M J Manyak

Radiological Associates of Sacramento Medical Group, Inc., Sacramento, California, United States

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Publications (41)94.99 Total impact

  • Michael J Manyak
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    ABSTRACT: The provision of accurate prognostic information is a long-standing goal for effective management of prostate adenocarcinoma. Nontargeted imaging modalities are less efficient at detecting slow-growing prostate cancers. Prostate-specific membrane antigen has emerged as a superior biomarker, especially for the evaluation of metastatic spread. Advances in imaging technology have focused clinical interest on indium-111 capromab ((111)In capromab) pendetide, a radioimmunoconjugate that detects prostate-specific membrane antigen expression in vivo. Single-photon emission computed tomography capromab pendetide images, fused with those generated by computed tomography or magnetic resonance, have engendered improvements in localization accuracy by correlating high signal intensity with anatomic structures. In long-term outcomes studies, fused (111)In capromab pendetide scans have delivered significant benefits for patient selection and improved treatment of prostate cancer.
    Expert Review of Anti-infective Therapy 03/2008; 8(2):175-81. · 3.06 Impact Factor
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    Michael J Manyak
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    ABSTRACT: Rapid advances in imaging technology have whetted our collective appetites for practical clinical applications to assist the physician and patient in therapeutic decisions. Current limitations of imaging technology are being addressed by the convergence of technology in materials science, the computer industry, and biology which have led to improvements of diagnostic imaging. Refinements in image acquisition, fusion of images, and outcomes data now suggest use for image-guided therapy. Novel imaging agents and technologies appear to provide improved capabilities to detect malignant lymph nodes. Future applications of optical coherence tomography, electron paramagnetic resonance imaging, nanotechnology, and other forms of molecular imaging promise further refinements to enhance our diagnostic armamentarium.
    The Canadian Journal of Urology 01/2008; 14 Suppl 1:32-8. · 0.74 Impact Factor
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    ABSTRACT: The vast majority of bladder cancers originate within 600 microm of the tissue surface, making optical coherence tomography (OCT) a potentially powerful tool for recognizing cancers that are not easily visible with current techniques. OCT is a new technology, however, and surgeons are not familiar with the resulting images. Technology able to analyze and provide diagnoses based on OCT images would improve the clinical utility of OCT systems. We present an automated algorithm that uses texture analysis to detect bladder cancer from OCT images. Our algorithm was applied to 182 OCT images of bladder tissue, taken from 68 distinct areas and 21 patients, to classify the images as noncancerous, dysplasia, carcinoma in situ (CIS), or papillary lesions, and to determine tumor invasion. The results, when compared with the corresponding pathology, indicate that the algorithm is effective at differentiating cancerous from noncancerous tissue with a sensitivity of 92% and a specificity of 62%. With further research to improve discrimination between cancer types and recognition of false positives, it may be possible to use OCT to guide endoscopic biopsies toward tissue likely to contain cancer and to avoid unnecessary biopsies of normal tissue.
