Cryosurgery of breast cancer.

OBJECTIVE: To determine the feasibility and efficacy of cryosurgery of breast cancer. DESIGN: In phase 1, carcinogen-induced mammary adenocarcinomas in 13 Sprague-Dawley rats were treated by cryosurgery and were then examined for histopathologic change. In phase 2, transplantable mammary adenocarcinomas in 50 DBA/IJ mice were treated by cryosurgery to determine the effect of varying tumor temperatures, and duration and number of freeze-thaw cycles on tumor viability. In phase 3, 2- to 3-cm ultrasound-monitored cryolesions were formed in the breasts of 4 dogs and 4 sheep. These animals were followed up for procedure-related complications; the histopathologic necrosis of the cryolesions were correlated with the ultrasound images. Based on the results of these experiments, ultrasound-guided cryosurgery of breast cancer was initiated in a human clinical trial. RESULTS: In phase 1, a single, short-term (< 7 minutes) freeze killed only tumors smaller than 1.5 cm in diameter, despite an apparent decrease to -40 degrees C at the periphery of each tumor. In phase 2, varying the peripheral tumor temperature to as low as -70 degrees C, using a single, short-term (< 7 minutes) freeze did not alter the results from phase 1. If the ice ball fully encompassed the tumor, however, maintaining it for at least 15 minutes achieved 100% tumor kill independent of tumor size. In phase 3, creation of a reproducible ultrasound-monitored cryolesion was facilitated when 2 freeze-thaw cycles were performed. No procedure-related complications were noted. In the human trial, 2 invasive lobular carcinomas from 1 patient were treated by cryosurgery and were negative for persistent tumor by core needle biopsy performed 4 and 12 weeks after a well-tolerated procedure. CONCLUSIONS: In situ breast cryosurgery has been proved to be feasible and efficacious in small and large animal studies and has been successfully performed in 1 patient with breast cancer. The results of this study suggest that ultrasound-guided cryosurgery of breast cancer warrants further investigation.

The evaluation of various bioabsorbable materials on the titanium fiber metal tracheal prosthesis.

A new type of tracheal prosthesis was studied. It consists of a rigid, porous cylinder of titanium fiber metal coated with a polymer that provides an initial air seal and then is absorbed to permit subsequent fibrous tissue ingrowth and reepithelialization. Fifteen such cylinders measuring 50 mm by 26 mm were coated with one of the following polymers: polycaprolactone 700 (3 coated internally and 3 externally); a copolymer of 75% poly-L-lactic acid and 25% polyglycolic acid (3 coated internally and 3 externally); and polyglactin 910 (3 coated externally). Fifteen kennel-conditioned mongrel dogs, each randomly assigned to one of these five groups, underwent implantation of the prosthesis through a right thoracotomy into a 5-cm defect in the distal intrathoracic trachea. There were no immediate postoperative deaths, and no instances of major air leak from the prosthesis. One animal died after two weeks secondary to a lower respiratory tract infection. Bronchoscopic evaluation revealed varying degrees of tissue ingrowth into the prostheses, with no evidence of infection or distal accumulation of secretions. Histological evaluation showed superior tissue ingrowth and reepithelialization with internally coated prostheses; two out of three polymers gave good results.

Distribution of a somatostatin analog after continuous intraventricular administration.

Decreased somatostatin in the brains of patients with Alzheimer's disease has led to an investigation of the efficacy of neurotransmitter replacement therapy. The distribution of a somatostatin analog, octreotide, was determined after 2 to 6 days of continuous intraventricular infusion at 40 micrograms/h in dogs. The tissue concentration was greater than 100 ng/g wet weight in all parts of the brain, which is greater than the normal concentration of native somatostatin. There was no reduction in native somatostatin production because of the infusion of the analog. The cerebrospinal fluid octreotide concentration was 1000 times greater than the plasma concentration. The results demonstrate that neurotransmitter replacement for somatostatin can be achieved by chronic intraventricular infusion of a metabolically stable analog.

The effect of lasers, electrocautery, and sharp dissection on cutaneous flaps.

