Prostate brachytherapy postimplant dosimetry: automatic plan reconstruction of stranded implants.

PURPOSE: Plan reconstruction for permanent implant prostate brachytherapy is the process of determining the correspondence between planned and implanted seeds in postimplant analysis. Plan reconstruction informs many areas of brachytherapy quality assurance, including the verification of seed segmentation, misplacement and migration assessment, implant simulations, and the dosimetry of mixed-activity or mixed-species implants. METHODS: An algorithm has been developed for stranded implants which uses the interseed spacing constraints imposed by the suture to improve the accuracy of reconstruction. Seventy randomly selected clinical cases with a mean of 23.6 (range 18-30) needles and mean density of 2.0 (range 1.6-2.6) 2.0 (range 1.6-2.6) seeds/cm3 were automatically reconstructed and the accuracy compared to manual reconstructions performed using a custom 3D graphical interface. RESULTS: Using the automatic algorithm, the mean accuracy of the assignment relative to manual reconstruction was found to be 97.7 +/- 0.5%. Fifty-two of the 70 cases (74%) were error-free; of seeds in the remaining cases, 96.7 +/- 0.3% were found to be attributed to the correct strand and 97.0 +/-0.3% were correctly connected to their neighbors. Any necessary manual correction using the interface is usually straightforward. For the clinical data set tested, neither the number of seeds or needles, average density, nor the presence of clusters was found to have an effect on reconstruction accuracy using this method. CONCLUSIONS: Routine plan reconstruction of stranded implants can be performed with a high degree of accuracy to support postimplant dosimetry and quality analyses.

Baja california: late cretaceous dinosaurs.

Late Cretaceous dinosaurs have been discovered along the Pacific margin of Baja California. The presence of Hypacrosaurus sp. is suggestive of correlation with the Upper Edmonton Formation, Alberta. Dissimilarities between the Baja California fauna and those from contemporary units along the eastern trend of the Rocky Mountains suggest that Baja California was ecologically separated from mainland Mexico during late Campanian and early Maastrictian time.

Fossil mammals from baja california: new evidence on early tertiary migrations.

Ungulates belonging to the family Barylambdidae were found in the same geologic unit with, but stratigraphically above, a specimen assigned to the Tillodontia and above several molars of the perissodactyl cf. Hyracotherium sp. This arrangement is unusual, as in the well-documented faunas from the Rocky Mountain Region Barylambdidae are known only from the Paleocene, Tillodontia from the Paleocene and Eocene, while Hyracotherium is known only from the Eocene. The expected stratigraphic order would be, from lowest to highest, Barylambdidae, Tillodontia, and Hyracotherium. It is suggested that the Baja California assemblage is late Paleocene on the basis of the generalized molars of cf. Hyracotherium sp. and the characters of cf. Esthonyx sp.

Volumetric modulated Arc therapy and conventional intensity-modulated radiotherapy for simultaneous maximal intraprostatic boost: a planning comparison study.

AIMS: Volumetric modulated arc therapy (VMAT) is a novel extension of intensity-modulated radiotherapy (IMRT) where an optimised three-dimensional dose distribution may be delivered in a single gantry rotation. This optimisation algorithm is the predecessor to Varian's RapidArc. The aim of this study was to compare the ability of conventional static nine-field IMRT (cIMRT) and VMAT to boost as much of the clinical target volume (CTV) as possible to 88.8Gy without exceeding organ at risk (OAR) dose-volume constraints. MATERIALS AND METHODS: Optimal cIMRT and VMAT radiotherapy plans were produced for 10 patients with localised prostate cancer using common planning objectives: (1) Treat >or=98% of the planning target volume (PTV) to >or=95% of the prescription dose (74Gy in 37 fractions); (2) keep OAR doses within predefined limits; (3) treat as much of prostate CTV (minus urethra) as possible to >or=120% of prescription dose (=88.8Gy); (4) keep within maximum dose limits in and out of target volumes; (5) conformality index (volume of 95% isodose/volume of PTV)or=120% of the prescription dose (P=0.002). All dose constraints were kept within predefined limits. VMAT and cIMRT required an average of 949 and 1819 monitor units and 3.7 and 9.6min, respectively, to deliver a single radiation fraction. CONCLUSIONS: VMAT is able to boost more of the CTV to >or=120% than cIMRT without contravening OAR dose constraints, and uses 48% fewer monitor units. Treatment times were 61% less than with cIMRT.