    Journal of Biomedical Optics 01/2008; 13(2):024003. · 2.75 Impact Factor
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    ABSTRACT: Optical coherence tomography (OCT) has been used to evaluate tissue in nearly every genitourinary structure including the kidney, adrenal gland, ureter, bladder, seminal vesicle, prostate, urethra, testicle, and vas deferens. The most common urologic cancers, those of the prostate, kidney, and bladder, account for about 300,000 new cases of cancer per year in men with another 32,000 new renal and bladder cancer cases arising in women [1, 2]. The first OCT images of human urologic tissue ex vivo were demonstrated in 1997 paper [3] while the first in vivo OCT studies in urology were performed on the bladder urothelium in 1997 [4, 5]. Since then, a number of papers have been published exploring OCT for urological clinical applications. In brief, the spectrum of potential clinical use includes: – Differential diagnosis of urinary bladder conditions – Early detection of bladder neoplasia, including visualization of carcinoma in situ (Tis) – Preoperative planning and intraoperative guidance of surgery for adequate resection with maximal bladder preservation – Differentiation of fluorescent bladder lesions – Identification and preservation of neurovascular tissue during prostatectomy – Detection of capsular penetration of prostate cancer during prostatectomy – Preservation of retroperitoneal nerves during lymph node dissection for testicular cancer – Identification of dilated seminiferous tubules in evaluation of male infertility – Differentiation of renal tumors
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    ABSTRACT: Central abdominal uptake (CAU) on immunoscintigraphy with capromab pendetide (CP) (ProstaScint) suggests the presence of metastases from prostate cancer, but tissue confirmation is difficult and invasive. We report the outcomes data from a cohort of patients with CAU on CP images obtained for staging. The records of 341 men with prostate cancer who underwent CP imaging at two institutions from 1994 to 1999 were reviewed. The patients were divided according to the presence or absence of CAU. Metastases were confirmed in 36 patients (52%) with CAU. The median follow-up was 4.1 years. Statistical analyses compared the differences in baseline characteristics, subsequent radiotherapy, intervention with androgen ablation, and survival. CAU was detected in 69 patients (20%). A total of 262 patients underwent pelvic radiotherapy after the scan, 57 (83%) with CAU and 205 (75%) without (P = 0.2). Of the 69 patients with positive CAU findings and the 272 patients with negative CAU findings, 10 (14.5%) and 14 (5.1%) had died during the follow-up period (P = 0.007). Prostate cancer-specific death occurred in 5 (7.2%) of 69 patients with CAU-positive findings versus 2 of 272 with CAU-negative findings, for a rate 10 times greater in the CAU-positive group (P = 0.02). The results were independent of either the use or timing of androgen blockade. The results of our study have shown that CAU on CP immunoscintigraphy is clinically important and correlates with a significantly greater risk of prostate cancer-specific death. These findings suggest that patients with CAU should be considered for earlier intervention with systemic therapy.
    Urology 09/2007; 70(2):303-8. · 2.42 Impact Factor
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    ABSTRACT: Medical advances will be driven by the enhancement of imaging for diagnosis, refinement of treatment, and evaluation of treatment efficacy. The convergence of technology in materials science, biology, and the computer industry has greatly advanced diagnostic imaging. Precision in control of the spatial and temporal properties of light and its heterogeneous scattering properties have extended our capability for imaging. Refinements in radioimmunoscintigraphy for image acquisition, fusion of images, and outcome data now suggest use for image-guided therapy. Novel MRI agents appear to provide significant imaging capabilities to detect malignant lymph nodes. Future applications of optical coherence tomography, electron paramagnetic resonance imaging, nanotechnology, molecular imaging, and hyperspectral spectroscopy promise further refinements to image tissues for diagnosis.
    Urologic Clinics of North America 06/2006; 33(2):133-46, v. · 1.39 Impact Factor
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    Stephen B Williams, Gregory R Szlyk, Michael J Manyak
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    ABSTRACT: Malignant peripheral nerve sheath tumors are rare in the genitourinary organs, with few reports of occurrence in the kidney. We describe a patient with a renal malignant peripheral nerve sheath tumor, discovered after excision of a malignant peripheral nerve sheath scalp lesion, with additional masses in the lung and shoulder on metastatic evaluation. This patient underwent neoadjuvant intravenous doxorubicin therapy, followed by surgical resection of the scalp, lung and shoulder lesions in addition to a radical nephrectomy.
    International Journal of Urology 02/2006; 13(1):74-5. · 1.73 Impact Factor
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    ABSTRACT: Optical coherence tomography (OCT) is a new modality that allows noninvasive examination of the internal structure of biological tissue in vivo with a spatial resolution of 10 to 15 microm. This study evaluated the clinical application of OCT to determine epithelial and subepithelial anatomic structure and invasiveness of bladder epithelial lesions. The OCT examination was performed with a 980-nm 10 mW superluminescent diode using a 2.7-mm-diameter optical fiber positioned cystoscopically. A total of 261 scans of 1.5 seconds' duration, which generated 200 x 200-pixel images, were performed on 87 areas in 24 patients at high risk of having transitional-cell carcinoma (TCC). Lesions, visually suspect, and normal areas were photographed, scanned, and biopsied. The scans were evaluated independently before comparison with histopathology findings. Of the 87 areas, 29 of 36 visually suspect areas and 35 of 35 normal areas, were correctly diagnosed with OCT. Of the 16 areas with papillary TCC, all 16 were diagnosed correctly as tumor, and 9 of 10 were diagnosed correctly as invasive, including 6 with lamina propria invasion only. Papillary and flat tumors, carcinoma in situ, inflammation, chronic cystitis, and von Brunn's nests were scanned. Overall, OCT had a sensitivity of 100%, overall specificity of 89%, positive predictive value of 75%, and negative predictive value of 100%. The accuracy was 92%. The positive predictive value for invasion was 90%. Optical coherence tomography is a simple, portable, promising modality for evaluation of bladder lesions and depth of tumor penetration. Further refinement of this technology may lead to the development of an optical surrogate for biopsy.
