Pre-operative evaluation prior to soft tissue sarcoma excision - Why can't we get it right?

BACKGROUND: To define the association between an appropriate pre-operative workup (pre-operative advanced imaging studies, diagnostic biopsy) and incomplete soft tissue sarcoma (STS) excision. PATIENTS AND METHODS: This was a retrospective review of 397 consecutive patient records (2000-2008), looking at primary site advanced imaging (MRI or CT) and diagnostic biopsy procedures completed prior to the initial attempt at definitive surgical excision. Downstream effects of an inadequate pre-operative workup were also evaluated, including time to referral to a sarcoma multi-disciplinary care team and perceived alteration of surgical care in order to obtain a complete excision of the altered sarcoma bed. RESULTS: Thirty-eight percent (149/397) of soft tissue sarcomas identified underwent an incomplete excision prior to referral. A significant difference in the incidence of pre-operative primary site advanced imaging (91% vs. 42%, p < 0.001) and a pre-operative diagnostic biopsy (85% vs. 16%, p < 0.001) was found between the wide excision group and incomplete excision groups. Pre-operative biopsy (p < 0.001), tumor size >5 cm (p < 0.001), and a referral from an orthopaedic surgeon (p < 0.02) were all associated with reduced risk of incomplete excision in multivariate analysis. Seventy-four percent of patients in the incomplete excision group required an alteration in their definitive wide margin surgical resection, including rotational muscle flap coverage (37%), free flap coverage (11%), or amputation (11%). CONCLUSION: A minority of patients referred following incomplete excision of a STS had undergone an appropriate pre-operative workup prior to referral, leading to increased long-term morbidity following definitive re-excision. Education efforts to heighten awareness of suspicious soft tissue lesions remain vital.

Amputation for extremity soft tissue sarcoma does not increase overall survival: a retrospective cohort study.

To determine if amputation increases survival when compared to limb salvage surgery in patients with a soft tissue sarcoma (STS) of the extremity when there is often a misconception among physicians and patients that ablative surgery eliminates local recurrence and increases overall survival. This retrospective cohort study assessed 278 patients with STS and compared 18 patients who had undergone amputations for soft tissue sarcomas of the extremities to a comparative cohort of 260 patients who underwent limb salvage surgery during the same time period. Our limb salvage surgery (LSS) rate was 94% overall for soft tissue sarcomas with a median follow-up of 3.1 years. Patients undergoing amputations either had tumors that involved a critical neurovascular bundle (in particular nerve rather than vessel resection was more responsible for a decision toward ablation), or underlying bone or had neoplasms whose large size would require such an enormous resection that a functional limb would not remain. In comparing prognostic effects, mainly death due to sarcoma, distant metastasis and local recurrence, it was found that there was no statistically significant difference between patients undergoing amputation to those undergoing limb salvage surgery (p > 0.05). While amputations do not increase overall survival in soft tissue sarcomas of the extremity as compared to LSS, they are still a valuable option in a surgeon's arsenal. In particular, amputations can provide improved local control and symptomatic treatment in patients who might not be candidates for limb salvage surgery.

Clonality studies in giant cell tumor of bone.

Genetic studies including chromosome analysis, telomere reduction and telomere activity, DNA microsatellites and loss of heterozygosity (LOH) studies have been performed on giant cell tumor (GCT) of bone however whether this primary skeletal neoplasm represents a monoclonal or polyclonal proliferation is unknown. Utilizing a new assay to study the polymorphic human androgen receptor locus (HUMARA), the ratio of maternal inactive X-chromosome to the paternal inactive X (Lyon hypothesis) is determined via a methylation--specific polymerase chain reaction (PCR) technique to detect X-chromosome polymorphisms. Characterization of the genetic tumorigenesis of this unpredictable neoplasm may lend insight into its biological behavior and offer improvements in therapeutic intervention, as new information emerges regarding osteoclastic bone resorption. Seventeen female patients with giant cell tumor of bone had their DNA harvested and their X-chromosome inactivation pattern and polymorphisms determined and compared to control. A polyclonal proliferation pattern was identified in all informative samples studied.

