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The Bone & Joint Journal
Vol. 100-B, Issue 7 | Pages 984 - 988
1 Jul 2018
Gortzak Y Vitenberg M Frenkel Rutenberg T Kollender Y Dadia S Sternheim A Morag G Farkash U Rath E Kramer M Drexler M

Aims

Intra-articular 90Yttrium (90Y) is an adjunct to surgical treatment by synovectomy for patients with diffuse-type tenosynovial giant-cell tumour (dtTGCT) of the knee, with variable success rates. Clinical information is, however, sparse and its value remains unclear. We investigated the long-term outcome of patients who underwent synovectomy with and without adjuvant treatment with 90Yttrium.

Patients and Methods

All patients with dtTGCT of the knee who underwent synovectomy between 1991 and 2014 were included in the study. Group A patients underwent synovectomy and an intra-articular injection of 90Yttrium between six and eight weeks after surgery. Group B patients underwent surgery alone.


The Bone & Joint Journal
Vol. 97-B, Issue 12 | Pages 1704 - 1709
1 Dec 2015
Drexler M Gortzak Y Sternheim A Kollender Y Amar E Bickels J

Excision of the proximal femur for tumour with prosthetic reconstruction using a bipolar femoral head places a considerable load on the unreplaced acetabulum.

We retrospectively reviewed the changes which occur around the affected hip joint by evaluating the post-operative radiographs of 65 consecutive patients who underwent proximal prosthetic arthroplasty of the femur, and in whom an acetabular component had not been used. There were 37 men and 28 women with a mean age of 57.3 years (17 to 93). Radiological assessment included the extent of degenerative change in the acetabulum, heterotopic ossification, and protrusio acetabuli.

The mean follow-up was 9.1 years (2 to 11.8). Degenerative changes in the acetabulum were seen in three patients (4.6%), Brooker grade 1 or 2 heterotopic ossification in 17 (26%) and protrusion of the prosthetic head in nine (13.8%).

A total of eight patients (12.3%) needed a revision. Five were revised to the same type of prosthesis and three (4.6%) were converted to a total hip arthroplasty.

We conclude that radiological evidence of degenerative change, heterotopic ossification and protrusion occur in a few patients who undergo prosthetic arthroplasty of the proximal femur for tumour. The limited extent of these changes and the lack of associated symptoms do not justify the routine arthroplasty of the acetabulum in these patients.

Cite this article: Bone Joint J 2015;97-B:1704–9


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XIV | Pages 54 - 54
1 Apr 2012
Dadia S Gortzak Y Kollender Y Bickels J Meller I
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Aim

Giant cell tumour (GCT) of bone is a benign but locally aggressive tumour. Although topical adjuvants have been used in the past, local recurrence following intralesional excision of GCT of bone continues to remain a problem. The use of bisphosphonates as an anti-osteoclastic agent in the management of osteolytic bone metastases is well accepted. Therefore our study aims to retrospectively demonstrate whether the administration of bisphosphonate as an adjuvant can control aggressive local recurrence of GCT and prevent wide resections of bones or amputations.

Method

A retrospective study was performed between 2004 and 2010. 6 patients were diagnosed with aggressive local recurrence of appendicular GCT. All patients were treated for the primary tumour by surgical curettage and cryoablation followed by cementation or biological reconstruction. In 5 patients the tumour was located in the distal radius and in one in the first metacarpal bone. All recurrences were in the bone with large soft-tissue extension. After histological diagnosis – by CT core needle biopsy – the patients were treated by intravenous bisphosphonate, followed by clinical & radiological assessments.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XIV | Pages 27 - 27
1 Apr 2012
Gortzak Y Kollender Y Bickels J Merimsky O Issakov J Flusser G Nirkin A Weinbrum A Meller I Dadia S
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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.