    Journal of Endourology 07/2005; 19(5):570-4. · 2.07 Impact Factor
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    ABSTRACT: Two clinical studies on evaluation of Optical Coherence Tomography (OCT) capabilities in urinary bladder cancer and precancer detection are reported, enrolling 70 patients. Preliminary results show good sensitivity and specificity in recognition of early neoplasia.
    Biomedical Topical Meeting; 04/2004
  • Michael J Manyak, Kenneth Ogan
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    ABSTRACT: Diffuse superficial transitional-cell carcinoma (TCC) refractory to standard therapies poses a clinical dilemma. Photodynamic therapy (PDT), which uses an interaction between absorbed light and a retained photosensitizing agent to destroy tissue, has been used to treat diffuse superficial bladder TCC, although there are few reports of long-term outcomes. A series of 34 patients, 29 with TCC carcinoma in situ (CIS) and 5 with multiple small papillary stage T(a) or T(1) lesions, received porfimer sodium (P) 48 hours before whole-bladder PDT with 630-nm laser light. A 0.02% soybean emulsion diffusion medium was instilled into the bladder, and the laser optical fiber was positioned under triplanar sonography prior to PDT. The mean follow-up was 52 months. At 3 months, a complete response (CR) in 14 (44%) of the 32 evaluable patients, a partial response (PR) in 4 (12%), and no response (NR) in 14 (44%). Four of the five patients with extensive papillary lesions did not respond. The NR rate for patients with CIS with or without resected papillary lesions was 37%. The mean time to recurrence in the CR group was 9.8 months, and five members of this group (36%) underwent cystectomy (mean time 20 months) for persistent/progressive disease (N = 3) or bladder contracture (N = 2). In the NR group, 6 (43%) underwent cystectomy (mean time 14 months) for persistent/progressive disease. Metastatic bladder cancer was the cause of death in only 4 of the 12 patients who have died. Of the remaining 22 patients, 15 are still alive and have an intact bladder, nine with no disease and six with only superficial disease. This is the first report of long-term results following whole-bladder PDT using diffusion medium for isotropic light distribution. More than half of the patients with TCC refractory to traditional intravesical therapy received benefit from a single PDT session. Patients with extensive flat papillary lesions do not appear to respond well. Patients who achieve a CR have less likelihood of and longer time interval before needing cystectomy for progressive disease than NR patients. Our PDT protocol is associated with minimal morbidity in these high-risk patients.
    Journal of Endourology 11/2003; 17(8):633-9. · 2.07 Impact Factor
  • Advances in experimental medicine and biology 02/2003; 539(Pt B):841-52. · 1.83 Impact Factor
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    ABSTRACT: Currently, there are very few diagnostic or therapeutic strategies targeted at controlling tumor growth and progression towards metastasis. Uteroglobin (UG) is a naturally occurring, small, stable, secretory protein that is normally expressed by most cells of epithelial origin but is known to be lost during the progression of prostate, lung, and uterine cancers to invasive malignancy. Uteroglobin -/- knockout mice appear to be extremely cancer prone. Both pharmacological and transgenic reconstitution of recombinant human UG (rhUG) to prostate, lung, and endometrial tumor cell lines markedly inhibits their invasiveness and antagonizes the neoplastic phenotype. In preliminary studies, rhUG inhibited angiogenesis in the ex vivo rat aorta model and showed antitumor activity against human prostate tumor cells (PC-3) in the chick chorioallantoic membrane assay, reducing both tumor volume and vascularity. A recent in vivo pilot study showed that twice daily dosing with rhUG resulted in a statistically significant increase in survival without evidence of toxicity in severe combined immunodeficient mice challenged with a PC-3 cell metastasizing tumor. Thus, rhUG may slow the progression of cancer by inhibiting both tumor cell invasiveness and tumor angiogenesis. It therefore holds the potential to serve as a new weapon in the arsenal of cytostatic, antimetastatic, adjuvant treatment for cancer. In this paper, we will briefly discuss the therapeutic potential of uteroglobin-based strategies for managing prostate cancer.