Growth factor modulation of distraction osteogenesis in a segmental defect model.

A model was established in 39 dogs to investigate the growth factor modulation of regenerate bone in distraction osteogenesis. A segment of the diaphysis of the radius was resected unilaterally. An osteotomy was made proximal to the segmental defect to create a transport segment. A monolateral external fixator was applied. After a latency period, the segment was transported across the defect. One week after the transport assembly contacted the distal pin clamp, an ipsilateral osteotomy of the proximal ulna was performed. In 20 dogs, transforming growth factor-beta was injected into the regenerate bone halfway through the transport period. Four dogs were sacrificed before docking, when the regenerate bone was still immature. In specimens harvested halfway through the transport period, evidence was found of intramembranous ossification during distraction. In specimens harvested after the transport assembly contacted the distal pin clamp, evidence was found that the mature regenerate formed by endochondral ossification. Therefore, a combined mechanism of ossification is proposed for this segmental defect model that includes mechanical stimulus for bone differentiation. The one-time administration of transforming growth factor-beta retarded the formation of a stable, united regenerate. It is concluded that transforming growth factor-beta caused an effect opposite to that which was desired.

Microsatellite instability in sacral chordoma.

BACKGROUND AND OBJECTIVES: Microsatellite instability (MIN) is an indirect marker of globally defective DNA mismatch repair in the neoplastic cells of cancer patients. Chordomas are rare, primary skeletal malignancies for which few characteristic molecular genetic markers have been identified. Is MIN demonstratable in chordoma? METHODS: We evaluated sacral chordomas from 12 patients with sacral chordomas for the presence of MIN at 9 different genetic loci from chromosomes 1p, 5q, 7q, 9p, 11p, 12p, 13q, 17p, and 18q. Cells were scraped from glass slides so that tumor and control DNA could be isolated and then amplified by polymerase chain reaction (PCR). Heterozygosity indices were >/= 0.70. RESULTS: Six patients (50%) demonstrated MIN for at least 1 locus, and 2 patients demonstrated loss of heterozygosity (LOH) for at least 1 locus. Only 1 individual's chordoma manifested microsatellite instability (MIN) and loss of heterozygosity (LOH). Another patient manifested no MIN but LOH at 9p and 18q. Interestingly, this individual had the most aggressive clinical cancer course, presenting with lymph node metastasis and succumbing to widespread metastatic disease. CONCLUSIONS: Chordomas can be added to the list of malignancies demonstrating MIN. LOH may prove to portend a worse prognosis than MIN when more tumors are examined.

Publication rates of abstracts presented at the 1993 annual Academy meeting.

What percent of abstracts presented at the American Academy of Orthopaedic Surgeons annual meeting are submitted, survive peer review, and eventually are published? The answer to this fundamental question is important because many national meeting attendees use the unscrutinized information that is presented to alter their surgical practices. At the 1993 American Academy of Orthopaedic Surgeons meeting, 573 abstracts were presented. After a 5-year period, 44% of abstracts presented were published as papers in a peer reviewed journal. The results suggest that for various reasons, the majority of presented material at the Academy meeting has not been authenticated scientifically to be as accurate as papers that survive the rigors of peer review.

Marjolin ulcers: secondary carcinomas in chronic wounds.

Marjolin ulcers are malignant tumors arising in chronic wounds. Strictly defined, they include carcinomas that transform from the chronic open wounds of pressure sores or burn scars. They behave aggressively and have a propensity for local recurrence and lymph node metastases. A retrospective study was done at a single institution identifying six individuals who had chronic wound ulcers that underwent malignant transformation into a carcinoma. Sinus tract degeneration in osteomyelitis was not included. The average latency time between ulcer formation and documentation of a malignancy was 30 years. All wounds were about the pelvis or flank. Major oncologic surgical procedures were done in an attempt to eradicate the cancer. High-grade tumors had positive lymph node metastases, portending a grave prognosis. All four individuals with nodal metastases eventually died of systemic disease. Early recognition and proper staging offers the best chance for cure.

Update on giant cell tumor of bone.

