Budget impact analysis of a new prostate cancer risk index for prostate cancer detection.

The objective of this study was to evaluate the budget impact of a new prostate cancer risk index for detecting prostate cancer. The index is calculated as the combination of serum prostate-specific antigen (PSA), free PSA and a precursor form p2PSA. We constructed two budget impact models using PSA cutoff values of ≥2 ng ml(-1) (model #1) and ≥4 ng ml(-1) (model #2) for recommending a prostate biopsy in a hypothetical health plan with 100 000 male members aged 50-75 years old. The budgetary impact on the 1-year expected total costs for prostate cancer detection was calculated. Adding the index to the current PSA prostate cancer testing strategies including the total PSA and percent free PSA, the number of detected cancer cases decreased by 20 and 5, in models #1 and #2, respectively. The savings on expected 1-year cost for prostate cancer detection were $356 647 (or $0.30 per-member-per-month (PMPM)) in model #1 and $94 219 ($0.08 PMPM) in model #2. The index produced higher cost savings in the model #1 with PSA cutoff ≥2 ng ml(-1) than the model #2 with cutoff ≥4 ng ml(-1) with a small short-term reduction in the number of positive tests.

Liposome-mediated, nonviral gene transfer induces a systemic inflammatory response which can exacerbate pre-existing inflammation.

Cationic liposome and plasmid-mediated gene transfer has emerged as a novel technique for the targeted delivery of protein-based therapies in acute inflammatory diseases. However, concerns have arisen that cationic liposomes and plasmid DNA have inherent proinflammatory properties which could exacerbate pre-existing inflammatory processes. In healthy mice, intraperitoneal administration of cationic liposomes (200 nmol) complexed to plasmid DNA (100 microg) induced a proinflammatory response characterized by the induction of tumor necrosis factor alpha and interleukin-1beta mRNA expression. The plasma concentrations of the hepatic acute phase proteins interleukin-6, amyloid A, amyloid P, and seromucoid were also increased (P<0.05), and this response was seen in endotoxin-resistant (C3H/HeJ) mice. The inflammatory response associated with gene transfer increased the mortality and severity of experimentally induced sterile inflammation (pancreatitis). We conclude that systemic administration of cationic liposomes and plasmid DNA is associated with induction of the innate immune response which may exacerbate pre-existing inflammatory processes.

Development of stereotactically guided laser interstitial thermotherapy of breast cancer: in situ measurement and analysis of the temperature field in ex vivo and in vivo adipose tissue.

BACKGROUND AND OBJECTIVE: The size (0.5-1.0 cm) of early nonpalpable breast tumors currently detected by mammography and confirmed by stereotactic core biopsy is of the order of the penetration depth of near infrared photons in breast tissue. In principle, stereotactically biopsied tumors, therefore, could be safely and efficiently treated with laser thermotherapy. The aim of the current study is to confirm the controlled heating produced by clinically relevant power levels delivered with an interstitial laser fiber optic probe adapted for use with stereotactic mammography and biopsy procedures. STUDY DESIGN/MATERIALS AND METHODS: Temperature increases and the resultant thermal field produced by the irradiation of ex vivo (porcine and human) and in vivo (porcine) tissue models appropriate to the treatment of human breast tissue by using cw Nd:YAG laser radiation delivered with a interstitial fiber optic probe with a quartz diffusing tip, were recorded with an array of fifteen 23-gauge needle thermocouple probes connected to a laboratory computer-based data acquisition system. RESULTS: By using a stepwise decreasing power cycle to avoid tissue charring, acceptably symmetric thermal fields of repeatable volumetric dimensions were obtained. Reproducible thermal gradients and predictable tissue necrosis without carbonization could be induced in a 3-cm-diameter region around the fiber probe during a single treatment lasting only 3 minutes. The time-dependences of the temperature rise of the thermocouples surrounding the LITT probe were quantitatively modeled with simple linear functions during the applied laser heating cycles. CONCLUSION: Analysis of our experimental results show that reproducible, symmetric and predictable volumetric temperature increases in time can be reliably produced by interstitial laser thermotherapy.

A novel pancreatic model: the snip method of pancreatic isolation for in vitro study.

