Reconstruction of pelvic bone defect after resection for bone tumours is a challenging procedure especially when the hip joint is involved due to the anatomy and the complex biomechanical and structural function of the pelvic ring. This surgery is associated to high complication rate. The additive 3D printing technology allows us to produce trabecular titanium custom based implants with an accurate planning of resection using bone cutting jigs.

From August 2013 to January 2017, we treated 8 patients for bone pelvic sarcoma with custom-made osteotomy jigs (Nylon) and custom-made trabecular titanium prosthesis produced through rapid prototyping technology based on mirroring of the contralateral hemipelvis. Mean follow up time was 18 months (range 2–30) Wide margins were obtained in all cases, in one a local recurrence developed. Surgical time was 4 hours average (from 180 to 250 mins). No postoperative complications were reported.

Rapid prototyping is a promising technique in order to achieve wide surgical margins and restore the anatomy in pelvic bone tumour resection as well as reducing complications.

The purpose of our study was to identify possible risk factors of patients with GCT of the long bones after curettage and packing the bone cavity with bone cement or bone allografts.

We retrospectively reviewed the records of 249 patients with GCT of the limbs treated at Musculoskeletal Oncology Department of our institution between 1990 and 2013, confirmed histologically and recorded in the Bone Tumor Registry. We reviewed 219 cases located in the lower limb and 30 of the upper limb. This series includes 135 females and 114 males, with mean age 32 years (ranging 5 to 80 yrs). According to Campanacci's grading system, 190 cases were stage 2, 48 cases stage 3, and 11 cases stage 1. Treatment was curettage (intralesional surgery). Local adjuvants, such as phenol and cement, were used in 185 cases; whereas in the remaining 64 cases the residual cavity was filled with allografts or autografts only.

Oncological outcome shows 203 patients alive and continuously disease-free (CDF), 41 patients NED1 after treatment of local recurrence (LR), 2 patients NED1 after treatment of lung metastases, 2 AWD with lung metastases. One patient died of unrelated causes (DOD).

LR rate was 15.3% (38 pts). Lung metastases rate was 1.6% (4 pts). In patients treated by curettage and cement (185 cases) LR was 12% (22 pts). Conversely, in patients treated curettage and bone allografts it was higher (16/64 cases), with an incidence of 25% of cases (p=0.004). Oncological complications seemed to be related with site, more frequently occurring in the proximal femur (p=0.037). LR occurred only in stage 2 or 3 tumors without statistical significance (p>0.05). The mean interval between the first surgical treatment and LR was 22 months (range: 3–89 mos). However, in the multivariate analysis no significant statistical effect on local recurrence rate could be identified for gender, patient's age, Campanacci's grading, or cement vs allografts. The only independent risk factor related to the local recurrence was the site, with a statistical significance higher risk for patients with GCT of the proximal femur (p= 0.008).

Our observation on the correlation of tumor location and risk of local recurrence is new. Therefore, special attention must be given to GCTs in the proximal femur. In fact, primary benign bone tumors in the proximal femur are difficult to treat due to the risk of secondary osteonecrosis of the femoral head or pathologic fracture.

Numerous methods of reconstructions have been reported. Among these, total hip arthroplasty (THA) or bipolar hip arthroplasty (BHA) should be avoided when possible as more cases are observed in young patients.

Therefore, we do not suggest different approach for the proximal femur. GCT in the proximal femur is much more difficult to treat than in other sites, but if curettage is feasible, the best way is to save the joint with a higher risk of local recurrence, knowing that the sacrifice of the hip articulation in case of recurrence is always possible with THA or BHA.

Osteosarcoma (OS) is a highly malignant primary tumor frequently occurring in children and adolescents. The mainstay of therapy is neoadjuvant chemotherapy and surgical removal of the lesion yielding a 50–70% of 5-year survival rate. Unfortunately, chemotherapy is currently unable to induce complete tumor necrosis leaving residual tumor cells free to metastasize or recidivate, thus resulting in a 30% mortality. The major limitation in those patients is the development of multidrug resistance (MDR) and the low water solubility of drugs such as Paclitaxel (PTX) that is in fact not included in the majority of chemotherapy protocols for OS treatment.

