Robert Schachner

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.

Induction of Donor-Specific Tolerance to Rat Islet Allografts by Intrathymic Inoculation of Solubilized Spleen Cell Membrane Antigens

The development of strategies that will allow permanent survival of islet allografts without continuous host immunosuppression continues to be the most important goal in the field of pancreatic islet cell transplantation. In our study, we demonstrated that intrathymic inoculation of allogeneic spleen cell membrane antigens with a single dose of anti-lymphocyte serum induces an unresponsive state that permits survival of a subsequent pancreatic islet allograft to an extrathymic site (renal subcapsular space). This effect is donor specific and cannot be reproduced by the intravenous injection of spleen cell membrane antigens. Our results offer a potential approach for establishing donor-specific allograft acceptance in adult recipients.

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.

Update of laser hyperthermic treatment for primary breast cancer: Ex-vivo and in-vivo models

The treatment of primary breast cancer in the last half century has progressively decreased in its disfiguring consequences while maintaining the same level of cure. Extending this philosophy beyond lumpectomy, we propose to treat small primary breast cancers by laser interstitial therapy with minimal possible cosmetic distortion. Our program to achieve that goal has made considerable progress in the preclinical instrument modification and development of physical, tissue, and live animal models. In anticipation of a clinical trial this report updates information presented in 1996.

Model development of laser fiber optic endoablative treatment for primary breast cancer

A mammographic stereotactic core biopsy instrument can be adapted for laser hyperthermic ablation of breast cancer. The object of this study is to characterize laser endohyperthermia ex-vivo and in-vivo to develop a reliable approach leading to human trials. Light of a Nd:YAG laser passed through a fiberoptic cable to a diffusing quartz tip upon entering surrounding tissues can bring about very high temperatures. This approach concentrating on the heat distribution to fat and fibrofatty tissue, first analyzed a physical model into which both the quartz tip and thermocouple needles were placed. Temperature recordings in volume through a time course demonstrated a progressive thermal increase around the tip. Additional light distribution studies in several media demonstrated the tips output. The technique transferred to ex-vivo human breast and porcine fibrofatty tissue showed similar findings leading to an in-vivo analysis of subcutaneous porcine fibrofatty tissue. A step-down energy program beginning at 20 watts and decreasing to 15 watts, 10 watts, and to 7 watts, at 30 second intervals was held at the latter power for the remainder of 6 minutes. Three such cycles appear to be the optimal treatment program to develop temperatures between 60 degrees Celsius and 80 degrees Celsius (approximately equals 9700 joules). In-vivo experiments conducted on 5 occasions revealed no skin change. At necropsy the treated tissues demonstrated a circular sharply defined 3 cm volume of necrosis with no change in adjacent tissue. Time-temperature correlations between ex-vivo and in-vivo tissues showed great similarity. Nd:YAG laser energy distributed to a quartz tip through a fiberoptic cable is capable of uniform, complete tissue destruction to a 1 1/2 cm radius with no change beyond that field. This technique with further refinement will be appropriate to the treatment of small breast cancers that have been stereotactically biopsied.