Aims. Limb salvage in bone tumour patients replaces the bone with massive segmental prostheses where achieving bone integration at the shoulder of the implant through extracortical bone growth has been shown to prevent loosening. This study investigates the effect of multidrug chemotherapy on extracortical bone growth and early radiological signs of aseptic loosening in patients with massive distal femoral prostheses. Methods. A retrospective radiological analysis was performed on adult patients with distal femoral arthroplasties. In all, 16 patients were included in the chemotherapy group with 18 patients in the non-chemotherapy control group. Annual radiographs were analyzed for three years postoperatively. Dimensions of the bony pedicle, osseointegration of the hydroxyapatite (HA) collar surface, bone resorption at the implant shoulder, and radiolucent line (RLL) formation around the cemented component were analyzed. Results. A greater RLL score (p = 0.041) was observed at three years postoperatively, with those receiving chemotherapy showing greater radiological loosening compared with those not receiving chemotherapy. Chemotherapy patients experience osteolysis at the shoulder of the ingrowth collar over time (p < 0.001) compared with non-chemotherapy patients where osteolysis was not observed. A greater median percentage integration of the collar surface was observed in the non-chemotherapy group (8.6%, interquartile range (IQR) 0.0% to 37.9%; p = 0.021) at three years. Bone growth around the collar was observed in both groups, and no statistical difference in amount of extracortical bony bridging was seen. Conclusion. Multidrug chemotherapy affects the osseointegration of ingrowth collars and accelerates signs of radiological loosening. This may increase the risk of aseptic loosening in patients with massive segmental implants used to treat bone cancer. Cite this article: Bone Joint Res 2020;9(7):333–340

We studied the safety of external fixation during post-operative chemotherapy in 28 patients who had undergone distraction osteogenesis (17, group A) or vascularised fibular grafting (11, group B) after resection of a tumour. Four cycles of multi-agent post-operative chemotherapy were administered over a mean period of 14 weeks (6 to 27). The mean duration of external fixation for all patients was 350 days (91 to 828). In total 204 wires and 240 half pins were used. During the period of post-operative chemotherapy, 14 patients (11 in group A, 3 in group B) developed wire- and pin-track infection. A total of ten wires (4.9%) and 11 half pins (4.6%) became infected. Seven of the ten infected wires were in periarticular locations. External fixation during post-operative chemotherapy was used safely and successfully for fixation of a vascularised fibular graft and distraction osteogenesis in 27 of 28 patients. Post-operative chemotherapy for malignant bone tumours did not adversely affect the ability to achieve union or cause hypertrophy of the vascularised fibular graft and had a minimal effect on distraction osteogenesis. Only one patient developed osteomyelitis which required further surgery

Aims. To assess the correlation between the histological response to preoperative chemotherapy and event-free survival (EFS) or overall survival (OS) in patients with high-grade localized osteosarcoma. Methods. Out of 625 patients aged ≤ 40 years treated for primary high-grade osteosarcoma between 1997 and 2016, 232 patients without clinically detectable metastases at the time of diagnosis and treated with preoperative high-dose methotrexate, adriamycin and cisplatin (MAP) chemotherapy and surgery were included. Associations of chemotherapy-induced necrosis in the resected specimen and EFS or OS were assessed using Cox model and the Pearson’s correlation coefficients (r). Time-dependent receiver operating characteristic analysis was applied to determine the optimal cut-off value of chemotherapy-induced necrosis for EFS and OS. Results. OS was 74% (95% confidence interval (CI) 67 to 79) at five years. Median chemotherapy-induced necrosis was 85% (interquartile range (IQR) 50% to 97%). In multivariate Cox model, chemotherapy-induced necrosis was significantly associated with EFS and OS (hazard ratio (HR) = 0.99 (95% CI 0.98 to 0.99); p < 0.001 and HR = 0.98 (95% CI 0.97 to 0.99); p < 0.001, respectively). Positive correlation was observed between chemotherapy-induced necrosis and five-year EFS and five-year OS (r = 0.91; p < 0.001, and r = 0.85; p < 0.001, respectively). The optimal cut-off value of chemotherapy-induced necrosis for five-year EFS and five-year OS was 85% and 72%, respectively. Conclusion. Chemotherapy-induced necrosis in the resected specimen showed positive correlation with EFS and OS in patients with high-grade localized osteosarcoma after MAP chemotherapy. In our analysis, optimal cut-off values of MAP chemotherapy-induced necrosis in EFS and OS were lower than the commonly used 90%, suggesting the need for re-evaluation of the optimal cut-off value through larger, international collaborative research. Cite this article: Bone Joint J 2020;102-B(6):795–803

The April 2023 Oncology Roundup. 360. looks at: Complete tumour necrosis after neoadjuvant chemotherapy defines good responders in patients with Ewing’s sarcoma; Monitoring vascularized fibular autograft: are radiographs enough?; Examining patient perspectives on sarcoma surveillance; The management of sacral tumours; Venous thromboembolism and major bleeding in the clinical course of osteosarcoma and Ewing’s sarcoma; Secondary malignancies after Ewing’s sarcoma: what is the disease burden?; Outcomes of distal radial endoprostheses for tumour reconstruction: a single centre experience over 15 years; Is anaerobic coverage during soft-tissue sarcoma resection needed?; Is anaerobic coverage during soft-tissue sarcoma resection needed?

We performed a randomised, controlled clinical trial to compare ambulant short-course chemotherapy with anterior spinal fusion plus short-course chemotherapy for spinal tuberculosis without paraplegia. Patients with active disease of vertebral bodies were randomly allocated to one of three regimens: a) radical anterior resection with bone grafting plus six months of daily isoniazid plus rifampicin (Rad6); b) ambulant chemotherapy for six months with daily isoniazid plus rifampicin (Amb6); or c) similar to b) but with chemotherapy for nine months (Amb9). Ten years from the onset of treatment, 90% of 78 Rad6, 94% of 78 Amb6 and 99% of 79 Amb9 patients had a favourable status. Ambulant chemotherapy for a period of six months with daily isoniazid plus rifampicin (Amb6) was an effective treatment for spinal tuberculosis except in patients aged less than 15 years with an initial angle of kyphosis of more than 30° whose kyphosis increased substantially

Aims. The aim of this study was to investigate the incidence and characteristics of instrumentation failure (IF) after total en bloc spondylectomy (TES), and to analyze risk factors for IF. Methods. The medical records from 136 patients (65 male, 71 female) with a mean age of 52.7 years (14 to 80) who underwent TES were retrospectively reviewed. The mean follow-up period was 101 months (36 to 232). Analyzed factors included incidence of IF, age, sex, BMI, history of chemotherapy or radiotherapy, tumour histology (primary or metastasis; benign or malignant), surgical approach (posterior or combined), tumour location (thoracic or lumbar; junctional or non-junctional), number of resected vertebrae (single or multilevel), anterior resection line (disc-to-disc or intravertebra), type of bone graft (autograft or frozen autograft), cage subsidence (CS), and local alignment (LA). A survival analysis of the instrumentation was performed, and relationships between IF and other factors were investigated using the Cox regression model. Results. A total of 44 patients (32.4%) developed IF at a median of 31 months (interquartile range 23 to 74) following TES. Most IFs were rod fractures preceded by a mean CS of 6.1 mm (2 to 18) and LA kyphotic enhancement of 10.8° (-1 to 36). IF-free survival rates were 75.8% at five years and 56.9% at ten years. The interval from TES to IF peaked at two to three years postoperatively and continued to occur over a period of time thereafter; the early IF-developing group had greater CS at one month postoperatively (CS1M) and more lumbar TES. CS1M ≥ 3 mm and sole use of frozen autografts were identified as independent risk factors for IF. Conclusion. IF is a common complication following TES. We have demonstrated that robust spinal reconstruction preventing CS, and high-quality bone grafting are necessary for successful reconstruction. Cite this article: Bone Joint J 2023;105-B(2):172–179

