Initial investigation of acoustic droplet vaporization for occlusion in canine kidney.

Acoustic droplet vaporization (ADV) shows promise for spatially and temporally targeted tissue occlusion. In this study, substantial tissue occlusion was achieved in operatively exposed and transcutaneous canine kidneys by generating ADV gas bubbles in the renal arteries or segmental arteries. Fifteen canines were anesthetized, among which 10 underwent laparotomy to externalize the left kidney and five were undisturbed for transcutaneous ADV. The microbubbles were generated by phase conversion of perfluoropentane droplets encapsulated in albumin or lipid shells in the blood. A 3.5-MHz single-element therapy transducer was aligned with an imaging array in a water tank with direct access to the renal artery or a segmental artery. In vivo color flow and spectral Doppler imaging were used to identify the target arteries. Tone bursts of 1 kHz pulse repetition frequency with 0.25% duty cycle vaporized the droplets during bolus passage. Both intracardiac (IC) and intravenous (IV) injections repeatedly produced ADV in chosen arteries in externalized kidneys, as seen by B-mode imaging. Concurrent with this in two cases was the detection by pulse-wave Doppler of blood flow reversal, along with a narrowing of the waveform. Localized cortex occlusion was achieved with 87% regional flow reduction in one case using IC injections. Vaporization from IV injections resulted in a substantial echogenicity increase with an average half-life of 8 min per droplet dose. Gas bubbles sufficient to produce some shadowing were generated by transcutaneous vaporization of intrarenal artery or IV-administered droplets, with a tissue path up to 5.5 cm.

Idiopathic retroperitoneal fibrosis: a role for mycophenolate mofetil.

PURPOSE: Idiopathic retroperitoneal fibrosis (IRPF) is an unusual progressive illness for which consistent therapeutic recommendations have not been devised. The present report describes a collaborative nephrology and urology approach to distinguish IRPF from secondary disease and then combine necessary acute surgical or radiological intervention with short-term corticosteroid and with mycophenolate mofetil (MM) to facilitate steroid tapering and long-term management. MATERIALS AND METHODS: 21 patients have been evaluated and followed over a 7-year period, 16 with characteristic IRPF and 5 with secondary retroperitoneal disease. IRPF patients initially received high-dose corticosteroid and MM. We report clinical follow-up along with imaging studies of the retroperitoneum and related organs, serologic markers for systemic disease, and nonspecific acute-phase reactants as indicators of ongoing disease activity. RESULTS: Among IRPF patients, uniform success in stabilizing clinical signs and symptoms, radiological disease in the retroperitoneum and associated organs, and inflammatory indicators have been observed. Corticosteroid therapy can be limited to 6 months or less and MM to approximately 2 years, all with substantial impact on the natural history of IRPF. CONCLUSIONS: This is not a randomized, controlled trial, and patients were often referred with prior complications and/or treatments, however, the systematic approach and consistent results support the utility of MM as a safe and effective choice for long-term stabilization in IRPF.

Renal ablation by histotripsy--does it spare the collecting system?

PURPOSE: The feasibility of histotripsy (transcutaneous nonthermal mechanical tissue fractionation) was previously demonstrated in an in vivo rabbit renal cortex model. We explored the spectrum of histotripsy bio-effects on different tissue types in an in vitro porcine kidney model. MATERIALS AND METHODS: Using an 18 element focused annular array ultrasound system we performed histotripsy treatments in 5 in vitro porcine kidneys, targeting 7 cortical volumes and 17 tissue volumes bridging the cortex, medulla and/or collecting system. Treated areas were observed using ultrasound. In 5 lesions methylene blue was infused into the collecting system to evaluate the preservation of collecting system integrity. Kidneys were sectioned and examined grossly for evidence of tissue fractionation, ie the presence of histotripsy paste, or fixed in formalin and prepared for histological analysis. RESULTS: Histotripsy of renal cortical tissue created tissue defects in the cortical area treated. Histotripsy targeting the renal collecting system, medulla and renal cortex resulted in tissue fractionation in the area of the cortex, intermediate damage in the medulla and minimal damage to the collecting system. CONCLUSIONS: There is a differential histotripsy treatment effect when comparing renal cortical tissue to renal collecting system. There is no significant architectural disruption of the renal collecting system after histotripsy. This differential effect is a notable finding that may prove useful in future planning of ablative treatments for renal tissue.

