The role of the fibula head flap for joint reconstruction after osteoarticular resections.

INTRODUCTION AND AIM: Endoprosthetic reconstruction is considered the mainstay of limb salvage in periarticular bone tumours. However, this procedure has limited durability especially when performed in young patients. The free fibula head flap including the proximal articular surface represents one option for hemiarthroplasty reconstruction. The aim of this study was to investigate the role of the fibula head flap for joint reconstruction after osteoarticular resections. PATIENTS AND METHODS: All patients who underwent hemiarthroplasty procedures between 2000 and 2006 using the free fibula head flap were included in the study. Functional assessments were performed using the American Musculoskeletal Tumor Society (AMTS) classification. RESULTS: There were five males and two females (mean age: 22.6 ± 15.9 years). Five patients underwent reconstruction following resection of malignant bone tumours and two for chronic osteomyelitis of the distal humerus. In three patients, the fibula was used for distal radius and wrist joint reconstruction, and the remaining four patients for reconstruction of the distal humerus and elbow joint. A vascularised growth plate transfer based on the lateral geniculate vessels was performed in two patients. Atechnetium-bone scan confirmed viability of all flaps 10 days after surgery, and radiographic bony union was confirmed on average 5 months following surgery. There were no complications with the recipient or donor site after a median follow-up of 71 months (range: 12 months to 10 years). All patients achieved reasonable return of function and were able to perform all activities of daily living. CONCLUSIONS: We demonstrate that the hemiarthroplasty procedure using the free fibula flap with its proximal head is a safe procedure with good functional results. Performing autologous arthroplasty using a free fibula head flap may be a promising alternative to an endoprosthesis or alloplastic reconstruction with a low risk of complications and morbidity.

Hypofractionated adjuvant radiation therapy of soft-tissue sarcoma achieves excellent results in elderly patients.

OBJECTIVE: Adjuvant radiation therapy (RT) is an essential part of combined limb-sparing treatment of soft-tissue sarcoma (STS). Elderly or medically unfit patients often have difficulty in completing 6-7 weeks of standard fractionated daily treatment. Our aim was to evaluate the efficacy of a hypofractionated adjuvant approach with RT for STS in elderly and debilitated patients. METHODS: 21 elderly patients were treated with a short course of adjuvant RT (39-48 Gy, 3 Gy per fraction) for STS. The medical records of the patients were retrospectively reviewed for local or distant recurrence and side effects of RT. RESULTS: At a mean 26 months of follow-up, three local recurrences (14%) were detected. Eight patients (38%) had lung metastases during the observed period. Three of them died from metastatic disease. The hypofractionated radiation was well tolerated with minimum long-term side effects. CONCLUSION: Hypofractionated adjuvant radiation appears to be an effective treatment in terms of local control in elderly and debilitated patients. ADVANCES IN KNOWLEDGE: The results of this study might provide an alternative to commonly used standard fractionation of radiotherapy in sarcoma patients.

Efficacy of high vs low dose TNF-isolated limb perfusion for locally advanced soft tissue sarcoma.

AIMS: The administration of a high dose of rTNF-alpha (3-4 mg) and Melphalan via isolated limb perfusion (ILP) for patients with locally advanced limb STS was shown to be effective. Reports that a low dose of TNF (1mg) is as effective, led to the adoption of the low dose regimen as the treatment of choice. The purpose of this study was to compare two groups of patients with locally advanced limb STS, that was treated with high and low dose TNF-ILP, in terms of limb preservation. METHODS: Retrospective study of 41 patients who underwent ILP, with "high dose" (HD) and "low dose" (LD) TNF. ILP/TNF was performed on candidates to either amputation or significantly mutilating surgery without this treatment. In both groups, all patients, with the exception of three in each group, underwent resection of the residual tumor or tumor bed or limb 8-12 weeks after the procedure. RESULTS: In the HD group, marked tumor softening occurred within 48 h, and in tumors protruding through the skin, hemorrhagic necrosis was evident within 24h. The overall response rate was 65.2%. Five patients achieved a CR and 10 had a PR; in five of these patients >90% necrosis of the tumor occurred. In eight patients, only minimal regression was observed (stabilization of disease). The rate of limb sparing was 69.5%. In the LD group, the overall response rate was 30.7%. CR was achieved in one patient. PR was observed in two. Two patients were lost to follow up. Of the remaining 15 patients, limb preservation was achieved in 53.3%. CONCLUSION: Despite the retrospective comparison and possible selection bias, it is possible to raise the concern that at least some patients may benefit from a higher TNF dose perfusion in ILP for advanced limb STS.

