Are Postoperative Infections in the First 12 Months after Wide Resection and Megaprosthetic Replacement Associated with the Survival of Osteosarcoma Patients? Results of a Multicenter Study.

Recent retrospective studies suggested that early postoperative infections might be associated with a survival benefit for extremity osteosarcoma patients, but the reported results have been conflicting. The files of 437 patients with a newly diagnosed, high-grade osteosarcoma of the extremities treated at 5 referral centers in Germany and Austria between 1989 and 2016 were retrospectively evaluated. All patients underwent multi-agent chemotherapy and limb-sparing tumor excision, followed by endoprothetic replacement. We used the Kaplan-Meier method to calculate survival curves, which we compared with the log-rank test. With a median follow-up of 100 months (interquartile range, 49-155 months), local recurrence (LR) probability, event-free survival (EFS), and disease-specific survival (DSS) after 5 years in this selected patient cohort amounted to 5%, 67%, and 79%, respectively, and 46 patients (10.5%) developed an early postoperative infection. We found no significant differences in LR, EFS, or DSS between patients with and without early infections, and there were no differences in known prognostic factors between the two groups. However, in subgroup analyses patients with a poor response to neoadjuvant chemotherapy and an early infection had a better DSS compared to patients without early infections (93% vs. 62% after 5 years, p = 0.044). Provided that our findings can be validated in separate patient cohorts, we believe that patient outcome after adjuvant immunomodulatory treatments in osteosarcoma patients should be evaluated and reported separately for good and poor responders to neoadjuvant chemotherapy in future studies.

Acetabular Erosion After Bipolar Hemiarthroplasty in Proximal Femoral Replacement for Malignant Bone Tumors.

BACKGROUND: Hemiarthroplasty megaprosthetic proximal femur reconstruction after tumor resection is a widespread procedure in orthopedic oncology. One potential complication is acetabular wear requiring secondary acetabular revision. The study's purpose is to investigate prevalence of acetabular erosion, secondary revisions, and potential risk factors. METHODS: We retrospectively identified 112 patients who underwent proximal femur replacement after resection of a malignant bone tumor and had radiological follow-up longer than 12 months. Patient demographic, surgical, and oncologic factors were recorded, acetabular wear was measured using the classification proposed by Baker, and prosthetic failure was classified using the International Society on Limb Salvage classification. Functional assessment was performed using the Musculoskeletal Tumor Society Score and Harris Hip Score. RESULTS: Prevalence of acetabular wear was 28.6%. Secondary conversion to total hip arthroplasty was required in 5 patients (4.6%), all treated for primary bone tumors. No patient treated for metastatic tumor had higher grade acetabular wear or required revision. Significant risk factors for the development of acetabular wear were age under 40 (P = .035) and longer follow-up (63 vs 43 months, P = .004). Other patient, surgical, or adjuvant treatment-related factors were not associated with acetabular revision or acetabular wear. The dislocation rate in the patient cohort was 0.9%. CONCLUSION: Bipolar hemiarthroplasty proximal femoral replacement represents a durable reconstruction after tumor resection. Hip instability is rare. Acetabular erosion is rare and can be successfully treated with conversion to total hip arthroplasty. Young patients with long-term survival over 10 years are at risk. In reconstruction for metastases, instability and acetabular wear are rare.

Megaprosthetic replacement of the distal humerus: still a challenge in limb salvage.

