Background

Cryosurgery is a well established modality in the treatment of benign aggressive and low grade malignant tumours. In this setting it allows for intra-lesional resection and preservation of function without compromising oncological outcome. Here we present the outcome of 87 patients treated with cryosurgery for low-grade chondrosarcoma of bone.

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.

Introduction: Cryosurgery of bone tumors using direct pour of liquid nitrogen has the advantage of joint preservation associated with good local tumor control. However, this technique does not allow accurate control of the temperature or of the overall time of freezing. Additionally, this is a gravity-dependent procedure that cannot be applied in all shapes and locations of tumor cavities. The authors report their experience with a novel cryosurgical technique that allows accurate determination of the temperature and freezing time as well as freezing of any geometry of tumor cavity.

Materials and Methods: From 1997 to 2000, 58 patients who were diagnosed with 13 malignant and 45 benign-aggressive bone tumors underwent argon-based cryoablation. This technique included tumor removal by means of curettage and burr-drilling, filling the tumor cavity with a gel medium, insertion of metal probes into this medium, and computer-controlled delivery of argon gas through the metal probes, and reconstruction of the tumor cavity with cemented hardware. All patients were followed for more than two years.

Results: None had skin necrosis, infection, thromboembolic complication, or neurapraxia. Fractures occurred in two patients (3.4%) and local tumor recurrence in two patients (3.4%), who were successfully treated with a second closed cryoablation.

Conclusions: The current study focuses on the concept and surgical technique of argon-based and computer-controlled, closed cryoablation of bone tumors. The main advantages of this system are the ability to control the freezing temperature and overall freezing time and the use of a gel medium, which evenly conducts the cold temperature throughout the tumor cavity and allows cryoablation of various cavital geometry and positions. The current technique of argon-based cryoablation is simple and easy to perform. It achieves good local tumor control and is associated with a low rate of complication. The authors recommend its use as an alternative to the traditional direct pour technique of cryosurgery.

Introduction: Diffused pigmented villonodular synovitis (PVNS) is a locally aggressive lesion for which surgery provides only marginal resection. An adjuvant treatment modality is therefore required to prevent local tumor recurrence. The authors describe their experience with intra-articular injection of Yttrium⁹⁰ (Y⁹⁰), a radioisotope, as an adjuvant for tumor resection.

Materials and Methods: Between 1989 and 2002, 20 patients with diffuse PVNS were treated with post-operative, intraarticular injection of Y⁹⁰. There were 15 male and 5 female patients who ranged in age from 13 to 67 years (mean, 35 years). Anatomic locations of the affected joints included: knee – 15, ankle – 4, hip – 1. Tumor resection was initially done in all patients: 13 patients required open arthrotomy, the remaining 7 underwent arthroscopic tumor resection. Ten patients were referred for treatment after having operation for a local tumor recurrence: 6 patients had one, 2 had two, 1 had three, and the remaining one had five local recurrences. Six to eight weeks after surgery, intraarticular injection of 15–25 mCi of Y⁹⁰ was done. These procedures were conducted in the operating room under local anesthesia and fluoroscopic guidance. All patients were followed for a minimum of two years (range, 25–168 months; mean, 65 months).

Results: Following Y⁹⁰ injection, all patients reported mild pain around the affected joint. This pain was well controlled with the use of NSAID’s and typically resolved within a few days or weeks. Three patients had superficial skin inflammation and associated blisters around the site of injection, probably the result of Y⁹⁰ effect on the soft-tissues. All were treated conservatively with complete resolution of their symptoms. All patients gained their pre-injection range-of-motion within 4–6 weeks. At the most recent follow-up, five patients had transient post-radiation skin changes (discoloration of the skin and dry and scaly skin) and local recurrence occurred in only one patient (5%) with PVNS around the knee; additional Y⁹⁰ injections were unsuccessful and he eventually underwent knee arthrodesis.

Conclusion: Y⁹⁰ injection is a reliable adjuvant for surgery in the management of diffused PVNS. Local tumor control and good function, associated with only mild morbidity are achieved in the majority of the patients.

