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The brain vasculature, especially capillaries, may function in a very dynamic fashion under neuroendocrine control to regulate the internal environment of the brain. This is exemplified by new observations on the regulation of brain water permeability using the tracer H215O in vivo in adult rhesus monkeys. These studies reveal that brain water permeability, and hence brain water content and volume, are, at least in part, under the influence of the central noradrenergic system and centrally released vasopressin.

Advanced tumors of the paranasal sinuses, parotid gland, orbit, parapharynx, and cranial cavity may invade the infratemporal fossa by direct extension or through natural anatomic pathways. The inability to control disease involving this region is reflected by the unacceptably high recurrence rates for both intracranial and extracranial neoplasms. Between 1983 and 1986, a pterional (or subtemporal) approach was combined with such conventional anterolateral procedures as a mandibulopharyngectomy, maxillectomy, orbitectomy, and parotidectomy in 13 patients with advanced skull base lesions. The tumor origin was extracranial in ten cases and intracranial in three patients. Seven of the neoplasms were malignant and six were histologically benign. Complete tumor removal was achieved in all patients. Repair of the ablative defect was achieved with a temporalis myogenous flap in ten patients, and primary closure or distant myocutaneous flaps in the remaining three patients. Postoperative complications included three lateral nasocutaneous fistulae secondary to temporalis myogenous flap necrosis and isolated cases of stroke, cerebral edema, pneumocephalus, and cerebrospinal fluid rhinorrhea. Twelve patients are alive without evidence of disease at a mean interval of 25 months. The remaining patient died from lung metastases 11 months after surgery.

Prostate cancer is the most common solid malignancy in men. Screening with PSA and DRE has led to an increased incidence of the disease, but has also contributed to decreasing mortality. Improved technology has led to treatments focused on maintaining cancer cure rates while minimizing the effect of prostate cancer treatment on quality of life. Recently, docetaxel has been added to standard androgen ablation as an effective treatment for advanced prostate cancer.

OBJECTIVE To evaluate the cancer yield of transrectal prostate biopsies in a 3-T magnetic resonance imaging (MRI) scanner in patients with elevated prostate specific antigen (PSA) levels and recent negative transrectal ultrasonography (TRUS)-guided prostate biopsies. PATIENTS AND METHODS Between July 2004 and November 2005, patients with at least one previous negative prostate biopsy within the previous 12 months had MRI-guided biopsy of the prostate in a 3-T MRI scanner. Patients with previous positive biopsies for cancer were excluded. Target selection was based on T2-weighted imaging and dynamic contrast-enhanced (DCE) imaging studies. RESULTS Thirteen patients were eligible; their median (range) age was 61 (47-74) years and PSA value 4.90 (1.3-12.3) ng/mL. Most patients had one previous negative biopsy (range 1-4). Four patients had a family history of prostate cancer. There were 37 distinct targets based on T2-weighted imaging. Fifteen of 16 distinct DCE abnormalities were co-localized with a target based on T2-weighted imaging. Despite this correlation, only one of 13 patients had a directed biopsy positive for cancer. Including systematic biopsies, two of 13 patients had a biopsy positive for prostate cancer. One patient had prostate intraepithelial neoplasia and one had atypical glands in the specimen. CONCLUSION The prostate-cancer yield of transrectal biopsies in a 3-T MRI scanner, among patients with recent negative TRUS-guided prostate biopsies, is similar to repeat systematic TRUS-guided biopsy. DCE correlates with T2-imaging but does not appear to improve prostate cancer yield in this population.

This review provides a perspective of spinal injuries related to invasive cardiology, an understanding of the anatomy and physiology of the spine, the etiology and pathophysiology of spinal injuries, and options for prevention and treatment. Because of the breadth of this review, it has been divided into two parts with the first describing the biomechanics and generation of back pain and the second discussing treatment options and prevention of back injury. A comprehensive overview of the biomechanics of the spine from the individual vertebral unit to the complex motions involved in everyday life is reviewed. The significant intrinsic and extrinsic factors playing a role in the mechanism of disc damage, including occupational hazards encountered by the invasive cardiologist, are discussed. We also address the mechanisms of pain generation in the spine and the role that inflammation plays, which explains the presence of symptoms with little or no detectable pathology on imaging studies.