Aims. Socioeconomic and racial disparities have been recognized as impacting the care of patients with cancer, however there are a lack of data examining the impact of these disparities on patients with bone sarcoma. The purpose of this study was to examine socioeconomic and racial disparities that impact the oncological outcomes of patients with bone sarcoma. Methods. We reviewed 4,739 patients diagnosed with primary bone sarcomas from the Surveillance, Epidemiology and End Results (SEER) registry between 2007 and 2015. We examined the impact of race and insurance status associated with the presence of metastatic disease at diagnosis, treatment outcome, and overall survival (OS). Results. Patients with Medicaid (odds ratio (OR) 1.41; 95% confidence interval (CI) 1.15 to 1.72) and uninsured patients (OR 1.90; 95% CI 1.26 to 2.86) had higher risks of metastatic disease at diagnosis compared to patients with health insurance. Compared to White patients, Black (OR 0.63, 95% CI 0.47 to 0.85) and Asian/Pacific Islander (OR 0.65, 95% CI 0.46 to 0.91) were less likely to undergo surgery. In addition, Black patients were less likely to receive chemotherapy (OR 0.67, 95% CI 0.49 to 0.91) compared to White patients. In patients with chondrosarcoma, those with Medicaid had worse OS compared to patients with insurance (hazard ratio (HR) 1.65, 95% CI 1.06 to 2.56). Conclusion. In patients with a bone sarcoma, the cancer stage at diagnosis varied based on insurance status, and racial disparities were identified in treatment. Further studies are needed to identify modifiable factors which can mitigate socioeconomic and racial disparities found in patients with bone sarcomas. Cite this article: Bone Joint Res 2022;11(5):278–291

Aims. The sacroiliac joint (SIJ) is the only mechanical connection between the axial skeleton and lower limbs. Following iliosacral resection, there is debate on whether reconstruction of the joint is necessary. There is a paucity of data comparing the outcomes of patients undergoing reconstruction and those who are not formally reconstructed. Methods. A total of 60 patients (25 females, 35 males; mean age 39 years (SD 18)) undergoing iliosacral resection were reviewed. Most resections were performed for primary malignant tumours (n = 54; 90%). The mean follow-up for surviving patients was nine years (2 to 19). Results. Overall, 27 patients (45%) were reconstructed, while 33 (55%) had no formal reconstruction. There was no difference in the use of chemotherapy (p = 1.000) or radiotherapy (p = 0.292) between the groups. Patients with no reconstruction had a mean larger tumour (11 cm (SD 5) vs 8 cm (SD 4); p = 0.014), mean shorter operating times (664 mins (SD 195) vs 1,324 mins (SD 381); p = 0.012), and required fewer blood units (8 (SD 7) vs 14 (SD 11); p = 0.012). Patients undergoing a reconstruction were more likely to have a deep infection (48% vs 12%; p = 0.003). Nine reconstructed patients had a hardware failure, with five requiring revision. Postoperatively 55 (92%) patients were ambulatory, with no difference in the proportion of ambulatory patients (89% vs 94%; p = 0.649) or mean Musculoskeletal Tumor Society Score (59% vs 65%; p = 0.349) score between patients who did or did not have a reconstruction. The ten-year disease-specific survival was 69%, with no difference between patients who were reconstructed and those who were not (78% vs 45%; p = 0.316). There was no difference in the rate of metastasis between the two groups (hazard ratio (HR) 2.78; p = 0.102). Conclusion. Our results demonstrate that SIJ reconstruction is associated with longer operating times, greater need for blood transfusion, and more postoperative infections, without any improvement in functional outcomes when compared to patients who did not have formal SIJ reconstruction. Cite this article: Bone Joint J 2024;106-B(1):93–98

The results are presented of thirty-seven patients with Ewing's sarcoma; ten were treated by a combination of operation, radiotherapy and cyclic chemotherapy, the remainder by radiotherapy and chemotherapy but without operation. The drugs, vincristine, cyclophosphamide and adriamycin were used in combination and were continued for two years. The follow-up ranged from twelve to sixty-two months. The mortality rate and the incidence of metastases were both markedly lower than in a comparable previous series treated by radiotherapy alone, or by operation plus radiotherapy, but all without chemotherapy. The percentage of local recurrences and of metastases was much higher in the twenty-seven patients who had radiotherapy and adjuvant chemotherapy, than in the ten in whom operation was also performed. It is suggested that on the basis of these results (and on theoretical grounds) treatment should consist of radiotherapy combined with chemotherapy plus, whenever feasible, operative excision of the primary tumour

Fifty-five cases of osteosarcoma of the extremities were treated between 1972 and 1976 by combined surgery and chemotherapy (vincristine, adriamycin and methotrexate in medium doses) for 18 months. The follow-up ranges from 30 to 80 months (mean = 48 months). Twenty-six patients remained free from any evidence of disease, two had local recurrences but no metastases and 27 had metastases (four of these also had local recurrences). In 12 patients, the metastases appeared after the end of chemotherapy. Both metastases and local recurrences were more frequent in patients who had segmental bone resection (7/8) than in those treated by more radical surgery (22/47). Comparison with an "historical" group (94 osteosarcoma patients treated by operation alone in our Institute between 1960 and 1971) showed that the percentage of patients free from evidence of disease was higher in the group who receiving chemotherapy. In addition, the appearance of metastases in this group was delayed (mean = 16 months) as compared with the historical controls (mean = 8 months). On the other hand, after the same kind of operative treatment, the rate of local recurrences and the time of their appearance was almost identical in both groups

We studied the CT and MR scans, and the histology of 50 patients with primary Ewing’s sarcoma of bone to determine the association between the change in tumour volume and necrosis after chemotherapy, and to ascertain their influence on prognosis. The mean age of the patients was 17 years. The limbs were involved in 40 and the axial bones in ten. The volume of the tumour at diagnosis varied from 31 to 1790 ml. There was a significant relationship between necrosis and the measured change in volume of the tumour after chemotherapy. Progression of the tumour despite chemotherapy was seen only in patients with necrosis of grades 4 to 6. Necrosis significantly influenced survival (p < 0.05), but the effect of change in volume was less significant. Change in volume of the tumour is a good predictor of necrosis induced by chemotherapy. Necrosis is a strong prognostic factor in Ewing’s sarcoma

Amalignant peripheral nerve-sheath tumour developed in the right S1 nerve root in a man aged 30 causing back pain and sciatica. CT and MRI revealed a destructive tumour of the sacrum invading the retroperitoneal space. The tumour was not resectable with an adequate margin. Chemotherapy, consisting of high-dose ifosfamide followed by a combination of vincristine, doxorubicin and cyclophosphamide, was given with success. Malignant peripheral nerve-sheath tumours are thought to respond weakly to chemotherapy, but the response in our patient was complete

We describe a patient who developed avascular necrosis of both humeral trochleae after combination chemotherapy for acute lymphoblastic leukaemia. This presented as progressive stiffness of both elbows with little pain. Radiography and MRI confirmed the presence of avascular necrosis at both sites. This region corresponds to a watershed between the medial and lateral vascular arcades which supply the distal humerus and may explain the susceptibility of this bony region to avascular necrosis. Treatment involved capsulectomy of the elbow and removal of osteophytes giving a good functional outcome on both sides

Surgical treatment of hydatid bone disease is rarely completely successful because radical excision is only possible at certain sites and secondary infection frequently occurs. Antihelmintic drugs have in the past been only palliative due to poor absorption and consequent low concentration in serum or cysts. We report five patients with Echinococcus granulosus infestation treated with a new chemotherapeutic agent albendazole; in two it was given postoperatively, in two pre-operatively and one child is being followed expectantly. We believe that a combination of chemotherapy and surgery may be efficacious in the treatment of hydatid bone disease

Prediction tools are instruments which are commonly used to estimate the prognosis in oncology and facilitate clinical decision-making in a more personalized manner. Their popularity is shown by the increasing numbers of prediction tools, which have been described in the medical literature. Many of these tools have been shown to be useful in the field of soft-tissue sarcoma of the extremities (eSTS). In this annotation, we aim to provide an overview of the available prediction tools for eSTS, provide an approach for clinicians to evaluate the performance and usefulness of the available tools for their own patients, and discuss their possible applications in the management of patients with an eSTS.