Fifteen years of bone tumor cryosurgery: a single-center experience of 440 procedures and long-term follow-up.

BACKGROUND: This summary of a single center's extensive cumulative experience in bone tumor cryosurgery assesses the long-term outcome of bone conservation surgery in which adjuvant cryosurgery plays a pivotal role. MATERIALS AND METHODS: We performed 440 cryosurgical procedures between January 1988 and December 2002. Two-thirds of the series comprised a variety of primary benign-aggressive and low-grade malignant lesions, and one-third were primary high-grade and metastatic bone tumors. The anatomical locations included almost every bone of the skeleton. Two methods of bone cryosurgery were used: Marcove's "open" direct-pour system using liquid nitrogen (1988-1997) and Meller's "closed" argon-based system (1998 to the present). RESULTS: The study cohort consisted of 214 males and 191 females (age range 5-82 years). The median follow-up was 7 years (range 3-18). The overall local recurrence rate was 8%: fractures=1%, infections=2% and skin burns=1.3%. There were three cases of transient nerve palsies in areas other than the sacrum, and four cases of late osteoarthritis of an adjacent joint. The functional outcome for the 372 patients with no evidence of disease was almost 100% "good" and "excellent" (American Musculo-skeletal Tumor Society System). Only two patients needed secondary amputations. CONCLUSIONS: Bone cryosurgery is a safe and effective limb-, joint- and even epiphysis-sparing surgical technique in suitable types of bone tumors, temporarily or permanently obviating the need for resection surgery.

Synovial sarcoma of the extremities and trunk: a long-lasting disease.

Synovial sarcoma (SS) of an extremity or trunk is relatively rare and is approached by limb sparing surgery (LSS), radiation therapy (RT) and chemotherapy. We conducted a retrospective analysis of the clinical and histopathological data of 73 patients with proven SS. At a median follow-up time of 6 years, local recurrence was seen in 17.8 and systemic recurrence 35.6% of patients (local-only, 6.8; systemic-only, 24.6; combined, 11%). The 10-year local recurrence-free survival (LRFS), systemic recurrence-free survival (SRFS) and overall survival (OS) rates were 78, 68 and 61%, respectively. LRFS was significantly better in patients treated with isolated limb perfusion (ILP); SRFS was influenced by the delay until diagnosis. The practical aspects of our observations are the need for long-term follow-up in order to diagnose recurrences, the fact that not all local or distant recurrences are necessarily associated with a shortening of OS time and the important role of induction ILP with TNF in cases of extremity SS.

A combined use of a free vascularised flap and an external fixator for reconstruction of lower extremity defects in children.

PURPOSE: To describe a combined use of a free vascularised flap and an external fixator for reconstruction of lower extremity defects in children, and correction of equinus contracture developed after removal of the external fixator using a circular dynamic frame. METHODS: Seven children (4 males) aged 4 to 12 (mean, 8) years were treated with 9 free vascularised flaps for 8 limbs (bilaterally in one patient and for a failed flap in another). Patient pathologies included: 3 soft tissue degloving injuries, one soft tissue and bone avulsion, one severe burn contracture, one resurfacing of soft tissue and bone necrosis, and one osteosarcoma resection defect. Free flap reconstruction was delayed in 6 patients (range, 3 weeks to 4 years). Static external fixators were used to stabilise the free vascularised flaps at the time of reconstruction, with the ankle in a neutral position. RESULTS: The mean follow-up was 5 (1-10) years. All flaps but one survived; the failed one was immediately reconstructed with a contralateral, latissimus dorsi flap. One anastomosis following a Kirschner-wire injury was successfully revised. Six patients had pin tract infections and were treated with oral antibiotics. Two patients developed equinus contracture 6 and 3 years later, after removal of the external fixator, and were corrected by distraction, using a dynamic Ilizarov frame. CONCLUSION: The combined use of a free flap and an external fixator for salvage of lower extremities is useful in children. Late development of equinus contracture can be safely corrected by distraction, without compromising flap viability.