OBJECTIVE To evaluate whether using endorectal-coil magnetic resonance imaging (erMRI) before transrectal ultrasonography (TRUS)-guided biopsies of the prostate increases the yield of cancer in a high-risk population, and in a subset analysis to compare the yield with high-field (3 T) vs lower field (1.5 T) MRI. PATIENTS AND METHODS Between March 2003 and November 2005, 26 consecutive patients had erMRI before their TRUS biopsy of the prostate (median age 62 years, range 32–76). The median prostate-specific antigen (PSA) level was 8.40 (2.1–85.9) ng/mL. All patients had at least one previous negative prostate biopsy (median 3, range 1–12). Twenty-three patients had at least one risk factor for prostate cancer (family history, high PSA velocity, low percentage of free PSA, prostatic intraepithelial neoplasia or atypical small acinar proliferation on previous biopsy). MRI studies consisted of T2-weighted and dynamic contrast-enhanced (DCE) imaging studies. RESULTS There was a close correlation between T2-weighted and DCE images (85% agreement, P

Animal studies have suggested that the reduction in stroke risk observed with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) therapy is owing to an increase in basal cerebral blood flow (CBF). The purpose of the study was to determine if statin therapy was associated with increased CBF in humans with cerebrovascular atherosclerotic disease. Quantitative measurements of CBF were obtained on study entry in 97 patients with carotid artery occlusion enrolled in a prospective study of cerebral hemodynamics and stroke risk. This study represents a post hoc analysis of CBF measurements based on whether patients were receiving statin therapy at the time of CBF measurement. Global and regional CBF (including hemispheric, basal ganglia, and arterial borderzones), and baseline clinical, epidemiologic, and laboratory stroke risk factors were compared between the two groups. Nineteen of the 97 patients were on a statin agent on study entry. The statin group was younger, had significantly lower LDL levels and included more women. Statin therapy was not associated with higher baseline values of CBF in global or regional analyses. Mean middle cerebral artery territory CBF (± s.d.) ipsilateral to the occluded carotid artery was 37.6 ± 12.7 mL/100 g min for the statin group ( n = 19) compared with 38.6 ± 12.7 mL/100 g min for the nonstatin group ( n = 78). Contralateral values were 42.9 ± 13.5 and 44.2 ± 13.3 mL/100 g min for the statin and nonstatin groups, respectively. We conclude that the stroke risk reduction observed with statin therapy in humans likely involves mechanisms other than an increased basal CBF.

BACKGROUND. Increased preoperative prostate-specific antigen (PSA) velocity (PSAV) has been associated with increased prostate cancer mortality and higher Gleason scores. The authors evaluated the relation between PSAV, biopsy Gleason score, and pathologic stage in men who were enrolled in a prostate cancer screening trial. METHODS. Data were analyzed from 1441 men who were enrolled in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial who received ≥2 PSA screens and were diagnosed with prostate cancer within 1 year of the last screen. PSAV was estimated by using all screening PSA values within 6 years prediagnosis. RESULTS. Both PSA and PSAV were related to biopsy Gleason score. The multivariable odds ratios (OR), controlling for PSA and demographics, for having a Gleason score of 7 to 10 were 1.3 (95% confidence interval [95% CI], 0.9–1.9), 2.2 (95% CI, 1.5–3.3), and 2.3 (95% CI, 1.4–3.9) for men with PSAV values from 0.5 to 1 ng/mL per year, from 1 to 2 ng/mL per year, and >2 ng/mL per year, respectively, compared with men who had PSAV values

BACKGROUND: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites.METHODS: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers.RESULTS: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, hl (2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (ρ = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (ρ = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (ρ = 0.51, SE =0.18), and bladder and lung (ρ = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures.CONCLUSION: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.