The Relationship between Hot Flashes and Testosterone Recovery after 12 Months of Androgen Suppression for Men with Localised Prostate Cancer in the ASCENDE-RT Trial.

AIMS: This study describes the proportion of men who experienced hot flashes (flashes), and the testosterone level at onset, peak frequency and cessation of flashes after 12 months of androgen deprivation therapy (ADT) in men undergoing curative-intent external beam radiation therapy (± brachytherapy boost). We also aimed to characterise testosterone recovery in this population. MATERIALS AND METHODS: This was a pre-specified secondary analysis of the ASCENDE-RT clinical trial. Three hundred and ninety-eight men were randomised. All received 12 months of ADT. The presence and frequency of flashes were patient reported. Cessation of flashes was defined as the first date a patient reported resolution of this symptom. Testosterone recovery was defined as any single serum testosterone above the threshold of 5, 7.5 or 10 nmol/l. RESULTS: The median age and follow-up were 68 years and 6.1 years. Flashes were reported in 93% of men. Flashes began and reached peak frequency at a median time of 4.0 months from the first luteinizing hormone-releasing hormone injection when testosterone levels had fallen to castrate. The median time to cessation of flashes was 7.6 months after the cessation of ADT (last injection + 3 months), when the median testosterone had risen to 5.7 nmol/l. A resolution of flashes was reported in 99% of patients. Baseline testosterone was available in 338 patients (85%). The median baseline testosterone was 13.2 nmol/l. The median (95% confidence interval) time of testosterone recovery to thresholds of 5 nmol/l, 7.5 nmol/l and 10 nmol/l were 9 (9-10) months, 13 (10-15) months and 18 (17-19) months from the cessation of ADT. At the time of censor, 96, 94 and 91% of patients had recovered testosterone to thresholds of 5, 7.5 and 10 nmol/l. CONCLUSION: Flashes occur at castrate levels of testosterone, with cessation of hot flashes antedating full recovery of testosterone in most patients. Rates of testosterone recovery after 12 months of ADT exceed 90%, although it can be delayed.

Hospital care by hospital-based and clinic-based faculty: a prospective, controlled trial.

BACKGROUND: The hospital length of stay decreases and clinical outcomes are maintained when teaching hospitals involve hospital-based attending physicians in comparison with traditional attending physicians. The attending physician's time commitment, including the number of hours per day and months per year, required to achieve this result is unknown. This study compared the clinical outcomes and cost of care for patients treated by hospital-based and clinic-based attending physicians devoting dramatically different amounts of time to supervising residents on the medical wards of a suburban county hospital. METHODS: Patients were alternately admitted to 2 groups of ward teams. Faculty who attended 10 months of the year supervised one group. The comparison group's attending physicians were on service for 2 months or less and maintained clinic responsibilities while on service. The cost of patient care was compared by means of the length of stay, total hospital costs, and costs for ancillary services. Hospital mortality and readmission rates compared clinical outcomes. RESULTS: There were 4456 patients hospitalized on the medical wards of a teaching service. No differences were detected in the length of stay (4.37 +/- 0.1 days for hospital-based and 4.39 +/- 0.1 days for clinic-based attending physicians). Hospital cost was observed to be similar (average cost, $5989 and $5977 per patient, respectively). The clinical outcomes were equivalent, with adjusted mortality rates for hospital-based attending physicians of 3.2% vs 3.9% for clinic-based attending physicians (P =.28). CONCLUSION: An increase of faculty time and involvement for supervision of resident-managed hospital care did not improve clinical outcomes or decrease costs during the 1-year study period.