Materials and methods

87 patients were treated between 1988 and 2005. The mean age was 51 years (range, 8-77 years), and included 47 females and 40 males. Minimal follow-up was two years. Patients were treated for lesions of the distal femur (n = 30), proximal humerus (n = 33), proximal femur (n = 5), proximal tibia (n = 10), and the remaining sites included the iliac bone, distal tibia, forearm, carpal and tarsal bones (n=10). Patients were treated with intralesional curettage through a cortical window, adjuvant burr drilling, cryotherpay and reconstruction with cement or bone graft and hardware fixation when that was clinically indicated.


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_III | Pages 518 - 518
1 Aug 2008
Bickels J Kollender Y Pritsch T Malawer M Meller I
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Multiple myeloma may be associated with extensive bone destruction, impending or present pathological fracture, and intractable pain. Chemotherapy and radiotherapy are usually effective, but surgical intervention may sometimes be required.

We analyzed the surgical technique and the functional and oncological outcomes of patients with multiple myeloma who underwent surgery in our services between 1993-2004.

There were 19 males and 15 females (age range 49– 75 years) who had destructive bone lesions located at the humerus (n=17), acetabulum (n=5), femur (n=5), or tibia (n=7). Indications for surgery included pathological fracture (n=20), impending pathological fracture (n=11), and intractable pain (n=3). Nineteen patients underwent marginal tumor resection, reconstruction with cemented hardware, and adjuvant radiation therapy and 15 patients underwent wide tumor resection with endoprosthetic reconstruction. All patients reported immediate and substantial postoperative pain relief. Function was good/excellent in 23 patients (68%), moderate in eight (23%), and poor in three (9%). Two patients (5.9%) had local tumor recurrence treated with local excision and adjuvant radiotherapy, with no evidence of further recurrence at 21 and 26 months, respectively. Thirty one (91%) patients survived > 1 year, 23 (68%) > 2 years, and 15 (44%) > 3 years postoperatively. All reconstructions remained stable at the most recent follow-ups.

The relatively prolonged survival of patients with multiple myeloma justifies an aggressive surgical approach, which is safe and associated with good local tumor control and functional outcome.


The Journal of Bone & Joint Surgery British Volume
Vol. 88-B, Issue 12 | Pages 1647 - 1651
1 Dec 2006
Issakov J Soyfer V Kollender Y Bickels J Meller I Merimsky O

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.


Orthopaedic Proceedings
Vol. 87-B, Issue SUPP_III | Pages 386 - 386
1 Sep 2005
Bickels J Meller I Wittig J Malawer M Kollender Y
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Introduction: Metastatic bone disease of the humerus may be associated with disabling pain and loss of function. Surgery must provide good local tumor control, immediate mechanical stability, and a short rehabilitation period. Between 1980 and 2000, the authors operated 59 patients with metastatic disease of the humerus. The current study summarizes the principles of the surgical technique and functional and oncological outcomes.

Materials and Methods: There were 33 females and 26 males. Indications for surgery included pathological fracture (40), impending fracture (11), and intractable pain (6). Anatomic locations of humeral metastases included: around the proximal humeral metaphysic and head (Type I) – 18, humeral diaphysis (Type II) – 39, and humeral condyles (Type III) – 2. Types I and III metastases were treated with resection and endoprosthetic reconstruction. Type II metastases were treated with intralesional tumor removal and cemented nailing. Postoperatively, 31 patients were treated with radiation therapy, 35 with chemotherapy, and 14 with immunotherapy.

Follow-up of the study patients included physical examination, radiological evaluation and functional evaluation according to the American Musculoskeletal Tumor Society system.

Results: Patients who had cemented nailing had better overall function, emotional acceptance, hand positioning, and lifting ability than patients who underwent endoprosthetic reconstruction. Pain alleviation and dexterity were comparable in both groups. All patients had a stable extremity and overall function of 56 patients (95%) was > 68% of normal upper extremity function. Only two patients (3%) had a local tumor recurrence.

Conclusions: An aggressive surgical approach in patients who have humeral metastases and meet the criteria for surgical intervention is beneficial; it provides durable reconstruction and is associated with good function and local tumor control in most patients.