This study evaluated the technical ease and wound-healing response of cutaneous flaps constructed on dogs using Nd:YAG laser, CO2 laser, electrocautery, and sharp dissection. Four flaps were constructed on the dorsum of 16 dogs using each of the four modalities. Parameters examined included drainage after both 48 hours and 1 week, time of dissection, bursting strength, and semiquantitative assessments of fibroblast, polymorphonuclear leukocyte, monocyte, and collagen content. Significantly less time was required to construct flaps with electrocautery as compared with CO2 laser, Nd:YAG laser, and sharp dissection (15 versus 18, 20, and 26 minutes, respectively; p < 0.01). Significantly fewer suture ligatures were necessary to obtain hemostasis for electrocautery, CO2 laser, and Nd:YAG laser as compared with sharp dissection (0, 2, and 2 versus 15 sutures, respectively; p < 0.01). Drainage was significantly less for flaps constructed using sharp dissection as compared with both CO2 and Nd:YAG lasers at 48 hours (12 versus 26 cc, p < 0.01, and 20 cc, p < 0.05, respectively). Significantly less drainage was observed after 48 hours for flaps created using electrocautery as compared with CO2 laser (14 versus 26 cc; p < 0.05). Bursting strength of flaps constructed using sharp dissection was significantly greater than that of those constructed using electrocautery, Nd:YAG laser, and CO2 laser (1086 versus 638 gm, p < 0.05, 714 gm, and 571 gm, p < 0.01, respectively). Semiquantitative histologic evaluation revealed a higher collagen content and fibroblast infiltration and less polymorphonuclear leukocyte infiltration in wounds created using sharp dissection as compared with CO2 laser, Nd:YAG laser, and electrocautery.(ABSTRACT TRUNCATED AT 250 WORDS)

Characteristics of Nd:YAG sculptured contact probes after prolonged laser application.

This study analyzed the functional and structural characteristics of cone, hemisphere, and modified sculptured contact fibers (1,000 microns) after 1 hour of continuous Nd:YAG laser application. Continuous laser application was performed on live porcine tissue using 20 watts of power. The fiber's appearance under a microscope as well as the power output was recorded after 0, 5, 10, 20, 30, 45, and 60 minutes of continuous laser application. (N = 3 for each fiber). At time 0, all fibers transmitted from 49 to 56% of the initial 20 watts (W); power transmission decreased to less than 9% relative power transmission after 20 minutes and then plateaued. The fibers exhibited severe distortion and carbonization of the surface where laser had been applied with evidence of quartz melting and shattering after only 10 minutes. By 30 minutes of laser application, all three fibers were fractured and essentially indistinguishable from one another; moreover, the fibers exhibited similar power transmission, and cutting and coagulation activity, as determined by a panel of independent, double-blinded surgeons. These data lead us to conclude that 1) Nd:YAG contact laser effects result from thermal heating of the fiber tip with subsequent tissue injury, 2) the unique structural configuration of the fiber's sculptured tip are lost after several minutes of laser application without appreciable change in functional integrity, and 3) fibers may be manually fractured allowing for multiple uses without significant sacrifice of power transmission or surgical utility.

Effect of cimetidine on intestinal adaptation following massive resection of the small intestine.

Gastric acid hypersecretion follows massive resection of the small intestine. Steatorrhea as well as other metabolic imbalances is a challenging management problem associated with massive resection of the small intestine. In the literature, it has been suggested that the empiric use of cimetidine controls gastric acid hypersecretion following massive resection of the small intestine. In this study, an 80 per cent resection of the small intestine was performed upon 12 mongrel dogs. Ileal pH measurements, fecal fat content and serial intestinal biopsies were obtained for morphometric measurements. Steatorrhea was reduced by approximately 40 per cent in the cimetidine treated dogs. Ileal pH measurements declined immediately following intestinal resection. The cimetidine treated dogs demonstrated a return to normal levels within ten days following intestinal resection, p less than 0.05. Intestinal adaptation morphometric parameters revealed an accelerated adaptational response in the cimetidine treated dogs, p less than 0.05. Results of this study colaborates with the empiric and clinical indication for the use of cimetidine in the short gut syndrome clinical situation. In addition, the data suggest an intestinal adaptation accelerated response during the first phase of intestinal adaptation following massive resection of the small intestine in the dog.

Protection of fiber function by para-axial fluid flow in interstitial laser therapy of malignant tumors.

In the past, interstitial laser therapy frequently has failed because of the damage to the bare fiber tip due to intense heat generated at the point of contact. Using a rat mammary tumor model, we describe a method of placing a 600 micron fiber inside a gauge 19 needle cannula after its insertion into the tumor. With this device continuous wave Nd:YAG laser is delivered to the target tumor while 0.9% saline flows para-axially into the tumor. Significant coagulation necrosis was induced with 500 joules at 5 watts, 100 seconds and 1 cc per minute of saline while the needle-fiber is pulled out of the tumor by 10 mm. The mean transmission loss after 500 joules was 2% in ten experiments. The tumor edema due to 1.5 ml of saline was transient. We conclude that successful hyperthermic coagulation necrosis by Nd:YAG laser can be achieved with minimal transmission loss by employing the above technique.