Pion conformal radiation of prostate cancer: results of a randomized study.

PURPOSE: To compare the efficacy of pion radiation therapy with conventional external beam photon therapy, for the treatment of locally advanced stage T3/4, N0, M0 adenocarcinoma of the prostate. METHODS AND MATERIALS: Two hundred seventeen eligible patients were randomly allocated to either photon or pion therapy. No adjuvant hormone therapy was used. RESULTS: Median follow-up was 42 months (range 2-90). Acute bladder toxicity was worse in the pion arm, p = 0.2, but other acute toxicity did not differ. Late grade 2 toxicity was significantly less in the pion arm (29% at 5 years versus 48%, p = 0.002), but late grade 3 or 4 toxicity did not differ. Clinical local control was not significantly different between treatment arms (64% after 5 years with photons, 56% with pions, p = 0.6). Cause-specific and overall survival also did not differ (p = 0.7). There was a significant delay in time to first failure in the photon arm, largely as a result of decreased biochemical relapse, p = 0.01. A multivariate analysis is presented. CONCLUSION: Pion therapy was well tolerated, with increased acute toxicity and significantly decreased late tissue injury. This contrasts with the late toxicity observed with higher LET particle therapy such as neutron therapy. No improvement in local control with pion therapy was observed.

Radiation response of murine eccrine sweat glands.

Following irradiation of the left-hind feet of mice, we measured the ability of the eccrine glands to secrete sweat following stimulation by pilocarpine. Silicone elastomer impression moulds of the foot pads gave repeatable, detailed localization of sweat ducts by retaining the impression of each emerging sweat droplet. Loss of gland function occurred rapidly following irradiation (within 2 weeks) and the rate of loss was dose-dependent, being over three times greater following a dose of 13.0 Gy than after 6.8 Gy. There was a dose-dependent nadir of function at around 8 weeks, followed by a gradual recovery that was complete by about 30 weeks after irradiation, leaving a dose-dependent residual functional deficit. Eccrine sweat glands are very radiosensitive organs compared with the epidermis. A single dose of 13 Gy resulted in complete loss of eccrine gland function at 8 weeks whilst about 23 Gy would be required to elicit transient moist desquamation, in oxygen-breathing mice. Substantial sparing was seen when two doses were split by intervals of up to 24 h.

A pilot study of a method of estimating the number of functional eccrine sweat glands in irradiated human skin.

Following stimulation with pilocarpine, the secretion from eccrine sweat glands produces characteristic imprints in hardening silicone polymers applied to the skin. This permits an accurate determination of the numerical density of functional eccrine glands in irradiated skin which can be compared to non-irradiated skin. A description of this inexpensive, noninvasive, and quantitative technique is presented as well as preliminary results determined in six normal subjects and 28 irradiated patients. Eleven patients, with atrophy and telangiectasia after radiotherapy to the skin to a high dose, were found to have no functional eccrine glands by this technique. A range of results from normal numbers of eccrine glands through partial and, rarely, complete loss was observed in patients given lower doses and in whom the skin was visually normal. When the irradiated side outside the boost area in 16 breast cancer patients who received postoperative radiotherapy was compared to an equivalent area on the untreated, contralateral side, 11 showed a greater than 50% reduction in the density of functional eccrine glands. The method appears to be a sensitive, quantitative assay for a permanent change in skin and so ought to facilitate meaningful comparison of different regimens of radiotherapy. Further studies are required to determine the dose-response relationship, latency and progression of the observed changes.

The role of the vitreous in the intraocular pressure rise after neodymium-YAG laser capsulotomy.