Background To determine whether prostate-specific antigen (PSA) testing in African American veterans (AAVs) aged 40 to 54 years is associated with high-risk prostate cancer characteristics compared with AAVs aged 55 to 70 years or white veterans (WVs) aged 40 to 54 years. Methods A total of 231,174 healthy veterans aged 40 to 70 years without clinical evidence of prostate cancer underwent PSA testing between October 1, 2000, and September 30, 2007. Clinicopathologic tumor characteristics were available for 1,044/1,059 AAVs and 1,006/1,971 age-matched WVs diagnosed with prostate cancer after a PSA level>4 ng/ml triggered prostate biopsy. Tumor characteristics of AAVs aged 40 to 54 years were compared with AAVs 55 to 70 years, WVs 40 to 54 years, and WVs 55 to 70 years. Results Of PSA-tested veterans aged 40 to 54 years diagnosed with prostate cancer, there were no racial differences in prebiopsy PSA levels, prostate cancer grade, or clinical stage at diagnosis. AAVs aged 40 to 54 years were more likely to have≥3 positive cores ( P = 0.0229) and were less likely to be active surveillance candidates ( P = 0.0340) compared with similarly aged WVs. AAVs aged 55 to 70 years were more likely to have high-grade ( P = 0.0204) and higher clinical stage ( P = 0.0195) prostate cancer than AAVs aged 40 to 54 years. Conclusions This large national cohort study suggests that PSA testing at an earlier age for African American men may allow diagnosis of lower risk prostate cancer, potentially reducing disparate outcomes between AAVs and WVs.

242 Background: The purpose of the study was to evaluate the utility of a 3 T pelvic magnetic resonance imaging (MRI) in detecting a local recurrence in post-prostatectomy prostate cancer patients prior to receiving adjuvant or salvage intensity-modulated radiation therapy (IMRT). Methods: Ninety prostate cancer patients status post-prostatectomy with rising prostate-specific antigen (PSA) had a 3 T pelvic MRI prior to IMRT. The following variables were analyzed for predicting positive findings on MRI: initial presenting and initial post-op PSA, PSA at the time of imaging, PSA velocity, surgical margins, Gleason score, pathological stage, pre-RT digital rectal examination, and type of surgical prostatectomy. Results: The only significant variable predictive of a positive MRI was positive margins. Specifically, 15 of 46 (33 %) patients with positive margins had a positive MRI, while 5 of 44 (11 %) patients with negative margins had a positive MRI. In the MRI positive group, the location of the positive findings on MRI corresponded with the pathology report in 9 of 12 (75 %) cases. Conclusions: Post-prostatectomy patients with pathologic positive margins are three times more likely to have positive findings on a 3 T MRI. [Table: see text]

Background and Purpose: The mechanism of stroke in patients with atherosclerotic occlusive disease and hemodynamic failure may be primarily hemodynamic or a combination of hemodynamic and embolic factors. The purpose of this study was to investigate the clinical and imaging features of stroke in these patients. Methods: Eleven patients with complete atherosclerotic carotid artery occlusion and increased oxygen extraction fraction measured in the hemisphere distal to the occlusion developed an ischemic stroke during the observation phase of a prospective study of cerebral hemodynamics and stroke risk. The medical and study records related to the endpoint event for these 11 patients were reviewed. Records were reviewed for evidence of associated hypotension and for specific details of the neurological deficit. Infarct location was characterized, based on review of imaging and clinical features, as: (1) middle cerebral artery (MCA) core; (2) possible cortical border zone, or (3) internal border zone. Results: One patient had a retinal infarction; the remaining 10 had MCA territory strokes. Six of the 10 infarctions occurred in the MCA core territory. Two of these 6 were fatal hemispheric events. One of the 10 infarctions occurred in the cortical border zone region. Two of the remaining 3 infarctions were localized to the internal border zone. One was indeterminate. Conclusions: The clinical features and radiological patterns of stroke in many patients with hemodynamic impairment failure and carotid occlusion are most consistent with large artery thromboembolic stroke. These data suggest a synergistic effect between embolic and hemodynamic mechanisms for large artery thromboembolic stroke.

Can preoperative PSA doubling time and PSA velocity predict outcomes following radical prostatectomy?