Laparoscopic donor nephrectomy: an update.

Laparoscopic donor nephrectomy was developed primarily to increase the number of kidneys available for donation. Further evidence of the safety and efficacy of laparoscopic donor nephrectomy has been reported in the literature, as have studies on the cost-effectiveness of this procedure and its role in removing disincentives for renal donation. Specific technical modifications have been developed and refined that improve outcomes when performing laparoscopic harvesting of right kidneys. Other technical modifications have been developed for use in obese patients. With the adoption of these modified techniques, equivalent results to open donor nephrectomy have been reported. Recently, a wide range of alternative approaches (hand-assisted, retroperitoneal, and gasless laparoscopy) have been utilized for laparoscopic donor nephrectomy.

Measurement of bio-impedance with a smart needle to confirm percutaneous kidney access.

PURPOSE: The traditional method of percutaneous renal access requires freehand needle placement guided by C-arm fluoroscopy, ultrasonography, or computerized tomography. This approach provides limited objective means for verifying successful access. We developed an impedance based percutaneous Smart Needle system and successfully used it to confirm collecting system access in ex vivo porcine kidneys. MATERIALS AND METHODS: The Smart Needle consists of a modified 18 gauge percutaneous access needle with the inner stylet electrically insulated from the outer sheath. Impedance is measured between the exposed stylet tip and sheath using Model 4275 LCR meter (Hewlett-Packard, Sunnyvale, California). An ex vivo porcine kidney was distended by continuous gravity infusion of 100 cm. water saline from a catheter passed through the parenchyma into the collecting system. The Smart Needle was gradually inserted into the kidney to measure depth precisely using a robotic needle placement system, while impedance was measured continuously. RESULTS: The Smart Needle was inserted 4 times in each of 4 kidneys. When the needle penetrated the distended collecting system in 11 of 16 attempts, a characteristic sharp drop in resistivity was noted from 1.9 to 1.1 ohm m. Entry into the collecting system was confirmed by removing the stylet and observing fluid flow from the sheath. This characteristic impedance change was observed only at successful entry into the collecting system. CONCLUSIONS: A characteristic sharp drop in impedance signifies successful entry into the collecting system. The Smart Needle system may prove useful for percutaneous kidney access.

Prognostic assessment of nonmetastatic renal cell carcinoma: a clinically based model.

OBJECTIVES: Determining the recurrence risk in patients treated for renal cell carcinoma (RCC) is important for providing prognostic information and planning potential surveillance strategies. The pathologic stage has been the most widely used single prognostic variable. However, with minimally invasive treatment modalities, the pathologic stage may not be readily available. We developed a biostatistical prognostic model for postoperative RCC that is independent of the pathologic stage. METHODS: The records of 296 patients who underwent open nephrectomy for RCC at Johns Hopkins Hospital between 1990 and 1999 were reviewed. Cox proportional hazards regression analysis was used to generate a prognostic model. RESULTS: The recurrence risk (R(rec)) was determined from this model: R(rec)=1.55 x presentation (0-1)+0.19 x clinical size (in centimeters). Using this equation, 79% of patients were identified as low risk compared with 45% of patients considered low risk by pathologic stage (pT1). Moreover, the separation between the high and low-risk survival curves increased. CONCLUSIONS: This model is the first to our knowledge that uses purely clinical variables to assess the postoperative prognosis in patients with RCC. These results, although not validated, provide substantial evidence that preoperative clinical variables may be used instead of the pathologic stage to determine the risk of recurrence. Uncoupling the reliance on pathologic stage for prognostic information removes a potential barrier to novel minimally invasive treatments for renal malignancy and provides a standard to which observation protocols can be compared. In the future, this model may facilitate selection of appropriate patients for less toxic adjuvant or neoadjuvant therapies.

Laparoscopic ablation of symptomatic parenchymal and peripelvic renal cysts.