Cite this article: Bone Joint J 2022;104-B(9):1011–1016.

We investigated the possible use of acrylic cement containing chemotherapeutic drugs in the treatment of malignant lesions in bone. The diffusion of methotrexate (MTX) from methylpolymethacrylate implants was studied in vitro: polymerisation of the cement did not destroy the drug; liberation began immediately and about 10% was released by 18 hours. Some release continued for as long as six months. In vivo experiments on rats with induced osteosarcoma showed that MTX in cement had both local and general effects which were dependent on the dosage. A series of 17 large dogs with spontaneous osteosarcoma were then treated by local resection and cement containing MTX. General chemotherapeutic effects were detectable from 2 hours to 5 days, survival was increased and local recurrence was reduced, but there were four cases of delayed wound healing. Preliminary studies in human patients confirm the possibility that this method of local chemotherapy could be a useful addition to the treatment of malignant tumours of bone

Desmoid tumours are a rare fibroblastic proliferation of monoclonal origin, arising in deep soft-tissues. Histologically, they are characterized by locally aggressive behaviour and an inability to metastasize, and clinically by a heterogeneous and unpredictable course. Desmoid tumours can occur in any anatomical site, but commonly arise in the limbs. Despite their benign nature, they can be extremely disabling and sometimes life-threatening, causing severe pain and functional limitations. Their surgical management is complex and challenging, due to uncertainties surrounding the biological and clinical behaviour, rarity, and limited available literature. Resection has been the first-line approach for patients with a desmoid tumour but, during the last few decades, a shift towards a more conservative approach has occurred, with an initial ‘wait and see’ policy. Many medical and regional forms of treatment are also available for the management of this condition, and others have recently emerged with promising results. However, many areas of controversy remain, and further studies and global collaboration are needed to obtain prospective and randomized data, in order to develop an appropriate shared stepwise approach.

Cite this article: Bone Joint J 2023;105-B(7):729–734.

The role of radiotherapy and/or surgery in the local treatment of Ewing’s sarcoma has still to be determined. The outcome of Ewing’s sarcoma may differ according to its location and a selection bias towards surgery limits the ability to compare methods of local treatment. We have carried out a retrospective review of 91 consecutive patients treated for non-metastatic Ewing’s sarcoma of the femur. They received chemotherapy according to four different protocols. The primary lesion was treated by surgery alone (54 patients), surgery and radiotherapy (13) and radiotherapy alone (23). One was treated by chemotherapy alone. At a median follow-up of ten years, 48 patients (53%) remain free from disease, 39 (43%) have relapsed, two (2%) have died from chemotherapeutic toxicity and two (2%) have developed a radio-induced second tumour. The probability of survival without local recurrence was significantly (p = 0.01) higher in patients who were treated by surgery with or without radiotherapy (88%) than for patients who received radiotherapy alone (59%). The five- and ten-year overall survival rates were 64% and 57%, respectively. Patients who were treated by surgery, with or without radiotherapy, had a five- and ten-year overall survival of 64%. Patients who received only radiotherapy had a five- and ten-year survival of 57% and 44%, respectively. Our results indicate that in patients with Ewing’s sarcoma of the femur, better local control is achieved by surgical treatment (with or without radiotherapy) compared with the use of radiotherapy alone. Further studies are needed to verify the impact of this strategy on overall survival

After exclusions, 265 patients with tuberculosis of the thoracic and/or lumbar spine were followed for three years from the start of treatment. They were randomly allocated to four daily regimens of chemotherapy: 1) isoniazid plus rifampicin for 6 months (6HR, 65); 2) the same drugs as in 1) but for 9 months (9HR, 71); 3) isoniazid plus paraaminosalicylic acid (PAS) or ethambutol for 9 months (9P/EH, 62); or 4) the same drugs as in 3) but for 18 months (18P/EH, 67). All patients were ambulatory from the start of chemotherapy and no form of splintage or support or operation was used in any case. Over half (55%) the patients were children and one-third had sinuses or clinically evident abscesses. At three years a favourable status, defined as no sinus nor clinically evident abscess, no myelopathy with functional impairment, no surgery nor additional chemotherapy, full physical activity with disease quiescent clinically and radiographically, was achieved in 203 patients (77%) and in another 41 (15%) in all respects except radiographically. Only 20 patients (8%) had an unfavourable status the proportion being highest (19%) in the 9P/EH series. Thirteen of these were classified as unfavourable solely because they had needed additional chemotherapy; only seven still had an unfavourable status at three years. The clinical results at three years were thus excellent in all series except the 9P/EH, in which more patients had required additional chemotherapy. In the 88 patients with sinuses or abscesses on admission, the rate of resolution was similar in all the series; most lesions (83%) had resolved by 12 months.(ABSTRACT TRUNCATED AT 250 WORDS)

1. Two hundred young Korean patients with a diagnosis of tuberculosis of the spine were allocated at random to in-patient rest in bed (IP) for six months followed by out-patient treatment, or to ambulatory out-patient treatment (OP) from the start. A second random allocation was made to chemotherapy with streptomycin for three months and PAS plus isoniazid for eighteen months (SPH), or to PAS plus isoniazid for eighteen months (PH). For various reasons twenty-nine patients had to be excluded from the study. The main analyses of this report therefore concern 171 patients, namely, forty IP/SPH, forty-six IP/PH, forty-two OP/SPH and forty three OP/PH. The comparisons made are a) of in-patient and out-patient treatment, and b) of the SPH and PH regimens. 2. The clinical and radiographic condition of the four groups on admission was similar. Many patients had extensive lesions. 3. Two in-patients died, probably from miliary tuberculosis, but neither had evidence of residual activity of the spinal lesion. 4. For the eighty-six in-patients the mean stay in hospital was 199 days and five were later readmitted. Of the eighty-five out-patients twenty-one (fourteen SPH, seven PH) were admitted to hospital in the first six months for complications of the spinal disease, for other medical conditions, or for domestic or geographical reasons; after the first six months eight more were admitted. 5. Three in-patients and five out-patients received chemotherapy beyond eighteen months for abscess or for paraparesis. 6. An abscess or sinus was either present initially or developed during treatment in 76 per cent of the in-patients and 72 per cent of the out-patients. Complete resolution occurred in most of the patients, some abscesses being aspirated. At three years 11 per cent of the in-patients and 5 per cent of the out-patients still had residual abscesses or sinuses. 7. On admission the mean total vertebral loss was 1·79 in the in-patients and 1·33 in the out-patients, and increased over the three-year period by 0·15 and 0·31 respectively. 8. The mean angulation of the spine at the start of treatment was 37 degrees for the in-patients and 27 degrees for the out-patients, the mean increase over the three-year period being 8 and 18 degrees respectively. 9. On admission six in-patients and four out-patients had incomplete motor paraplegia. This resolved completely within nine months in eight patients, as did the one cauda equina lesion. Only two patients (both out-patients) developed paraparesis during the course of the study; both recovered. 10. At eighteen months 66 per cent of the in-patients and 58 per cent of the out-patients had responded favourably. The corresponding percentages at thirty-six months were 84 and 88. 11. There was little difference in behaviour between the SPH and the PH series; at thirty-six months 82 per cent of eighty SPH and 90 per cent of eighty-eight PH patients had a favourable response. 12. A multiple regression analysis failed to identify any factor of clearly prognostic importance on admission