Purpose: Herein we describe the evaluation and management of renal tumors in Birt-Hogg-Dube (BHD), an autosomal dominant disorder predisposing to cutaneous fibrofolliculomas, pulmonary cysts, spontaneous pneumothorax and renal tumors. Materials and Methods: A total of 124 affected individuals underwent comprehensive clinical evaluation, including body computerized tomography, to determine cutaneous, pulmonary and renal manifestations of BHD. Of these individuals 14 had their renal tumors managed at our institution. Results: Of the 124 BHD affected individuals 34 (27%) had renal tumors of various histologies, most commonly hybrid oncocytic tumor and chromophobe renal carcinoma. Average age at renal tumor detection was 50.4 years and multiple tumors were found in a majority of patients. Some patients with renal tumors were identified that did not have the characteristic cutaneous hallmarks of BHD. In 4 of the 14 patients treated at our institution small (less than 3 cm) renal tumors were observed, while 10 others underwent a total of 12 renal procedures, including 4 radical and 8 partial nephrectomies. At a median of 38 months of followup 5 of these 10 patients remained free of disease, 3 had small renal tumors and 2 died of metastatic renal cancer. Conclusions: Patients with BHD are at risk for multiple renal tumors that are often malignant and can metastasize. Individuals at risk or affected by BHD should be radiographically screened for renal tumors at periodic intervals and they are best treated with nephron sparing surgical approaches. Genetic testing for this syndrome is now available.

Background The benefit of screening for prostate cancer using prostate-specific antigen (PSA) testing and digital rectal examination (DRE) is uncertain and is under evaluation in a randomized prospective trial, the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Although the final results are several years away, the initial round of screening is complete. We describe the population enrolled in the PLCO trial, their baseline PSA and DRE screening results, and diagnostic follow-up results during the first year of follow-up. Methods A total of 38,350 men were randomly assigned to the screening arm of the PLCO trial from November 1993 through June 2001. Men were advised to seek diagnostic follow-up from their primary care provider if their DRE was suspicious for cancer and/or if their serum PSA level was higher than 4 ng/mL. PLCO trial staff obtained records related to diagnostic follow-up. Results Compliance with both screening tests was high (more than 89%). At screening, 7.5% of men had a positive DRE (i.e., suspicious for cancer) and 7.9% had a PSA level higher than 4 ng/mL. Of the men with positive screening tests, 74.2% underwent additional diagnostic testing, and 31.5% underwent a prostatic biopsy within 1 year. Overall, 1.4% of the men in the screening arm were diagnosed with prostate cancer, the majority of whom had clinically localized cancer. These compliance, biopsy, and cancer detection rates appear to be representative of contemporary practice patterns. Conclusion The PLCO trial is evaluating PSA- and DRE-based screening for prostate cancer in a clinically valid manner. Whether such screening will result in a reduction of prostate cancer mortality cannot be answered until the randomized comparison is completed.

The St. Louis Carotid Occlusion Study demonstrated that ipsilateral increased O2 extraction fraction (OEF) (Stage II hemodynamic failure) measured by positron emission tomography (PET) is a powerful independent risk factor for subsequent stroke in patients with symptomatic complete carotid artery (CA) occlusion. The ipsilateral ischemic stroke rate at 2 years has been shown to be 5.3% in 42 patients with normal OEF and 26.5% in 39 patients with increased OEF (p = 0.004). In patients in whom hemispheric symptoms developed within 120 days, the 2-year ipsilateral stroke rates were 12% in 27 patients with normal OEF and 50% in 18 patients with increased OEF. Previous PET studies have demonstrated that anastomosis of the superficial temporal artery (STA) to a middle cerebral artery (MCA) cortical branch can restore OEF to normal. The authors discuss the undertaking of a study that will test the hypothesis that STA–MCA anastomosis, when combined with the best medical therapy, can reduce ipsilateral ischemic stroke by 40% at 2 years in patients with symptomatic internal CA occlusion and Stage II hemodynamic failure occurring within 120 days after surgery. Only patients with increased OEF distal to a symptomatic occluded CA will be randomized to surgery or medical treatment. The primary endpoint will be all strokes and death occurring between randomization and the 30-day postoperative cut off (with an equivalent period in the nonsurgical group), as well as subsequent ipsilateral ischemic stroke developing within 2 years. It is estimated that 186 patients will be required in each group. Assuming that 40% of PET scans will demonstrate increased OEF, this will require enrolling 930 clinically eligible individuals.