We thus hypothesized to prevent the emergence of MDR and obtain significant tumor reduction, by engineering innovative nanoparticles (NPs) able to vehiculate the PTX and induce a dual synergic action: the cytostatic effect of PTX and the cytotoxicity generated by reactive oxygen species produced from light triggered photoactivation (PDT) of Chlorin e6 photosensitizer. To further improve the efficacy and reduce the side effects of NPs systemic administration, Mesenchymal Stromal Cells (MSC) are used as a “Trojan horse” to deliver the NPs directly to tumor cells, taking advantage of MSC ability to selectively recognize and efficiently engraft in OS tumor stroma.

HSA were conjugated with photosensitizer Ce6 and the functionalized protein was used to produce PTX loaded nanoparticles through desolvation technique and drug-induced protein self-assembly (PTX-Ce6@HSA NP).

Human MSC lines, isolated from the Bone marrow (BM) of different donors, were then loaded with different dosages of nanoparticles and their ability to internalize and transport the NPs, migrate and induce cytotoxic ROS upon light treatment were tested in in vitro cultures.

Preliminary results showed that MSC efficiently internalize PTX-Ce6@HSA NPs and the photosensitizer Ce6 remains active inside the cells for at least 3 days after loading.

Electron microscopy performed onto loaded MSC showed that NPs internalization take places via clathrin mediated transport, whereas HPLC analysis demonstrated a release kinetics of PTX mediated by exocytosis. Finally, PTX-Ce6@HSA NPs loaded MSC co-cultured with the OS tumor cell line SaOS-2 showed a significant tumor cell growth reduction.

So fare, advances in drug delivery have failed to produce specific tool to improve the overall survival of OS patients. However, given our preliminary in vitro data we believe that the proposed multimodal therapy will minimize the side effects of the systemic chemotherapy and enhance the efficacy through the synergic effect of PTX and PDT.

In the future, our strategy could be intended as an innovative co-adjuvant approach for OS treatment to be performed right before surgery to eliminate residual tumors cells after tumor mass removal.

Delayed bone healing and nonunion are complications of long bone fractures, with prolonged pain and disability. Regenerative therapies employing mesenchymal stromal cells (MSC) and/or bone substitutes are increasingly applied to enhance bone consolidation. The REBORNE project entailed a multi-center orthopaedic clinical trial focused on the evaluation of efficacy of expanded autologous bone marrow (BM) derived MSC combined with a CaP-biomaterial, to enhance bone healing in patients with nonunion of diaphyseal fractures. To complement the clinical and radiological examination of patients, bone turnover markers (BTM) were assayed as potential predictors of bone healing or non-union.

Peripheral blood was collected from patients at fixed time-endpoints, that is at 6,12 and 24 weeks post-surgery for implantation of expanded autologus MSC and bone-like particles. Bone-specific alkaline phosphatase (BAP), C-terminal-propeptide type I-procollagen (PICP), osteocalcin (OC), β-Cross-Laps Collagen (CTX), soluble receptor activator of NFkB (RANKL), osteoprotegerin (OPG) were measured by ELISA assays in blood samples of 22 patients at BM collection and at follow-up visits.

A significant relationship with age was found only at 6 months, with an inverse correlation for CTX, RANKL and OC, and positive for OPG. BTM levels were not related to gender. As an effect of local regenerative process, some BTM showed significant changes in comparison to the baseline value. In particular, the time course of BAP, PICP and RANKL was different in patients with a successful healing in comparison to patients with a negative outcome. The BTM profile apparently indicated a remarkable bone formation activity 12 weeks after surgery. However, the paucity of failed patients in our case series did not allow to prove statistically the role of BTM as predictors of the final outcome.

