Ex-Vivo Ureteroscopy at the Time of Live Donor Nephrectomy

Background and Purpose: Potential transplant renal allograft recipients exceed the number of donors. Our institution now considers patients with small, unilateral, nonobstructing, incidental renal calculi for possible renal donation. We adopted ex-vivo ureteroscopy (ExURS) to render these kidneys stone free at the time of renal transplantation. We examined the safety and efficacy of ExURS. Patients and Methods: After confirming a lack of significant metabolic defects on 24-hour urinalysis, 23 patients with small nonobstructing unilateral nephrolithiasis detected on preoperative CT angiography underwent donor nephrectomy. Immediately after cold perfusion, ExURS was performed with ice cold saline irrigation. Retrospective review was performed. Results: Pyeloscopy was successfully performed in all 23 patients. A total of 28 calculi, mean largest diameter 3.9-mm (range 3-6-mm), were visualized in 19 kidneys. Basket extraction and holmium laser lithotripsy was performed in 12 and 6 kidneys, respectively. Treatment rendered 17/19 stone-containing kidneys stone free with a mean treatment time of 6.2 minutes (3-10-min). There were no intraoperative complications. Median serum creatinine level of recipients at 1 month and 1 year were 1.4+/-1.8-mg/dL and 1.3+/-0.6-mg/dL, respectively. At a median follow-up of 63+/-47.2 months, there were no transplant urinary calculi among the recipients. Conclusions: ExURS safely renders live donor kidney allografts stone free with low risk of recurrence. When used appropriately, ExURS could safely increase the number of potential kidney donors and minimize the risk of adverse stone events.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90444/1/end-2E2010-2E0627.pd

Endoscopic Assessment and Prediction of Prostate Urethral Disintegration After Histotripsy Treatment in a Canine Model*

Abstract Background and Purpose: Histotripsy is a nonthermal focused ultrasound technology that uses acoustic cavitation to homogenize tissue. Previous research has demonstrated that the prostatic urethra is more resistant to histotripsy effects than prostate parenchyma, a finding that may complicate the creation of transurethral resection of the prostate-like treatment cavities. The purpose of this study was to characterize the endoscopic appearance of the prostatic urethra during and after histotripsy treatment and to identify features that are predictive of urethral disintegration. Materials and Methods: Thirty-five histotripsy treatments were delivered in a transverse plane traversing the prostatic urethra in 17 canine subjects (1?3/prostate ≥1?cm apart). Real-time endoscopy was performed in the first four subjects to characterize development of acute urethral treatment effect (UTE). Serial postprocedure endoscopy was performed in all subjects to assess subsequent evolution of UTE. Results: Endoscopy during histotripsy was feasible with observation of intraurethral cavitation, allowing characterization of the real-time progression of UTE from normal to frank urethral disintegration. While acute urethral fragmentation occurred in 3/35 (8.6%) treatments, frank urethral disintegration developed in 24/35 (68.5%) within 14 days of treatment. Treating until the appearance of hemostatic pale gray shaggy urothelium was the best predictor of achieving urethral fragmentation within 14 days of treatment with positive and negative predictive values of 0.91 and 0.89, respectively. Conclusion: Endoscopic assessment of the urethra may be a useful adjunct to prostatic histotripsy to help guide therapy to ensure urethral disintegration, allowing drainage of the homogenized adenoma and effective tissue debulking.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98446/1/end%2E2011%2E0349.pd

The James Webb Space Telescope

The James Webb Space Telescope (JWST) is a large (6.6m), cold (50K), infrared-optimized space observatory that will be launched early in the next decade. The observatory will have four instruments: a near-infrared camera, a near-infrared multi-object spectrograph, and a tunable filter imager will cover the wavelength range, 0.6 to 5.0 microns, while the mid-infrared instrument will do both imaging and spectroscopy from 5.0 to 29 microns. The JWST science goals are divided into four themes. The End of the Dark Ages: First Light and Reionization theme seeks to identify the first luminous sources to form and to determine the ionization history of the early universe. The Assembly of Galaxies theme seeks to determine how galaxies and the dark matter, gas, stars, metals, morphological structures, and active nuclei within them evolved from the epoch of reionization to the present day. The Birth of Stars and Protoplanetary Systems theme seeks to unravel the birth and early evolution of stars, from infall on to dust-enshrouded protostars to the genesis of planetary systems. The Planetary Systems and the Origins of Life theme seeks to determine the physical and chemical properties of planetary systems including our own, and investigate the potential for the origins of life in those systems. To enable these observations, JWST consists of a telescope, an instrument package, a spacecraft and a sunshield. The telescope consists of 18 beryllium segments, some of which are deployed. The segments will be brought into optical alignment on-orbit through a process of periodic wavefront sensing and control. The JWST operations plan is based on that used for previous space observatories, and the majority of JWST observing time will be allocated to the international astronomical community through annual peer-reviewed proposal opportunities.Comment: 96 pages, including 48 figures and 15 tables, accepted by Space Science Review

Medical treatment of prolactinomas.