Tubing migration accounts for a significant number of shunt complications. In an attempt to reduce the likelihood of disconnection and tubing migration, we have developed a technique to rigidly fix the proximal catheter to the skull. The method involves the placement of a small twist drill hole adjacent to the catheter burr hole through which a suture is passed. The suture is then used to rigidly bind the proximal shunt tubing and valve to the skull. This approach provides an efficient and effective means for reducing complications related to shunt tubing migration.

A significant number of atherosclerotic lesions responsible for brain ischemia involve either intracranial arteries or the internal carotid or vertebral arteries at sites inaccessible to extracranial surgical approaches. 1 2 3 Although many of these atherosclerotic lesions are hemodynamically insignificant and produce ischemic symptoms due to embolization from diseased intima, others can obstruct blood flow to the brain. The development of sophisticated microvascular surgical techniques led to the development of extracranial-intracranial (EC/IC) arterial bypass procedures, which have been applied in an attempt to prevent stroke by improving the hemodynamic status of the circulation distal to a diseased vessel.

Objective: The accuracy and precision of resection with awake brain mapping is augmented when combined with frameless stereotaxy. Frameless stereotactic assisted surgery, however, typically involves immobilization in Mayfield pins. Rigid fixation, however, may be problematic for individuals undergoing awake craniotomy. We describe an alternate method of frameless stereotaxy without the use of pin fixation. Methods: The MRI fiducials are placed in proximity to the proposed incision and prepared and draped in the operative field. After craniotomy, the epidural skull clamp (standardly used to support the electrode holder during corticography) is attached. Using the Stealth Navigational System, a spinal reference arc is then clamped onto the skull clamp base. After the fiducials and arc are registered, the probe is used for frameless guidance. Results: In 14 of 15 cases (93%), this technique was successful. One case failed because of close proximity of the fiducials to the incision. The accuracy of the 14 successful cases was less than 4 mm. The error within the lesion itself was always less than 2 mm. Overall, these results are comparable to those achieved using a Mayfield head holder. In all tumor cases, postoperative imaging concurred with intraoperative assessment of a total versus subtotal resection. Conclusions: By affixing the spinal arc to the skull, the complications and discomfort associated with pin fixation are avoided completely. The patient is free to move without affecting the accuracy. The spine arc, in combination with the skull clamp, provides an efficient, well-tolerated, and accurate method of frameless navigation for the awake patient undergoing craniotomy.

Laparoscopic pyeloplasty has become a viable option for the treatment of select patients with primary ureteropelvic junction obstruction with success rates similar to those of open surgery. However, little has been written on the application of this technique for secondary ureteropelvic junction obstruction. We report the largest series of secondary ureteropelvic junction obstruction managed by laparoscopic pyeloplasty.Between March 1994 and March 2001, 36 patients underwent laparoscopic transperitoneal pyeloplasty for secondary ureteropelvic junction obstruction. The patients had undergone an average of 1.3 ureteropelvic junction procedures (range 1 to 4) prior to presentation, including cutting balloon retrograde endopyelotomy in 28, antegrade endoscopic endopyelotomy in 7, retrograde endoscopic endopyelotomy in 4, retrograde balloon dilation in 4 and open pyeloplasty in 3. A preoperative diagnosis of recurrent obstruction was confirmed by renal scan in 31 cases, retrograde pyelography in 2 and computerized tomography in 3. Of the 31 patients who underwent spiral computerized tomography angiogram 87% had crossing vessels. Laparoscopic repair comprised dismembered pyeloplasty in 31 cases, Fengerplasty in 3 and flap repair in 2. Postoperative renal scan or excretory urography objective followup was available for all patients at a mean of 10 months (range 3 to 40). Postoperative subjective patient well-being was assessed using an analog pain scale at a mean followup of 21.8 months (range 3 to 85).Average operative time was 6.2 hours (range 2.7 to 10). Average hospital stay was 2.9 days (range 1 to 7). One intraoperative complication occurred, that is bleeding necessitating conversion to an open procedure. Postoperative complications occurred in 8 cases, including anastomotic leakage in 4, and urinary tract infection, pneumonia, atelectasis, fever, bilateral upper extremity weakness and stone formation 2 months postoperatively in 1 each. On excretory urography, furosemide renal scan or the Whitaker test 32 of 36 patients (89%) had a widely patent ureteropelvic junction. Two patients (5.5%) had equivocal radiographic studies but were asymptomatic. In 2 patients the ureteropelvic junction was obstructed by renal scan. One patient had an indwelling stent for renal function deterioration and 1 was asymptomatic. Hence, 34 of the 36 patients (94%) had a reasonable objective response. Overall a 50% or greater decrease in pain was seen in 32 of 36 patients (89%). In the 4 patients with a less than 50% decrease in pain objective renal scans showed an open ureteropelvic junction. As such, the overall success rate of a greater than 50% decrease in pain, a patent ureteropelvic junction and stable or improved function of the affected renal unit was 83% (30 of 36 patients).For secondary ureteropelvic junction obstruction, laparoscopic pyeloplasty can be performed safely with a success rate comparable to that of standard open pyeloplasty. The patient benefits of laparoscopic ureteropelvic junction repair of secondary ureteropelvic junction obstruction are similar to the benefits of laparoscopic repair of primary ureteropelvic junction obstruction.