In two centres in Korea 350 patients with a diagnosis of tuberculosis of the thoracic and/or lumbar spine were allocated at random: in Masan to in-patient rest in bed (IP) for six months followed by out-patient treatment or to ambulatory out-patient treatment (OP) from the start; in Pusan to out-patient treatment with a plaster-of-Paris jacket (J) for nine months or to ambulatory treatment without any support (No J). All patients recieved chemotherapy with PAS with isoniazid for eighteen months, either supplemented with streptomycin for the first three months (SPH) or without this supplement (PH), by random allocation. The main analysis of this report concerns 299 patients (eighty-three IP, eighty-three OP, sixty-three J, seventy No J; 143 SPH, 156 PH). Pre-treatment factors were similar in both centres except that the patients in Pusan had, on average, less extensive lesions although in a greater proportion the disease was radiographically active. One patient (J/SPH) died with active spinal disease and three (all No J/SPH) with paraplegia. A fifth patient (IP/PH) who died from cardio respiratory failure also had pulmonary tuberculosis. Twenty-three patients required operation and/or additional chemotherapy for the spinal lesion. A sinus or clinically evident abscess was either present initially or developed during treatment in 41 per cent of patients. Residual lesions persisted in ten patients (four IP, two OP, one J, three No J; six SPH, four PH) at five years. Thirty-two patients had paraparesis on admission or developing later. Complete resolution occurred in twenty on the allocated regimen and in eight after operation or additional chemotherapy or both. Of the remaining four atients, all of whom had operation and additional chemotherapy, three died and one still had paraparesis at five years. Of 295 patients assessed at five years 89 per cent had a favourable status. The proportions of the patients responding favourably were similar in the IP (91 per cent) and OP (89 per cent) series, in the J (90 per cent) and No J (84 per cent) series and in the SPH (86 per cent) and PH (92 per cent) series

Streptomycin and the newer antibiotics have already belied the pessimistic agnosticism of 1947. In certain instances, notably in disease of the knee and hip and in some cases with draining sinuses, it appears that they are sufficient to produce a quiescence which may be a cure. For the rest it remains to map out in detail what has in part been explored. In particular it is essential to confirm how far antibiotics enable surgeons to treat tuberculosis upon the basic principles applicable to other infections of bone without fear of secondary infection: where there is diseased bone, to remove it: where there is pus, to relieve the tension and evacuate it. The surgeon fears not so much the infection itself as the inability of the tuberculous soil ordinarily to deal with secondary infection. With the control of the diseased soil the risk should be no greater than that of any other surgery of bone.

The early case and the advanced case; age and site of disease; these and other variables must subdivide basic method. What is the best application of the new "combined operation" to a child of three with thoracic Pott's disease and a globular abscess? What is the wisest plan for a man of forty with old disease in his lumbar vertebrae and discharging sinuses? We begin to see what we could do. At the present the question still remains: What should we do?

We studied 51 patients with osteo-articular tuberculosis who were divided into two groups. Group I comprised 31 newly-diagnosed patients who were given first-line antituberculous treatment consisting of isoniazid, rifampicin, ethambutol and pyrazinamide. Group II (non-responders) consisted of 20 patients with a history of clinical non-responsiveness to supervised uninterrupted antituberculous treatment for a minimum of three months or a recurrence of a previous lesion which on clinical observation had healed. No patient in either group was HIV-positive. Group II were treated with an immunomodulation regime of intradermal BCG, oral levamisole and intramuscular diphtheria and tetanus vaccines as an adjunct for eight weeks in addition to antituberculous treatment. We gave antituberculous treatment for a total of 12 to 18 months in both groups and they were followed up for a mean of 30.2 months (24 to 49). A series of 20 healthy blood donors served as a control group.

Twenty-nine (93.6%) of the 31 patients in group I and 14 of the 20 (70%) in group II had a clinicoradiological healing response to treatment by five months.

The CD4 cell count in both groups was depressed at the time of enrolment, with a greater degree of depression in the group-II patients (686 cells/mm³ (sd 261) and 545 cells/mm³ (sd 137), respectively; p < 0.05). After treatment for three months both groups showed significant elevation of the CD4 cell count, reaching a level comparable with the control group. However, the mean CD4 cell count of group II (945 cells/mm³ (sd 343)) still remained lower than that of group I (1071 cells/mm³ (sd 290)), but the difference was not significant. Our study has shown encouraging results after immunomodulation and antituberculous treatment in non-responsive patients. The pattern of change in the CD4 cell count in response to treatment may be a reliable clinical indicator.

Two hundred and eighty-three patients with tuberculosis of the thoracic and/or lumbar spine have been followed for 10 years from the start of treatment. All patients received PAS plus isoniazid daily for 18 months, either with streptomycin for the first three months (SPH) or no streptomycin (PH), by random allocation. There was also a second random allocation for all patients: in Masan to inpatient rest in bed (IP) for six months followed by outpatient treatment or to ambulatory outpatient treatment from the start (OP), and in Pusan to outpatient treatment with a plaster-of-Paris jacket (J) for nine months or to ambulatory treatment without any support (No J). A favourable status was achieved on their allocated regimen by 88% of patients at 10 years. Some of the remaining patients also attained a favourable status after additional chemotherapy and/or operation, and if these are included the proportion achieving such a status increases to 96%. There were five patients whose deaths were attributed to their spinal disease. A sinus or clinically evident abscess was present on at least one occasion in the 10-year period in 42% of the patients. Residual sinuses persisted at 10 years in two patients, at death at seven years in a third and at default in the seventh year in a fourth. Thirty-five patients had paraparesis at some time during the 10-year period, including two who died with paraplegia before five years. Complete resolution occurred in 26 patients (in six after additional chemotherapy and/or surgery). At 10 years two patients had severe paraplegia and one a moderate paraparesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Streptomycin and iso-nicotinic acid hydrazide are two powerful drugs lethal to tubercle bacilli, when access to the infected tissues is free. For early disease, before ischaemia and necrosis become established, they are curative: afterwards they are not. In this paper the use of surgery to augment their action has been discussed. The development of such methods may well revolutionise the treatment of skeletal tuberculosis. Therein lies a danger because attempts to cure the patient by exterminating the tubercle bacilli in his lesion may lead to a precarious recovery: treatment directed against the bacilli may greatly facilitate a real cure if constitutional treatment is also applied to make the patient immune. Revolutionary though the change may become, it will not be so great as the revolution which occurred thirty years ago when open-air hospitals were first provided for patients with skeletal tuberculosis. The first patient ever seen on a surgical ward by the author, when he was a student, suffices still as an example. A child with tuberculosis of the cervical spine was admitted from out-patients with multiple discharging sinuses from the neck which was supported in a sodden plaster jacket. "Whoever," said the house surgeon dramatically, "removes that plaster, will kill that child." Most unfortunately his words were true. Many other such patients could, in those days, be seen in the wards of city hospitals. It was largely due to the work of Sir Robert Jones, friend of children, that the value of constitutional treatment became recognised. With the combination of the old knowledge and the development of the new, a new chapter in the treatment of skeletal tuberculosis has opened and rapid restoration of function and permanent cure can now take the place of long and sometimes crippling illness.