    Clinical prostate cancer 10/2002; 1(2):118-24.
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    ABSTRACT: To provide a realistic experience of lower urinary tract endoscopic procedures, we have developed and continue to expand a computer-based surgical simulator that incorporates a surgical tool interface with anatomic detail and haptic feedback. Surface-based geometric data for the lower urinary tract were generated from the National Library of Medicine Visible Human dataset. The three-dimensional texture map of the surface geometry was developed from recorded endoscopic video procedures. Geometry and associated texture maps were rendered in real time using the Silicon Graphics Extreme Impacts program. The surgical interface device incorporated all normal ranges of motion and resistance that occur within an actual operative environment. The hands-on endoscopic device attached to the interface device was provided by Circon-ACMI, Inc. Urologic residents evaluated the program for correlation with actual endoscopic procedures. Texture-mapped digitized images provided a close anatomic similarity to actual videoendoscopic images. Virtual endoscopy of the lower urinary tract was reproducible and closely simulated actual visual and tactile endoscopic experience. Virtual reality surgical simulation is feasible for a variety of lower urinary tract procedures. This system coordinates visual perception with appropriate haptic feedback in both longitudinal and rotational axes. These types of procedures may be incorporated into future educational experiences for urologists to introduce new techniques and to provide documentation of surgical experience.
    Journal of Endourology 05/2002; 16(3):185-90. · 2.07 Impact Factor
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    ABSTRACT: To evaluate the cost effectiveness of minimally invasive therapy relative to medical (alpha-blocker) therapy and transurethral resection (TURP) for patients with moderate to severe symptoms of benign prostatic hyperplasia (BPH). We constructed a decision-analytic Markov model for a hypothetical cohort of 65-year-old men with moderate to severe BPH symptoms. Microwave thermotherapy was selected to represent minimally invasive treatment. Cost-effectiveness analysis was performed with 25 health states using the 3 treatments, 5 short-term clinical events, and 17 possible long-term outcomes. Each health state had an associated cost and utility. Quality of life (QoL) and utility estimates were obtained by interviewing 13 men with BPH symptoms using the standard gamble reference methods. Patients were classified as risk averse (RA) or non-risk averse (NRA) on the basis of their attitudes to risk. We calculated the incremental cost effectiveness of microwave thermotherapy relative to medical therapy and TURP over 5 years after treatment initiation. Event probabilities were obtained from the literature, a consensus panel, and published randomized clinical trials. The utility values generated were internally consistent and externally valid for a hypothetical cohort of 10,000 RA patients. Microwave thermotherapy was preferred by the NRA group, while medical therapy was preferred by the RA group. Surgery was least preferred by both groups. Microwave thermotherapy had a small incremental cost but improved QoL in comparison with medical therapy. Microwave thermotherapy had a higher utility and lower cost than TURP and thus was dominant over TURP. This analytical method can be applied to evaluate the cost effectiveness of any BPH therapy.
    Journal of Endourology 03/2002; 16(1):51-6. · 2.07 Impact Factor
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    ABSTRACT: Cryotherapy is a treatment modality that uses a technique to selectively freeze tissue and thereby cause controlled tissue destruction. The procedure involves placement of multiple small diameter probes through the perineum into the prostate tissue at selected spatial intervals. Transrectal ultrasound is used to properly position the cylindrical probes before activation of the liquid Argon cooling element, which lowers the tissue temperature below -40 degrees Centigrade. Tissue effect is monitored by transrectal ultrasound changes as well as thermocouples placed in the tissue. The computer-based cryotherapy simulation system mimics the major surgical steps involved in the procedure. The simulated real-time ultrasound display is generated from 3-D ultrasound datasets where the interaction of the ultrasound with the instruments as well as the frozen tissue is simulated by image processing. The thermal and mechanical simulations of the tissue are done using a modified finite-difference/finite-element method optimized for real-time performance. The simulator developed is a part of a comprehensive training program, including a computer-based learning system and hands-on training program with a proctor, designed to familiarize the physician with the technique and equipment involved.