Blood markers related to bone cell function are useful to measure the efficacy of a expanded MSC-regenerative approach applied to long bone non-unions. Changes of the markers may provide a support to radiological assessment of bone healing.

Demineralized bone matrix (DBM) is a natural, collagen-based, well-established osteoinductive biomaterial. Nevertheless, there are conflicting reports on the efficacy of this product. The purpose of this study was to evaluate whether DBM collagen structure is affected by particle size and can influence DBM osteoinductivity.

Sheep cortical bone was ground and particles were divided in three fractions with different sizes, defined as large (L, 1–2 mm), medium (M, 0.5–1 mm), and small (S, < 0.5 mm). After demineralization, the three DBM samples were characterized by DTA analysis, XRD, ICP-OES, and FTIR. Data clearly showed a particle size-dependent alteration in collagen structure, with DBM-M being altered but not as much as DBM-S. The in vivo study showed that only DBM-M was able to induce new bone formation in a subcutaneous ectopic mouse model. When sheep MSC were seeded onto DBM particles before implantation, all DBM particles were able to induce new bone formation with the best incidence for DBM-M and DBM-S. Gene expression analysis performed on recovered implants supports the histological results and underlines the supportive role of MSC in DBM osteoinduction through the regulation of host cells. In conclusion, our results show a relation between DBM particle size, structural modification of the collagen and in vivo osteoinductivity. The medium particles represent a good compromise between no modification (largest particles) and excessive modification (smallest particles) of collagen structure, yielding highest osteoinduction. We believe that these results can guide researchers to use DBM particles of 0.5–1 mm size range in applications aimed at inducing new bone formation, obtaining results more comparable and reliable among different research groups. Furthermore, we suggest to carefully analyze the structure of the collagen when a collagen-based biomaterial is used alone or in association with cells to induce new bone formation.

Introduction

The delay looks radiographically as a fracture callus not very evident or absent 6 months after osteosynthesis. Patients undergo a long period of immobilization and this fact causes the increase the social cost of the disease. The technique we suggest aims to the reduce the period of immobilization and as a consequence the management costs of the disease.

Reconstruction following internal hemipelvectomy for bone tumors remains a major surgical challenge. Most of the cases are considered not suitable for reconstruction because of high complication occurrence. Allografts coupled with standard prosthesis is a reliable method of reconstruction.

26 patients received a McMinn stemmed cup (Link, Germany) after periacetabular tumor resection from February 1999 to 2006. In 18 patients the reconstruction followed resection of the acetabular area while in other 8 an extrarticular resection of the proximal femur was performed. In 21 cases a stemmed acetabular cup were associated with massive bone allograft. There were 13 female and 13 male with a mean age of 41 years (13 to 70). Average follow-up was 45 months (7 to 105).

Six patients were affected by local recurrence of the tumour and five underwent hindquarter amputation. In 4 of them the index surgery followed a previous recurrence of the tumour. Finally 6 patients died for related causes within 2 years. All the other 20 have been followed clinically and radiographically for a minimum of 24 months.

Deep infection occurred in one case, there were no cases of dislocation. Radiolucency at the prosthesis-bone interface was observed in 3 cases, 2 patients had proximal migration < of 20 mm. Only one patient was treated for aseptic loosening because of incorrect initial position of the implant. The iliac osteotomy was consolidated in all cases, while a delayed union was frequently observed in the pubic osteotomy, however without compromise the stability of implant. Functional result were evaluated according to the MSTS system and this showed 65% of excellent or good clinical results.

The procedure requires appropriate patient selection, accurate preoperative planning, meticulous selection and preparation of allograft. Usually artificial ligaments are applied to reduce hip instability, however, this type of reconstruction do not require complex fixation, thus reducing surgical time and early complications.