One hundred and fifty patients in Hong Kong with a diagnosis of tuberculosis of the thoracic, thoracolumbar or lumbar spine were allocated a random to the "Hong Kong" radical resection of the lesion and the insertion of autologous bone grafts (Rad. series) or to debridement of the spinal focus without bone grafting (Deb. series). All patients received daily chemotherapy with para-aminosalicylic acid (PAS) plus isoniazid for 18 months, with streptomycin for the first three months. After exclusions, the main analyses of this report concern 119 patients (58 Rad., 61 Deb.) followed up for 10 years. During the first five years the allocated regimen was modified because of the spinal lesion in 14 patients, but there were no further modifications between five and 10 years. No patient developed a sinus or clinically evident abscess or a neurological abnormality between five and 10 years. Bony fusion occurred earlier and in a higher proportion of patients in the Rad, series but at five and 10 years there was vary little difference between the series. Over the period of 10 years there was a mean increase in vertebral loss of 0.05 of a vertebral body in the Rad. series and 0.23 in the Deb. series. In both series most of this loss occurred in the first 18 months, with very little subsequent change in the next eight and a half years. Over the 10 years there was a mean reduction in the angle of kyphosis in the Rad. series of 1.4 degrees for patients with thoracic and thoracolumbar lesions and 0.5 degrees for those with lumbar lesions. By contrast, in the Deb. series there were mean increases in the angle of 9.8 degrees and 7.6 degrees respectively. In both series most of the changes had occurred early, and persisted subsequently. At 10 years 57 of 58 Rad. and all 61 Deb. patients had a favourable status, 50 (86 per cent) and 54 (89 per cent) respectively on the allocated regimen without modification

Aims. The aim of this study was to determine the rate of indocyanine green (ICG) staining of bone and soft-tissue tumours, as well as the stability and accuracy of ICG fluorescence imaging in detecting tumour residuals during surgery for bone and soft-tissue tumours. Methods. ICG fluorescence imaging was performed during surgery in 34 patients with bone and soft-tissue tumours. ICG was administered intravenously at a dose of 2 mg/kg over a period of 60 minutes on the day prior to surgery. The tumour stain rate and signal-to-background ratio of each tumour were post hoc analyzed. After tumour resection, the tumour bed was scanned to locate sites with fluorescence residuals, which were subsequently inspected and biopsied. Results. The overall tumour stain rate was 88% (30/34 patients), and specific stain rates included 90% for osteosarcomas and 92% for giant cell tumours. For malignant tumours, the overall stain rate was 94%, while it was 82% for benign tumours. The ICG tumour stain was not influenced by different pathologies, such as malignant versus benign pathology, the reception (or lack thereof) of neoadjuvant chemotherapies, the length of time between drug administration and surgery, the number of doses of denosumab for patients with giant cell tumours, or the tumour response to neoadjuvant chemotherapy. The overall accuracy rate of successfully predicting tumour residuals using fluorescence was 49% (23/47 pieces of tissue). The accuracy rate after en bloc resection was significantly lower than that after piecemeal resection (16% vs 71%; p < 0.001). Conclusion. A high percentage of bone and soft-tissue tumours can be stained by ICG and the tumour staining with ICG was stable. This approach can be used in both benign and malignant tumours, regardless of whether neoadjuvant chemotherapy is adopted. The technique is also useful to detect tumour residuals in the wound, especially in patients undergoing piecemeal resection. Cite this article: Bone Joint J 2023;105-B(5):551–558

Aims. The aim of this study was to report the long-term prognosis of patients with multiple Langerhans cell histiocytosis (LCH) involving the spine, and to analyze the risk factors for progression-free survival (PFS). Methods. We included 28 patients with multiple LCH involving the spine treated between January 2009 and August 2021. Kaplan-Meier methods were applied to estimate overall survival (OS) and PFS. Univariate Cox regression analysis was used to identify variables associated with PFS. Results. Patients with multiple LCH involving the spine accounted for 15.4% (28/182 cases) of all cases of spinal LCH: their lesions primarily involved the thoracic and lumbar spines. The most common symptom was pain, followed by neurological dysfunction. All patients presented with osteolytic bone destruction, and 23 cases were accompanied by a paravertebral soft-tissue mass. The incidence of vertebra plana was low, whereas the oversleeve-like sign was a more common finding. The alkaline phosphatase was significantly higher in patients with single-system multifocal bone LCH than in patients with multisystem LCH. At final follow-up, one patient had been lost to follow-up, two patients had died, three patients had local recurrence, six patients had distant involvement, and 17 patients were alive with disease. The median PFS and OS were 50.5 months (interquartile range (IQR) 23.5 to 63.1) and 60.5 months (IQR 38.0 to 73.3), respectively. Stage (hazard ratio (HR) 4.324; p < 0.001) and chemotherapy (HR 0.203; p < 0.001) were prognostic factors for PFS. Conclusion. Pain is primarily due to segmental instability of the spine from its destruction by LCH. Chemotherapy can significantly improve PFS, and radiotherapy has achieved good results in local control. The LCH lesions in some patients will continue to progress. It may initially appear as an isolated or single-system LCH, but will gradually involve multiple sites or systems. Therefore, long-term follow-up and timely intervention are important for patients with spinal LCH. Cite this article: Bone Joint J 2023;105-B(6):679–687

Aims. For paediatric and adolescent patients with growth potential, preservation of the physiological joint by transepiphyseal resection (TER) of the femur confers definite advantages over arthroplasty procedures. We hypothesized that the extent of the tumour and changes in its extent after neoadjuvant chemotherapy are essential factors in the selection of this procedure, and can be assessed with MRI. The oncological and functional outcomes of the procedure were reviewed to confirm its safety and efficacy. Methods. We retrospectively reviewed 16 patients (seven male and nine female, mean age 12.2 years (7 to 16)) with osteosarcoma of the knee who had been treated by TER. We evaluated the MRI scans before and after neoadjuvant chemotherapy for all patients to assess the extent of the disease and the response to treatment. Results. The mean follow-up period was 64.3 months (25 to 148) after surgery and no patients were lost to follow-up. On MRI evaluation, 13 tumours were near but not in contact with the physes and three tumours were partially in contact with the physes before neoadjuvant chemotherapy. Bone oedema in the epiphysis was observed in eight patients. After neoadjuvant chemotherapy, bone oedema in the epiphysis disappeared in all patients. In total, 11 tumours were not in contact and five tumours were in partial contact with the physes. The postoperative pathological margin was negative in all patients. At the last follow-up, 12 patients were continuously disease-free and three had no evidence of disease. One patient died due to the disease. Functionally, the patients with retained allograft or recycled autograft had a mean knee range of flexion of 126° (90° to 150°). The mean Musculoskeletal Tumor Society functional score was 27.6 (23 to 30). Conclusion. TER is an effective limb-salvage technique for treating malignant metaphyseal bone tumours in paediatric and young osteosarcoma patients with open physes when a good response to chemotherapy and no progression of the tumour to the epiphysis have been confirmed by MRI. Cite this article: Bone Joint J 2020;102-B(6):772–778

The February 2024 Oncology Roundup. 360. looks at: Does primary tumour resection improve survival for patients with sarcomas of the pelvis with metastasis at diagnosis?; Proximal femur replacements for an oncologic indication offer a durable endoprosthetic reconstruction option: a 40-year experience; The importance of awaiting biopsy results in solitary pathological proximal femoral fractures: do we need to biopsy solitary pathological fractures?; Effect of radiotherapy on local recurrence, distant metastasis, and overall survival in 1,200 extremity soft-tissue sarcoma patients; What to choose in bone tumour resections? Patient-specific instrumentation versus surgical navigation; Optimal timing of re-excision in synovial sarcoma patients: immediate intervention versus waiting for local recurrence; Survival differences of patients with resected extraskeletal osteosarcoma receiving two different (neo) adjuvant chemotherapy regimens; Solitary versus multiple bone metastases in the appendicular skeleton: should the surgical treatment be different?