Giant cell tumor of bone is a benign, primary skeletal neoplasm with an unpredictable pattern of biological aggressiveness. Molecular biological research has increased our understanding of these tumors. This article reviews recent advances in the study of this interesting bone tumor.

Telomerase activity in skeletal sarcomas.

BACKGROUND: Telomerase is a ribonucleoprotein that adds TTAGGG nucleotide repeats onto the ends of eukaryotic chromosomes to maintain telomere integrity. Somatic cells do not express telomerase and stop dividing when the chromosomal ends are shortened critically after many cell divisions. Immortal cell lines and cancer cells apparently have telomerase activity that contributes to an unlimited number of cell cycles. The purpose of our study is to investigate whether telomerase activity is expressed in primary malignant tumors of the skeletal system when compared to adjacent normal tissue. METHODS: Fresh tumor and normal tissue was collected from 14 patients (10 males, 4 females; age range, 8 to 76 years) and protein extraction performed. The tumors included seven osteosarcomas (three examined before and after chemotherapy), two chondrosarcomas, two spindle cell tumors, one hemangiopericytoma, one chordoma, and one adamantinoma. Telomerase activity was analyzed by using a highly sensitive polymerase chain reaction (PCR)-based assay (telomere repeat amplification protocol [TRAP]). RESULTS: Telomerase activity was found in 8 of 14 sarcoma patients (57%) using the TRAP assay. Compared to HeLa cell extract (positive control), telomerase activity in the tumor specimen ranged from 0 (in osteosarcoma) to 11.7% (in hemangiopericytoma). There was variation in the number of telomeric repeats generated by telomerase. At least five telomeric bands (e.g. 50, 56, 62, 68, 74 bp) in a ladder pattern had to be present before telomerase activity was considered positive in our analysis. CONCLUSIONS: Telomerase activity may be an oncogenic sustaining event helping to maintain the transformed phenotype seen in malignant tumors of the bone. The degree of telomerase activity varies among skeletal malignancies, but was less than that observed in HeLa cells. The majority of osteosarcomas showed no telomerase activity.

An analysis of concordance among hospital databases and physician records.

BACKGROUND: Hospital databases contain vital demographic patient information, which is increasingly being used as a basis to dictate care. It is hypothesized that the validity of data administratively generated from such sources is suboptimal, especially for rare subspecialties. The authors examined three databases to determine their concordance in an academic orthopaedic oncology subspecialty practice. METHODS: A 2-year retrospective review was performed on three databases searching for seven fundamental variables: additions/deletions; identification number; birthdate; procedure date; admit/discharge date; procedure code; and diagnostic code. Two university-maintained hospital databases (medical records and physician billing) were compared to the surgeon's personal handwritten daily log, which served as the "gold standard." RESULTS: All seven variables were in agreement with the physician's log in only 60% of the medical records and 61% of the physician billing patient entries (n = 564). On more detailed statistical analysis using chi(2), cross tabulations, and the K statistic for interobserver agreement, it was determined that poor concordance exists among the databases. CONCLUSION: Surgeons delivering quartenary care should maintain his or her own database because the hospital's information often differs on one or more important variables. Further investigation into the accuracy of hospital databases regarding commonly practiced medical disciplines appears warranted.

Clear cell sarcoma or malignant melanoma of soft parts: molecular analysis of microsatellite instability with clinical correlation.

Malignant melanoma of soft parts, also termed clear cell sarcoma (CCS), is a rare malignancy of neural crest origin which is different from cutaneous malignant melanoma. Although a translocation involving chromosomes 12 and 22 is characteristic of clear cell sarcoma and not malignant melanoma, there are a paucity of methods to differentiate the two. Therefore, a study of microsatellite instability (MIN) was undertaken to determine if mechanisms of DNA mismatch repair can differentiate these malignancies. MIN has been described in a variety of malignancies including 25% of malignant melanomas. Paraffin-embedded neoplastic and non-neoplastic cells were obtained from 11 individuals (five males; six females; age range from seven to 60 years) with CCS. Isolated DNA was PCR amplified at 17 separate microsatellite loci using radioactive-labeled primers. Tumor tissue was compared to normal tissue for each analysis. No MIN was detected. Loss of heterozygosity was detected in only one patient at a single locus (IFNA). The lack of MIN in clear cell sarcoma further defines the distinction between this tumor and malignant melanoma. Clinically, local recurrence and metastasis were indicators of poor outcome. The size of the tumor was not a significant prognostic indicator. Local recurrence, satellitosis, or nodal metastasis was not proven to be uniformly fatal. Utilization of chemotherapy and/or radiation demonstrated no obvious survival advantage. The histologic parameters of mitotic rate and the presence of necrosis were not prognostic. Limb-preserving surgical procedures were as effective as amputation for local disease control. The actuarial survival rate was calculated to be 48% at five years.

