Norman S. Schachar

Cryopreservation of intact human articular cartilage

Damaged articular cartilage (AC) impairs joint function and many treatment techniques are being investigated to determine their long term results. Successful cryopreservation of AC can provide a reliable source of intact matrix with viable chondrocytes to maintain the cartilage over long periods of time. This study investigated the application of an established cryopreservation protocol to determine the recovery of intact chondrocytes from human AC. Ten millimeter diameter osteochondral dowels were harvested from two human donors. The cryopreservation protocol was performed and the samples were rapidly warmed from varying experimental holding temperatures (−10, −20, −30, −40°C), with and without plunging into liquid nitrogen, using 1 M dimethyl sulfoxide as cryoprotectant. The cartilage was stained with membrane integrity dyes and viewed under fluorescence microscopy. The percent of intact chondrocytes was compared to fresh controls. Low recovery of intact chondrocytes was recorded from all temperature levels with and without cryoprotectant. The results of this experiment demonstrated that the cryopreservation procedure used to achieve moderate success with intact sheep AC was not successful with intact human AC and further investigation is required.

An update on the nonoperative treatment of patients with metastastic bone disease

Bone metastases constitute a major problem in oncology because of their frequency and the therapeutic problems they present. Treatment indications depend on accurate diagnosis including histologic type, number, location, and sensitivity to treatment. New findings in the pathophysiology of bone metastases, new staging procedures, new treatment modalities, and better guidelines improve therapeutic effectiveness and the quality of life of patients. There are biologic and biomechanical indications for treatment. The goals of treatment are pain relief, restoration and maintenance of function, and the prevention of complications. The nonsurgical treatment of patients with metastatic bone disease includes analgesics, hormones, radiation therapy, cytotoxic drugs, radiopharmaceuticals, chemoablation, vertebroplasty, and bisphosphonates. The future of the treatment of patients with metastatic bone disease may involve the identification of biochemical markers. The author presents an overview of the current scientific concepts of metastatic bone disease and indications and specific strategies for nonoperative treatment of patients with tumor-induced osteolysis from metastatic bone disease.

Prospective cohort study of neoadjuvant treatment in conservative surgery of soft tissue sarcomas.

AbstractBackground: 1994 marked a decade since the inception of a prospective population-based study on the value of a neoadjuvant approach for soft tissue sarcomas of head, neck, and limbs at the Tom Baker Cancer Centre, Calgary, Alberta. To date, 42 patients have been followed for a minimum of 5 years or until death. Methods: Each patient received a protocol of 60 mg to 90 mg of Adriamycin infused intraarterially or intravenously over 3 days into a vessel feeding the involved area, 30 Gy of radiotherapy given over 10 days, and complete resection of the sarcoma 4 to 6 weeks later. The lower dose was used empirically for smaller limbs (e.g., arm). Results: Two of the 42 patients were immediate failures of protocol, with one requiring amputation and one requiring later reexcision. In the 38 appendicular lesions, the ultimate limb salvage rate was 97.5%. All tumors were associated with a high risk of local recurrence, with 15 being previous local failures. The rest were deep and grade 2 or 3 lesions. Serious local complications were seen in one patient (2.5%) who had wound necrosis requiring reoperation. Minor wound complications were seen in five patients (12.5%) (one wound infection, one resolved edema, three long-term drainage). There was one local recurrence; thus 5-year local control was 97%. No patient had long-term morbidity related to the treatment. No effect on systemic control was suggested. Conclusion: Our report demonstrates that this combined modality approach provides superior local control of soft tissue sarcomas with low postoperative morbidity.

Investigations of low-temperature storage of articular cartilage for transplantation.