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. Cite this article: Bone Joint J 2024;106-B(5):425–429

The December 2022 Oncology Roundup. 360. looks at: Is high-dose radiation therapy associated with early revision with a cemented endoprosthesis?; Neoadjuvant chemotherapy and endoprosthetic reconstruction for lower extremity sarcomas: does timing impact complication rates?; Late amputation after treatment for lower extremity sarcoma; Osteosarcoma prediagnosed as another tumour: a report from the Cooperative Osteosarcoma Study Group; The influence of site on the incidence and diagnosis of solitary central cartilage tumours of the femur: a 21st century perspective

Aims. Clear cell sarcoma (CCS) of soft-tissue is a rare melanocytic subtype of mesenchymal malignancy. The aim of this study was to investigate the clinical and therapeutic factors associated with increased survival, stratified by clinical stage, in order to determine the optimal treatment. Methods. The study was a retrospective analysis involving 117 patients with histologically confirmed CCS, between July 2016 and November 2017, who were enrolled in the Bone and Soft Tissue Tumour Registry in Japan. Results. The five- and ten-year survival rates were 41% (95% confidence interval (CI) 29 to 52) and 37% (95% CI 25 to 49), respectively. On multivariable analysis, the size of the tumour of > 10 cm (p = 0.006), lymph node metastasis at the time of diagnosis (p < 0.001), distant metastases at the time of diagnosis (p < 0.001), and no surgery for the primary tumour (p = 0.019) were independently associated with a poor survival. For N0M0 CCS (n = 68), the development of distant metastases was an independent prognostic factor for survival (early (< 12 months), hazard ratio (HR) 116.78 (95% CI 11.69 to 1,166.50); p < 0.001; late (> 12 months), HR 14.79 (95% CI 1.66 to 131.63); p = 0.016); neoadjuvant/adjuvant chemotherapy (p = 0.895) and/or radiotherapy (p = 0.216) were not significantly associated with survival. The five-year cumulative incidence of local recurrence was 19% (95% CI 8 to 35) and the size of the tumour was significantly associated with an increased rate of local recurrence (p = 0.012). For N1M0 CCS (n = 18), the risk of mortality was significantly lower in patients who underwent surgery for both the primary tumour and lymph node metastases (HR 0.03 (95% CI 0.00 to 0.56); p = 0.020). For M1 CCS (n = 31), excision of the primary tumour was independently associated with better survival (HR 0.26 (95% CI 0.09 to 0.76); p = 0.013). There was no significant difference in survival between the different types of systemic treatment (p = 0.523). Conclusion. Complete excision of the primary tumour and lymph nodes is associated with a better survival in patients with CCS. Systemic treatment appears to provide limited benefits, demonstrating a pressing need for novel systemic agents. Cite this article: Bone Joint J 2023;105-B(11):1216–1225

Aims. The aim of this study was to identify factors that determine outcomes of treatment for patients with chondroblastic osteosarcomas (COS) of the limbs and pelvis. Patients and Methods. The authors carried out a retrospective review of prospectively collected data from 256 patients diagnosed between 1979 and 2015. Of the 256 patients diagnosed with COS of the pelvis and the limbs, 147 patients (57%) were male and 109 patients (43%) were female. The mean age at presentation was 20 years (0 to 90). Results. In all, 82% of the patients had a poor response to chemotherapy, which was associated with the presence of a predominantly chondroblastic component (more than 50% of tumour volume). The incidence of local recurrence was 15%. Synchronous or metachronous metastasis was diagnosed in 60% of patients. Overall survival was 51% and 42% after five and ten years, respectively. Limb localization and wide surgical margins were associated with a lower risk of local recurrence after multivariable analysis, while the response to chemotherapy was not. Local recurrence, advanced patient age, pelvic tumours, and large volume negatively influenced survival. Resection of pulmonary metastases was associated with a survival benefit in the limited number of patients in whom this was undertaken. Conclusion. COS demonstrates a poor response to chemotherapy and a high incidence of metastases. Wide resection is associated with improved local control and overall survival, while excision of pulmonary metastases is associated with improved survival in selected patients. Cite this article: Bone Joint J 2019;101-B:739–744

Aims. The purpose of this study was to clarify the clinical behaviour, prognosis, and optimum treatment of dedifferentiated low-grade osteosarcoma (DLOS) diagnosed based on molecular pathology. Patients and Methods. We retrospectively reviewed 13 DLOS patients (six men, seven women; median age 32 years (interquartile range (IQR) 27 to 38)) diagnosed using the following criteria: the histological coexistence of low-grade and high-grade osteosarcoma components in the lesion, and positive immunohistochemistry of mouse double minute 2 homolog (MDM2) and cyclin-dependent kinase 4 (CDK4) associated with MDM2 amplification. These patients were then compared with 51 age-matched consecutive conventional osteosarcoma (COS) patients (33 men, 18 women; median age 25 years (IQR 20 to 38)) regarding their clinicopathological features. Results. The five-year overall survival (OAS) rates in the DLOS and COS patients were 85.7% and 77.1% (p = 0.728), respectively, and the five-year progression-free survival (PFS) rates were 57.7% and 44.9% (p = 0.368), respectively. A total of 12 DLOS patients received chemotherapy largely according to regimens for COS. Among the nine cases with a histological evaluation after chemotherapy, eight showed a poor response, and seven of these had a necrosis rate of < 50%. One DLOS patient developed local recurrence and five developed distant metastases. Conclusion. Based on our study of 13 DLOS cases that were strictly defined by histological and molecular means, DLOS showed a poorer response to a standard chemotherapy regimen than COS, while the clinical outcomes were not markedly different. Cite this article: Bone Joint J 2019;101-B:745–752

Aims. The aim of this study was to analyse a group of patients with non-metastatic Ewing’s sarcoma at presentation and identify prognostic factors affecting the development of local recurrence, in order to assess the role of radiotherapy. Patients and Methods. A retrospective review of all patients with a Ewing’s sarcoma treated between 1980 and 2012 was carried out. Only those treated with chemotherapy followed by surgery and/or radiotherapy were included. Patients were grouped according to site (central or limb) for further analysis of the prognostic factors. Results. A total of 388 patients were included in the study. Of these, 60 (15%) developed local recurrence at a mean median of 27 months (. sd. 24, range 7 to 150) and the five-year local recurrence-free survival (5yrLRFS) was 83%. For central tumours, the size of the tumour and histological response to chemotherapy were found to be significant factors for local recurrence. For limb tumours, local recurrence was affected by intralesional and marginal resections, but not by the histological response to chemotherapy. Radiotherapy in those with a marginal resection reduced the risk of local recurrence (5yrLRFS: 96% versus 81%, p = 0.044). Conclusion. Local recurrence significantly affects the overall survival in patients with a Ewing’s sarcoma. For those with a tumour in a limb, radiotherapy reduced the risk of local recurrence, especially in those with a marginal margin of excision, but the effect in central tumours was less clear. Radiotherapy for those who have had a wide margin of resection does not reduce the risk of local recurrence, regardless of the histological response to chemotherapy. Cite this article: Bone Joint J 2018;100-B: 247–55