Microsatellite instability in malignant melanoma.

Defective mismatch repair has been detected in human colorectal and endometrial carcinomas which exhibit microsatellite instability (MIN). The purpose of this study was to search for MIN in melanoma. Paraffin-embedded neoplastic and non-neoplastic control cells were obtained from 20 untreated individuals with cutaneous malignant melanoma. Breslow thickness ranged from 0.2-7.4 mm (mean 1.4). Cells were carefully scraped from glass slides so that tumor and control DNA could be isolated and then amplified by polymerase chain reaction (PCR) at seven separate microsatellites localized to specific chromosome regions: 1p22 (D1S187), 5q11.2-13.3 (D5S107), 6q21-23.3 (D6S357), 9p21 (IFNA), 11p15.2 (D11S861), 17p13.1 (D17S786), and 18q11 (D18S34). Heterozygosity indices were > or = 0.70. Loci from these chromosome regions were chosen because of cytogenetic abnormalities reported in melanoma (1p, 6q, 9p), location of common oncogenes (11p-HRAS, 17p-TP53), or use in other MIN studies (5q, 18q). Five individuals (25%) demonstrated MIN. There was no correlation with tissue thickness. One individual demonstrated MIN at two loci and one individual demonstrated loss of heterozygosity. The results indicate that MIN occurs in melanoma, albeit less frequently than reported in carcinomas.

Microsatellite instability in sarcomas.

BACKGROUND: Microsatellite instability (MIN) has been studied in a variety of carcinomas and gynecologic sarcomas, but never in musculoskeletal sarcomas. METHODS: We evaluated 16 skeletal and soft tissue sarcomas at nine genetic loci from chromosomal regions 1q, 5q, 7q, 12p, 13q, 17p, 19q, and two at 11p--all potential regions of interest regarding musculoskeletal sarcomas. RESULTS: MIN was identified at one or more loci in seven of the cancers studied (44%). Three tumors had more than one locus with MIN and one tumor, a high-grade osteogenic sarcoma, had five of nine loci positive for MIN. CONCLUSION: These results indicate that musculoskeletal sarcomas show instability in areas inside and outside the loci of known oncogenes. Areas of mismatch repair, as heralded by MIN, may contribute to the vast heterogeneity of these neoplasms.

Recognizable magnetic resonance imaging characteristics of intramuscular myxoma.

Extremity intramuscular myxoma is an uncommon, deep, benign soft-tissue neoplasm. It is characterized clinically by slow growth and minimal symptoms. Resection achieving wide surgical margins is curative. This article presents the imaging characteristics of five extremity intramuscular myxomas. Images of this benign neoplasm, especially magnetic resonance imaging, are characteristic enough for preoperative recognition. This knowledge can facilitate treatment by avoiding biopsy, permitting primary myectomy, and assisting the pathologist in diagnosing a neoplasm that frequently has overlapping histologic characteristics with other soft-tissue tumors.

Needle tract recurrences after closed biopsy for sarcoma: three cases and review of the literature.