Positron emission tomography/computed tomography with 18fluoro-deoxyglucose in the detection of local recurrence and distant metastases of pediatric sarcoma.

BACKGROUND: Combined positron emission tomography with (18)fluoro-deoxyglucose and computed tomography (FDG-PET/CT) has been used in the diagnosis and staging of various malignancies, but their use in the management of pediatric sarcomas is less well defined. The potential role of FDG-PET/CT in the diagnosis of local recurrence and distant metastases of pediatric sarcomas was investigated. PROCEDURE: Nineteen children (aged 2-21) with sarcoma (9 Ewing sarcoma, 3 osteogenic sarcoma, 7 rhabdomyosarcoma) were evaluated between January 2000 and December 2005 by FDG-PET/CT for suspected local relapse or distant metastases. The results of 21 FDG-PET studies, 16 CT scans, 9 magnetic resonance imaging (MRI) studies, and 7 bone scans (BSs) were compared with surgical pathology or clinical follow-up for at least 3 months. RESULTS: FDG-PET detected local relapse in all seven patients and distant metastases in 10/13 (77%). FDG-PET/CT and CT/MRI/BS results were discordant in eight patients. FDG-PET/CT was the only modality that detected distant metastases in two patients. PET/CT was true negative and excluded disease in three patients with abnormal CT/BSs and was false negative in three patients with distant metastases. CONCLUSION: FDG-PET/CT may be useful and complementary to other imaging modalities for the detection of recurrent pediatric sarcomas, especially at the primary site. Its potential advantages and limitations compared with conventional imaging modalities need to be further investigated in larger homogenous patient groups.

Liposarcoma in adult limbs treated by limb-sparing surgery and adjuvant radiotherapy.

Between December 1995 and March 2003, 38 adult patients with intermediate or high-grade liposarcoma in a limb were treated by limb-sparing surgery and post-operative radiotherapy. The ten-year local recurrence-free survival was 83%, the ten-year metastasis-free survival 61%, the ten-year disease-free survival 51% and the ten-year overall survival 67%. Analysis of failure and success showed no association with the age of the patients, gender, the location of the primary tumour, the type of liposarcoma and the quality of resection. Our results indicate that liposarcoma may recur even ten years after the end of definitive therapy and may spread to unexpected sites as for soft-tissue sarcoma.

Physical health and depressive symptoms in older Europeans. Results from EURODEP.

BACKGROUND: Associations between physical health and depression are consistent across cultures among adults up to 65 years of age. In later life, the impact of physical health on depression is much more substantial and may depend on sociocultural factors. AIMS: To examine cross-national differences in the association between physical health and depressive symptoms in elderly people across western Europe. METHOD: Fourteen community-based studies on depression in later life in nine western European countries contributed to a total study sample of 22 570 respondents aged 65 years and older. Measures were harmonized for depressive symptoms (EURO-D scale), functional limitations and chronic physical conditions. RESULTS: In the majority of the participating samples, the association of depressive symptoms with functional disability was stronger than with chronic physical conditions. Associations were slightly more pronounced in the UK and Ireland. CONCLUSIONS: The association between physical health and depressive symptoms in later life is consistent across western Europe.

Closed argon-based cryoablation of bone tumours.

