Limb-salvage reconstruction with MUTARS hemipelvic endoprosthesis: a prospective multicenter study.

BACKGROUND: Limb-sparing surgery with hemipelvic megaprosthetic replacement is often limited by the high rate of associated complications. The aim of this evaluation was to assess clinical and oncological findings with respect to type, treatment and outcome of post-operative complications. METHODS: First results of 40 patients treated with individual MUTARS hemipelvic endoprostheses were evaluated in a prospective multicenter study. RESULTS: The mean follow-up period of the 27 male and 13 female patients was 24 months (range 1-61). The diagnosis was, in 29 cases, a primary bone or soft tissue sarcoma, in 11 patients, a metastasis. Clinical evaluation showed a mean Enneking score of 50% (range 10-70%). The oncological outcome revealed 25 patients (62.5%) alive with no evidence of disease. Seventeen of them had a primary tumour, eight a metastatic malignancy. Seven patients (17.5%) had died of their disease and eight (20%) were still alive but had developed a metastases and/or had had a recurrence of the primary tumour. The one- and two-year overall survival rate of the patients was 89% (+/- 0.10) and 81% (+/- 0.19), respectively. Post-operative complications occurred in 75% of the patients, predominantly wound-related disorders. The rate of implant revision was 22.5% with three septic and six aseptic cases of implant loosening. The estimated three-year-survival rate of the implant was 61.4% [CI95%: 0.36;0.87]. CONCLUSIONS: Periacetabular endoprosthetic replacement showed an acceptable functional and oncological outcome but had a high complication rate owing, predominantly, to infection. The indication for hemipelvic prosthesis in patients with a metastatic disease must be considered seriously.

Prospective, randomized, double-blind, multi-center, Phase III clinical study on transarterial chemoembolization (TACE) combined with Sorafenib versus TACE plus placebo in patients with hepatocellular cancer before liver transplantation - HeiLivCa [ISRCTN24081794].

BACKGROUND: Disease progression of hepatocellular cancer (HCC) in patients eligible for liver transplantation (LTx) occurs in up to 50% of patients, resulting in withdrawal from the LTx waiting list. Transarterial chemoembolization (TACE) is used as bridging therapy with highly variable response rates. The oral multikinase inhibitor sorafenib significantly increases overall survival and time-to-progression in patients with advanced hepatocellular cancer. DESIGN: The HeiLivCa study is a double-blinded, controlled, prospective, randomized multi-centre phase III trial. Patients in study arm A will be treated with transarterial chemoembolization plus sorafenib 400 mg bid. Patients in study arm B will be treated with transarterial chemoembolization plus placebo. A total of 208 patients with histologically confirmed hepatocellular carcinoma or HCC diagnosed according to EASL criteria will be enrolled. An interim patients' analysis will be performed after 60 events. Evaluation of time-to-progression as primary endpoint (TTP) will be performed at 120 events. Secondary endpoints are number of patients reaching LTx, disease control rates, OS, progression free survival, quality of live, toxicity and safety. DISCUSSION: As TACE is the most widely used primary treatment of HCC before LTx and sorafenib is the only proven effective systemic treatment for advanced HCC there is a strong rational to combine both treatment modalities. This study is designed to reveal potential superiority of the combined TACE plus sorafenib treatment over TACE alone and explore a new neo-adjuvant treatment concept in HCC before LTx.

Therapy outcome after multidisciplinary treatment for chronic neck and chronic low back pain: a prospective clinical study in 365 patients.

OBJECTIVES: This prospective longitudinal clinical study analyses the therapy outcome of 365 patients with either chronic neck (n = 134) or low back (n = 231) pain treated with a multidisciplinary biopsychosocial therapy approach. METHODS: Patients with chronic neck pain (NP) or low back pain (LBP) for 3 months or longer, corresponding sick leave for longer than 6 weeks, and clearly defined inclusion and exclusion criteria underwent a 3-week standardized inpatient multidisciplinary biopsychosocial therapy. Baseline sociodemographic, occupational, functional, and psychological data at entry into the study (T0) were comparable in both groups. At the 6-month follow-up (T1), five different therapy outcomes were analysed in both groups: back-to-work status, generic health status (the 36-item Short Form Health Survey, SF-36), pain intensity (visual analogue scale), functional capacity (Hannover back capacity score), and satisfaction with the therapy. RESULTS: Both treatment groups improved significantly in all outcome criteria between T0 and T1. In the total group, the back-to-work rate was 67.4%. At the final follow-up there were no significant differences between the group with chronic NP and the group with chronic LBP in the outcome criteria back-to-work status, improvement of health status and functional capacity, satisfaction with therapy, and reduction of pain. CONCLUSION: Evaluation of the main results of this study suggests that patients with chronic NP also derive significant benefit from a multidisciplinary treatment strategy, demonstrated in the literature so far mainly for patients with chronic LBP.