Introduction: Megaprosthetic failures around the knee and especially those who are infection-related are difficult to manage. Although most of these cases are effectively managed with a two-stage prosthetic revision, selected cases eventually require sacrifice of the knee joint. The authors present their experience with knee-arthrodesis using a vascularized fibula and allograft reinforcement.

Materials and Methods: Between 1998 and 2002, eight patients with failed knee prosthesis were referred for resection-arthrodesis; all patients had at least two previous revision attempts using a spacer or a new implant. Knee-arthrodesis included resection of the distal femur and proximal tibia and reconstruction with a free micro-vascularized fibular graft and allograft reinforcement. Fibular grafts were harvested with a large musculocutaneous flap to facilitate soft-tissue coverage and monitor flap viability. Following surgery, patients were kept non-weight-bearing for 3 months. Radiographs were performed 6 and 12 weeks postoperatively to establish fibular graft incorporation. If healing had progressed satisfactorily, weight-bearing was gradually allowed.

Results: At the most recent follow-up’ all eight patients had a stable and painless reconstruction, associated with radiological evidence of solid fibular graft union. The latter was typically observed between 6 to 12 weeks from surgery. Complications included one emergent surgery for anastamotic rupture in one patient and surgical debridement with skin grafting of musculocutaneous flap necrosis in another patient.

Conclusions: Knee-arthrodesis using microvascularized fibula and allograft reinforcement is a safe and reliable salvage procedure in end-stage failures of megaprosthetic knee implants.

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%).

Introduction: Modern cancer treatment has substantially increased the survival of patients with various malignancies. One of the late sequelae of a successful treatment is the development of a second malignant tumor. However, in many cases of second primary cancers, exposure to chemotherapy or radiation therapy is not evident, and it should be postulated that the putative mechanism for the development of the second cancer is different.

Material and Methods: Retrospective search of data files of 610 patients with soft-tissue or bone sarcomas that were treated by the authors from January 1995 through December 1999 were performed.

Results: Out of 375 patients with soft-tissue sarcoma (STS), 28 (7.5%) developed other malignant neoplasm either before or after its diagnosis. The second tumor types included mainly STS and renal cell carcinoma. The time interval between the diagnosis of STS and the second malignancy was o to 21 years. Three patients developed a third primary tumor within 0–3 years after the diagnosis of the second tumor. The median overall survival was > 78 months.

Conclusions: The phenomenon of two or three primary neoplasms in patients in whom one of the tumors was STS occurs in a rate of 7.5% – a significantly higher rate than the occurrence of STS among the general cancer population (1%). Most cases are detected incidentally. The clinical implications are the need to search for an occult second primary in patients with STS as an integral part of their follow-up. It is especially true in patients with primary MFH who show increased risk for developing a renal cell carcinoma.

Background: The c-ebB-2 gene and its products (also designated HER-2 and c-neu) encode for a 185-kd transmembrane glycoprotein with intracellular tyrosine kinase activity. C-erbB-2 belongs to the epidermal growth factor receptor family, of which there are four known members, and has molecular homology to the epidermal growth factor receptor. It seems that this family is critical in control of growth, differentiation, and mobility of many normal and transformed epithelial cell types.

Materials and Methods: We have looked for over expression of c-erbB-2 gene product in 230 cases of soft tissue sarcoma, in order to establish a possible new prognostic marker, and a potentially new treatment option.

Results: In all the cases, irrespective of the sarcoma histological type, the immunostaining for erbB-2 was negative.

Conclusions: Applications of erbB-2 for prognostication as well as the option of receptor targeting by trastuzumab monoclonal antibodies were aborted.

Background: We have recently observed that many of our sarcoma patients presented also with thyroid disorders. Literature data are almost unavailable on this topic.

Materials and Methods: Retrospective analysis of files of patients with sarcoma and clinically overt thyroid disorders.

Results: Out of 375 patients with soft tissue sarcomas (STS) and 235 with bone sarcoma (BS) including small blue round cell tumors (SBRC), 28 patients (4.6%) had an associated significant thyroid disorder. The types of sarcoma were mainly liposarcoma followed by malignant fibrous histiocytoma, leiomyosarcoma and bone sarcoma. The primary sites were mainly limb and trunk. The interval between the diagnosis of the thyroid disorder and the sarcoma varied between {−14} years (thyroid first) and {+16.5} years (thyroid later) with a median of {−0.2} years. Thyroid disorders included goiter, thyroiditis and carcinoma.