We aimed to devise a method of preparing the pancreas for in vitro study that would provide tissue that is viable and functional for 24 h, with preservation of integral functional cell-membrane structures. Pancreata of NIH Swiss mice were excised, gently insufflated with media, and carefully snipped into portions of < 0.5 mm. Snips were incubated in cell culture for 0, 8, 24, and 48 h, with viability measured by 3-[4,5-dimethylthiazol-2-yl]-2,3-diphenyltetrazolium bromide (MTT) assay and amylase production quantified after stimulation with cerulein. Recombinant tumor necrosis factor-alpha (TNF-alpha) was added to cell culture, and apoptosis demonstrated by Hoechst staining at 0, 24, and 48 h. At 0, 8, and 24 h, pancreatic snips were determined to be viable by MTT assay. They also were functional with intact cell-membrane apparatuses at these same time points, as evidenced by amylase production in response to a cholecystokinin analogue. We were able to induce apoptosis with TNF-alpha ligand in these pancreatic snips in support of viability and overall cellular function. We conclude that the snip method provides an effective in vitro pancreatic model. Acinar cells are viable and functional for > or = 24 h, with evidence that their cell-surface receptors are preserved in their operational state.

Minimally invasive radioguided parathyroidectomy in the reoperative neck.

BACKGROUND: Operations for hyperparathyroidism (HPT) in a previously operated neck present a significant challenge and carry much higher morbidity rates than first-time operations. Our extensive experience with minimally invasive radioguided parathyroidectomy (MIRP) for first-time surgery for HPT has shown this method to be a directed approach to the offending adenoma, suggesting that the technique could be used to minimize reoperative neck surgery as well. METHODS: Over an 11-month period 24 consecutive patients with primary HPT who had undergone at least one previous neck operation were referred for re-exploration. All patients underwent preoperative sestamibi scanning; 21 localized sufficiently to undergo MIRP. RESULTS: All patients were cured after reoperation. Eighteen patients underwent MIRP under local anesthesia as outpatients; 3 MIRPs were done under general anesthesia. Average total operative time was 44 minutes, average incision length was 3.0 cm +/- 0.2 cm. Nineteen of the procedures were completed without any frozen sections. There were no complications. CONCLUSION: MIRP is extremely effective in patients with HPT who have undergone previous neck exploration for parathyroid or thyroid disease. The technique allows for such a directed dissection that smaller incisions and local anesthesia in an outpatient setting are routine.

[Keratoprosthesis by posterior fixation and mechanical biocompatibility: determination of intraocular pressure provoking aqueous humor leak and/or extrusion]. / Kératoprotheses à fixation postérieure et biocompatibilité mécanique: détermination de la pression intraoculaire provoquant une fuite d'humeur aqueuse et/ou une extrusion.

The effect of a sudden increase in intraocular pressure (IOP) on Eye Bank eyes implanted with a posterior fixation keratoprosthesis PCL5 type (Lacombe) is evaluated. The IOP was artificially increased at a rate close to that observed in direct eye trauma. The critical pressure values causing aqueous humor leak and/or keratoprosthesis extrusion were compared to those found to blow up unoperated eyes. No statistical difference was found between operated and control eyes (6 pairs of eyes). This KPro type showed its efficacy for keratoprosthesis fixation.

In situ temperature measurements with thermocouple probes during laser interstitial thermotherapy (LITT): quantification and correction of a measurement artifact.