Context Patients with symptomatic atherosclerotic internal carotid artery occlusion (AICAO) and hemodynamic cerebral ischemia are at high risk for subsequent stroke when treated medically. Objective To test the hypothesis that extracranial-intracranial (EC-IC) bypass surgery, added to best medical therapy, reduces subsequent ipsilateral ischemic stroke in patients with recently symptomatic AICAO and hemodynamic cerebral ischemia. Design Parallel-group, randomized, open-label, blinded-adjudication clinical treatment trial conducted from 2002 to 2010. Setting Forty-nine clinical centers and 18 positron emission tomography (PET) centers in the United States and Canada. The majority were academic medical centers. Participants Patients with arteriographically confirmed AICAO causing hemispheric symptoms within 120 days and hemodynamic cerebral ischemia identified by ipsilateral increased oxygen extraction fraction measured by PET. Of 195 patients who were randomized, 97 were randomized to receive surgery and 98 to no surgery. Follow-up for the primary end point until occurrence, 2 years, or termination of trial was 99% complete. No participant withdrew because of adverse events. Interventions Anastomosis of superficial temporal artery branch to a middle cerebral artery cortical branch for the surgical group. Antithrombotic therapy and risk factor intervention were recommended for all participants. Main Outcome Measure For all participants who were assigned to surgery and received surgery, the combination of (1) all stroke and death from surgery through 30 days after surgery and (2) ipsilateral ischemic stroke within 2 years of randomization. For the nonsurgical group and participants assigned to surgery who did not receive surgery, the combination of (1) all stroke and death from randomization to randomization plus 30 days and (2) ipsilateral ischemic stroke within 2 years of randomization. Results The trial was terminated early for futility. Two-year rates for the primary end point were 21.0% (95% CI, 12.8% to 29.2%; 20 events) for the surgical group and 22.7% (95% CI, 13.9% to 31.6%; 20 events) for the nonsurgical group (P = .78, Z test), a difference of 1.7% (95% CI, −10.4% to 13.8%). Thirty-day rates for ipsilateral ischemic stroke were 14.4% (14/97) in the surgical group and 2.0% (2/98) in the nonsurgical group, a difference of 12.4% (95% CI, 4.9% to 19.9%). Conclusion Among participants with recently symptomatic AICAO and hemodynamic cerebral ischemia, EC-IC bypass surgery plus medical therapy compared with medical therapy alone did not reduce the risk of recurrent ipsilateral ischemic stroke at 2 years. Trial Registration clinicaltrials.gov Identifier: NCT00029146