Conclusions: There are basic-science and clinical evidences to a possible common pathway that leads to the association between overt thyroid disorders and sarcomas of bone or soft tissues. Oncogene erbA activity is related to thyroid receptors to T3 and to development of sarcoma. Cross talk of the sarcoma oncogene and the erbA might contribute to the development of sarcoma. The thyroid hormone receptor and the highly related viral oncoprotein v-erbA are found exclusively in the nucleus as stable constituents of chromatin. It has been shown that v-erbA can block the spontaneous differentiation in erythroid cells transformed by various retroviral oncogenes. V-erbA can alter the spectrum of neoplasia induced by the v-src oncogene, which causes predominantly sarcomas and erythroblastosis in chicks. The erbA can cooperate with other oncogenes such as v-erbB or with v-fms, v-ras, and c-kit. Cooperation with v-myc may play a role in the development of rhabdomyosarcoma especially in thyroid hormone deficiency state. The possible clinical implications are the need to screen patients with sarcoma to thyroid disorders, and patients with thyroid disorders for malignant diseases.

Introduction: Telomerase is a ribonucleoprotein that adds TTA GGG nucleotide repeated into the ends of eukaryotic chromosomes to maintain their integrity. Most of the normal somatic cells do not express telomerase while telomerase is expressed in the vast majority of malignant tumor cells. Contradictory and limited data have been reported concerning the telomerase expression in soft-tissue sarcomas. The current study evaluates telomerase expression in a single histologic type of a high-grade soft-tissue sarcoma.

Materials and Methods: A non-radioactive in situ hybridization (ISH) method was used to study the expression of the RNA component of human telomerase in 55 paraffin embedded archives tissue samples of patients who were diagnosed with synovial sarcoma, the diagnosis of which was based on morphologic, immunohistochemical, and cytogenetic characteristics. The intensity and distribution of telomerase RNA was scored by two different investigators. Intensity was graded as weak, moderate, or intensive. These parameters were further correlated to the oncologic status of the patient.

Results: The majority of the investigated specimens demonstrated moderate to intensive telomerase RNA intensity with a diffuse distribution throughout the specimen. A positive correlation was found between telomerase intensity and progression of the underlying disease.

Conclusions: Results of the current series suggest that upregulating of telomerase expression may play a role in the pathogenesis and biological activity of synovial sarcoma. This upregulation as detected by ISH assay may be a useful prognostic tool in the evaluation of these patients.

Background: The surgical treatment of extensive diffuse Pigmented Villonodular Synovitis (PVNS) of large joints alone, is unsatisfactory, with high rates of local recurrence. Postsynovectomy adjuvant treatment with external beam radiation therapy or intraarticular injection of Yttrium90 (Y90) yielded better results.

Aims: Experience with 10 cases treated with debulking surgery followed by intraarticular injection of Y90 is reported.

Methods: Between January 1989 and June 1998, 10 patients (8 males and 2 females aged 15049 years) with extensive diffuse PVNS were treated. In 6 patients the knee joint, in 3 patients the ankle joint, and in 1 patient the hip joint were involved. The 10 patients underwent 15 operations, 1 patient had 3 surgical procedures, and 3 patients underwent 2 surgeries (interval between re-operations for local recurrence were 2–4 years). All patients had an intraarticular injection of 15–25 mCi of Y90, 6–8 weeks after the last surgery.

Results: Follow up time was 2.5–12 years (mean 6 years). All patients were followed by repeated computerized tomography (CT) scans, magnetic resonance imaging (MRI), plain X-ray films and bone scans semi-annually. In 9 patients no evidence of disease and no progression of bone or articular destruction have been noted. In 1 patient stabilization of disease was achieved with no further evidence of bony or articular damage. No complications were noticed after surgery, nor after the intraarticular Y90 injection.

Conclusions: A combination of debulking surgery with intraarticular injection of Y90 for extensive diffuse PVNS of major joints is a reliable way of treatment with good results.