BACKGROUND AND OBJECTIVE: The purpose of this work was to quantify the magnitude of an artifact induced by stainless steel thermocouple probes in temperature measurements made in situ during experimental laser interstitial thermo-therapy (LITT). A procedure for correction of this observational error is outlined. STUDY DESIGN/MATERIALS AND METHODS: A CW Nd:YAG laser system emitting 20W for 25-30 s delivered through a fiber-optic probe was used to create localized heating. The temperature field around the fiber-optic probe during laser irradiation was measured every 0.3 s in air, water, 0.4% intralipid solution, and fatty cadaver pig tissue, with a field of up to fifteen needle thermocouple probes. RESULTS: Direct absorption of Nd:YAG laser radiation by the thermocouple probes induced an overestimation of the temperature, ranging from 1.8 degrees C to 118.6 degrees C in air, 2.2 degrees C to 9.9 degrees C in water, 0.7 C to 4.7 C in intralipid and 0.3 C to 17.9 C in porcine tissue after irradiation at 20W for 30 s and depending on the thermocouple location. The artifact in porcine tissue was removed by applying exponential and linear fits to the measured temperature curves. CONCLUSION: Light absorption by thermocouple probes can induce a significant artifact in the measurement of laser-induced temperature increases. When the time constant of the thermocouple effect is much smaller than the thermal relaxation time of the surrounding tissue, the artifact can be accurately quantified. During LITT experiments where temperature differences of a few degrees are significant, the thermocouple artifact must be removed in order to be able accurately to predict the treatment outcome.

Directed antisense therapy confirms the role of protein kinase C-alpha in the tumorigenicity of pancreatic cancer.

BACKGROUND: The level of expression of the alpha isoform of protein kinase C (PKC-alpha) has been shown to correlate inversely with the pathologic differentiation of human pancreatic cancers. METHODS: We stably transfected a moderately differentiated pancreatic cell line (HPAC) to overexpress PKC-alpha and examined the survival rates compared with parent HPAC according to an orthotopic model. Next we used a PKC-alpha antisense oligonucleotide specifically to down-regulate this isoform in vitro and examine the effect of treatment in vivo again according to the orthotopic model. RESULTS: Animals implanted with the overexpressing cell line had a mortality rate almost twice that of those implanted with the parent cell line (P < .01). Treatment with antisense oligonucleotide in increasing concentrations down-regulated PKC-alpha mRNA by Northern blot analysis and reverse transcriptase-polymerase chain reaction. Animals treated with antisense oligonucleotide after orthotopic implantation of pancreatic cancer cells survived statistically longer than those treated with vehicle alone (P = .005). Treatment with a scrambled oligonucleotide also conferred a survival benefit compared with vehicle alone (P < .01). CONCLUSIONS: Tumorigenicity of pancreatic cancer is related directly to PKC-alpha expression in vivo as demonstrated by decreased survival when overexpressed. PKC-alpha expression can be down-regulated directly (antisense) and indirectly (scrambled) in vitro, which subsequently confers a dramatic survival benefit in vivo.

Transient human gene therapy: a novel cytokine regulatory strategy for experimental pancreatitis.

OBJECTIVE: The purpose of this study was to evaluate the ability to transfect a murine pancreas with a human cytokine regulatory gene (interleukin-10 [IL-10]) and examine the duration of transgene expression, its effect on the normal pancreas, and its antiinflammatory effect during acute pancreatitis. SUMMARY BACKGROUND DATA: Interleukin-1beta and tumor necrosis factor-alpha are known detrimental mediators during the progression of acute pancreatitis, and blockade of either cytokine results in decreased severity of pancreatitis and improved survival. Although gene therapy has been proposed as a method to deliver protein-based therapy during a number of conditions, no means of effectively transfecting the pancreas without inducing injury has been developed. METHODS: A plasmid-human IL-10 construct (pMP6-hIL-10) complexed with cationic liposomes was administered by single intraperitoneal injection to healthy mice. Effective transfection (reverse transcriptase-polymerase chain reaction for hIL-10 mRNA), transfected cell type (in situ polymerase chain reaction for hIL-10 DNA), and the effect on the normal pancreas were determined. Additional animals were transfected to determine the effects of this regulatory gene on the severity of pancreatitis. RESULTS: Nearly 80% of all pancreatic cells expressed human DNA that was subsequently transcribed into mRNA through day 14. The transfection event had no effect on amylase, lipase, or pancreatic histologic appearance. Successful transfection could attenuate subsequently induced pancreatitis (all parameters p < 0.05). CONCLUSIONS: Transient transfection of a human IL-10 gene can be accomplished into all cell types of murine pancreata using a plasmid/ liposome vector. The DNA is effectively transcribed into intact mRNA and does not cause inflammation or acinar cell damage. Transfer of this cytokine regulatory gene decreases the severity of pancreatitis, demonstrating a benefit of gene therapy during this acute inflammatory process.