Using nonabsorbable titanium staples in the lower urinary tract during laparoscopic nephroureterectomy has been shown to be safe. Laboratory studies of titanium staples in the upper urinary tract have likewise been favorable. Therefore, we used titanium Endo-GIA tissue staples (United States Surgical, Norwalk, Connecticut) to facilitate laparoscopic reduction pelvioplasty during laparoscopic pyeloplasty.Of the 17 cases of reduction pelvioplasty closure was done in 12 using absorbable sutures, while in 5 reduction was done with an Endo-GIA stapler. Followup consisted of office visits and telephone interviews plus radionuclide renal scans.Average operative time was 5.5 hours in the Endo-GIA group compared with 6.8 hours in the sutured group. In the latter group extravasation in 2 patients postoperatively was managed conservatively. There was no extravasation in the stapled group. At a median subjective followup of 27 months none of the 5 patients who underwent reduction with titanium staples had symptomatic nephrolithiasis, although new onset urolithiasis developed in 1 in the sutured group. All patients had a greater than 50% decrease in pain. Renal scans at a median of 9 months showed that all ureteropelvic junction repairs were unobstructed. Additional radiographic studies in 2 patients in the stapled group showed a patent ureteropelvic junction and no stones.Titanium staples provide rapid, secure closure of the renal pelvis during laparoscopic pyeloplasty. While the risk of stone formation is an ongoing concern, it has yet to materialize.

Iatrogenic diaphragmatic injury during laparoscopy has necessitated intracorporeal suturing and occasionally thoracostomy tube placement. We describe a technique to repair the diaphragm quickly using a novel gelatin thrombin matrix. The matrix can be administered through a trocar or hand-assist device and can rapidly seal small injuries, obviating the need for formal suture repair. The presented case and technique should be considered in selected small diaphragmatic injuries.

Object. Ischemic stroke or transient ischemic attack (TIA) may occur after the treatment of intracranial aneurysms with Guglielmi detachable coils (GDCs). The purpose of the present study is to investigate possible risk factors for thromboembolic events and to determine their frequency and time course. Methods. The records of 178 consecutive patients with 193 treated intracranial saccular aneurysms were reviewed. A total of 159 GDC procedures were performed to treat 143 aneurysms in 133 of those patients who were in good neurological condition, allowing clinical detection of postprocedure ischemic events (TIA or stroke). The association of clinical, anatomical, and pharmacological factors with intraprocedure intraarterial thrombus and with postprocedure ischemic events was investigated by using uni- and multivariate analyses. Thrombus protruding into the parent artery was noted during six of 159 GDC procedures, resulting in a clinical deficit in one patient. No factor was associated with intraprocedure intraarterial thrombus. Ten postprocedure ischemic events occurred in nine patients. Seven events occurred within 24 hours, and three events occurred between 24 hours and 58 days. Aneurysm diameter and protruding coils were significant independent predictors of postprocedure ischemic events in multivariate analysis (both p = 0.02). The actuarial risk of stroke was 3.8%. Conclusions. Larger aneurysm diameter and protruding loops of coils are associated with postprocedure ischemic events after GDC placement. It is unlikely that GDC-treated aneurysms retain thromboembolic potential beyond 2 months.

298 Background: Level 1 evidence supports a survival benefit for BlCa pts that receive periop cisplatin chemotherapy in addition to radical cystectomy (RC). Underutilization of multimodal therapy has been reported nationally. We instituted a multicenter QCI to improve the use of periop chemotherapy. Methods: A two phase effort was initiated at 16 academic institutions. Phase 1 was initiated in 2010 and designed to evaluate baseline patterns of periop chemotherapy use for T2-4N0M0 BlCa pts that underwent RC between 2003-2008. Phase 2 was a prospective QCI. The quality indicators included (1) referral to medical oncology for consideration of multimodality therapy, (2) neoadjuvant, if recommended, be cisplatin based and at least 3 cycles, (3) adjuvant, if recommended, be cisplatin based and at least 3 cycles, (4) all treatment be completed within 6 months. Data on all eligible pts were collected prospectively for 12 months on a web-based survey system. Results: All 16 centers participated in phase 1. Of 4,344 pts on whom data was available, 34% received periop chemotherapy. Neoadjuvant and adjuvant therapy use was 14% and 20%, respectively. 65% of pts receiving periop chemotherapy were treated with a cisplatin-based regimen. Of those treated neoadjuvantly, cisplatin was received in 70% of cases. Nine of the 16 institutions completed phase 2 data collection. Over 700 pts that underwent RC were evaluated. 395 pts with T2-4N0M0 disease were deemed eligible for data entry. Fifty-six percent of eligible pts received periop systemic chemotherapy. Of this 56%, 47% received neoadjuvant cisplatin chemotherapy and 9% received adjuvant cisplatin chemotherapy. This represented a 64.7% increase in the use of any periop chemotherapy and a 3.4 fold increase in neoadjuvant chemotherapy compared to baseline data. Conclusions: We have successfully completed a multi-institutional QCI to improve the use of periop chemotherapy in pts undergoing RC for resectable, non-metastatic bladder cancer. Our data demonstrates that significant improvements can be achieved in not only overall use of periop chemotherapy but most notably in the use of neoadjuvant chemotherapy.