We report our experience with a new technique for cryosurgical ablation of bone tumours which allows accurate determination of the temperature and freezing time within a cavity of any geometrical shape. Between 1997 and 2000, 58 patients diagnosed with 13 malignant and 45 aggressive benign bone tumours underwent argon-based cryoablation. This technique includes removal of the tumour by curettage and filling the cavity with a gel medium into which metal probes are inserted. Argon gas is delivered through the metal probes and both time and temperature are computer-controlled. After formal reconstruction, all patients were followed for more than two years. None had skin necrosis, infection, neurapraxia or thromboembolic complication. Fractures occurred in two patients (3.4%) and the tumour recurred in two patients (3.4%).

Association between telomerase activity and outcome in patients with nonmetastatic Ewing family of tumors.

PURPOSE: Telomerase is considered a molecular marker for malignancy. The aim of this study was to determine telomerase activity (TA) as a prognostic factor at diagnosis and as a marker for minimal residual disease during therapy and follow-up in nonmetastatic Ewing family of tumors (EFT). PATIENTS AND METHODS: Primary tumor specimens and 97 peripheral blood (PBL) samples from 31 EFT patients were analyzed for TA by the Telomeric Repeat Amplification Protocol (TRAP assay). The telomerase catalytic subunit (human telomerase reverse transcriptase [hTERT]) gene expression was evaluated by quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and telomere length was determined by Southern blotting. The presence of the EFT chimeric transcripts was analyzed by RT-PCR. Correlations with progression-free survival were evaluated. RESULTS: At diagnosis, TA in primary tumors did not correlate with outcome. During therapy and follow-up, highly significant correlation was observed between high TA in PBL samples and adverse prognosis (P <.0001). None of the patients harboring low TA progressed, with a long follow-up (median, 60 months) and a progression-free survival (PFS) of 100%. In nine patients, high TA actually could predict relapse, long before overt clinical relapse. The group of patients with high TA and positive RT-PCR had the most adverse outcome; PFS of 20% (P =.0025). TA was found to be a better prognostic factor than RT-PCR and histopathologic response at surgery. CONCLUSION: The results suggest that TA is a significant prognostic variable, superior to the established clinical prognostic parameters during therapy and tumor surveillance. It could be used in combination with RT-PCR for a new risk classification.

A jeep trip with young adult cancer survivors: lessons to be learned.

The paper describes major areas of concern and preferred coping mechanisms among 17 young survivors of childhood cancer who participated in an 8-day adventure jeep trip in Greece. The paper also deals with various aspects of "adventure therapeutic activity." The participants were videotaped and interviewed during and after the trip. The data gathered were studied through a process of content analysis. Survivors' main areas of concern included: coping with uncertainty, dependency versus autonomy, social exclusion, separation processes, body image, intimacy, sexuality and fertility, and occupation. Preferred coping styles included use of humor, religious beliefs, cognitive reframing, and use of imagination. The trip provided the young adults with an opportunity for physical challenges, and they reported improvements in self-confidence, independence, and social contacts. The trip served as a catalyst for further group activities and group support. An adventure trip seems to be a suitable therapeutic milieu for young adult cancer survivors, where they can profit from a nurturing setting in which rehabilitation-promoting resources are available. It still remains to be seen which components of such an activity are more health promoting, what contraindications there could be, if any, for participation in such a trip, and what role health professionals should play in this kind of activity.

Osteosarcoma over the age of forty.

The European Musculo Skeletal Oncology Society (EMSOS) has carried out a retrospective review of patients over the age of 40 years with osteosarcoma. 481 patients from 12 centres or multicentric groups were included. 42 patients had osteosarcoma arising in Paget's disease, median survival was 9 months. Patients with axial or metastatic tumours also did badly whilst 41 patients with radiation-induced osteosarcoma had a prognosis paralleling conventional osteosarcoma matched for patient age and site of the tumour. 238 patients had high grade non-metastatic osteosarcoma and had a survival of 46% at 5 years. Older patients had less chemotherapy and fared worse. Osteosarcoma in the elderly is a curable condition and warrants intensive treatment with chemotherapy and surgical resection.