TNF but not IL-1 decreases pancreatic acinar cell survival without affecting exocrine function: a study in the perfused human pancreas.

Substantial quantities of interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) are produced within the pancreatic parenchyma during acute pancreatitis. Recent evidence suggests that IL-1 beta and TNF-alpha propagate acute pancreatitis and intensify the resulting pancreatic acinar cell death. This study examines the direct effect of IL-1 beta and TNF-alpha on pancreatic acinar cells. Human pancreata (n = 6), harvested during organ procurement, were perfused ex vivo through the splenic artery using a sterile, oxygenated colloid solution. Each pancreas was perfused with either recombinant human IL-1 beta or TNF-alpha for 2 h and subsequently with the cholecystokinin analogue caerulein (positive control). Venous effluent was collected continuously and amylase and lipase were determined at 15-min intervals. Pancreatic histology was graded at baseline and following cytokine and caerulein perfusion. To examine the long-term effects of these cytokines on acinar cell viability, additional in vitro studies utilized the AR42J acinar cell line which was exposed to either IL-1 beta or TNF-alpha with survival determined daily by MTT assay. Perfusion of the human pancreas with either IL-1 beta or TNF-alpha did not alter amylase, lipase, or histology. Caerulein did induce pancreatitis as measured by increased amylase, lipase, and pancreatic histology. Survival of pancreatic acinar cells decreased when they were incubated with TNF-alpha but not IL-1 beta. Although present in large amounts within the pancreas during acute pancreatitis, IL-1 beta and TNF-alpha have no direct effect on acinar cell viability or exocrine function acutely nor do they induce pancreatitis. When present for more than 24 h, however, TNF-alpha but not IL-1 beta has a dramatic effect on acinar cell survival.

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.

Cost-effectiveness of preoperative sestamibi scan for primary hyperparathyroidism is dependent solely upon the surgeon's choice of operative procedure.

BACKGROUND: In 1991, a National Institutes of Health Consensus Panel stated that preoperative localization for primary hyperparathyroidism is not cost effective. Since then, the sestamibi scan has been applied to parathyroid disease with excellent results, even allowing unilateral exploration under local anesthesia. STUDY DESIGN: A metaanalysis of the English literature over the past 10 years was performed to determine the collective sensitivity and specificity of sestamibi scanning to establish its utility in directing a unilateral procedure. The cost effectiveness of scanning all patients with sporadic primary hyperparathyroidism was examined by determining the costs of seven operative technique-dependent variables that could be reduced with a limited procedure. RESULTS: The average sensitivity and specificity of sestamibi were 90.7% and 98.8%, respectively, indicating its ability to guide an accurate unilateral exploration. The analysis of 6,331 patients showed that 87% had solitary adenomas. An average cost savings of $650 was demonstrated for a unilateral operation, which could be realized in as many as 90% (sestamibi sensitivity) of those with solitary adenomas. CONCLUSIONS: A preoperative sestamibi scan is specific enough in identifying solitary adenomas to allow unilateral exploration with a < 1% failure rate. The sensitivity of this scan suggests that 78% of all patients with sporadic primary hyperparathyroidism (90% of the 87% with solitary adenomas) are candidates for unilateral exploration. This rate is significantly higher than the 51% rate at which scanning all patients becomes cost effective.

Modelling variability in lymphatic filariasis: macrofilarial dynamics in the Brugia pahangi--cat model.