    Studies in health technology and informatics 02/2002; 85:173-8.
  • Journal of Women's Imaging. 01/2002; 4(2):58-65.
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    ABSTRACT: To evaluate the diagnostic and prognostic value of the nuclear matrix protein-22 (NMP22) and bladder tumour antigen (BTAstat) tests compared with voided urinary cytology (VUC) in detecting and following bladder cancer, assessing particularly the prognostic value of false-positive test results in patients followed up for bladder cancer. From 739 patients suspected of having bladder cancer, voided urine samples for the NMP22 and BTAstat tests, and for VUC and urine analysis, were collected before cystoscopy. All patients underwent transurethral resection of bladder lesions or mapping. and were followed for a mean (range) of 27.3 (3-65) months. In the 406 patients with bladder cancer, the overall sensitivity was 85% for NMP22, 70% for BTAstat and 62% for VUC. For histological grades 1-3 the sensitivity in detecting transitional cell carcinoma was 82%, 89% and 94% for NMP22, 53%, 76% and 90% for BTAstat, and 38%, 68% and 90% for VUC, respectively. Although the sensitivity in detecting invasive carcinoma was >85% for all the tests. NMP22 and BTAstat were statistically more sensitive than VUC for superficial tumours. The optimal threshold value for NMP22, calculated using the receiver operating characteristics curve was 8.25 U/mL. The specificity was 68% for NMP22, 67% for BTAstat, and 96% for VUC. The specificity of VUC remained >87% and was independent of benign histological findings. In contrast, in patients with no apparent genitourinary disease on histology, NMP22 and BTAstat had significantly higher specificity (94% and 92%, respectively: P=0.003) than in the group with chronic cystitis (52% for both tests). Forty patients having no bladder cancer at biopsy had a recurrence after a mean (range) follow-up of 7.7 (3-15) months: all had a previous history of bladder cancer. According to subsequent recurrence, the prognostic positive and negative predictive values were 18% and 91% for NMP22, 13% and 88% for BTAstat, and 79% and 91% for VUC. Both false-positive VUC and NMP22 tests predicted recurrence (log-rank test, P<0.001 and P=0.004, respectively), but the BTAstat test produced no similar correlation (P=0.778). The NMP22 and BTAstat tests are better than VUC for detecting superficial and low-grade bladder cancer but they have significantly lower specificity. After excluding diseases with the potential to interfere in these tests the overall specificity of both tests is increased considerably. False-positive results from NMP22 and VUC but not from BTAstat in patients followed up for bladder cancer correlate with future recurrences.
    BJU International 11/2001; 88(7):692-701. · 3.05 Impact Factor
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    ABSTRACT: To evaluate the cost effectiveness of transurethral microwave thermotherapy relative to medical therapy (alpha-blocking agents) and transurethral resection of the prostate (TURP) for patients with moderate-to-severe benign prostatic hyperplasia (BPH) symptoms. A cost-effectiveness analysis was performed from the societal perspective for a hypothetical cohort of 65-year-old men with moderate-to-severe BPH symptoms. We calculated the incremental cost effectiveness of thermotherapy relative to medical therapy and TURP during 5 years after treatment initiation. Event probabilities were obtained from published reports, a consensus panel, and the Targis System (Urologix) randomized clinical trial. Costs were estimated using the national Medicare reimbursement schedules. Costs are reported in 1999 U.S. dollars. Total thermotherapy procedure costs were estimated at $2629. Quality-of-life and utility estimates were obtained by interviewing 13 patients with moderate-to-severe BPH symptoms. On the basis of their risk attitudes, patients were classified into risk-averse or non-risk-averse groups. The costs and health effects were discounted at 3% annually. In a hypothetical cohort of 10,000 non-risk-averse patients who were candidates for all three modalities, the 5-year costs were highest for patients undergoing TURP and lowest for those receiving medical therapy ($7334 and $6294, respectively). The thermotherapy group exhibited the highest 5-year utility value (53.52 quality-adjusted life-months). Compared with medical therapy, thermotherapy resulted in an additional 0.23 quality-adjusted life-months, with an incremental cost of $741. This yielded an incremental cost per quality-adjusted life-year gained of $38,664 for thermotherapy compared with medical therapy. Thermotherapy had a higher utility (difference of 1.71 quality-adjusted life-months) and lower cost (difference of $299) compared with TURP and thus was dominant over TURP. The results were similar for a hypothetical cohort of 10,000 risk-averse patients. From a societal perspective, thermotherapy appears to be a reasonable and cost-effective alternative to both medical and surgical treatment. However, the actual treatment decision should be based on multiple factors, only one of which is cost effectiveness.