OBJECTIVES: To assess the safety and efficacy of laparoscopic ablation of symptomatic renal cysts as minimally invasive therapeutic techniques have largely supplanted open surgical intervention for the treatment of symptomatic renal cysts. METHODS: The records of 32 consecutive adult patients who underwent laparoscopic ablation of renal cysts (11 peripelvic, 21 parenchymal) were retrospectively reviewed. All patients were symptomatic at presentation; 26 had a single cyst, 5 had two cysts, and 1 had four cysts. RESULTS: Twenty patients underwent a transperitoneal laparoscopic approach, and 12 patients underwent a retroperitoneal laparoscopic approach. An average of 3.2 ports were used for each procedure, and no open conversions or transfusions were necessary. When comparing patients with parenchymal and peripelvic cysts, statistically significant differences were noted in the mean operative time (164 versus 233 minutes, respectively; P = 0.003) and mean operative blood loss (98 versus 182 mL, respectively; P = 0.04). Four patients (13%) had complications (one major and three minor), including a persistent ureteral stricture. One patient with negative preoperative aspiration cytology and negative intraoperative frozen section analysis was later found to have malignancy within the cyst wall, necessitating radical nephrectomy and trocar site excision. One patient (3%) developed a recurrence. CONCLUSIONS: Laparoscopic ablation of symptomatic renal cysts is a safe and efficacious procedure. We report an overall complication rate of 13% and a recurrence rate of 3% with a mean follow-up of 18.1 months (median 10.0).

Contemporary identification of patients at high risk of early prostate cancer recurrence after radical retropubic prostatectomy.

OBJECTIVES: To develop a model that will identify a contemporary cohort of patients at high risk of early prostate cancer recurrence (greater than 50% at 36 months) after radical retropubic prostatectomy for clinically localized disease. Data from this model will provide important information for patient selection and the design of prospective randomized trials of adjuvant therapies. METHODS: Proportional hazards regression analysis was applied to two patient cohorts to develop and cross-validate a multifactorial predictive model to identify men with the highest risk of early prostate cancer recurrence. The model and validation cohorts contained 904 and 901 men, respectively, who underwent radical retropubic prostatectomy at Johns Hopkins Hospital. This model was then externally validated using a cohort of patients from the Mayo Clinic. RESULTS: A model for weighted risk of recurrence was developed: R(W)'=lymph node involvement (0/1)x1.43+surgical margin status (0/1)x1.15+modified Gleason score (0 to 4)x0.71+seminal vesicle involvement (0/1)x0.51. Men with an R(W)' greater than 2.84 (9%) demonstrated a 50% biochemical recurrence rate (prostrate-specific antigen level greater than 0.2 ng/mL) at 3 years and thus were placed in the high-risk group. Kaplan-Meier analyses of biochemical recurrence-free survival demonstrated rapid deviation of the curves based on the R(W)'. This model was cross-validated in the second group of patients and performed with similar results. Furthermore, similar trends were apparent when the model was externally validated on patients treated at the Mayo Clinic. CONCLUSIONS: We have developed a multivariate Cox proportional hazards model that successfully stratifies patients on the basis of their risk of early prostate cancer recurrence.

Noninvasive vasectomy using a focused ultrasound clip: thermal measurements and simulations.

INTRODUCTION: Conventional surgical vasectomy may lead to complications including bleeding, infection, and scrotal pain. Noninvasive transcutaneous delivery of therapeutic focused ultrasound has previously been shown to thermally occlude the vas deferens. However, skin burns and inconsistent vas occlusion have presented complications. This study uses bio-heat transfer simulations and thermocouple measurements to determine the optimal ablation dosimetry for vas occlusion without skin burns. METHODS: A 2-rad ultrasound transducer mounted on a vasectomy-clip-delivered ultrasound energy at 4 MHz to the canine vas deferens co-located at the focus between the clip jaws. Chilled degassed water was circulated through an attached latex balloon, providing efficient ultrasound coupling into the tissue and active skin cooling to prevent skin burns. Thermocouples placed at the vas, intradermal, and skin surface locations recorded temperatures during ablation. Procedures were performed with transducer acoustic powers of 3-7 W and sonication times of 60-120 s on both the left and right vas deferens (n = 2) in a total of four dogs (precooling control, 3 W/120 s, 5 W/90 s, 7 W/60 s). Measurements were compared with bio-heat transfer simulations modeling the effects of variations in power and sonication time on tissue temperatures and coagulation zones. RESULTS: Active skin cooling produces a thermal gradient in the tissue during ablation, allowing sufficient thermal doses to be delivered to the vas without skin burns. However, low-power, long-duration heating produced excessive tissue necrosis due to thermal diffusion, while high power and short heating times reduced the therapeutic window and produced skin burns presumably due to direct ultrasound absorption. CONCLUSIONS: Both simulations and experiments suggest that a therapeutic window exists in which thermal occlusion of the vas may be achieved without the formation of skin burns in the canine model (power = 5-7 W, surface intensity = 1.4-1.9 W/cm2, time = 20-50 s). This range of ablation parameters will help guide future experiments to refine incisionless vasectomy using focused ultrasound.