A striking feature of lymphatic filariasis is the considerable heterogeneity in infection burden observed between hosts, which greatly complicates the analysis of the population dynamics of the disease. Here, we describe the first application of the moment closure equation approach to model the sources and the impact of this heterogeneity for macrofilarial population dynamics. The analysis is based on the closest laboratory equivalent of the life cycle and immunology of infection in humans--cats chronically infected with the filarial nematode Brugia pahangi. Two sets of long-term experiments are analysed: hosts given either single primary infections or given repeat infections. We begin by quantifying changes in the mean and aggregation of adult parasites (inversely measured by the negative binomial parameter, kappa in cohorts of hosts using generalized linear models. We then apply simple stochastic models to interpret observed patterns. The models and empirical data indicate that parasite aggregation tracks the decline in the mean burden with host age in primary infections. Conversely, in repeat infections, aggregation increases as the worm burden declines with experience of infection. The results show that the primary infection variability is consistent with heterogeneities in parasite survival between hosts. By contrast, the models indicate that the reduction in parasite variability with time in repeat infections is most likely due to the 'filtering' effect of a strong, acquired immune response, which gradually acts to remove the initial variability generated by heterogeneities in larval mortality. We discuss this result in terms of the homogenizing effect of host immunity-driven density-dependence on macrofilarial burden in older hosts.

Cytokine activation through sublethal hemorrhage is protective against early lethal endotoxic challenge.

OBJECTIVES: To determine the immunologic consequences of nonlethal hemorrhage on subsequent exposure to lipopolysaccharide (LPS) and to determine the role of interleukin 1 beta (IL-1) specifically in mediating the response to LPS with and without prior hemorrhage. DESIGN: Prospective, randomized, controlled experimental trial. PARTICIPANTS: Male BALB/c mice and transgenic mice deficient in IL-1 converting enzyme. INTERVENTIONS: Animals were subjected to hemorrhage (by cardiac puncture), LPS challenge by intraperitoneal injection, or hemorrhage followed 24 hours later by LPS challenge. Mortality was assessed every 4 hours for 96 hours following hemorrhage or LPS exposure. Serum IL-1 levels were determined 24 hours after exposure to hemorrhage and LPS. SETTING: University of South Florida Core General Surgery Research Facility, Tampa. MAIN OUTCOME MEASURES: Mortality and serum IL-1 levels. RESULTS: Hemorrhage alone resulted in complete survival, whereas LPS alone resulted in near-complete (95%) mortality. Hemorrhage, when given 24 hours before LPS challenge, afforded significant protection compared with LPS alone (67% survival vs 5% survival; P < .001). Serum IL-1 levels 24 hours after exposure to LPS were significantly lower in prehemorrhaged mice than in those receiving LPS alone. Transgenic mice incapable of producing biologically active IL-1 were further protected, demonstrating near-complete (95%) survival following hemorrhage and LPS challenge. CONCLUSIONS: Cytokine activation through nonlethal hemorrhage attenuates subsequent IL-1 response to early immunologic challenge. Such immune suppression appears to be protective early on and is supported by the near-complete immunity to LPS in animals incapable of producing biologically active IL-1.

Gene targeting demonstrates additive detrimental effects of interleukin 1 and tumor necrosis factor during pancreatitis.

BACKGROUND & AIMS: During severe pancreatitis, interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha are produced in large quantities. The aim of this study was to determine whether either one plays a more dominant role and if their detrimental effects are additive. METHODS: Necrotizing pancreatitis was induced in transgenic (-/-) knockout mice deficient in either IL-1 type 1 receptors, TNF type 1 receptors, or both IL-1 and TNF type 1 receptors. Wild-type mice served as controls. Mortality was assessed for 10 days. Additional animals were killed on days 0, 1, 2, 3, and 4 for determination of pancreatitis severity. RESULTS: All three knockout groups showed decreased amylase and lipase, histological score, serum IL-6, and mortality compared with wild-type groups. Animals devoid of receptors for both cytokines showed improved survival and decreased IL-6 levels compared with those devoid of either IL-1 or TNF receptors individually, yet they failed to show a further decrease in pancreatitis severity. CONCLUSIONS: Preventing the activity of IL-1beta or TNF-alpha has a nearly identical beneficial effect on the severity and mortality of acute pancreatitis. Preventing the activity of both cytokines concurrently has no additional effect on pancreatitis severity but further attenuates the systemic stress response and is associated with an additional but modest decrease in mortality.

Ablation rate of PMMA and human cornea with a frequency-quintupled Nd:YAG laser (213 nm).