Preoperative elevation of serum C--reactive protein is predictive for prognosis in myeloma bone disease after surgery.

We investigated whether preoperative levels of serum C-reactive protein (CRP) and its correlation with tumour clinicopathological findings adds prognostic information beyond the time of diagnosis in patients with myeloma bone disease (MM) to facilitate the surgical decision-making process. Six hundred and fifty-eight myeloma patients were evaluated retrospectively for surgery. Clinicopathological variables of patients who underwent surgery (n=71) were compared between patients with preoperative CRP>or=6 mg l-1 and those with CRP<6 mg l-1. Univariate and multivariate analyses were performed to identify prognostic factors after surgery. Patients with an increase of CRP prior to surgery showed inferior survival compared to patients with normal levels. Patients with normal CRP levels at diagnosis but elevations prior to surgery do seem to have a similar unfavourable overall survival (OS) than patients with an increase both, at diagnosis and at surgery. Conversely, patients with normal CRP levels prior to surgery still have the best OS, irrespective of their basic values. Multivariate analysis revealed preoperative CRP levels above 6 mg l-1 Lactate dehydrogenase (LDH) above normal, and osteolyses in long weight bearing bones as independent predictors of survival. These findings suggest that in patients with MM serum levels of CRP increase during disease activity and might be significantly correlated with specific disease characteristics including adverse prognostic features such as osteolyses in long weight bearing bones. Thus, preoperative elevated CRP serum levels might be considered as independent predictor of prognosis and could provide additional prognostic information for the risk stratification before surgical treatment in patients with myeloma bone disease.

[Multimodal therapy patients with chronic cervical and lumbar pain. Results of a comparative prospective study]. / Multimodale Therapie bei chronischem HWS- und LWS-Schmerz. Ergebnisse einer prospektiven Vergleichsstudie.

BACKGROUND: Multimodal therapy has been established for patients with chronic low back pain, but studies reporting results in patients with chronic neck pain are rare. METHODS: This prospective clinical study compared the results in 97 patients with chronic cervical pain and 231 patients with chronic lumbar pain after three weeks of multimodal therapy. The following factors were analyzed in both groups at the beginning and after 6 months: ability to work, pain intensity and functional back capacity. RESULTS: Both groups had improved significantly after 6 months in all outcome parameters. Functional back capacity and ability to work at 6 months were not different between the two groups, but pain intensity was significantly lower in patients with low back pain compared to patients with neck pain. CONCLUSION: Multimodal therapy is also an efficient treatment strategy for patients with chronic cervical pain as has already been shown for patients with chronic lumbar pain.

Long-term survival after surgical intervention for bone disease in multiple myeloma.

BACKGROUND: We describe the surgical treatment, outcome and long-term survival of patients with multiple myeloma (MM) in response to conventional (CC) or high-dose (HDT) chemotherapy. PATIENTS AND METHODS: Eighty-four patients diagnosed with MM were recruited for the study (51 male, 33 female; median age 62 years) and consecutively surgically treated in a single institution during a 12-year period. The main end point of the study was overall survival after surgery. Cox regression analysis was used to estimate the effect of factors that may predict survival. RESULTS: Spinal surgery was performed in 54 cases, and 30 patients were surgically treated at the extremities. The post-surgical complication rate was low (17%; 14/84 patients). The median overall survival time was 47 months. Patients receiving HDT had a longer 5-year overall survival rate than patients receiving CC (51% versus 33%). Univariate predictors of mortality included age >65 years [risk ratio (RR) 1.62; P=0.023], osteolyses in long weight-bearing bones (RR 2.23; P=0.007) and an elevated C-reactive protein level >5 mg/l (RR 1.82; P=0.016); the latter remained significant as a predictor in multivariate analysis (RR 2.66; P=0.0209). CONCLUSIONS: Given the high number of patients reaching 5-year overall survival and the low post-surgery complication rate, surgery should pursue a long-term stable reconstruction of the affected bone.

[Bone and soft-tissue tumors of the foot and ankle]. / Knochen- und Weichteiltumoren des Fusses und Sprunggelenkes Epidemiologie, Versorgungsstrategie und klinisch-funktionelle Ergebnisse nach operativer Therapie.