BACKGROUND: The distal humerus is a rare location of bone tumors. Because of the complexity of the elbow joint, poor soft-tissue coverage, and proximity of nerves and vessels, resection and endoprosthetic reconstruction are demanding. METHODS: This retrospective study evaluated the clinical results after distal humeral resection and megaprosthetic reconstruction in 12 patients with an average age of 46 years. All patient files were reviewed for clinical information, and postoperative function and patients' contentment were assessed using the Musculoskeletal Tumor Society score. RESULTS: The predominant diagnoses were bone and soft-tissue sarcoma (n = 6), giant cell tumor (n = 2), and renal cell carcinoma metastasis (n = 2). Local recurrence was the reason for secondary amputation in all cases (n = 3). The prosthetic survival rate after surgery was 82% at 2 years and 64% at 5 years. Reconstruction failure was mainly caused by aseptic loosening of the humeral stem, occurring in 27% (n = 3), followed by aseptic loosening of the ulnar stem in 9% (n = 1) and periprosthetic infection in 9% (n = 1). The mean Musculoskeletal Tumor Society score was 24 points (range, 20-30 points). An extension lag of more than 10° was noted in 6 patients (55%). CONCLUSION: Our results suggest that limb salvage with a distal humeral replacement can achieve good functional results in most patients, although the complication rate with special emphasis on the loosening rate of the humeral stem is high. However, limb salvage was not achieved in 27% of patients because of local recurrence.

Silver-coated megaprostheses in the proximal femur in patients with sarcoma.

BACKGROUND: Proximal femur replacements in patients with sarcoma are associated with high rates of infection. This study is the largest one comparing infection rates with titanium versus silver-coated megaprostheses in sarcoma patients. METHODS: Infection rates were assessed in 99 patients with proximal femur sarcoma who underwent placement of a titanium (n = 35) or silver-coated (n = 64) megaprosthesis. Treatments administered for infection were also analyzed. RESULTS: Infections occurred in 14.3% of patients in the titanium group, in comparison with 9.4% of those in the silver group, when the development of infection was the primary end point. The 5- and 10-year event-free survival rates for the prosthesis relative to the parameter of infection were 90% in the silver group and 83% in the titanium group. The overall infection rates were 10.9% in the silver group and 20% in the titanium group. Two patients each in the silver and titanium groups ultimately had to undergo amputation. The need for two-stage prosthesis exchanges (57.1% in the titanium group) declined to 14.3% in the silver group. CONCLUSION: Using a silver-coated proximal femoral replacement nearly halved the overall infection rate. When infections occurred, it was usually possible to avoid two-stage prosthesis exchanges in the silver group.

Tumour endoprosthesis replacement in the proximal tibia after intra-articular knee resection in patients with sarcoma and recurrent giant cell tumour.

PURPOSE: Proximal tibia replacements are commonly associated with post-operative complications and poor functional results due to an insufficiency of the extensor mechanism. METHODS: This study evaluated the clinical results with a special emphasis of the extensor mechanism reconstruction with a reattachment tube and complications after intra-articular resection of the proximal tibia and reconstruction with a tumour endoprosthesis (MUTARS®) in 98 patients (median age 18 years) with malignant bone tumours or giant cell tumours. RESULTS: Kaplan-Meier analysis showed that the limb survival rates were 94.9, 90.5 and 74.5% at one, two and ten years, respectively. Periprosthetic infection was the most common reason for secondary amputation (eight patients). The cumulative incidence rates of prosthetic failure (Henderson II-IV) were 18% at two years and 29% at five years post-operatively. An active extension deficit of more than 10° was noted in six patients only. CONCLUSIONS: These results suggest that limb salvage with tumour prostheses after intra-articular resection can achieve good functional results with an active extension of the knee in the majority of patients. While mechanical complications can be treated successfully with revision surgery, periprosthetic infection continues to be the main reason for secondary amputation.

Silver-Coated Megaprosthesis of the Proximal Tibia in Patients With Sarcoma.

BACKGROUND: Proximal tibia arthroplasty is associated with high rates of infection. This study is the largest one that has compared the infection rates with titanium vs silver-coated megaprostheses in patients treated for sarcomas. METHODS: The infection rate in 98 patients with sarcoma or giant-cell tumor in the proximal tibia who underwent placement of a titanium (n = 42) or silver-coated (n = 56) megaprosthesis (MUTARS) was assessed, along with the treatments administered for any infection. RESULTS: As the primary end point of the study, the rates of infection were 16.7% in the titanium group and 8.9% in the silver group, resulting in 5-year prosthesis survival rates of 90% in the silver and 84% in the titanium group. Whereas in the titanium group 37.5% of patients ultimately had to undergo amputation in the present study, these mutilating surgical procedures were only necessary in the silver group in one patient (14.3%). CONCLUSION: The use of silver-coated prosthesis reduced the infection rate in a relatively large and homogeneous group of patients. In addition, less-aggressive treatment of infection was possible in the group with silver-coated prosthesis.