BACKGROUND: Percutaneous closed needle biopsy of musculoskeletal neoplasms has gained in popularity. However, it remains controversial whether or not to resect the needle tract for fear of a local recurrence. A single published case report exists, noting the lone tract recurrence of an extremity skeletal osteosarcoma. METHODS: We report on three additional individuals who demonstrated that tract local recurrences may occur after a closed needle biopsy for nonosteosarcoma, nonextremity sarcomas. For perspective, the world literature is reviewed to identify tract recurrences for other malignancies and the results of needle biopsy in musculoskeletal neoplasms. RESULTS: Eighty-nine percent of needle tract local recurrences occur when carcinomas are subjected to biopsy, as reported in the literature. Forty-seven cases since 1950 are described representing essentially all tumor types. The nature of musculoskeletal neoplasms makes closed biopsy more difficult than for softer, more homogeneous, and easier to access neoplasms. CONCLUSIONS: Local recurrences of sarcoma may occur in closed needle biopsy tracts. Strong consideration should be given to open biopsy and tract resection.

Operative treatment of fractures of the tibial plafond. A randomized, prospective study.

We performed a randomized, prospective study to compare the results of two methods for the operative fixation of fractures of the tibial plafond. Surgeons were assigned to a group on the basis of the operation that they preferred (randomized-surgeon design). In the first group, which consisted of eighteen patients, open reduction and internal fixation of both the tibia and the fibula was performed through two separate incisions. An additional patient, who had an intact fibula, had fixation of the tibia only through an anteromedial incision. The second group consisted of twenty patients who were managed with external fixation with or without limited internal fixation (a fibular plate or tibial interfragmentary screws). Ten (26 per cent) of the thirty-nine fractures were open, and seventeen (44 per cent) were type III according to the classification of Rüedi and Allgöwer. There were fifteen operative complications in seven patients who had been managed with open reduction and internal fixation and four complications in four patients who had been managed with external fixation. All but four of the complications were infection or dehiscence of the wound that had developed within four months after the initial operation. The complications after open reduction and internal fixation tended to be more severe, and amputation was eventually done in three patients in this group. At a minimum of two years postoperatively (average, thirty-nine months; range, twenty-five to fifty-one months), the average clinical score was lower for the patients who had had a type-II or III fracture, regardless of the type of treatment. With the numbers available, no significant difference was found between the average clinical scores for the two groups. All of the patients, in both groups, who had had a type-II or III fracture had some degree of osteoarthrosis on plain radiographs at the time of the latest follow-up. With the numbers available, there was no significant difference between the two groups with regard to the osteoarthrotic changes. We concluded that external fixation is a satisfactory method of treatment for fractures of the tibial plafond and is associated with fewer complications than internal fixation.

The spinal nail: a new implant for short-segment anterior instrumentation of the thoracolumbar spine.

The biomechanics of a new spinal implant were evaluated and its dependence on an anterior strut graft was determined. Six fresh-frozen adult porcine spines were used. An L3 corpectomy was created. The spinal nail was inserted intraosseously into the middle column of the L2-L4 vertebral bodies in a trough. Implant drill holes were made for proximal and distal locking bolts in L2 and L4. A locking plate bridged the L2 and L4 trough and anchored the exposed ends of the locking bolts. Testing was performed in axial compression, torsion, and flexion. The axial and torsional stability of the spine instrumented with the spinal nail are similar to results with other devices when used with anterior strut grafting. The axial and flexural stiffnesses of the instrumented spine are independent of strut grafting. This study suggests that this device may be useful for reconstruction of the anterior spine because of instability.

Lack of microsatellite instability in giant cell tumor of bone.

Microsatellite instability was searched for at six different loci on chromosome arms 5q, 18q, 15q, 17p, 19q, and 11p in 22 patients (12 men and 10 women; average age of 31.8 years, range of 20-55 years) with giant cell tumor of bone (GCT). These loci were chosen because of their use in microsatellite instability studies in other tumors such as colorectal cancer (e.g., 5q, 18q, 17p) or because of the presence of chromosomal abnormalities such as telomeric associations commonly occurring at 19q and 11p termini (thus the reason for including the 19q and 11p termini microsatellites in our study of GCT). No microsatellite instability or loss of heterozygosity were detected when comparing normal and tumor cells from any of the GCT patients. Unlike several other tumors, our study indicates that microsatellite instability does not appear to play a role in the tumorigenesis of GCT although other abnormal cytogenetic, biochemical, and molecular genetics data do exist for this musculoskeletal tumor.