Isolated bovine articular cartilage chondrocytes and intact slices of cartilage were investigated to determine the effects of low-temperature cryopreservation on articular cartilage. Studies have focused on prefreezing conditions of cartilage, including the incubation medium and temperature of incubation, type and toxicity of the cryopreservative used, and the penetration of cryopreservative agents into cartilage cells. Cartilage freezing conditions were examined with respect to rate of freezing, controlled differential freezing rates, the ultimate storage temperature, and the time of storage. Cartilage thawing conditions were observed to ascertain the role of membrane osmotic stress during thawing and the effect of variable thawing rates on the viability of chondrocytes. Careful control of these variables can yield cartilage with cellular viability of over 50%. Optimum cryopreservation of viable cartilage should include prefreezing treatment with 7.5%-10% DMSO in nutrient medium, controlled slow freezing to —70°, and rapid thawing in DMSO containing medium. A significant number of chondrocytes in deep-frozen cryopreserved articular cartilage can survive. The work recommends continued clinical use of deep-frozen cartilage.

Electromagnetic stimulation of ligament healing in rabbits.

To evaluate the effect of a specific noninvasive method of electrical stimulation on ligament healing in rabbits, a solid core electromagnet energized by a square wave unidirectional current was applied to injured and repaired medial collateral ligaments seven hours per day, five days per week for intervals of up to six weeks. Healing was evaluated by gross, histologic, biochemical, and biomechanical parameters. Stimulation was shown to increase histologic maturity relatively, restore stiffness and failure strength earlier, and return collagen content toward normal unoperated values sooner in these healing ligaments. It is uncertain whether the end point of healing is affected by this technique, but at six weeks both histologic and biochemical evidence of acceleration remains. Further investigation into the effect of electromagnetic stimulation by this and other fields on non-osseous tissues and their components is indicated.

Outcomes of surgical treatment alone in patients with superficial soft tissue sarcoma regardless of size or grade.

Currently, standard treatment of soft tissue sarcoma (STS) is wide local excision and adjuvant radiation, but radiation may be unnecessary in superficial STS. The primary objective is to assess local recurrence rates in patients treated with surgical management alone for superficial STS.

Reconstructive limb-sparing surgery following resection of aggressive tumors of the extremities and pelvis

Current strategies for limb-salvage surgery for bone and soft tissue tumors include improved staging and surgical techniques and neoadjuvant and adjuvant therapy. Conservative surgery for soft tissue tumors, using adjuvant therapy, is now established as a standard approach. A population-based, prospective cohort trial of neoadjuvant treatment in conservative surgery for soft tissue sarcomas has recetly been carried out. Data available on 40 patients followed for 24–110 months found that local control for conservative surgery for soft tissue sarcomas overall was 97.5%. Survival at 10 years was approximately 40% and did not seem to be changed despite a drop in local recurrence. These results have been applied to a cohort of patients with bone sarcoma, with equally promising results. Limb-sparing resection with osteoarticular allograft reconstruction in the proximal tibia, the distal femur, and the proximal humerus have yielded very good to excellent results. Osteoarticular allografts do give rise to a number of complications. Alternatives to allografts involve the use of implant arthroplasties, either custom-designed or modular in design, as well as intercalary allografts. There is increasing interest in using outcome data collection methodology to assess the quality of life of patients who have undergone reconstruction with limb-salage surgery following resection of aggressive lesions of the extremities and pelvis.

A modified eilber protocol provides maximum local control and minimum major morbidity in soft tissue sarcoma

S: PLENARY and PARALLEL SESSIONS 2 of 5 animals showing a complete response out to 60 days). There was no significant change in tumor LPAM concentration with addition of heat. Average proliferation index following ILP with saline, saline + HT, LPAM, or LPAM + HT was 40%, 28%, 27%, and 16% respectively. CONCLUSIONS: Administration of LPAM with increasing amounts of localized heat yielded increasing growth delay and decreased proliferative index. This demonstrates that the application of hyperthermia, rather than the prevention of hypothermia, is the cause for enhanced therapeutic effect in HILE The interaction between HT and melphalan was synergistic. This interaction could not be explained by increased uptake of drug with the addition of heat. These findings underscore the importance of the use of HT in regional chemotherapy.

Prospective cohort study of neoadjuvant treatment in conservative surgery of soft tissue sarcomas

Background: 1994 marked a decade since the inception of a prospective population-based study on the value of a neoadjuvant approach for soft tissue sarcomas of head, neck, and limbs at the Tom Baker Cancer Centre, Calgary, Alberta. To date, 42 patients have been followed for a minimum of 5 years or until death.