Introduction: The role of surgery for local control in the multimodal management of Ewing’s sarcoma has substantially increased during the past 20 years. However, selection bias due to location (extremities vs axial skeleton) and relatively non-homogeneous treatment received by patients in multi-institutional trials may limit objective evaluation and comparison of the relative role of surgery and radiation therapy in this setting. Purpose of this study was to review a large series of patients homogeneously treated at a single institution.

Methods: 268 patients with non-metastatic Ewing’s sarcoma of the extremities treated by contemporary multimodal management were reviewed. Chemotherapy was administered according to 4 sequential protocols of adjuvant (1) and neoadjuvant (3) treatment. Local control consisted of surgery in 136 patients, surgery and radiation therapy in 70 patients, and radiation therapy in 60 patients. Two patients underwent only chemotherapy.

Results: The 5-year event-free survival (EFS) and overall survival (OS) were 62 and 69 per cent respectively. The rates of 5-year EFS and local control were significantly lower in patients treated with radiation therapy compared to patients treated by surgery or surgery and radiation therapy (48 vs 66 per cent, p=0.002; 80 vs 94 per cent, p= 0,0001). In group 3 (Radiation Therapy only) there were also 6 secondary malignancies.

Conclusion: Surgery was associated with better survival and local control in this series. In our opinion, surgery should always be considered in the local treatment of Ewing’s sarcoma of the extremities. Postoperative Radiation Therapy must be added in cases of inadequate surgical margins.

Long-term clinical study to explore the curative effect and mechanism of the treatment of adult chronic osteomyelitis by implant Osteoset T.

The study object were 65 case adult chronic osteomyelitis patient from November 1977 to April 2003 in a University-based hospital. Age ranged from 18 to 69 years old. 40 cases were treated by general debridement (Method I); 25 cases were treated by general debridement and implant Osteoset T in dead space (Methods II). Stage IA(The UTMB Staging System) osteomyelitis 39 cases; The Organism was Staphylococcus Aureus 28 cases. In all cases (group A), 40 cases were treated with Method I (group AI), 25 cases were treated with Method II (group AII). The majority of the patients, 39 resulted as Stage IA (group B); 22 were treated with Method I (group BI) and 17 cases were treated with Method II (groupBII). Finally, 28 patients were chronic Staph Aureus osteomyelitis (Group C); 13 were treated with Method I (group CI) and 15 cases with Method II (group CII); Followed from 36 to 334 months, mean 75.0 months. Then respectively evaluate and analysis analyze the success rate of different method with standard.

The success rate of group BI was 59.09%, group BII was 94.12%, contrast the success rate there was significant difference (p< 0.05). The success rate of group AI was 60.00%, group AII was 80.00%. The success rate of group CI was 46.15%, group CII was 80.00%.

The use of Osteoset T has demostrated better healing rate than left the empty cavity there after debridement and irrigation. Osteoset T can local delivery antibiotic, filler of the dead space, It can be mixed with different antibiotics, reduces the hospitalization time, reduces the number of operation. Unfortunately, Osteoset dos not help with the bone growth.

Introduction: The use of allograft prosthetic composite (APC) of the proximal tibia offers advantages over prosthetic replacement or osteoarticular graft with a better functional outcome since the possibility of a careful soft tissue reconstruction;

Materials and Methods: From 1994 to 2002, 62 APC of the proximal tibia were performed in our department after bone tumor resection (56 malignant bone tumors, 4 cases of previously failed knee implant and 2 stage 3 benign tumors). The patients median age was 18 yrs (range: 11–77 yrs) and the mean resected length was 13.2 cm (range: 8.5–28 cm). The median follow up was 59 months (range: 13–137 months)

Results: In three patients (4,8%) a recurrence was reported at 22, 33 an 40 months and amputation was performed.

Infection was reported in 15 patients (24.2%): 2 early infections (healed with surgical debridment), 1 femoral stem septic loosening (treated with early revision with cemented stem); in 8 cases removal of the infected APC was required followed by implant of a new prosthetic device after cement spacer; two infections did not healed and patient underwent amputation; in two cases a good functional result was achieved removing the infected graft and covering the proximal tibia with cement and no other surgery was required.