    Urology 01/2001; 56(6):981-7. · 2.42 Impact Factor
  • The Journal of Urology 12/2000; 164(5):1644-5. · 3.75 Impact Factor
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    ABSTRACT: Eicosanoids modulate the interaction of tumor cells with various host components in cancer metastasis. Their synthesis involves the release of arachidonic acid (AA) from cellular phospholipids by phospholipase A2 (PLA2), followed by metabolism by cyclooxygenases (COXs) and lipooxygenases (LOXs). This study aimed to identify the pathway(s) of AA metabolism that are required for the invasion of prostate tumor cells. DU-145 and PC-3 human prostate cancer cell lines were used to test the effect of inhibitors of PLA2, COX, or LOX on the invasion of prostate tumor cells through Matrigel in vitro using the Boyden chamber assay and fibroblast-conditioned medium as the chemoattractant. We used nontoxic doses that did not inhibit simple cell motility and did not decrease clonogenic survival. All of the inhibitors caused a significant reduction in AA release from treated cells compared with control cells, which indicated that the treatments were biochemically active. Invasion through Matrigel was inhibited by the PLA2 inhibitor 4-bromophenacyl bromide (4-BPB), the general COX inhibitor ibuprofen (IB), and the highly selective COX-2 inhibitor NS398. Inhibition of cell invasiveness by 4-BPB (1.0 microM), IB (10.0 microM), and NS398 (10.0 microM) was reversed by the addition of prostaglandin E2 (PGE2). PGE2 alone, however, did not stimulate invasiveness, which suggests that its production is necessary for rendering the cells invasive-permissive but not sufficient for inducing invasiveness. In contrast, we found no significant inhibition of invasion of prostate tumor cells treated with esculetin (1.0 microM) or nordihydroguiaretic acid (1.0 microM), which are specific inhibitors of LOX. We also tested the effect of 4-BPB, IB, NS398, and esculetin on the secretion of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs), as key enzymes in the proteolysis of Matrigel during invasion, using gelatin zymograms and Western blots. Cells that received 4-BPB, IB, or NS398, but not esculetin showed a significant reduction in the levels of proMMP-2, MMP-9, and proMMP-9 in the culture medium. DU-145 cells did not secrete TIMP-1, and the drugs did not alter the secretion of TIMP-2. This work highlights the role played by COX in disturbing the balance between MMPs and TIMPs in prostate cancer cells, and it points to the potential use of COX inibitors, especially COX-2 selective inhibitors, in the prevention and therapy of prostate cancer invasion.
    Cancer Research 09/2000; 60(16):4629-37. · 8.65 Impact Factor

Publication Stats

739 Citations
94.99 Total Impact Points


  • 2007
    • Radiological Associates of Sacramento Medical Group, Inc.
      Sacramento, California, United States
    • Walter Reed National Military Medical Center
      • Center for Prostate Disease Research
      Washington, Washington, D.C., United States
  • 1991–2006
    • George Washington University
      • • Department of Urology
      • • Department of Pharmacology and Physiology
      Washington, D. C., DC, United States
  • 2001
    • Mayo Clinic - Rochester
      Rochester, Minnesota, United States
  • 2000
    • Washington Hospital Center
      Washington, Washington, D.C., United States