Forequarter amputation: a safe rescue procedure in a curative and palliative setting in high-grade malignoma of the shoulder girdle.

BACKGROUND: Forequarter amputation (FQA) is a surgical treatment of tumors in the upper extremity and shoulder girdle that infiltrate the neurovascular bundles. In both curative and palliative settings, FQA can serve as an effective oncological treatment. METHODS: This study presents the FQA-related data of 30 patients (mean age 50 years) treated between 2000 and 2012. Their medical condition was high-grade bone or soft tissue sarcoma in 26 and high-grade carcinoma in four cases. RESULTS: Mean operation time was 119 min. One major and five minor complications occurred in the postoperative period. Resection margins were wide in 91 % of patients. Local recurrence was observed in four patients after 19 months on average. Patients treated with curative intention had a 5-year survival chance of 39 %. Average survival after palliative amputation was 11 months. CONCLUSIONS: FQA provides an opportunity for adequate oncological margins in large tumors, while offering relief from tumor-induced distress in palliative situations.

Analysis of surgical and oncological outcome in internal and external hemipelvectomy in 34 patients above the age of 65 years at a mean follow-up of 56 months.

BACKGROUND: With an increasing life expectancy and improved treatment regimens for primary or secondary malignant diseases of soft tissue or bone, hemipelvectomy will have to be considered more often in elderly patients in the future. Scientific reviews concerned with the surgical and oncological outcome of elderly patients undergoing hemipelvectomy are scarce. Therefore, it is the purpose of this study to review the outcome of patients treated with that procedure at our hospital and investigate the feasibility of such extensive procedures at an increased age. METHODS: A retrospective analysis of thirty-four patients who underwent hemipelvectomy at an age of 65 years or older was performed to determine their surgical and oncological outcome. The Kaplan-Meier method was used to calculate the cumulative probability of survival using the day of tumor resection as a starting point. Univariate analysis was carried out to investigate the influence of a particular single parameter. RESULTS: The mean age at operation was 70.2 years. Thirty patients were treated for intermediate- to high-grade sarcoma and 81.8% of tumors were larger than or equal to 10 cm in the longest diameter. Thirteen patients underwent internal hemipelvectomy and nine patients external hemipelvectomy as a primary procedure. Twelve patients were treated with external hemipelvectomy after failed local tumor control at primary operation. Wound infection occurred in 61.7% of cases. Three patients underwent amputation for non-manageable infection after internal hemipelvectomy. Hospital mortality was 8.8%. Clear resection margins were obtained in 88% of patients; in another 6% of patients planned intralesional resections were performed. Local recurrence occurred in 8.8% of patients at a mean time of 26 months after operation. Eleven patients are alive with no evidence of disease and 23 patients died of disease or other causes. Patients with pulmonary metastases had a mean survival period after operation to DOD of 22 months compared to 37 months in the curative group. CONCLUSION: Despite an elevated rate in hospital mortality and wound infection, this study suggests that hemipelvectomy is feasible in elderly patients, although requiring long hospitalization periods and causing a limited functional outcome.

Improvement of the shoulder function after large segment resection of the proximal humerus with the use of an inverse tumour prosthesis.