Prolactinomas, the most prevalent type of neuroendocrine disease, account for approximately 40% of all pituitary adenomas. The most important clinical problems associated with prolactinomas are hypogonadism, infertility and hyposexuality. In patients with macroprolactinomas, mass effects, including visual field defects, headaches and neurological disturbances, can also occur. The objectives of therapy are normalization of prolactin levels, to restore eugonadism, and reduction of tumor mass, both of which can be achieved in the majority of patients by treatment with dopamine agonists. Given their association with minimal morbidity, these drugs currently represent the mainstay of treatment for prolactinomas. Novel data indicate that these agents can be successfully withdrawn in a subset of patients after normalization of prolactin levels and tumor disappearance, which suggests the possibility that medical therapy may not be required throughout life. Nevertheless, multimodal therapy that involves surgery, radiotherapy or both may be necessary in some cases, such as patients who are resistant to the effects of dopamine agonists or for those with atypical prolactinomas. This Review reports on efficacy and safety of pharmacotherapy in patients with prolactinomas

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

Assessment of Urostomy Parastomal Herniation Forces Using Incisional Prevention Strategies with an Abdominal Fascia Model

Background: Approximately 10 000 patients undergo cystectomy/ileal conduit annually in the USA, of whom over 70% subsequently develop a parastomal hernia (PSH). Still, no well-established “best” practice for stoma creation to prevent a PSH exists. Objective: To measure the relationship between incision size/type/material and axial tension force (ATF) as a surrogate for herniation force, using several models to mimic abdominal fascia. Design, setting, and participants: Abdominal fascia models included silicone membrane, ex vivo porcine, and embalmed human cadaveric fascia. A dynamometer pulled a Foley catheter (20 mm/min) with the balloon inflated to 125% incision (linear, cruciate, and circular) diameter using a motorized positioning system. The maximum ATF before herniation was recorded. The study was repeated in unused silicone/tissue for suture reinforcement. We evaluated silicone, ex vivo porcine, and human abdominal fascia. Intervention: Incision sizes (1–3 cm) in 0.5-cm increments were evaluated in silicone. A 3-cm incision was used in porcine/human tissue. Outcome measurements and statistical analysis: ATF for herniation was recorded/compared across incision types/sizes using Mann-Whitney U and Kruskal-Wallis tests as appropriate, with α = 0.05. Results and limitations: Linear incision ATF was significantly greater than cruciate and circular incisions. A cruciate incision had significantly greater ATF than a circular incision. In cadaveric tissue, incisions were significantly greater for linear (34.5 ± 12.8 N) versus cruciate (15.3 ± 2.9 N, p = 0.004) and for cruciate versus circular (p = 0.023) incisions. Results were similar in ex vivo porcine fascia and silicone. Reinforcement with a suture significantly increased ATF in all materials/incision sizes/types. The ex vivo nature is this study’s main limitation. Conclusions: This study suggests that urostomy fascial incision type may influence ATF required for herniation. Linear incisions may be preferable. Urostomy reinforcement may significantly increase ATF required for a PSH. These data may help establish best practices for PSH risk reduction. Patient summary: The results of this study illustrate that urostomy fascia incision type may influence the force required to create a parastomal hernia. Linear incisions may be preferable

A novel canine model for prostate cancer

BACKGROUND No existing animal model fully recapitulates all features of human prostate cancer. The dog is the only large mammal, besides humans, that commonly develops spontaneous prostate cancer. Canine prostate cancer features many similarities with its human counterpart. We sought to develop a canine model of prostate cancer that would more fully represent the features of human prostate cancer than existing models. METHODS The Ace‐1 canine prostate cancer cell line was injected transabdominally under transrectal ultrasound (TRUS) guidance into the prostates of immunosuppressed, intact, adult male dogs. Tumor progression was monitored by TRUS imaging. Some dogs were subjected to positron emission tomography (PET) for tumor detection. Time of euthanasia was determined based on tumor size, impingement on urethra, and general well‐being. Euthanasia was followed by necropsy and histopathology. RESULTS Ace‐1 tumor cells grew robustly in every dog injected. Tumors grew in subcapsular and parenchymal regions of the prostate. Tumor tissue could be identified using PET. Histological findings were similar to those observed in human prostate cancer. Metastases to lungs and lymph nodes were detected, predominantly in dogs with intraprostatic tumors. CONCLUSIONS We have established a minimally invasive dog model of prostate cancer. This model may be valuable for studying prostate cancer progression and distant metastasis. Prostate 73: 952–959, 2013. © 2013 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98364/1/22642_ftp.pd

Release of Cell-free MicroRNA Tumor Biomarkers into the Blood Circulation with Pulsed Focused Ultrasound: A Noninvasive, Anatomically Localized, Molecular Liquid Biopsy.

Purpose To compare the abilities of three pulsed focused ultrasound regimes (that cause tissue liquefaction, permeabilization, or mild heating) to release tumor-derived microRNA into the circulation in vivo and to evaluate release dynamics. Materials and Methods All rat experiments were approved by the University of Washington Institutional Animal Care and Use Committee. Reverse-transcription quantitative polymerase chain reaction array profiling was used to identify candidate microRNA biomarkers in a rat solid tumor cell line. Rats subcutaneously grafted with these cells were randomly assigned among three pulsed focused ultrasound treatment groups: (a) local tissue liquefaction via boiling histotripsy, (b) tissue permeabilization via inertial cavitation, and (c) mild