Orthopaedic Proceedings
Vol. 87-B, Issue SUPP_III | Pages 387 - 387
1 Sep 2005
Bickels J Merimsky O Isaakov J Nirkin A Flusser G Meller I Kollender Y
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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.


Orthopaedic Proceedings
Vol. 87-B, Issue SUPP_III | Pages 387 - 387
1 Sep 2005
Kollender Y Bender B Nirkin A Shabat S Merimsky O Isaakov J Flusser G Meller I Bickels J
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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.


Orthopaedic Proceedings
Vol. 87-B, Issue SUPP_III | Pages 387 - 388
1 Sep 2005
Maman E Bickels J Wittig J Malawer M Kollender Y Meller I
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Introduction: Tumors of the axilla impose a surgical difficulty because they are usually large at presentation and in close proximity to the major neurovascular bundle of the upper extremity. Attempted tumor resection via the base of the axilla is difficult because of limited exposure of the axillary content and neurovascular bundle. The authors have used a safe and reliable exposure for these situations.

Methods: Between 1980 and 1997, 35 patients underwent extensile exposure of an axillary tumor. Diagnoses included 19 primary and 16 metastatic tumors of the axilla. The axillary cavity was fully exposed via the deltopectoral groove after detachment and reflection of two layers of muscles: first, the pectoralis major and, second, the coracoid origin of the pectoralis minor, cora-cobrachialis, and the short head of the biceps muscle. This surgical approach allowed full tumor visualization and determination of the exact anatomic relation of the tumor to the neurovascular bundle and as a result, tumor respectability. Following resection, the pectoralis minor and conjoined tendons were reattached to the coracoid process with a nonabsorbable suture, and the pectoralis major was reattached to its insertion site on the proximal humerus in the same manner.

Results: Exposure revealed a safe plane of dissection between the tumor and the major neurovascular bundle in 23 patients and invasion of the major neurovascular bundle in 12 patients who subsequently underwent a forequarter amputation. At the most recent follow-up, none of these patients had functional limitation, which could be attributed to the extensile approach itself. All patients gained their presurgical pectoralis major and biceps function.

Complications in the group of patients that underwent tumor resection included three (13%) superficial wound infections. Due to intended enbloc resection of an involved nerve with the tumor, two nerve palsies (8.7%) were documented. None of the remaining 21 patients had numbness, paresthesias, or nerve pain. There were three (13%) local recurrences; two were managed with wide excision and adjuvant radiation therapy and one necessitated amputation.

Conclusions: The extensile exposure of the axilla allows full visualization of axillary tumors. It allows determination of tumor respectability and safe and reliable resection, when indicated. This exposure is associated with good functional outcome and an acceptable morbidity and is recommended in the management of axillary tumors.


The presentation of this huge monoinstitutional cumulative experience in bone tumor cryosurgery serves as an illustration of our basic phylosophycal concent: “No man-made implants are even close to God’s natural implants yet”. The result is the concept of conservation surgery in which cryotherapy plays the major role.

Materials and Methods: During the period of 1/88 to 12/02 (15 years, FUT 2→17 years, median=6 years) 440 cryosurgical procedures were performed in 405 people. There were 214 male and 191 female patients. The age range was 5 to 80 years but most were between 20 and 59 years. 2/3 of the series included a variety of primary benign aggressive and low grade malignant lesions and 1/3 included primary high grade and metastatic bone tumors. The anatomical location is highly variable and includes almost every bone of the skeleton.

Two methods of bone cryosurgery will be presented (including combinations of them and other adjuvants or techniques): The open system according to Marcove and our Closed System.

Results and Complications: Overall local recurrence (LR) rate=8%, fractures=1%, infections=2%, skin burns= 1.3%.

There were 3 cases of temporary nerve palsies and 2 cases of late OA of an adjacent joint. Functional outcome in 372 NED patients is almost 100% good and excellent (AMSTS, Enneking’s scoring system).