Bioimpedance: novel use of a minimally invasive technique for cancer localization in the intact prostate.

BACKGROUND: Prostate cancer is presently diagnosed by transrectal ultrasound (TRUS)-guided sextant needle biopsy. While echo texture of the tissue can prompt localization of tumor, it is presently imprecise. From 50-75% of men biopsied, based on an abnormal digital rectal examination (DRE) or elevated prostate-specific antigen (PSA) level, have negative biopsy results. Improvements in tumor localization during TRUS-guided prostate biopsy are greatly needed. Bioimpedance is an electrical property of biologic tissue. Electric current is limited in living tissue by highly insulating cell membranes; however, different tissue architecture such as cancer may impede current differently and allow detection of differences between normal and abnormal or malignant prostate tissue. Our goal was to assess the utility of bioimpedance measurements in differentiating tumor from normal prostatic tissue in an ex vivo model. METHODS: Bioimpedance was measured in six ex vivo prostates, which were removed for clinically localized prostate cancer. Two bioimpedance needles, 1 mm apart, were inserted 3 mm into the posterior surface of the prostate an average of 16 times per gland. Frequencies ranging from 100 kHz-4 MHz were used to obtain 594 bioimpedance measurements from the six glands. These measurements were then correlated with histology to determine the presence or absence of prostate cancer. RESULTS: Prostate cancer was found to have a higher impedance, of 932+/-170 ohms, compared to areas of no cancer within the same prostate, 751+/-151 ohms, P < 0.0001, at 2 MHz. This phenomenon was observed across all frequencies tested. CONCLUSIONS: This study demonstrates for the first time application of bioimpedance to distinguish areas of prostate cancer from areas of normal prostate. This technology may improve identification and localization of cancer within the prostate. Moreover, bioimpedance can potentially guide needle placement during prostate biopsy and thus improve sampling of tumors. Currently, our ex vivo model is limited by variables such as temperature and lack of blood flow. Further studies in an in vivo model will be needed to assess their effect.

Ureteral stricture formation after removal of impacted calculi.

PURPOSE: We retrospectively evaluated the records of 21 patients a mean of 46.1 years old with ureteral stones that had been impacted for greater than 2 months to determine predisposing factors for stricture formation. MATERIALS AND METHODS: Between January 1993 and September 1996, 21 patients were referred for ureteral stones that had remained unchanged in location for at least 2 months. In 11 patients previous attempts at stone removal had failed. Each patient underwent successful stone extraction by retrograde or percutaneous antegrade ureteroscopy, or laparoscopic or open ureterolithotomy. Outcome was determined by reviewing the clinical records and radiographic studies, including excretory urography and nephrostography. RESULTS: Average duration of stone impaction before definitive treatment was 8.8 months (range 2 to 48) and mean stone size was 10.3 mm. (range 1 to 30). All stones were calcium based. There were 3 proximal, 8 mid and 10 distal ureteral calculi. At a mean followup of 7 months ureteral strictures developed in 5 patients (24%) at the previous stone site. Mean duration of stone impaction was 11 months (range 5 to 17) in patients with stricture versus 8.2 months (range 2 to 48) in those with no stricture. Four of the 5 strictures occurred in patients who had had iatrogenic ureteral perforation during previous unsuccessful attempts at stone removal. CONCLUSIONS: Ureteral stone impaction more than 2 months in duration is associated with a 24% incidence of stricture formation. Ureteral perforation at the site of the stone was identified as the primary risk factor for stricture formation in these cases.

Laparoscopic infrared imaging.

