Alan J. Herron

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.

Diagnosis of Enteritis and Enterotoxemia due to Clostridium Difficile in Captive Ostriches (Struthio Camelus)

petted normal ranges. Seven of the expired birds were necropsied immediately after death. Two live ostriches with clinical signs were euthanized, and tissues were obtained for histopathology, bacterial culture, and viral isolation. At necropsy, all of the ostriches examined had similar gross lesions that differed only in severity. The colon and cecum were markedly dilated and diffusely hemorrhagic and contained no formed feces. The lungs were variably congested, and the liver was frequently pale yellow in color. Two of the birds had hemorrhagic foci in the proventriculus. No other significant gross lesions were observed in any of the birds. Microscopic examination of the tissues revealed an acute, severe, necrotizing typhlitis and colitis in all birds, with massive numbers of large gram-positive bacilli present within glands and in the intestinal lumen (Figs. 1, 2). There was moderate, diffuse hepatocellular vacuolar change in 6 birds and multifocal lymphoid necrosis in the bursa of Fabricius of 2 of the ostriches. No viral inclusions were noted. Moderate to severe congestion was present in the lungs of 7 of 9 birds. Two of the birds had a mild necrotizing proventriculitis with mild hemorrhage. Sections of the intestine were submitted for aerobic and anaerobic culture. Enrichment for Salmonella in selenite broth for 12 hours yielded negative results, and no clinically significant aerobic pathogenic bacteria were found. Two different species of Clostridium were anaerobically cultured from the intestine. They were tentatively identified as C. hastiforme and C. clostridiiforme by API 20A biochemical assay. b After isolation and subculture of the original cultures in cycloserine-cefoxitin-fructose agar and additional biochemical analysis by An-IDENT biochemical assay, b the C. hastiforme culture was shown to be C. difficile. The API-20A biochemical assay was then repeated on the pure culture, and it too indicated the presence of C. difficile. The intestine was submitted for clostridial enterotoxin assay c by enzyme-linked immunosorbent assay (ELISA). Extracts of multiple sections

Immunoblastic malignant lymphoma in dolphins: Histologic, ultrastructural, and immunohistochemical features

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Metastasis of a myxoid leiomyosarcoma via the renal and hepatic portal circulation in a sarus crane (Grus antigone)

A 12-year-old female sarus crane (Grus antigone) developed a recurrent proliferative lesion in the subcutaneous tissue of the tarsometatarsus, which failed to respond to medical and surgical therapy. The crane was killed and microscopic examination of the tissues taken at necropsy revealed a myxomatous, poorly-differentiated sarcoma with metastasis to the liver and kidney. Immunohistochemical staining for muscle actin, smooth muscle myosin and vimentin were positive, indicating that the primary and metastatic tumours were leiomyosarcomas. Location of the metastatic lesions in only the portal venous system of the liver and veins of the kidney indicated that the route of metastasis was the portal circulation via the ischiatic vein, caudal mesenteric vein and both the renal-portal shunt and hepatic portal vein. This is the first report of metastatic subcutaneous leiomyosarcoma in an avian species.

Salivary gland oncocytes in african hedgehogs (Atelerix albiventris) mimicking cytomegalic inclusion disease

The salivary glands from three African hedgehogs contained multiple foci of cytomegalic cells, which occasionally had a mild to moderate infiltrate of lymphocytes at the periphery. The cytomegalic cells were 35 to 40 microns in diameter with abundant acidophilic granular to hyalin cytoplasm. The nuclei were enlarged with clumped marginalized chromatin and a large, (6 to 8 microns in diameter) central, brightly eosinophilic nucleolus that had the appearance of an inclusion body by light microscopy. Histochemically most of the cytomegalic cells contained cytoplasmic metachromatic granules with Feyrters thionine inclusion stain. Scattered cells at the periphery of the cytomegalic foci contained periodic acid-Schiff-positive cytoplasmic granules. Ultrastructurally the cytomegalic cells contained numerous tightly-packed, often bizarre, enlarged mitochondria that completely filled the cytoplasm. The nucleus consisted of a dense central core of chromatin associated with the nucleolus and the remaining chromatin was clumped and marginalized. Nuclear and cytoplasmic virions consistent with cytomegalovirus were not present. Histochemical stains of the nucleus for heavy metals were negative. The ultrastructural and histochemical findings of the cytomegalic cells were consistent with oncocytes. Previous reports in the literature of similar cells in the salivary glands of insectivores appear to have been erroneously described as cytomegalovirus infections.

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.