Autologous liquid vitreous injected into the anterior chamber of the phakic owl monkey eye leads to markedly increased intraocular pressure (IOP) peaking at one to two hours. In contrast, neodymium-YAG laser shock waves focused in the center of the anterior chamber of the same animal led to a mild decrease in IOP. Debris produced by laser pulses focused on the residual cortex of owl monkey eyes that had undergone extracapsular surgery failed to increase the IOP. Similarly, injection of dialyzed vitreous did not have any significant influence on IOP. We conclude that the disruption of the integrity of the anterior cortical gel and the subsequent release of a dialyzable intravitreal substance with a molecular weight of less than 10,000 daltons into the anterior chamber may contribute to the IOP rise after surgical discission, including neodymium-YAG laser posterior capsulotomy.

A histologic study of ovarian endometriosis with emphasis on hyperplastic and atypical changes.

One hundred ninety-four cases of ovarian endometriosis, encountered during a 3-year period, were studied. In addition to endometrial-type epithelium and stroma that were present in each of these cases, oviduct-type epithelium was demonstrated in 26, papillary epithelial-lined projections in 7, and hobnail cells in 36 patients. Forty-three cases showed reactive epithelial changes, probably due to inflammation and regeneration. There were 4 cases of adenomatous hyperplasia. Severe epithelial atypism was seen in 7 patients (3.6%), 1 in conjunction with adenomatous hyperplasia. Although the areas of severe epithelial atypism in ovarian endometriosis may be of reactive origin, one must also consider the possibility that in some instances these atypical changes may constitute a neoplastic potential.

Chiasmal osteoma following tuberculous meningitis. Case report.

Clinical and radiological signs of a chiasmal lesion developed in a man 25 years after successful treatment of tuberculous meningitis. Surgical exploration and pathological examination demonstrated a mature chiasmal osteoma. The bony growth may have been a sequela of the prior infection.

Time evolution of the number of functional murine eccrine sweat glands after irradiation: a quantitative analysis of experimental data using a model of proliferative and functional organization.

The function of eccrine sweat glands in the beta-pad of the mouse foot after irradiation was followed over time. Graded doses of X-rays were given to the foot, either as single doses or in two equal fractions separated by a 24-h interval. A quantitative, non-invasive, functional assay was used allowing repeated evaluation of the animals. Sweat gland function was assessed once a week for the first 6 weeks, and at 8, 10, 14, 18, 28, 38 and 45 weeks after irradiation. The beta-pad of the unirradiated foot was used as a control. The function dropped to a nadir within 8-10 weeks after irradiation, whereafter it gradually recovered, reaching a stable level 20-25 weeks after irradiation. These data were analyzed using a mathematical model of proliferative and functional organization of the sweat pore. The model provides a description of the time evolution of pore function, and its basic features were as follows. The functional subunit is a single sweat pore, which will be assayed as functional provided that it contains a number of functional cells above a critical threshold. The functional cells are capable of self renewal (a so-called 'flexible' tissue), and the proportion of proliferating cells is subject to homeostatic control. Irradiation is assumed to transfer a certain fraction of the cells into a state with a limited probability of successful division. This fraction is assumed to have a linear-quadratic dependence on dose. The values of all free model parameters were optimized by a maximum-likelihood fit to the experimental data. With optimized parameter values, the initial decrease, nadir, and long-term level of tissue function estimated from the model were in close agreement with the experimental observations for all the 28 dose groups. Some of the estimated model parameters are: growth fraction 4.2 +/- 0.2%; cell cycle time, 0.95 +/- 0.04 days; number of functional cells in a single pore in the unirradiated animal, 9.9 +/- 0.5; and alpha/beta ratio, 4.3 Gy (95% confidence interval 3.1-5.0 Gy). It is concluded that the present model, despite its relative mathematical simplicity, provides a close description of the postirradiation kinetics of functional cells in the mouse sweat gland.

Traumatic bitemporal hemianopsia and diabetes insipidus.

