation to the type of treatment and the administration of denosumab. The files of 72 patients with distal radius GCTB treated from 1984 to 2018 were reviewed. Fourteen patients were administered denosumab. Surgical treatment consisted of curettage (25 patients) or resection (47 patients) and allograft or vascularized fibular head graft reconstruction. Median follow-up was 63.1 months (interquartile range [IQR], 35.5–107.1 months). The authors evaluated local recurrences, metastasis, function, and complications. The local recurrence rate was 30.6% at a median of 14.0 months (IQR, 10–19 months), with no difference between curettage and resection. The local recurrence rate was significantly higher in the patients who received denosumab. The metastasis rate was 9.7% at a median of 41.0 months (IQR, 15–114 months), with no difference regarding denosumab administration. Function was significantly better in patients after curettage. The complication rate was 25%; vascularized fibular graft reconstruction was associated with fewer complications. This study found that denosumab increases the risk of local recurrence after curettage, function is better after curettage, and vascularized fibular graft is the optimal reconstruction after resection of distal radius GCTB. [ Orthopedics . 2020;43(5):284–291.]

Background: Surgical options for long bone metastases include intramedullary nail fixation or prosthetic reconstruction. Patients with a short life expectancy may benefit from less invasive surgery such as intramedullary nail fixation, while patients with a long life expectancy could be treated with more invasive surgery such as prosthetic reconstruction. Thus, life expectancy at 12 months seems to be the most important factor in determining the surgical treatment modality in patients with a metastatic bone disease. Methods: We investigated prospectively potentially clinical and laboratory prognostic factors in 173 patients with metastatic bone disease who underwent surgery with intramedullary nail fixation or prosthetic reconstruction. Clinical data were collected, recording the following data: age, sex and Karnofsky performance of patients, primary tumor and time of diagnosis, skeletal location and numbers of bone metastases, presence of visceral metastases. The following laboratory data were analyzed: hemoglobin, leukocyte counts, lymphocyte counts, platelets count, alkaline phosphatase and C-reactive protein. Findings: Our study showed that pathological C-reactive protein and primary tumor diagnosis were significant negative independent prognostic factors at 12-month survival. Based on our results, we created a score using C-reactive Protein and primary tumor diagnosis, creating three different prognostic groups: (A) good prognosis primary tumor and physiological C-reactive protein; (B) bad prognosis primary tumor and physiological C-reactive protein or good prognosis primary tumor and pathological C-reactive protein; (C) bad prognosis primary tumor and pathological C-reactive protein. Our prognostic score, named the Rizzoli Score, was able to predict the 12-month survival of patients with metastatic bone disease and could be helpful in choosing the best treatment for patients with symptomatic long bone metastases. Interpretation: The results of our study may be utilized by general orthopaedic surgeons in every community hospital to improve decision-making in the care of patients with long bone metastases, avoiding over- or under-treatment. Trial Registration: ClinicalTrials.gov (identifier NCT03188926). Funding: None Declaration of Interests: All authors declare no conflict of interest. Ethics Approval Statement: An independent ethics committee approved the study.