Summary: Bone cryosurgery is a safe, reliable and inexpensive technique of conservative limb, joint and even epiphysis sparing surgery in the suitable types of bone tumors, eliminating temporarily or permanently the need for resection surgery.


Orthopaedic Proceedings
Vol. 87-B, Issue SUPP_III | Pages 387 - 387
1 Sep 2005
Kollender Y Meller I Wittig J Malawer M Bickels J
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Multiple myeloma may be associated with extensive bone destruction, impending or present pathological fracture, and intractable pain. However, surgical intervention is rarely indicated since local bone crises are effectively managed with chemotherapy and radiotherapy in the majority of the patients. The current retrospective analysis of patients who eventually required surgical intervention emphasized indications for surgery, surgical technique, and functional and oncological outcomes.

Materials and Methods: Between 1982 and 2000, the authors operated on 18 patients with multiple myeloma. There were 11 females and 7 males whose age ranged from 4 to 67 years (median, 59 years). Anatomic locations: proximal humerus – 5, proximal femur – 4, distal femur – 5, proximal tibia – 3. One patient had total femur involvement. Preoperatively, 11 patients were treated with chemotherapy and 4 received radiotherapy. Seven patients were referred with a bone lesion as their initial presentation and, therefore, did not receive pre-operative treatment.

Indications for surgery: pathological fractures – 11 patients, impending pathological fractures – 5 patients, and intractable pain in 2 patients. Surgeries included 12 marginal resections with cryosurgery and 6 wide resections with endoprosthetic reconstructions. Postoperative radiotherapy was given to three patients and chemotherapy to 11. Follow-up included physical and radiological evaluation and functional evaluation according to the American Musculoskeletal Tumor Society System.

Results: Fifteen patients (83%) survived more than 1 year and 12 patients (66%) survived more than 2 years after surgery. There were no postoperative deep wound infections, thromboembolic complications, or local tumor recurrences. Functional outcome was good to excellent in 14 patients (78%), moderate in 3 (16%), and poor in one patient (6%).

Conclusions: Multiple myeloma rarely may require surgical intervention because of impending or present pathological fracture or intractable pain. The relatively prolonged survival of patients with multiple myeloma justifies an aggressive surgical approach. Resection of these tumors was shown to be safe, reliable, and associated with good local tumor control and functional outcome.


Orthopaedic Proceedings
Vol. 87-B, Issue SUPP_III | Pages 387 - 387
1 Sep 2005
Kollender Y Merimsky O Isaakov J Nirkin A Flusser G Meller I Bickels J
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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.


The Journal of Bone & Joint Surgery British Volume
Vol. 86-B, Issue 5 | Pages 714 - 718
1 Jul 2004
Bickels J Kollender Y Merimsky O Isaakov J Petyan-Brand R Meller I

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%).


Orthopaedic Proceedings
Vol. 84-B, Issue SUPP_III | Pages 309 - 309
1 Nov 2002
Bickels J Wittig J Kollender Y Malawer M Meller I
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Introduction: Surgical removal by means of curettage is the mainstay of treatment of enchondromas of the hand. Methods of reconstruction after tumor removal usually entail no reconstruction or filling of the tumor cavity with a bone graft. These techniques necessitate a prolonged period of protected activity until bone healing of the tumor cavity occurs. The authors have utilized hardware and bone cement for the purpose of reconstruction of the tumor cavity. This technique provides immediate mechanical stability and allows early mobilization.

Methods: Between 1986 and 1999 the authors treated 13 patients (8 females, 4 males) who ranged in age from 23 to 58 years (median, 32 years) and diagnosed with enchondroma of the hand. Eight patients presented with a pathological fracture. Anatomic locations included: metacarpal bones – 5, proximal phalanx – 4, and middle phalanx – 4. Tumors were approached through the retained thinned or destroyed cortex to minimize additional bone loss. Surgery included removal of all gross tumor with hand curettes; this was followed by high speed burr drilling of the inner reactive bone shell. Reconstruction included intramedullary metal wire along the longitudinal axis of the cavity and polyme-hylmethacrylate (PMMA). Full activity as tolerated was allowed immediately after surgery. All patients were followed for more than 2 years.