A system was developed to determine the potential role of infrared imaging as a tool for localizing anatomic structures and assessing tissue viability during laparoscopic surgical procedures. A camera system sensitive to emitted energy in the midinfrared range (3-5 micron) was incorporated into a two-channel visible laparoscope. Laparoscopic cholecystectomy, dissection of the ureter, and assessment of bowel perfusion were performed in a porcine model with the aid of this infrared imaging system. Inexperienced laparoscopists were asked to localize and differentiate structures before dissection using the visible system and then using the infrared system. Assessment of bowel perfusion was also conducted using each system. Infrared imaging proved to be useful in differentiating between blood vessels and other anatomic structures. Differentiation of the cystic duct and arteries and transperitoneal localization of the ureter were successful in all instances using the infrared system when use of the visible system had failed. This system also permitted assessment of bowel perfusion during laparoscopic occlusion of mesenteric vessels. These initial studies demonstrate that infrared imaging may improve the differentiation and localization of anatomic structures and allow assessment of physiologic parameters such as perfusion not previously attainable with visible laparoscopic techniques. It may thus potentially be a powerful adjunct to laparoscopic surgery.

A robotic system for percutaneous renal access.

PURPOSE: Percutaneous renal access can be challenging, particularly when the collecting system is not distended. Precise entry into a selected calyx facilitates subsequent percutaneous manipulations, but this skill requires extensive experience. In an attempt to improve accuracy while decreasing technical challenges, we developed a robotic system that automates the task of fluoroscopic image-guided percutaneous needle placement. MATERIALS AND METHODS: The prototype system consisted of a three degree-of-freedom robot with a needle injector end-effector. Imaging was provided by a biplanar fluoroscope. After correction of image distortion and fluoroscope calibration, robot to image-space registration was completed. To validate the system's ability to insert a needle into a calyx, ex vivo porcine kidneys suspended in agarose gel and distended with iodinated contrast solution were used as a model. In situ renal access tests with three 20 kg. pigs were performed. Access was confirmed by passing a flexible wire or aspirating iodinated contrast from the collecting system. RESULTS: The diameter of target calyces ranged from 3 to 7 mm. The in vitro accuracy of final needle tip positioning was 0.43 mm. In the ex vivo model, successful "one stick" access occurred on 10 of 12 attempts (83%). In situ access on the first attempt was successful for 6 of 12 target calyces (50%). Needle or tissue deflection accounted for each failure. CONCLUSION: The feasibility of a robotic system to assist in the percutaneous access of small and delicate renal calyces has been demonstrated. Additional work in reducing procedural steps and correcting for tissue deflection during needle passage is necessary to improve accuracy and to allow for clinical application.

First-order projections activated by stimulation of hypothalamic sites eliciting attack and flight in rats.

14C-deoxyglucose autoradiographs of attack rats were compared densitometrically with those of control rats whose electrodes were located nearby and elicited nonaggressive behaviors like those that accompanied the attack. Most closely associated with attack was the path from the ventromedial hypothalamus through the ventral supraoptic commissural pathway to the peripeduncular area, subparafascicular nucleus, zona incerta, and cuneiform area. Moderately correlated with attack were 4 visual areas: the dorsal and ventral lateral geniculate nuclei, pretectal area, and superior colliculus. Activity in the periaqueductal gray was unrelated to attack ipsilaterally and only weakly related contralaterally. In an orthogonal analysis, upward-oriented flight thresholds were significantly correlated with medial activation extending anteriorly to the lateral septal nucleus, dorsally to the thalamic paraventricular-parataenial region, and posteriorly to the periaqueductal gray.

Differential thermosensor control of thermoregulatory grooming, locomotion, and relaxed postural extension.