Bitemporal hemianopsia and diabetes insipidus are infrequently occurring complications of closed head injuries. Porter and Miller found 18 cases of posttraumatic diabetes insipidus among more than 5000 patients with nonfatal closed head injuries. Of these, five also manifested damage to the optic chiasm. In 1971 Laursen surveyed the literature regarding traumatic bitemporal hemianopsia and found associated diabetes insipidus in 26 of 50 patients for whom information on this was given. Both conditions were present in a patient seen at Walter Reed Army Medical Center.

Brain wounds and their treatment in VII Corps during Operation Desert Storm, February 20 to April 15, 1991.

OBJECTIVE: To evaluate field neurosurgery supporting VII Corps during combat in Operation Desert Storm. RESULTS: (1) Only 1 of 22 patients who had a head wound died. (2) The one computed tomography unit in a forward hospital worked well, aiding diagnosis and surgical management. The occurrence of hematoma at a distance from the missile track has been worrisome to past field neurosurgeons, but none of 9 patients who had predebridement scans had a distant clot. (3) The number of brain wounds was fewer than expected for Americans, and the wounds were basilar in location. Iraqis, by contrast, had wounds that were randomly distributed about the head. CONCLUSIONS: (1) Although computed tomography is a useful diagnostic adjunct, its availability should not be a sine qua non for forward neurosurgery. (2) The current Kevlar helmet design appears successful.

Population-based study of biochemical and survival outcomes after permanent 125I brachytherapy for low- and intermediate-risk prostate cancer.

OBJECTIVES: To analyze the biochemical and survival outcomes after permanent low-dose-rate prostate brachytherapy in a large, consecutive, population-based cohort of patients. METHODS: A total of 1006 consecutive implants were performed from July 20, 1998 to October 23, 2003 for men with low-risk and "low-tier" intermediate-risk prostate cancer. The prescribed minimal peripheral dose was 144 Gy, using 0.33 mCi (125)I sources and a preplan technique with a strong posterior-peripheral dose bias. Most patients (65%) had received 6 months of androgen deprivation therapy. Supplemental external beam radiotherapy was not used. The prognostic features, dose metrics, and follow-up data were prospectively collected. Kaplan-Meier and Cox regression analyses were used to assess the factors associated with freedom from biochemical recurrence and survival. RESULTS: The median patient age at treatment was 66 years. The median follow-up was 54 months for biochemical outcomes and 66 months for survival. The actuarial freedom from biochemical recurrence rate was 95.6% +/- 1.6% at 5 years and 94.0% +/- 2.2% at 7 years. On multivariate analysis, the pretreatment prostate-specific antigen level (P = .03) and androgen deprivation therapy use (P = .04) were predictive of the freedom from biochemical recurrence. The actuarial rates of distant metastasis and disease-specific death at 5 years were both <1%. The overall survival rate at 5 years was 95.2% +/- 1.4% and was 93.4% +/- 1.8% at 7 years. On multivariate analysis, only age was predictive of overall survival (P = .011). CONCLUSIONS: When consistently planned and delivered, low-dose-rate brachytherapy, without supplemental external beam radiotherapy or intraoperative planning, can produce cancer-specific outcomes for men with low- and "low-tier" intermediate-risk prostate cancer at least equal to that produced by dose-escalated external beam radiotherapy or surgical prostatectomy.

Viscoelasticity modeling of the prostate region using vibro-elastography.

We present an ultrasound vibro-elastography system designed to acquire viscoelastic properties of the prostate and peri-prostatic tissue. An excitation stage imparts low-frequency (<20 Hz), limited amplitude (< +/- 2 mm), broadband vibratory motion to an endorectal transducer, along a radial/transversal direction. The induced tissue motion is estimated from ultrasound radio-frequency data and is used to estimate the mechanical frequency response of tissue to the excitation at different spatial locations. This can be used to determine the spatial distribution of various mechanical parameters of tissue, such as stiffness and viscosity. Phantom and in-vivo images are presented. The results obtained demonstrate high phantom and tissue linearity and high signal-to-noise ratio.