BACKGROUND: This study reports the epidemiology of bone and soft-tissue tumors of the foot and ankle, presents therapy strategies, and evaluates mid-term clinicofunctional outcome after surgery for malignant tumors. METHODS: Two hundred four patients with tumors of the foot and ankle were analyzed (163 benign and 41 malignant). Epidemiology and surgical therapy are reported. RESULTS: The most frequent tumors were exostosis, bone cyst, and osteoid osteoma for benign tumors and metastases and chondrosarcoma and Ewing's sarcoma for malignant tumors. In more than 90% of the benign tumors, local resection could be carried out, whereas in malignant tumors, ablative procedures and arthrodeses were almost as common as limb- and joint-sparing techniques. However, follow-up revealed good functional results and a 5-year survival rate of 84% for patients with primary malignant tumors. CONCLUSION: Tumors of the foot and ankle require a thorough therapeutic strategy. Mid-term functional results and survival rate after surgical treatment are good, although a high percentage of ablative procedures or fusions could not be avoided in our patients.

Primary malignant tumours of bone and soft tissue in the elderly.

AIMS: This study reports outcome, functional results and quality of life of 45 elderly patients with age over 70 after surgery for primary malignant bone and soft tissue tumours. METHODS: There were 24 primary malignant bone tumours and 21 soft tissue sarcomas. The most frequent diagnoses were: chondrosarcoma, malignant fibrous histiocytoma and liposarcoma. Local tumour resection with and without osteosynthesis, endoprostheses, and amputations had been performed for surgery. The patients were prospectively followed in a tumour register. RESULTS: Complication and revision rate, functional outcome using the Musculoskeletal Tumor Society score, 5-year survival rate, median survival time and quality of life according to the Life Satisfaction Index A and the global health and quality-of-life scale of the QLQ-C30 revealed results that are only slightly inferior to those reported in younger tumour patients. CONCLUSIONS: The results of this study generally justify even extensive tumour surgery in the elderly patient over 70 although outcomes are not quite as good as those reported for younger adults. However, especially in the old patient indications like general condition and comorbidity should be given due consideration before any decision is made on whether surgery should be performed and if so what surgical technique should be applied.

Complications following operative treatment of primary malignant bone tumours in the pelvis.

AIM: To report the complication rates of limb-salvage reconstruction in the pelvis. Detailed analyses about the type, treatment and outcome of post-operative complications, various reconstruction options are presented. METHODS: Factors that might influence the occurrence of complications were evaluated of 50 consecutive surgically treated patients. RESULTS: The mean follow-up was 57 months. Limb-salvage procedures were used in 42/50 patients, amputations in 8/50 patients. After limb-salvage procedures complications occurred in 32/42 patients, after hemipelvectomy in 6/8 patients. The 1 and 5-year overall survival rate was 92 and 68%, respectively. CONCLUSION: There is a high complication rate in reconstructive techniques using hemipelvic autografts and/or allografts. These procedures are appropriate only in well selected patients. The complication rates following endoprosthetic reconstruction are comparably low.

Equal quality of life after limb-sparing or ablative surgery for lower extremity sarcomas.

This study investigated quality of life (QoL) and function of 124 patients with lower extremity sarcoma who underwent either amputation or limb-salvage surgery (LSS) in order to assess potential differences in subjective treatment outcome. The results reflect similar QoL in both treatment groups. However, in contrast to patients with LSS, who described QoL in terms of a high physical performance status with sports and recreational activities, amputees' QoL was strongly associated with their social acceptability. High QoL in amputees brings into question the expectations held with time-consuming advanced technical skills for LSS by physicians.

[Experiences with vascular pedicled fibula in reconstruction of osseous defects in primary malignant bone tumors]. / Erfahrungen mit der gefässgestielten Fibula in der Rekonstruktion von ossären Defekten bei primär malignen Knochentumoren.

To bridge large bone defects after resection of primary malignant bone tumors, an autologous free vascularized fibular graft was used in 31 patients (15 x upper limb, 16 x lower limb). The median bone defect measured 16 cm (7-29.5 cm). At the lower extremity the vascularized fibular transplant was reinforced with an allograft and different osteosyntheses. At the upper limb stabilization of the transplant was obtained exclusively by plate osteosynthesis or condylar plate. Applications and the authors' experiences are described and discussed in terms of clinical outcome, graft union, functional outcome, and complications for each localization. After a median of 48 months, ten complications at the upper limb and eight complications at the lower limb, respectively, were seen requiring secondary surgical revision. Major complications such as perioperative deaths or secondary amputations were not observed. Functional evaluation showed better results for the lower than for the upper extremity, due mainly to en bloc resection of proportionally large amounts of soft tissues around the shoulder girdle for local tumor control. Despite the demanding operative procedure and a large number of controllable complications, the good functional outcome and high patient satisfaction indicate that the free vascularized fibular graft is an option for limb-sparing surgery of primary malignant bone tumors.