Follow-up included physical and radiological evaluation and functional evaluation.

Results: Following surgery, all patients returned to their presurgical functional capability within two weeks. At the last follow-up, none of the patients had local tumor recurrence and although three patients had 15° to 20° decrease in flexion of the metacarpophalangeal joint, none reported a functional limitation. There were no postoperative infections or fractures.

Conclusions: Reconstruction of the tumor cavity, remaining after curettage of enchondroma of the hand, with intramedullary hardware and PMMA provides immediate mechanical stability and allows early mobilization. This technique is associated with good short- and long-term functional outcomes.


Orthopaedic Proceedings
Vol. 84-B, Issue SUPP_III | Pages 303 - 303
1 Nov 2002
Merimsky O Kollender Y Issakov J Bickels J Flusser G Meller I
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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.


Orthopaedic Proceedings
Vol. 84-B, Issue SUPP_III | Pages 304 - 304
1 Nov 2002
Kollender Y Bickels J Shomrat R Yaron Y Goldstein M Junig D Issakov J Bar-Am I Orr-Urtreger A Meller I
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Introduction: Chromosomal analysis is becoming increasingly useful in the diagnosis and management of bone and soft-tissue sarcomas. The identification of chromosomal aberrations such as translations, deletions, additions of a part or whole chromosome, and other markers are associated with specific tumor subtypes.

Material and Methods: Between 1998 and 2000, 78 bone and soft-tissue tumors were analyzed. Cytogenetic analysis was carried on a short-term cultured tissues by G-banding FISH and SKY procedures, as needed. Histopathological diagnoses included osteosarcoma – 16, Ewing’s sarcoma – 13, synovial sarcoma – 4, rhabdomyosarcoma – 4 (alveolar – 3, embryonal – 1), liposarcoma – 3, extra-abdominal fibromatosis – 3, alveolar soft part sarcoma – 12, and other soft-tissue sarcoma – 12. Other diagnoses included 8 hematological malignancies and 13 benign tumors.

Results: Eight of the 16 osteosarcomas studies demonstrated complex hyperploid karyotypes compatible with the diagnosis of high-grade osteosarcoma. In most Ewing’s sarcoma, including three cases with a typical t(11;22) translocation, other chromosomal abnormalities such as trisomies of chromosomes 5,6,8, and 14 were observed. Three of the four synovial sarcomas had the typical t(X;18)(p11.2;q11.2) translocation. One of the synovial sarcomas was initially diagnosed on a histopathological basis as Ewing’s sarcoma but the cytogenetic analysis showed a complex X;18 translocation and led to change in diagnosis and related treatment. Only one of the alveolar rhabdomyosarcomas demonstrated the typical t(2;13)(q35;q14) translocation, while hypertetraploid set with double minutes (dmin) was detected in the other two cases. By using SKY, chromosome 1 was determined as the origin of one of the dmins, suggesting that PAX7 amplification could be involved in the pathogenesis of this tumor.

Conclusions: Cytogenetic analysis of bone and soft-tissue tumors are of important clinical value for accurate diagnosis of tumor type. It can also provide information suggesting the pathogenesis of these tumors.


Orthopaedic Proceedings
Vol. 84-B, Issue SUPP_III | Pages 317 - 317
1 Nov 2002
Merimsky O Issakov J Dadia S Kollender Y Schwartz I Bickels J Flusser G Inbar M Meller I
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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.


Orthopaedic Proceedings
Vol. 84-B, Issue SUPP_III | Pages 317 - 317
1 Nov 2002
Merimsky O Issakov J Kollender Y Inbar M Bickels J Meller I
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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.


Orthopaedic Proceedings
Vol. 84-B, Issue SUPP_III | Pages 317 - 317
1 Nov 2002
Solar I Meller I Kollender Y Bickels J Merimsky O Flusser G Lifschitz-Mercer B Eisenthal A Schwartz I Issakov J
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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.