BACKGROUND AND OBJECTIVE: As an alternative to the standard excimer laser used for PRK, we investigated the ablation rate at 213 nm of PMMA, and human corneas under controlled hydration. STUDY DESIGN/MATERIALS AND METHODS: The output of a frequency-quintupled Nd:YAG laser (213 nm) was transformed into a quasi-Gaussian beam. PMMA and corneal lenticules maintained under controlled hydration were ablated until perforation was detected. RESULTS: The ablation rate of PMMA and cornea at 213 nm were similar to that at 193 nm when radiant exposure was below 200 mJ/cm2 and increased gradually between one and two times faster than that at 193 nm when radiant exposure was > 200 mJ/ cm2. CONCLUSIONS: PMMA and cornea ablation at 213 nm are similar to that at 193 nm and are different from that at 248 nm. The difference between PMMA and cornea ablation rates should be considered when using PMMA to test ablated diopter and smoothness for photorefractive surgery.

HLA and elephantiasis revisited.

A recent case-control study in Indonesia suggested that the course of Brugian filariasis and in particular resistance to the development of elephantiasis was associated with certain HLA class II alleles. In order to see whether these data could be confirmed we conducted a similar study in another Indonesian population from South Sulawesi. We could not confirm our earlier results and therefore concluded that HLA-DR and -DQ alleles are at least not strongly associated with progression to elephantiasis in Brugian filariasis. The complete data are presented also for anthropological reference purposes.

Uncertainty of historical measurements of 131I in Hanford-area vegetation.

The Hanford Environmental Dose Reconstruction (HEDR) Project was conducted to estimate the radiation dose that individuals could have received as a result of emissions to the air and water from Hanford Site operations since 1944. The largest doses were to the human thyroid gland from 131I released into the atmosphere from Hanford facilities in the 1945-1947 time period. In support of the dose reconstruction effort, a database of historical environmental radioactivity measurements was constructed. This database includes measurements of total radioactivity for vegetation samples collected from 1945-1948 and counted using a Geiger-Mueller (GM) detector system. Because the factors used at that time to convert the GM counts to 131I activity did not take all parameters into account, and because some parameter values were inaccurate, more accurate conversion factors were developed as part of the HEDR Project. These factors can be used to estimate the actual historical activity levels. This paper summarizes the Monte Carlo uncertainty and sensitivity analysis methods used to assess the uncertainty of the newly reconstructed historical vegetation 131I activities and to identify the parameters that contributed the most uncertainty to these reconstructed activities. Based on the study of two vegetation (sagebrush) samples collected in the mid-1940's, it appears that the true 131I activity of the historical vegetation samples should be within a factor of three of the reconstructed activity. Also, the uncertainty in the parameter Icf (the fraction of the background-corrected GM measurement of a vegetation sample that resulted from 131I) was found to contribute the most uncertainty to the reconstructed 131I activities when the uncertainty in Icf was large.

Stereotactic uses beyond core biopsy: model development for minimally invasive treatment of breast cancer through interstitial laser hyperthermia.

Light of a Nd:YAG laser presented through a fiberoptic cable to a diffusing tip can be adapted to mammographic stereotactic instruments now used for core biopsy in the hyperthermic endoablation of breast cancer. This approach to cancer destruction extends breast preservation to the point of no observable surface skin change. The initial analysis characterizes the effects of laser endohyperthermia in a physical model as well as in tissue, both ex vivo and in vivo, to create a reliable technique that will lead to human trials. A fiberoptic cable with a diffusing quartz tip placed deep within soft tissue can pass light of a neodymium laser and consequent thermal energy for the destruction of surrounding soft tissues. Because breast cancer occurs with greatest frequency in the involuted breasts of women more than 50 years of age and because this tissue is predominantly fibro-fatty in nature, our work has concentrated on model development and the determination of heat distribution and destruction of fat and fibro-fatty tissue. Following the development of a physical model, time-temperature courses were found to be similar in ex vivo human breast tissue and subcutaneous porcine fat. This led to in vivo porcine studies that confirmed similar time-temperature courses. For tissues brought to a range of 60 degrees C to 80 degrees C and sustained for the better part of 20 minutes, gross and histological analyses reveal complete destruction over a 1 1/2 cm radial region around the laser tip. This approach offers great promise for the treatment of stereotactically biopsied small T1 breast carcinomas.