[Amputation or limb salvage? Assessing quality of life after tumor operations of the lower extremity]. / Amputation oder Extremitätenerhalt? Beurteilung der Lebensqualität nach Tumoroperationen an der unteren Extremität.

The purpose of this study was to compare quality of life and subjective well-being between patients who underwent either amputation or limb-salvage procedures for lower extremity sarcomas in order to determine if this aspect can be considered in the decision on the type of surgery. Sixty-six patients were evaluated at least 1 year after surgery and systemic therapy for lower extremity sarcomas. Self-report questionnaires such as the Quality of Life Questionnaire (QLQ-C30), the Life Satisfaction Questionnaire (FLZ), and the Enneking Score (MSTS) were used. There were no differences in quality of life and subjective well-being between the two groups. Scores of the symptom scale (14.1 vs 13.2), the global quality of life (70.9 vs 71.0) as well as scores of the function scale (51.7 vs 50.3) were similar. Small differences in scores were found in social functioning but not in scores of physical, cognitive, and emotional functioning. Global subjective well-being in both groups was also similar (219.5 vs 223.7). High satisfaction was found in marital life and partnership as well as in self-assessment. The least satisfaction was found in finances. Results in functional outcome after limb-salvage procedures (77% vs 65%) were better. Although more complications were reported after limb-salvage procedures, they did not seem to have any impact on quality of life ( p=0.235, r(p)=0.112) and subjective well-being ( p=0.856, r(p)=0.140) of the patients whereas a correlation to function could be shown ( p<0.001, r(p)=0.595; p=0.015, r(p)=0.304). Additionally, a correlation between subjective well-being and the location of either amputation or reconstruction ( p=0.039, r(p)=- 0.309) could be shown. These findings demonstrate that the type of surgery has no influence on quality of life and subjective well-being after lower extremity sarcomas. Thus the decision for either limb-salvage procedures or amputation cannot be based on quality of life and subjective well-being but must be determined by oncological criteria.

[Parosteal osteosarcoma (POS). Clinical and therapeutic aspects]. / Das parossale Osteosarkom Klinische und therapeutische Aspekte.

Parosteal osteosarcoma is a malignant bone-forming tumor, which is characterized by its superficial origin and its high structural differentiation. Because of the radiological and histological variability, finding the right diagnosis is a great challenge for physicians, radiologists, and pathologists, especially at the time of primary manifestation. Usually there is a low-grade malignancy. Often a benign tumor is imitated so that finding the correct diagnosis is indispensable. Wide resection with sufficient margin is the adequate therapy. High-grade parosteal osteosarcoma needs adjuvant chemotherapy. Our own experience with secondary dedifferentiation and the possibility of primary undergrading shows that regarding diagnostics, operative therapy, and follow-up parosteal osteosarcoma should be treated like conventional osteosarcoma.

[Improving local control in patients with aggressive fibromatosis by combined surgery and radiotherapy]. / Verbesserung der lokalen Kontrolle bei Patienten mit aggressiver Fibromatose durch die Kombination von Chirurgie und Strahlentherapie.

INTRODUCTION: The purpose of this retrospective analysis is to evaluate whether the combination of surgery and radiation therapy in patients with aggressive fibromatosis influences the therapeutic outcome. METHOD: Clinical, radiological and pathological results of 23 consecutive cases with histologically proven aggressive fibromatosis were retrospectively analyzed. The median follow-up was 59 months. RESULTS: Twelve patients received surgery alone for their first treatment, 10 patients had a combination of surgery and radiotherapy and 1 patient had radiochemotherapy. Of 23 patients 14 (63%) had one or more local recurrences and 9 (39%) were recurrence-free. The patients received a total of 50 treatments: 29/50 (58%) treatments were followed by a local recurrence and 21/50 (42%) were without relapse. Twenty-nine treatments with local recurrence consisted of 25/29 (86%) surgical treatments, 3/29 (10%) combinations of surgery and radiation therapy, and 1/29 (3%) radiochemotherapy. Of the patients who had only surgery for their first treatment, after one year 8 of 12 (66%) and after 5 years all patients had a local recurrence. In the group with surgery and radiotherapy, there was no recurrence after 1 year and 1 recurrence after 5 years (p = 0.0001). CONCLUSION: We recommend a complete tumor resection, without mutilating the patient. Radiation therapy in combination with surgery in contrast to surgery alone is an efficient treatment option for reducing local recurrence.