PURPOSE: Active shoulder function after segmental tumour resection of the proximal humerus and endoprosthetic reconstruction is regularly compromised, while the overall arm function allows a satisfying use in daily activities. The main functional problem remains the loss of huge parts of the shoulder girdle musculature and its bony attachment. In revision arthroplasty inverse shoulder implants can improve the active range of motion significantly in comparison to anatomical shaped prostheses. The aim of this study was to investigate if these promising experiences are transferable to reconstructions after tumour resection of the proximal humerus by using a modular inverse tumour prosthesis. METHODS: In this study we observed the functional and oncological results of 18 inverse proximal humerus endoprosthetic replacements (IPHP) with the MUTARS system (Implantcast®) after resection of benign (1x giant cell) and malignant (11x primary bone sarcoma, 5x bone metastasis of carcinoma) bone tumours. Mean age at operation was 42 years. The mean postoperative follow-up was 33 months (range ten to 120). RESULTS: Resection margins were wide in 13 and marginal in five patients. Mean reconstruction length was 15.1 cm (range 6-25 cm). Mean operation time was 191 minutes. The axillary nerve was mostly preserved in 78 % (n = 14). At latest follow-up the patients presented a medium MSTS-score of 24.6/30. The mean active arm abduction in the shoulder joint was 78° and 88° active arm elevation for patients with intact axillary nerve function, but significantly reduced for the four patients with compromised deltoid function. One patient needed a surgical revision due to a deep implant infection. CONCLUSIONS: The IPHP offers a significant improvement of active shoulder function in patients in whom the axillary nerve can be preserved in comparison to anatomically-shaped implants. However, for patients without any deltoid function there is no benefit regarding an improved active range of motion using an IPHP.

Stump lengthening procedure with modular endoprostheses - the better alternative to disarticulations of the hip joint?

We report outcomes of 28 patients after stump-lengthening procedures (SLPs) with modular tumor endoprostheses following high-thigh amputation and hip disarticulation over 11years. Mean follow up was 41.3months (range 7.4 to 133.6months). Mean Musculoskeletal Tumour Society Score was 56% (n=11); ten out of eleven patients alive used an exoprosthesis regularly. Complications occurred in 15 patients with infection being most common. In 2 cases, the prostheses had to be explanted. Our data suggest that SLP facilitates post-operative rehabilitation and prosthesis usage. Modular endoprostheses for stump-lengthening allow optimization of remnant soft-tissue envelope, reducing the risk of stump perforation.

Modular tumor endoprostheses in surgical palliation of long-bone metastases: a reduction in tumor burden and a durable reconstruction.

BACKGROUND: Surgical treatment of bone metastases has become increasingly important as patients live longer with metastatic cancer and one of the main aims is a long-lasting reconstruction which survives the patient. Conventional osteosynthesis may not be able to achieve this objective in the context of modern day cancer care. METHODS: This study evaluates the oncological outcomes, treatment-related complications, and function after resection of metastases and reconstruction with modular tumor endoprostheses in 80 patients. All patients who underwent surgical treatment with modular tumor prostheses for bone metastases from 1993 to 2008 were traced by our tumor database and clinical information was recorded from patient case. RESULTS: Mean age was 63 years. The most common primary tumors were renal cell (47%), breast (21%), and lung (8%). The proximal femur was affected in 45%, proximal humerus in 26%, and the distal femur in 17% of cases. In 22 cases, the tumor prosthesis was implanted during a revision operation. Mean overall survival after surgery was 2.9 years. Overall survival rate was 70% at one year and 20% at five years. Implant survival was 83% after one year and 74% at five years. Overall rate of operative revision was 18%. CONCLUSIONS: Our data collectively suggest that despite higher costs, implantation of modular tumor endoprostheses may be a suitable treatment for bone metastases with a low complication rate and rapid improvement in function in appropriately selected patients.

Short-stem reconstruction for megaendoprostheses in case of an ultrashort proximal femur.

