Interstitial laser hyperthermia model development for minimally invasive therapy of breast carcinoma.

BACKGROUND: This investigation describes the preclinical development of a laser fiberoptic interstitial delivery system for the thermal destruction of small breast cancers. We propose adaptation of this technology to stereotactic mammographic instrumentation currently employed for diagnostic core biopsy to thermally ablate a site of disease with maximal treatment efficacy, minimal observable superficial change, reduced patient trauma, and lowered overall treatment costs. STUDY DESIGN: Laser hyperthermia is a clinical modality that seeks to achieve tumor destruction through controlled tissue heating. The advantage of laser-induced hyperthermia over traditionally used heat sources such as ultrasound, microwave, or radiowave radiation lies in the ability to focus heat localization to the specific tumor tissue site. Neodymium:yttrium aluminum garnet (Nd:YAG) laser light transmitted through a fiberoptic cable to a diffusing quartz tip can induce such temperature increases leading to localized tissue destruction. Because breast cancer occurs with greatest frequency in the mature woman whose breast tissue has undergone glandular involution with fatty replacement, this study concentrates on determining the resultant laser energy heat distribution within fat and fibrofatty tissue. This investigation studied the time-temperature responses of ex vivo human breast and porcine fibrofatty tissue, which led to an in vivo subcutaneous porcine model for the practical demonstration of a laser hyperthermia treatment of small volumes of porcine mammary chain tissue. RESULTS: Spatial recordings of the resultant temperature fields through time exhibited similar, reproducible thermal profiles in both ex vivo human breast and subcutaneous porcine fat. In vivo laser-produced temperature fields in porcine subcutaneous fat were comparable to those in the ex vivo analyses, and showed a histologically, sharply defined, and controllable volume of necrosis with no injury to adjacent tissues or to overlying skin. CONCLUSIONS: Interstitially placed, fiberoptically delivered Nd:YAG laser energy is capable of controlled tissue denaturation to a defined volume for the treatment of small breast cancers. It is hoped that this minimally invasive approach, with further investigation and refinement, may lead to the effective treatment of small, well-defined breast cancers that are commonly diagnosed through stereographic mammography and stereotactic core biopsy. The juxtaposition of such a localized treatment modality with these increasingly used diagnostic tools is of considerable promise.

The influence of donor specific vertebral body derived bone marrow cell infusion on canine islet allograft survival without irradiation conditioning of the recipient.

In recent studies in rodents, it was shown, that donor specific tolerance towards islet allografts without irradiation therapy of the recipient is induced by bone marrow cell infusion in combination with temporary immunosuppression. In the present study, the effect of donor specific bone marrow cell (DBMC) infusion at the time of intrahepatic islet allotransplantation without irradiation conditioning of the recipient was investigated in the canine model, paralleling ongoing clinical trials. It was observed, that unfractionated bone marrow cells given simultaneous to islet allografts led to higher frequencies of rejection periods and decreased islet allograft survival, when administered to recipients immunosuppressed with Cyclosporine A only. In contrast, an additional short inductive treatment of the recipient with an anti-dog-T-lymphocyte monoclonal antibody (5G2) abrogated the enhanced immunogenicity of the unfractionated bone marrow preparation, prolonging islet allograft survival with no rejection episodes observed during the immunosuppressive treatment with Cyclosporine. The composition of bone marrow cells might have contributed to the higher immunogenicity, since the percentage of MHC-class II antigen bearing cells is similar to man, but significantly higher than compared to rodents. It is therefore suggested, that further studies should encompass both timing of bone marrow cell infusion, appropriate immunosuppression and strategies to functionally inactivate mature MHC-class-II positive cells prior to DBMC infusion.

A minimally invasive technique for intrathymic cell transplantation in the dog.

As an alternative to drug immunosuppression, attempts at inducing donor-specific tolerance by intrathymic (IT) inoculations to transplant recipient of donor origin alloantigenic products has proven very promising. Using fiber optic thoracoscopy, a technique for the study of this phenomena was developed for the dog. We show an approach to the dog thymus using fiber optics for injection of bone marrow (BM) cells as the tolerogen. Bone marrow was retrieved from the donor beagles and purified using an automated Ficoll-Paque gradient technique. The purified cellular suspension was injected into the thymus through a small intercostal incision with the use of an injection needle port guided by the use of a rigid fiberoptic scope. To demonstrate engraftment, supravital staining with Fluorescein Diacetate of the BM cells was performed prior to inoculation. Immunofluorescence of cryostat sections obtained at necropsy confirmed the presence of viable BM cells up to several days after transplantation. Results of this study show that the thoracoscopic approach to the thymus can be safely and effectively used for IT inoculation studies in dogs.