Sigmund Skjeldal

The Scandinavian Sarcoma Group skeletal metastasis register: Survival after surgery for bone metastases in the pelvis and extremities

INTRODUCTION The assessment of the prognosis for the individual patient is important for the choice of surgical treatment of skeletal metastases. In 1999 the Scandinavian Sarcoma Group (SSG) initiated the Skeletal Metastasis Register as a multicentric, prospective study to provide a scientific basis for treatment recommendations. To improve prognostication we analyzed the survival of patients with skeletal metastases surgically treated at 9 SSG centres. PATIENTS AND METHODS 460 patients with an average age of 64 years underwent 501 operations for non-spinal skeletal metastases. 7% were operated for more than one metastasis. Carcinoma of the breast, prostate, kidney and lung were the dominating primary tumors. RESULTS The survival rate was 0.4 at 1 year, 0.3 at 2 years and 0.2 at 3 years. Univariate analysis showed that survival was related to bone localization, skeletal metastatic load, presence of visceral metastases, Karnofsky performance score, primary tumor type, presence of a complete pathological fracture and preoperative hemoglobin content. Multivariate regression analysis showed that pathological fracture, visceral metastases, haemoglobin content < 7 mmol/L and lung cancer were negative prognostic factors for survival. Myeloma was the sole positive prognostic factor for survival.

Detection of a t(1;22)(q23;q12) translocation leading to an EWSR1-PBX1 fusion gene in a myoepithelioma.

Chromosome banding as well as molecular cytogenetic methods are of great help in the diagnosis of mesenchymal tumors. Myoepithelial neoplasms of soft tissue including myoepitheliomas, mixed tumors, and parachordomas are diagnoses that have been increasingly recognized the last few years. It is still debated which neoplasms should be included in these morphologically heterogeneous entities, and the boundaries between them are not clear‐cut. The pathogenetic mechanisms behind myoepithelial tumors are unknown. Only five parachordomas and one mixed tumor have previously been karyotyped, and nothing is known about their molecular genetic characteristics. We present a mesenchymal tumor classified as a myoepithelioma that had a balanced translocation t(1;22)(q23;q12) as the sole karyotypic change. A novel EWSR1‐PBX1 fusion gene consisting of exons 1–8 of the 5′‐end of EWSR1 and exons 5–9 of the 3′‐end of PBX1 was shown to result from the translocation. Both genes are known to be targeted also by other neoplasia‐specific translocations, PBX1 in acute lymphoblastic leukemia and EWSR1 in several solid tumors, most of which are malignant. Based on the structure of the novel fusion gene detected, its transforming mechanism is thought to be the same as for other fusion genes involving EWSR1 or PBX1.

Real time MRI-guided excision and cryo-treatment of osteoid osteoma in os ischii--a case report.

A 36-year-old electrician had not been able towork during the last 8 months due to intense painin his left buttock. Plain radiographs were normal,but scintigraphy, MRI and CT indicated an osteoidosteoma in the left tuber os ischii. The patient wasgiven spinal anesthesia, and placed in a 0.5T GESigna SP/i open MRI (General Electric, Milwau-kee, USA) (Figure 1). With the patient in decubi-tus position, a surface coil was attached and thenidus located. A biopsy needle was placed in thecenter of the lesion, using an optical tracking sys-tem integrated in the magnet gantry, for placementof the needle. A 4 mm cylinder was cored out andfixed in formaldehyde for histologic examinationwhich confirmed the diagnosis osteoid osteoma.Then a 3 mm cryo probe (Galil Medical, Haifa,Israel) was placed centrally in the lesion (Figure2). 4 cycles (1/2–2 min) with cooling to –180€°Cinterrupted by passive thawing were used. ControlMRI showed the defect after the biopsy. The pa-tient was pain-free one day after the operation,soon resumed full-time work, and had no symp-toms 1 year later.

Radiation-induced sarcoma: 25-year experience from The Norwegian Radium Hospital

Background. The aim of this study was to determine the prevalence and outcome of radiation-induced sarcomas (RISs) among sarcoma patients referred to the Norwegian Radium Hospital (NRH). Material and Methods. Ninety patients were identified from the institutional sarcoma data base. Medical records and histological and cytological material from both primary and secondary tumours were reviewed. Results. RIS represented 3.0 % of the sarcomas in the data base. The median latency time from radiotherapy of the primary tumour to the diagnosis of RIS was 13.6 years (range 2.5-57.8 years). Gynaecological, breast and testicular cancers were the most common primary diagnoses. For the RISs 13 different histological types were identified including 25 malignant fibrous histiocytomas (28% of all) and 22 osteosarcomas (24%). The sarcoma-related 5-year crude survival was 33% (95 % CI 23-43 %). Unfavourable prognostic factors were metastases at presentation, incomplete surgery and presence of tumour necrosis. Conclusion. Radiation-induced sarcoma is rare and harbours an aggressive clinical behaviour. Complete surgical resection is mandatory for cure.

Coracoid process transfer for acromioclavicular dislocation

Seventeen patients with complete separation of the acromioclavicular joint were operated on acutely with transposition of the coracoid tip to the clavicle. All the patients were examined after a mean follow-up time of 7.5 years. Twelve patients had good function, 3 had slight pain in extreme positions, and 2 had poor function with pain at rest. Eleven patients had the screw removed, 2 of them because of deep infection. In 3 patients the coracoid tip fragmented during the operation. Two patients had an unsatisfying cosmetic result. As long as nonoperative treatment gives equal or better long-term functional results, we do not recommend this operation in acute dislocations.