BACKGROUND: Tumors of the distal femur and diaphysis with proximal metaphyseal extension into the femur present a challenge for limb salvage. The conventional treatment consists of limb salvage with total femur replacement. This case study aims to present preliminary results and experience with short-stem reconstruction, focusing on the mechanical stability of the procedure. METHODS: Sixteen short stems were implanted in 15 patients. The patients' mean age was 33,3 years (range 11-73). In 10 patients, the stem was used for distal femur reconstruction, in one patient for diaphyseal reconstruction, and in four for a stump lengthening procedure. All of the patients had a primary sarcoma in their history. The mean follow-up period was 37 months (range 5-95 months). The clinical and functional follow-up data were analyzed. RESULTS: Ten patients (67%) were still alive at the time of evaluation. Three complications associated with the stem were noted. In one case, there was aseptic loosening after 58 months; in another, aseptic loosening occurred because the diameter of the stem had initially been too small; and in one case, there was breakage of the fixation screw, without any clinical symptoms. The average Musculoskeletal Tumor Society score for all patients was 23 (range 9-28). The mean result for the distal femur replacement was 24 (range 22-28). None of the surviving patients with distal femur replacements needed any crutches or had a Trendelenburg limp. Both living patients who underwent a stump lengthening procedure were able to walk with an exoprosthesis. CONCLUSIONS: The short stem is a good solution that can prevent or delay proximal femur resection in patients with tumors extending into the proximal metaphyseal femur. Additional risks of proximal femur resection, such as dislocation, opening of another oncological compartment, Trendelenburg limp, and chondrolysis can be avoided.

Small sharp exostosis tip in solitary osteochondroma causing intermittent knee pain due to pseudoaneurysm.

BACKGROUND: Complications of solitary or multiple osteochondromas are rare but have been reported in recent literature. Most reported complications arose in patients with multiple and/or sizable osteochondromas. CASE PRESENTATION: A 22-year-old, female, Caucasian patient with obesity presented with intermittent knee pain and hematoma of the right calf. The MRI depicted a small, sharp exostosis tip of the dorsal distal femur with a surrounding soft-tissue mass. After profuse bleeding occurred during biopsy of the soft tissue mass, angiography revealed a pseudoaneurysm of the right popliteal artery. In a second-stage surgery the exostosis tip and pseudoaneurysm were resected. CONCLUSION: Complications can also arise in small, seemingly harmless osteochondromas. Surgical resection should be considered as a preventive measure when exostoses form sharp tips close to neurovascular structures regardless of total osteochondroma size.

Evaluation of a reconstruction reverse shoulder for tumour surgery and tribological comparision with an anatomical shoulder arthroplasty.

PURPOSE: The functional results after reconstruction of the proximal humerus in tumour surgery are poor. Therefore, a reversed proximal humerus replacement was developed in our institution (MUTARS humerus inverse). A low degree of wear on the polyethylene is required because of the patients' youth and demands on shoulder function. A special type of polyethylene with shock-absorbing properties has been developed to minimise polyethylene wear in the MUTARS inverse proximal humerus replacement. We compared the tribological properties of an anatomical shoulder prosthesis (CAPICA) with the new reversed proximal humerus replacement (MUTARS humerus inverse). METHODS: Both prostheses were tested up to 5 × 10(6) cycles. Every millionth cycle the surface was inspected and a gravimetric measurement was performed. A measurement of surface roughness was done before testing and after 5 × 10(6) cycles. RESULTS: In both prostheses after 5 × 10(6) cycles there were no major defects, such as delamination, observed. In the reversed proximal humerus replacement abrasion of 28 mg/10(6) cycles was detected. The mean abrasion of the anatomical prosthesis was 9.28 mg/ 10(6) cycles. CONCLUSION: The glenoid component of the first reversed humerus replacement (MUTARS humerus inverse) has wear properties comparable to those of normal reversed shoulder prostheses. This is important, as this type of prosthesis is used in young patients after resection of bone tumours, with a good functional outcome. It can, therefore, be expected that the revision rate due to wear will be as high as in patients with normal reversed shoulder prostheses.

Scar sarcoidosis on a finger mimicking a rapidly growing soft tissue tumour: a case report.