Non union of the graft was observed in 8 patients (12.9%): in 4 patients autologous bone grafting was necessary to heal the osteotomy line. In other 3 cases non union was associated with graft fracture. In one case non union was associated with tibial stem loosening and revision of the whole implant was done.

Polyethylene wear was assessed in 5 patients (8%) and revision of the polyethylene components was always required.

Nine patellar tendon rupture (14.5%) were assessed and repaired was performed in seven cases.

The functional outcome of 42 patients with more than two years of follow up was excellent in 25 cases, good in 13, fair in 2 and poor in 2.

Discussion: APC of the proximal tibia is an effective alternative to osteoarticular graft and modular prosthesis because it allows good to excellent results in most of the patients (90.4%). The major concern is infection rate (24.2%) that usually lead to amputation (80%). Non union does not usually represent a problem because it’s tendency to spontaneous or bone grafting induced healing. Aseptic loosening of the tibial or femoral stem is rare. Patellar tendon rupture rate (14.5%) is similar to modular prosthetis rate and can be lowered using a femoral component with patellar groove.

Introduction: Allograft-Prosthesis Composite represents a reliable option for proximal femur replacement after resection for bone tumor. It provides advantages over megaprostheses because of better soft tissue repair and superior abduction strength, quality of gait, hip stability, and load transfer by healed bone rather than prosthetic stem, with potential impact on implant survival. Purpose of this paper was to review details of the surgical technique and results.

Methods: A retrospective study of 62 patients who had resection of the proximal femur because of a bone tumor and reconstruction with an Allograft-Prosthesis Composite was undertaken. The basic surgical technique consisted of an uncemented tapered long stem prosthesis (i.e. Wagner or Wagner-type stem) cemented in the allograft and press-fitted in the host bone, achieving bone-bone contact through a transverse osteotomy. Details of the surgical technique included: 1) accurate preoperative planning, canal sizing and implant selection; 2) under-reaming of the proximal 5–10 mm of the host medullary canal, depending upon bone quality and diameter of the selected stem; 3) allograft preparation and prosthesis cementation in the allograft; 4) introduction of the composite implant, pressfitted in host medullary canal, until bone-bone contact is achieved; 5) careful repair of abductors and iliopsoas to corresponding allograft tendon insertions.

Key points for successful fixation are absolute rotational stability and satisfactory circumferential bone-bone contact at the time of surgery.

Postoperative regimen consisted of hip, followed by progressive bracing and toe-touch weight-bearing for 6 weeks, weight-bearing.

Results: There were 2 septic failures. Two patients developed asymptomatic nonunion. There were no dislocations. Most common complication was fracture of the allograft greater trochanter (30%), which required surgery in only 1 case and never substantially affected function. The incidence of trochanteric fracture decreased from 63% in the first 27 patients to 5% in the following 35 patients by switching implant design from a valgus 145° neck angle to 135° neck angle, improving offset and abductors function. Bone grafting of the allograft-host union was required in 10% of the cases.

According to MSTS, results were satisfactory in 90% of the patients, with average score 91% (75%–96%).

Discussion and Conclusion: Allograft-Prosthesis Composite is a successful procedure for reconstruction of the proximal femur. Careful surgical technique is the key to excellent function and low complication rate.

Aim: This study wants to investigate whether the administration of stromal stem cells (SSC) in a platelet-rich plasma (PRP) scaffold could promote angiogenesis which resulted in a better allograft integration.

Methods: surgery: A monolateral resection of 3cm segment of the metatarsus, was perfomed in 10 adult cross-breed sheep (3–4 years old), weighting 60–70 kg.

Isolation and ex-vivo expansion of SSC: nucleated cells were isolated with density gradient and expanded ex-vivo with alpha-MEM containing 20% FCS.