The use of surgery and yttrium 90 in the management of extensive and diffuse pigmented villonodular synovitis of large joints.

OBJECTIVE: The surgical treatment of extensive diffuse pigmented villonodular synovitis (PVNS) of large joints alone is unsatisfactory, with high rates of local recurrence. Post-synovectomy adjuvant treatment with external beam radiation therapy or intra-articular injection of yttrium 90 (90Y) yielded better results. We report our experience with 10 cases treated with debulking surgery followed by intra-articular injection of 90Y. PATIENTS AND METHODS: Between January 1989 and June 1998, 10 patients (eight males and two females aged 15-49 yr) with extensive diffuse PVNS were treated. In six patients the knee joint, in three patients the ankle joint, and in one patient the hip joint were involved. The 10 patients underwent 15 operations, one patient had three surgical procedures, and three patients underwent two surgeries (the intervals between re-operations for local recurrence were 2-4 yr). All patients had an intra-articular injection of 15-25 mCi (555-925 MBq) 90Y, 6-8 weeks after the last surgery. RESULTS: Mean follow-up time was 6 yr (range 2.5-12 yr). All patients were followed using repeated computerized tomography (CT) scans, magnetic resonance imaging (MRI), plain X-ray films and bone scans semi-annually. In nine patients, neither evidence of disease nor progression of bone or articular destruction were noted. In one patient, stabilization of disease was achieved with no further evidence of bony or articular damage. No complications were noticed after surgery or after the intra-articular 90Y injection. CONCLUSION: A combination of debulking surgery with intra-articular injection of 90Y for extensive diffuse PVNS of major joints is a reliable treatment method, with good results.

ErbB-4 expression in limb soft-tissue sarcoma: correlation with the results of neoadjuvant chemotherapy.

ErbB-4 is a recently described growth factor receptor. Relatively little is known about its expression in human tumours. In this study, we assessed the possible role of erbB-4 as a tissue marker for soft-tissue sarcomas (STS) and its correlation with the response to chemotherapy. The histological specimen of 29 patients with STS of a limb who had received preoperative doxorubicin (ADR)-based chemotherapy were studied for the degree of necrosis and the expression of erbB-4 (by an avidin-biotin-peroxidase technique). ErbB-4 expression in the preoperative tissue samples was compared with the expression in the postchemotherapy resected tumour. The true objective response rate to preoperative chemotherapy was 34%. Wide resection of the tumour was done in 12 patients, marginal in 14, amputation in 2 and no surgery in 1. The tumour necrosis was above 90% in 9 patients, 60-90% in 12, and less than 60% in 7 patients. An increase in erbB-4 expression was more common in cases with no response to chemotherapy, while no change or a decrease in erbB-4 was more common in responsive tumours (P=0.004). No correlation could be found between the degree of necrosis or the chemotherapeutic regimen and the change in expression of erbB-4. The median disease-free survival (DFS) was longer for patients with a decrease or no change in expression of erbB-4 than for patients with increased expression. It is believed that postchemotherapy new expression or no downregulation of the erbB-4 molecule represents tumour aggressiveness and increased capability of growth and spread.

Cellular and molecular properties associated with osteosarcoma cells.

Osteosarcoma cells are recognized by abnormal function that causes a primary bone tumor. Osteosarcoma cells U(2)OS and SAOS-2 were analyzed for the expression of cell surface markers. High expression was quantified for hyaloronidase receptor (CD-44) > moderate for integrins (CD-51 and -61), > and lower for selectins (CD-62). High mitotic capacity were demonstrated by gene expression (measured by RT-PCR) and the protein level (measured by FACS) for cFOS, cMYC, and cJUN. The basic definition of osteosarcoma is excessive production of pathological osteoid. Expression of mRNA for matrix genes osteocalcin, osteonectin, and biglycan was studied. Osteocalcin and osteonectin were detected in RNA from primary cultured marrow stromal, trabecular bone cells, and osteosarcoma cell lines (U(2)OS, SAOS-2). mRNA for biglycan was detected only in primary cells and MG-63 cell line and was undetectable in RNA from U(2)OS, SAOS-2 osteosarcoma cell lines and by RNA extracted from bone biopsies of osteosarcoma patients. The absence of biglycan message observed in osteosarcoma samples provides evidence for the alterations in the extra cellular matrix which result with non-mineralized osteoid produced by the osteosarcoma cells.