BACKGROUND: Scar sarcoidosis is a rare and uncommon but specific cutaneous manifestation of sarcoidosis. In general it arises in pre-existing scars deriving from mechanical traumas. As most surgeons dealing with scars might not be aware of cutaneous sarcoidosis and its different types of appearance the appropriate staging and treatment might be missed or at least delayed. To our knowledge this is the first case in literature of scar sarcoidosis on a finger. CASE PRESENTATION: We present a case of a 33-year-old carpenter who developed scar sarcoidosis on his right index finger 4 years after the tendon of the long digital flexor got accidentally cut by an angle grinder. He was referred due to a swelling of the finger suspected to be a malignant soft tissue tumour. The circumference of the affected finger had almost doubled, adding up to 94 mm. Incision biopsy revealed typical noncaseating granulomas. Further investigation showed a systemic extent of the disease with involvement of the lung. A systemic treatment with oral steroids led to an almost full regression of the swelling with restoration of function and resolution of lung infiltrates. CONCLUSION: In case of a suspicious and/or progressive swelling a definite diagnosis should be achieved by biopsy within a short time to enable a proper treatment. If scar sarcoidosis is proven further investigation is necessary to exclude a systemical involvement. A surgical treatment of the swelling is not indicated.

Giant cell tumors of the axial skeleton.

Background. We report on 19 cases of giant cell tumor of bone (GCT) affecting the spine or sacrum and evaluate the outcome of different treatment modalities. Methods. Nineteen patients with GCT of the spine (n = 6) or sacrum (n = 13) have been included in this study. The mean followup was 51.6 months. Ten sacral GCT were treated by intralesional procedures of which 4 also received embolization, and 3 with irradiation only. All spinal GCT were surgically treated. Results. Two (15.4%) patients with sacral and 4 (66.7%) with spinal tumors had a local recurrence, two of the letter developed pulmonary metastases. One local recurrence of the spine was successfully treated by serial arterial embolization, a procedure previously described only for sacral tumors. At last followup, 9 patients had no evidence of disease, 8 had stable disease, 1 had progressive disease, 1 died due to disease. Six patients had neurological deficits. Conclusions. GCT of the axial skeleton have a high local recurrence rate. Neurological deficits are common. En-bloc spondylectomy combined with embolization is the treatment of choice. In case of inoperability, serial arterial embolization seems to be an alternative not only for sacral but also for spinal tumors.

Patellar resurfacing as a second stage procedure for persistent anterior knee pain after primary total knee arthroplasty.

PURPOSE: Knee pain after total knee arthroplasty may be caused by an unresurfaced patella. Secondary isolated resurfacing of the previously unresurfaced patella in total knee arthroplasty remains controversial. The aim of this retrospective study was to evaluate the outcome after patellar resurfacing as a second stage procedure. METHODS: The study included 22 patients (13 female/nine male) who underwent resurfacing of the patella with a mean follow-up of 61.8 ± 39.2 months. The mean age of the patients was 60 ± 9.7 years at the time of operation. The average period between total knee arthroplasty and patellar resurfacing was 26.3 ± 15.2 months. The patient's subjective satisfaction was assessed by a custom-made questionnaire. RESULTS: The mean Knee Society Score improved significantly from 60.1 ± 8.3 to 77.0 ± 6.3 (p = 0.0063). The mean functional score also improved significantly from 42.7 ± 2.3 to 60.2 ± 3.9 (p = 0.001). Three patients (13.6%) needed further operative revision. CONCLUSIONS: Although clinical scores showed significant improvement some patients continued to have pain and remained dissatisfied without detecting a specific reason. Further studies are needed to better elucidate the benefit of patellar resurfacing as second stage procedure.

Reconstruction of forearm deformity by distraction osteogenesis in children with relative shortening of the ulna due to multiple cartilaginous exostosis.