The rat displays three behaviors when surface and/or deep body temperatures rise above their normal levels: grooming, which spreads saliva over the fur to cool by evaporation; locomotion, which results in escape to a cooler environment; and relaxed postural extension, which reduces heat production by muscle activity and increases heat dissipation by increasing body surface area. Each of these behaviors can be elicited in pure or nearly pure form by localized warming of thermosensors in different brain areas. In addition, localized warming of superficial and deep peripheral thermosensors elicits grooming and locomotion, but little or no postural extension. Because of the marked differences in the behaviors induced by localized warming of different sets of thermosensors, it is concluded that sensors are linked to the effector mechanisms for these behaviors by relatively separate and independent pathways rather than a master controller through which sensory signals are integrated to produce a unitary error signal that drives all responses. When more generalized hyperthermia in natural heat stress situations affects mainly superficial thermosensors, as during the initial phase of exposure to ambient heat, grooming and locomotion are predominant and extension is absent or weak. When deep hyperthermia is predominant and superficial hyperthermia is relatively weak, as occurs after escape from ambient heat to thermoneutrality or during and following exercise in a thermally neutral environment, the resulting predominant activation of deep sensors elicits marked postural extension, but little or no grooming or locomotion. When both superficial and deep sensors are hyperthermic, as in the later stages of exposure to ambient heat, all three behaviors are present, although locomotion is somewhat greater and grooming is somewhat less than during predominantly superficial hyperthermia, and extension is somewhat less than during predominantly deep hyperthermia. As a consequence, grooming is maximal during predominantly superficial hyperthermia, locomotion during mixed deep and superficial hyperthermia, and extension during predominantly deep hyperthermia. It is concluded that the relatively fractionated control of the rat's thermoregulatory behaviors by different groups of central and peripheral thermosensors makes possible a differentiation of responses to different distributions of hyperthermia between superficial and deep sensors that optimizes cost-benefit trade-offs in different kinds of heat stress.

A segmental approach to mandibular molar uprighting.

Diagnosis and treatment in molar uprighting are discussed. The over-all objective in molar uprighting is ideal positioning of the molar which will eventually become an abutment tooth for a fixed prosthesis. The ideal position will provide an optimal periodontal environment for the molar(s). The specific objectives concerning protection against inflammatory periodontal diseases and occlusal traumatism, which together determine the optimal periodontal environment, are explained. Emphasis is placed on the biomechanics of molar uprighting which will achieve the desired periodontal treatment result. The specific technique recommended for the instances in which the molar is considerably angulated involves a segmental approach which utilizes a modification of the Burstone root spring. Proper application results in the dissociation of the correction of angulation and the extrusion of the molar tooth. When extrusion of the periodontally involved molar is required, then it should follow the correction of molar angulation. Other advantages of this approach involve the precision and ease of symmetrical preactivation, favorable load/deflection considerations, the low level of patient discomfort, and the reduced tendency of normal function distorting or dislodging the spring. This technique is compared by these parameters to other popular molar-uprighting techniques. It is recognized that a multidisciplinary approach to this type of dental therapy is ideal and that since treatment planning in individual cases varies greatly, each malocclusion and associated periodontal involvement should be evaluated on an individual case basis.

[14C]Deoxyglucose mapping of first-order projections activated by stimulation of lateral hypothalamic sites eliciting gnawing, eating, and drinking in rats.

Rats having hypothalamic electrodes that elicited gnawing, eating, and drinking in free-moving tests received intermittent electrical stimulation for 45 min following i.v. injection of [14C] deoxyglucose. Autoradiographs of regional brain glucose utilization were made by the method of Sokoloff et al. ('77). To maximize the detectability of first-order neuronal effects and minimize potentially complex transsynaptic effects, baseline metabolism and synaptic transmission were reduced by light barbiturate anesthesia. Laterally asymmetrical increases in glucose utilization indicative of elicited activity were largely coterminous with the known projections of the lateral hypothalamus and some projections of adjoining areas, indicating that most first-order efferents were above threshold for deoxyglucose visualization, while most transsynaptic effects were subthreshold. Although the majority of hypothalamic projections were similarly affected in control rats that received hypothalamic stimulation that elicited other responses, a number were activated significantly less than in the rats whose electrodes induced gnawing, eating, and drinking. Chief among these areas was a continuous descending pathway from the ventral tegmental area through the lateral tegmentum to the cuneiform and parabrachial nuclei. Smaller and/or less reliable increases above controls were found in the dorsomedial caudate-putamen, the posterolateral zona incerta, the anterior lateral central gray, the caudal linear nucleus, the laterodorsal tegmental nucleus, the pontine tegmental nucleus, and a previously undescribed pathway lying medially between the pontine medial lemniscus and cerebral peduncle. These areas, especially the lateral tegmental and parabrachial zone, are the most likely candidates for the pathways and/or destinations of the directly excited efferents or fibers of passage that constitute the first link in the elicitation of gnawing, eating, and drinking by lateral hypothalamic stimulation. Since self-stimulation and exploratory activity were elicited by control as well as experimental electrodes, they are probably dependent on other projections among those affected similarly in both groups.