Aims. The purpose of this study was to review a large cohort of patients and further assess the correlation between the histological response to chemotherapy in patients with Ewing’s sarcoma with the overall (OS) and event-free survival (EFS). Patients and Methods. All patients treated for Ewing’s sarcoma between 1980 and 2012 were reviewed. Of these, 293 patients without metastases at the time of diagnosis and treated with chemotherapy and surgery were included. Patients were grouped according to the percentage of necrosis after chemotherapy: Group I: 0% to 50%, Group II: 51% to 99% and Group III: 100%. Results. The mean age at diagnosis was 16 years (1 to 62) and the mean follow-up was 9.1 years (six months to 32.6 years). The OS and EFS for the series were 75% and 65% at five years. There were significant differences in survival between the groups of necrosis: 0% to 50% (OS: 49% and EFS: 45% at five years, respectively) compared with 51% to 99% (OS: 72% and EFS: 59% at five years, respectively) and 100% (OS: 94% and EFS: 81% at five years, respectively) (p <  0.001). There were no significant differences in survival between patients treated between 1980 and 1989 compared with those treated between 1990 and 1999, and those treated between 2000 and 2012 (p = 0.55). Conclusion. Only patients with 100% necrosis after chemotherapy should be classified as having a good response to chemotherapy because they have significantly better rates of survival compared with those with any viable tumour in the surgical specimen. Cite this article: Bone Joint J 2016;98-B:1138–44

Aims. The aim of this study was to determine the risk of local recurrence and survival in patients with osteosarcoma based on the proximity of the tumour to the major vessels. Patients and Methods. A total of 226 patients with high-grade non-metastatic osteosarcoma in the limbs were investigated. Median age at diagnosis was 15 years (4 to 67) with the ratio of male to female patients being 1.5:1. The most common site of the tumour was the femur (n = 103) followed by tibia (n = 66). The vascular proximity was categorized based on the preoperative MRI after neoadjuvant chemotherapy into four types: type 1 > 5 mm; type 2 ≤ 5 mm, > 0 mm; type 3 attached; type 4 surrounded. Results. Limb salvage rate based on the proximity type was 92%, 88%, 51%, and 0% for types 1 to 4, respectively, and the overall survival at five years was 82%, 77%, 57%, and 67%, respectively (p < 0.001). Local recurrence rate in patients with limb-salvage surgery was 7%, 8%, and 22% for the types 1 to 3, respectively (p = 0.041), and local recurrence at the perivascular area was observed in 1% and 4% for type 2 and 3, respectively. The mean microscopic margin to the major vessels was 6.9 mm, 3.0 mm, and 1.4 mm for types 1 to 3, respectively. In type 3, local recurrence-free survival with limb salvage was significantly poorer compared with amputation (p = 0.025), while the latter offered no overall survival benefit. In this group of patients, factors such as good response to chemotherapy or limited vascular attachment to less than half circumference or longitudinal 10 mm reduced the risk of local recurrence. Conclusion. The proximity of osteosarcoma to major blood vessels is a poor prognostic factor for local control and survival. Amputation offers better local control for tumours attached to the blood vessels but does not improve survival. Limb salvage surgery offers similar local control if the tumour attachment to blood vessels is limited. Cite this article: Bone Joint J 2019;101-B:1024–1031

Aims. Bone metastasis ultimately occurs due to a complex multistep process, during which the interactions between cancer cells and bone microenvironment play important roles. Prior to colonization of the bone, cancer cells must succeed through a series of steps that will allow them to gain migratory and invasive properties; epithelial-to-mesenchymal transition (EMT) is known to be integral here. The aim of this study was to determine the effects of G protein subunit alpha Q (GNAQ) on the mechanisms underlying bone metastasis through EMT pathway. Methods. A total of 80 tissue samples from patients who were surgically treated during January 2012 to December 2014 were used in the present study. Comparative gene analysis revealed that the GNAQ was more frequently altered in metastatic bone lesions than in primary tumour sites in lung cancer patients. We investigated the effects of GNAQ on cell proliferation, migration, EMT, and stem cell transformation using lung cancer cells with GNAQ-knockdown. A xenograft mouse model tested the effect of GNAQ using micro-CT analyses and histological analyses. Results. GNAQ-knockdown showed down-regulation of tumour growth through mitogen-activated protein kinase (MAPK) signalling in lung cancer cells, but not increased apoptosis. We found that GNAQ-knockdown induced EMT and promoted invasiveness. GNAQ-knockdown cells injected into the bone marrow of murine tibia induced tumour growth and bone-to-lung metastasis, whereas it did not in control mice. Moreover, the knockdown of GNAQ enhanced cancer stem cell-like properties in lung cancer cells, which resulted in the development of resistance to chemotherapy. Conclusion. The present study reveals that the GNAQ-knockdown induced cancer stem cell-like properties. Cite this article: Bone Joint Res 2021;10(5):310–320

Aims. The aim of this study was to assess orthopaedic oncologic patient morbidity resulting from COVID-19 related institutional delays and surgical shutdowns during the first wave of the pandemic in New York, USA. Methods. A single-centre retrospective observational study was conducted of all orthopaedic oncologic patients undergoing surgical evaluation from March to June 2020. Patients were prioritized as level 0-IV, 0 being elective and IV being emergent. Only priority levels 0 to III were included. Delay duration was measured in days and resulting morbidities were categorized into seven groups: prolonged pain/disability; unplanned preoperative radiation and/or chemotherapy; local tumour progression; increased systemic disease; missed opportunity for surgery due to progression of disease/lost to follow up; delay in diagnosis; and no morbidity. Results. Overall, 25 patients met inclusion criteria. There were eight benign tumours, seven metastatic, seven primary sarcomas, one multiple myeloma, and two patients without a biopsy proven diagnosis. There was no priority level 0, two priority level I, six priority level II, and 17 priority level III cases. The mean duration of delay for priority level I was 114 days (84 to 143), priority level II was 88 days (63 to 133), and priority level III was 77 days (35 to 269). Prolonged pain/disability and delay in diagnosis, affecting 52% and 40%,respectively, represented the two most frequent morbidities. Local tumour progression and increased systemic disease affected 32% and 24% respectively. No patients tested positive for COVID-19. Conclusion. COVID-19 related delays in surgical management led to major morbidity in this studied orthopaedic oncologic patient population. By understanding these morbidities through clearer hindsight, a thoughtful approach can be developed to balance the risk of COVID-19 exposure versus delay in treatment, ensuring optimal care for orthopedic oncologic patients as the pandemic continues with intermittent calls for halting surgery. Cite this article: Bone Jt Open 2021;2(4):236–242