Model for Skeletal Muscle Ischemia in Rat Hindlimb: Evaluation of Reperfusion and Necrosis

In this study we describe a technique for complete arrest of blood flow in rat hindlimbs. After graded periods of ischemia, immediate reperfusion in the leg was demonstrated by direct microscopy and scintigraphy. Laser Doppler flowmetry indicated microvascular hypoperfusion in the anterior tibial muscle during the first 2 h of reperfusion. The extent and distribution of necrosis in the middle part of the anterior tibial muscle of the legs were determined histologically 3 days after the ischemic insult. We found a reproducible degree of necrosis under constant experimental conditions. The necrosis was most pronounced in the central part of the muscle, leaving the subfascial fibers undamaged. After 4.0 h of ischemia, 46% of the cross-section area was necrotic. After 4.5 h, the necrosis increased to 70%. This difference was significant. Two types of necrotic zones were detected. One type was characterized by numerous macrophages and partial resorption of the muscle fibers, the other by a lack of macrophages and no resorption. Most cases with little damage had only the first type of necrosis, while most cases with extensive damage had both types. The areas that had no signs of resorption and therefore had been without circulation during most of the postischemic period, measured 8% after 4.0 h of ischemia and 22% after 4.5 h.

Fracture strength prediction in rat femoral shaft and neck by single photon absorptiometry of the femoral shaft.

The bone mineral content (BMC) and bone mineral density (BMD) of the femoral midshaft from 15 skeletally mature male rats were measured by Single Photon Absorptiometry (SPA), and comparisons made to fracture strength of the femoral diaphysis and the femoral neck. In stepwise regression the factors contributing significantly to the ultimate bending moment of the shaft were BMC and femoral length. BMC correlated strongly with the ultimate bending moment of the femoral diaphysis (r2 = 0.63, P < 0.01). The correlation between BMC and ultimate moment of the femoral neck was moderate (r2 = 0.51, P < 0.01). The correlations between BMD and mechanical parameters were lower than the corresponding values for BMC, with a significant result only for the bending moment of the femoral diaphysis (r2 = 0.48, P < 0.01). In conclusion, BMC rather than BMD, is most predictive for fracture strength of the femur in rats.

Protective Effect of Low-Grade Hypothermia in Experimental Skeletal Muscle Ischemia

In the present study, a rat hindlimb tourniquet model was used to investigate the effect of moderate hypothermia on ischemic muscle necrosis. Complete circulatory arrest was maintained for 4.5 h. During the ischemic period the animals were kept in an infant incubator at different temperatures. After 72 h survival the percentage of necrosis in the anterior tibial muscle was measured morphometrically on histological slides. At an ambient temperature of 24 degrees C there was 80% necrosis in the anterior tibial muscle. At 22 degrees C the necrosis was reduced to 29%. This reduction corresponds to more than 30 min shortening of the ischemia time. Differences in tissue temperature may explain some of the discrepancies reported in tolerance limits for muscle ischemia. To achieve consistent results in experimental muscle ischemia, it is necessary to control the ambient temperature.

Reliability of Margin Assessment after Surgery for Extremity Soft Tissue Sarcoma: The SSG Experience

Surgery remains the mainstay of soft tissue sarcoma (STS) treatment and has been the primary treatment for the majority of patients in Scandinavia during the last 30 years although the use of adjuvant radiotherapy has increased. Patient and treatment characteristics have been recorded in the Scandinavian Sarcoma Group (SSG) Register since 1987. When the effect of new radiotherapy guidelines from 1998 was evaluated, the reliability of surgical margin assessments among different Scandinavian institutions was investigated. Margins were reevaluated by a panel of sarcoma surgeons, studying pathology and surgical reports from 117 patients, randomly selected among 470 recorded patients treated between 1998–2003. In 80% of cases, the panel agreed with the original classification. Disagreement was most frequent when addressing the distinction between marginal and wide margins. Considered the element of judgment inherent in all margin assessment, we find this reliability acceptable for using the Register for studies of local control of STS.

Why do patients with radiation-induced sarcomas have a poor sarcoma-related survival?

Background:This study aims to provide reasons for the poor sarcoma-related survival in patients with radiation-induced sarcoma (RIS).Methods:We performed a case–control study comparing sarcoma-related survival of 98 patients with RIS to that of 239 sporadic high-grade malignant sarcomas.Results:The cumulative sarcoma-related 5-year survival was 32% (95% confidence interval (CI): 22–42) for patients with RIS vs 51% (95% CI: 44–58) for controls (P<0.001). Female gender, central tumour site and incomplete surgical remission were significantly more frequent among RIS patients than in controls. In multivariate analysis incomplete surgical remission (hazard ratio (HR) 4.48, 95% CI: 3.08–6.52), metastases at presentation (HR 2.93, 95% CI: 1.95–4.41), microscopic tumour necrosis (HR 1.88, 95% CI: 1.27–2.78) and central tumour site (HR 1.71, 95% CI: 1.18–2.47) remained significant adverse prognostic factors, but not sarcoma category (RIS vs sporadic).Conclusion:The poor prognosis of RIS patients are not due to the previous radiotherapy per se, but related to the unfavourable factors – central tumour site, incomplete surgical remission, microscopic tumour necrosis and the presence of metastases, the two former factors overrepresented in RIS.