Radiographic and histomorphometric analysis: Radiographs were made after surgery and after 1, 2 and 4 months. Histomorphometric studies were carried out to study the defect and the new bone formation at the implant site

Results: Union had occurred in all the 5 animals of the SSC group after 4 months as observed radiographically and morphologically, while in the control group the osteotomy line was still visible. Histomorphometric analysis demonstrated a higher % of new-bone formation in both the host (%section quadrant) and the grafted bone in SSC animals.

Conclusions: Results presented suggest that SSC in PRP-based scaffold have improved allograft integration. In conclusion the application of this surgical approach may result in an increased and accelerated bone graft integration, reducing the time required for bone healing and increasing the chances of a successful bone implant.

Aims: Purpose of this study was to evaluate the results of a staged revision technique in the treatment of deep infection after limb salvage surgery for bone tumors and to identify factors possibly affecting the outcome. Methods: A retrospective study of 19 consecutive patients with an infected bone tumor reconstruction treated at our Institution in the period 1986–1997 was undertaken. All the patients underwent staged revision (two stages in 13 cases, three stages in 5, four stages in 1) using one or more antibiotic loaded cement spacers after debridement and partial (10 cases) or complete (9 cases) removal of the original implant. Postoperatively, all the patients received oral or parenteral antibiotics for a minimum of 4 weeks. Delayed reimplantation was performed in 15 cases, average time to reimplantation being 7 months (4–14). A minimum follow up of 3 years was available in all patients. Cultures identiþed S. Epider-midis in 12 cases (63%), S. Aureus in 4 (21%), mixed organisms in 2 (11%), and were negative in 1 case (5%) despite clinical evidence of infection. Results: At a minimum follow-up of 3 years, 13 patients were continuously infection-free (68%) while 6 relapsed (32%). Two of the 6 relapses were cleared by amputation while 4 remained infected. Average functional result of infection-free patients according to the International Society Of Limb Salvage (ISOLS) was 71% (21.2 points), ranging from 60% to 80% (18 to 24 points). Conclusions: Staged revision with antibiotic loaded cement spacer for infected bone tumor reconstruction is a demanding and expensive technique requiring prolonged inability. Overall success rate in this series approaches 70%. Complete removal of the infected implant, microbiology, appropriate antibiotic selection, and negative cultures before reimplantation are crucial.

Purpose of this study is to examine the long-term follow-up in prosthesis reconstruction after proximal humerus resections.

Material and methods From February 1975 to December 1990, 144 patients have been operated for a musculoskeletal tumor of the shoulder girdle with resection and reconstruction using a modular cemented prosthesis. The MRS prosthesis is assembled in three parts with a ball shaped rotating head stitched to the glenoid and acromium. Seventy patients died and 3 patients were lost to follow-up: 71 achieved a follow-up more than 10 years (123–259, av 175 mo). Age ranged from 9 to 73 years (mean 29.7). The resection was intrarticular in 44 cases, in 12 more the glenoid was resected along with the proximal humerus (extrarticular resection) and in 15 cases we performed a Tikhoff –Lindberg procedure.

Infection occurred in 7 patients (10%) from 1 to 144 months (median 12 mo): in 6 patients prosthesis removal was needed to achieve healing.

Mechanical complications were present in 19 patients (27%): 15 (21%) had prosthetic head instability (5 surgically treated), 2 breakage of the prosthetic stem and 2 prosthetic disassembly.

Results: A detailed roentgen graphic analysis has been developed to better define the long-term course of the cement bone interface. Only 3 aseptic stem loosening were detected at 1, 3 and 11 years (after a supercondylar fracture occurred 8 months before). Eighteen patients were reoperated (25%); in 4 cases with minor surgery. Failure of the system occurred in 11 cases (15%).

Conclusion: The long durability of this cemented prosthesis has been demonstrated with very few cases of stem loosening in the early follow-up time. The problem of a good prosthetic head suture is still under concerning particularly in Tikhoff-Lindberg procedure.