Aims. Tocilizumab, an interleukin-6 (IL-6) receptor (IL-6R) targeting antibody, enhances the anti-tumour effect of conventional chemotherapy in preclinical models of cancer. We investigated the anti-tumour effect of tocilizumab in osteosarcoma (OS) cell lines. Methods. We used the 143B, HOS, and Saos-2 human OS cell lines. We first analyzed the IL-6 gene expression and IL-6Rα protein expression in OS cells using reverse transcription real time quantitative-polymerase chain reaction (RT-qPCR) analysis and western blotting, respectively. We also assessed the effect of tocilizumab on OS cells using proliferation and invasion assay. Results. The OS cell lines 143B, HOS, and Saos-2 expressed IL-6R. Recombinant human IL-6 treatment increased proliferation of 143B and HOS cells. Tocilizumab treatment decreased proliferation and invasion of 143B, HOS, and Saos-2. Conclusion. In conclusion, we confirmed the production of IL-6 and the expression of IL-6R in OS cells and demonstrated that tocilizumab inhibits proliferation and invasion in OS cells. Cite this article: Bone Joint Res 2020;9(11):821–826

A poor response to chemotherapy (≤ 90% necrosis) for osteosarcomas leads to poorer survival and an increased risk of local recurrence, particularly if there is a close margin of excision. We evaluated whether amputation confers any survival benefit over limb salvage surgery (LSS) with narrow margins in patients who respond poorly to chemotherapy. We only analysed patients with an osteosarcoma of the limb, a poor response to chemotherapy and close margins on LSS (marginal/intralesional) or primary amputation: 360 patients (36 LSS (intralesional margins), 197 LSS (marginal margins) and 127 amputations) were included. Local recurrence developed in 13 (36%) following LSS with intralesional margins, and 39 (20%) following LSS with marginal margins. There was no local recurrence in patients who underwent amputation. The five-year survival for all patients was 41% (95% confidence interval (CI) 35 to 46), but for those treated by LSS with marginal margins was 46.2% (95% CI 38 to 53), 36.3% (95% CI 27 to 45) for those treated by amputation, and 28% (95 CI 14 to 44) for those treated by LSS with intralesional margins. Patients who had LSS and then developed local recurrence as a first event had the same survival as those who had primary amputation without local recurrence. Prophylactic adjuvant radiotherapy was used in 40 patients but had no discernible effect in preventing local recurrence. Although amputation offered better local control, it conferred no clear survival benefit over LSS with marginal margins in these patients with a poor overall prognosis. Cite this article: Bone Joint J 2015;97-B:115–20

Aims. Malignancy and surgery are risk factors for venous thromboembolism (VTE). We undertook a systematic review of the literature concerning the prophylactic management of VTE in orthopaedic oncology patients. Methods. MEDLINE (PubMed), EMBASE (Ovid), Cochrane, and CINAHL databases were searched focusing on VTE, deep vein thrombosis (DVT), pulmonary embolism (PE), bleeding, or wound complication rates. Results. In all, 17 studies published from 1998 to 2018 met the inclusion criteria for the systematic review. The mean incidence of all VTE events in orthopaedic oncology patients was 10.7% (1.1% to 27.7%). The rate of PE was 2.4% (0.1% to 10.6%) while the rate of lethal PE was 0.6% (0.0% to 4.3%). The overall rate of DVT was 8.8% (1.1% to 22.3%) and the rate of symptomatic DVT was 2.9% (0.0% to 6.2%). From the studies that screened all patients prior to hospital discharge, the rate of asymptomatic DVT was 10.9% (2.0% to 20.2%). The most common risk factors identified for VTE were endoprosthetic replacements, hip and pelvic resections, presence of metastases, surgical procedures taking longer than three hours, and patients having chemotherapy. Mean incidence of VTE with and without chemical prophylaxis was 7.9% (1.1% to 21.8%) and 8.7% (2.0% to 23.4%; p = 0.11), respectively. No difference in the incidence of bleeding or wound complications between prophylaxis groups was reported. Conclusion. Current evidence is limited to guide clinicians. It is our consensus opinion, based upon logic and deduction, that all patients be considered for both mechanical and chemical VTE prophylaxis, particularly in high-risk patients (pelvic or hip resections, prosthetic reconstruction, malignant diagnosis, presence of metastases, or surgical procedures longer than three hours). Additionally, the surgeon must determine, in each patient, if the risk of haemorrhage outweighs the risk of VTE. No individual pharmacological agent has been identified as being superior in the prevention of VTE events. Cite this article: Bone Joint J 2020;102-B(12)1743:–1751

Breast cancer is generally managed surgically with adjuvant agents which include hormone therapy, chemotherapy, radiotherapy and bisphosphonate therapy. However, some of these adjuvant therapies may cause adverse events, including wound infection, neutropenia, bone marrow suppression and fever. The simultaneous presentation of osteonecrosis and osteomyelitis has not previously been described in patients with breast cancer undergoing hormone therapy and chemotherapy. We report a patient with breast cancer who developed bone infarcts in both legs as well as osteomyelitis in the right distal tibia after treatment which included a modified radical mastectomy, hormone therapy and chemotherapy. Simultaneous osteonecrosis and osteomyelitis should be considered in patients with breast cancer who are receiving chemotherapy and hormone therapy who present with severe bone pain, especially if there have been infective episodes during treatment

Between 1986 and 2002, 42 patients with synchronous multifocal osteosarcoma were treated with two different protocols of neoadjuvant chemotherapy. When feasible, the primary and secondary tumours were excised as a combined procedure. After initial chemotherapy 26 patients were excluded from simultaneous excision of all their secondary bone lesions as their disease was too advanced. In 12 patients only isolated excision of the primary lesion was possible. For 16 patients simultaneous operations were conducted to excise the primary and secondary lesions. This involved two supplementary sites in 15 patients and four additional sites in one patient. Of these, 15 attained remission but 12 relapsed and died (11 within two years). Three patients remained disease-free at five, six and 17 years. The histological response to pre-operative chemotherapy of the primary and secondary lesions was concordant in 13 of the 16 patients who underwent simultaneous operations at more than one site. The prognosis for synchronous multifocal osteosarcoma remains poor despite combined chemotherapy and surgery. The homogeneous histological responses in a large proportion of the primary and secondary lesions implies that synchronous multifocal osteosarcoma tumours are not multicentric in origin, but probably represent bone-to-bone metastases from a single tumour

The February 2015 Oncology Roundup. 360 . looks at: Achieving global collaboration; A new standard for limb salvage; Inoperable chondrosarcoma and chemotherapy; Soft-tissue sarcoma and adjuvant chemotherapy; Missed diagnoses and malpractice in sarcoma; Radiofrequency and cartilage tumours

The aim of this study was to evaluate the prognostic and therapeutic factors which influence the oncological outcome of parosteal osteosarcoma. A total of 80 patients with a primary parosteal osteosarcoma were included in this retrospective study. There were 51 females and 29 males with a mean age of 29.9 years (11 to 78). The mean follow-up was 11.2 years (1 to 40). Overall survival was 91.8% at five years and 87.8% at ten years. Local recurrence occurred in 14 (17.5%) patients and was associated with intralesional surgery and a large volume of tumour. On histological examination, 80% of the local recurrences were dedifferentiated high-grade tumours. A total of 12 (14.8%) patients developed pulmonary metastases, of whom half had either a dedifferentiated tumour or a local recurrence. Female gender and young age were good prognostic factors. Local recurrence was a poor prognostic factor for survival. Medullary involvement or the use of chemotherapy had no impact on survival. The main goal in treating a parosteal osteosarcoma must be to achieve a wide surgical margin, as inadequate margins are associated with local recurrence. Local recurrence has a significant negative effect on survival, as 80% of the local recurrences are high-grade dedifferentiated tumours, and half of these patients develop metastases. The role of chemotherapy in the treatment of parosteal osteosarcoma is not as obvious as it is in the treatment of conventional osteosarcoma. The mainstay of treatment is wide local excision. Cite this article: Bone Joint J 2015;97-B:1698–1703