BACKGROUND: In patients with multiple cartilaginous exostosis, distal ulnar osteochondromas frequently cause forearm deformities, with relative ulnar shortening, wrist joint deviation, and varus bowing. Progressive deformation often leads to pain, functional impairment, and cosmetic problems. Surgical ulnar lengthening is necessary to restore the carpal balance. The results of fixator-controlled ulnar lengthening were investigated in this study, using appropriate clinical and radiologic parameters and focusing on medium-term functional and structural outcomes. METHODS: Twelve children (3 boys, 9 girls; mean age 9.8 y) with multiple cartilaginous exostosis-induced ulnar shortening treated with fixator-controlled ulnar callotasis were evaluated retrospectively based on clinical and radiographic examinations preoperatively, after fixator removal, and at a follow-up investigation. Subjective symptoms and objective joint function were assessed clinically, whereas the extent of ulnar shortening, radial articular angle, carpal slip, and radial head dislocation were determined radiographically. RESULTS: The average follow-up period was 24.6 months. The mean ulnar shortening and radial articular angle improved significantly, from 14.3 mm or 38.7 degrees preoperatively to 1.7 mm or 25.6 degrees after fixator removal and showed a slight but significant increase to 5.2 mm or 30.1 degrees at the follow-up. Carpal slip and radial head dislocation remained unchanged. With the exception of radial abduction, no notable functional advancement was observed. One unintended ulnar overlengthening with a subsequent ulnocarpal impaction syndrome, one premature callus consolidation, and two fixator dislocations were noted. CONCLUSIONS: In agreement with literature reports, carpal balance can be restored over the medium term. However, mild recurrences of ulnar shortening and radial malformation were observed during further development. To prevent deformity progression in immature patients, surgery should be carried out early. The optimal timing of surgery needs to be calculated precisely to take advantage of the high remodeling potential and an acceptable degree of recurrent deformity. Ulnar lengthening is necessary, but overcorrection is inadvisable due to possible ulnocarpal impaction syndrome. As significant remodeling effects on the radius were observed, simultaneous radial correction procedures are not recommended a priori.

AML1/ETO induces self-renewal in hematopoietic progenitor cells via the Groucho-related amino-terminal AES protein.

The most frequent translocation t(8;21) in acute myeloid leukemia (AML) generates the chimeric AML1/ETO protein, which blocks differentiation and induces self-renewal in hematopoietic progenitor cells. The underlying mechanisms mediating AML1/ETO-induced self-renewal are largely unknown. Using expression microarray analysis, we identified the Groucho-related amino-terminal enhancer of split (AES) as a consistently up-regulated AML1/ETO target. Elevated levels of AES mRNA and protein were confirmed in AML1/ETO-expressing leukemia cells, as well as in other AML specimens. High expression of AES mRNA or protein was associated with improved survival of AML patients, even in the absence of t(8;21). On a functional level, knockdown of AES by RNAi in AML1/ETO-expressing cell lines inhibited colony formation. Similarly, self-renewal induced by AML1/ETO in primary murine progenitors was inhibited when AES was decreased or absent. High levels of AES expression enhanced formation of immature colonies, serial replating capacity of primary cells, and colony formation in colony-forming unit-spleen assays. These findings establish AES as a novel AML1/ETO-induced target gene that plays an important role in the self-renewal phenotype of t(8;21)-positive AML.

Proximal fibula resection in the treatment of bone tumours.

BACKGROUND AND OBJECTIVES: We present a large study of patients with proximal fibula resection. Moreover we describe a new classification system for tumour resection of the proximal fibula independent of the tumour differentiation. METHODS: In 57 patients the functional and clinical outcomes were evaluated. The follow-up ranged between six months and 22.2 years (median 7.2 years). The indication for surgery was benign tumours in ten cases and malignant tumours in 47 cases. In 13 of 45 patients, where a resection of the lateral ligament complex was done, knee instability occurred. In 32 patients a resection of the peroneal nerve with resulting peroneal palsy was necessary. RESULTS: Patients with peroneal resection had significantly worse functional outcome than patients without peroneal resection. An ankle foot orthosis was tolerated well by these patients. Three of four patients with pathological tibia fracture had local radiation therapy. There was no higher risk of tibia fracture in patients with partial tibial resection. CONCLUSIONS: Resection of tumours in the proximal fibula can cause knee instability, peroneal palsy and in cases of local radiation therapy, a higher risk of delayed wound healing and fracture. Despite the risks of proximal fibula resection, good functional results can be achieved.