Carcinoid tumor of the coccyx: case report and review of the literature.

STUDY DESIGN: Report of a patient with a carcinoid tumor of the coccyx. OBJECTIVES: To describe the clinical presentation, diagnosis, and treatment of a patient with a carcinoid tumor of the coccyx and to review the relevant medical literature in English. SUMMARY OF BACKGROUND DATA: No reports of a carcinoid tumor of the coccyx were found in the literature. Seven reports of carcinoid of the sacrum are described. METHODS: Clinical history, magnetic resonance imaging studies, and light and electronic microscope micrographs are reviewed. RESULTS: A coccygeal mass was detected during evaluation of coccygodynia in a 40-year-old woman. Four years after extended coccygectomy, there are no signs of local tumor recurrence. CONCLUSIONS: Carcinoid tumor of the coccyx is extremely rare. An extended coccygectomy may lead to a cure or at least to a prolonged disease-free interval.

Reconstruction of the extensor mechanism after proximal tibia endoprosthetic replacement.

The proximal tibia is a difficult area in which to perform a wide resection of a bone tumor. This difficulty is due to the intimate relationship of tumor in this location to the nerves and blood vessels of the leg, inadequate soft tissue coverage after endoprosthetic reconstruction, and the need to reconstruct the extensor mechanism. Competence of the extensor mechanism is the major determinant of functional outcome of these patients. Between 1980 and 1997, 55 patients underwent proximal tibia resection with endoprosthetic reconstruction for a variety of malignant and benign-aggressive tumors. Reconstruction of the extensor mechanism included reattachment of the patellar tendon to the prosthesis with a Dacron tape, reinforcement with autologous bone-graft, and attachment of an overlying gastrocnemius flap. All patients were followed for a minimum of 2 years; 6 patients (11%) had a transient peroneal nerve palsy, 4 patients (7.2%) had a fasciocutaneous flap necrosis, and 2 patients (3.6%) had a deep wound infection. Full extension to extension lag of 20 degrees was achieved in 44 patients, and 8 patients required secondary reinforcement of the patellar tendon. Function was estimated to be good to excellent in 48 patients (87%). Reattachment of the patellar tendon to the prosthesis and reinforcement with an autologous bone-graft and a gastrocnemius flap are reliable means to restore extension after proximal tibia endoprosthetic reconstruction.

Religion as a cross-cultural determinant of depression in elderly Europeans: results from the EURODEP collaboration.

BACKGROUND: The protective effects of religion against late life depression may depend on the broader sociocultural environment. This paper examines whether the prevailing religious climate is related to cross-cultural differences of depression in elderly Europeans. METHODS: Two approaches were employed, using data from the EURODEP collaboration. First, associations were studied between church-attendance, religious denomination and depression at the syndrome level for six EURODEP study centres (five countries, N = 8398). Secondly, ecological associations were computed by multi-level analysis between national estimates of religious climate, derived from the European Value Survey and depressive symptoms, for the pooled dataset of 13 EURODEP study centres (11 countries, N = 17,739). RESULTS: In the first study, depression rates were lower among regular church-attenders, most prominently among Roman Catholics. In the second study, fewer depressive symptoms were found among the female elderly in countries, generally Roman Catholic, with high rates of regular church-attendance. Higher levels of depressive symptoms were found among the male elderly in Protestant countries. CONCLUSIONS: Religious practice is associated with less depression in elderly Europeans, both on the individual and the national level. Religious practice, especially when it is embedded within a traditional value-orientation, may facilitate coping with adversity in later life.