Object. Hyperventilation has been used for many years in the management of patients with traumatic brain injury (TBI). Concern has been raised that hyperventilation could lead to cerebral ischemia; these concerns have been magnified by reports of reduced cerebral blood flow (CBF) early after severe TBI. The authors tested the hypothesis that moderate hyperventilation induced early after TBI would not produce a reduction in CBF severe enough to cause cerebral energy failure (CBF that is insufficient to meet metabolic needs).Methods. Nine patients were studied a mean of 11.2 ± 1.6 hours (range 8–14 hours) after TBI occurred. The patients' mean Glasgow Coma Scale score was 5.6 ± 1.8 and their mean age 27 ± 9 years; eight of the patients were male. Intracranial pressure (ICP), mean arterial blood pressure, and jugular venous oxygen content were monitored and cerebral perfusion pressure was maintained at a level higher than 70 mm Hg by using vasopressors when needed. Measurements of CBF, cerebral blood volume (CBV), cerebral metabolic rate for oxygen (CMRO2), oxygen extraction fraction (OEF), and cerebral venous oxygen content (CvO2) were made before and after 30 minutes of hyperventilation to a PaCO2 of 30 ± 2 mm Hg. Ten age-matched healthy volunteers were used as normocapnic controls.Global CBF, CBV, and CvO2 did not differ between the two groups, but in the TBI patients CMRO2 and OEF were reduced (1.59 ± 0.44 ml/100 g/minute [p < 0.01] and 0.31 ± 0.06 [p < 0.0001], respectively). During hyperventilation, global CBF decreased to 25.5 ± 8.7 ml/100 g/minute (p < 0.0009), CBV fell to 2.8 ± 0.56 ml/100 g (p < 0.001), OEF rose to 0.45 ± 0.13 (p < 0.02), and CvO2 fell to 8.3 ± 3 vol% (p < 0.02); CMRO2 remained unchanged.Conclusions. The authors conclude that early, brief, moderate hyperventilation does not impair global cerebral metabolism in patients with severe TBI and, thus, is unlikely to cause further neurological injury. Additional studies are needed to assess focal changes, the effects of more severe hyperventilation, and the effects of hyperventilation in the setting of increased ICP.

Background and Purpose —Misery perfusion, identified by increased oxygen extraction fraction (OEF), predicts subsequent stroke in patients with carotid occlusion. The purpose of this investigation was to determine the relationship of angiographic findings to increased OEF in these patients. Methods —Forty-seven patients with carotid occlusion were studied with cerebral angiography and positron emission tomography (PET). The following angiographic data were collected blind to PET results: (1) pial collateralization, defined as retrograde filling of the MCA branches to the level of the insula; (2) presence of border zone shift; (3) presence of delayed venous phase; and (4) measurement of posterior communicating artery size. Patients were divided into 2 groups based on the PET measurement of normal or increased OEF. Results —Seventeen of 47 patients had increased OEF distal to the occluded carotid artery. No significant relationship between increased OEF and any angiographic finding was found. Pial collateralization was present in only 2 patients, both with increased OEF ( P =0.105). Border zone shift was equally distributed between the 2 groups (12 of 30 with normal OEF and 6 of 15 with increased OEF). Delayed venous phase was present in 4 patients, 3 of whom had increased OEF ( P =0.073). The relationship between the size of the posterior communicating artery and OEF was not significant by linear regression analysis ( P =0.242). Conclusions —With the possible but infrequent exceptions of delayed venous phase and pial collateralization, anatomic findings made on routine angiographic studies of patients with carotid occlusion do not correlate with increased OEF.

Background and Purpose —The purpose of this experiment was to assess long-term cerebral hemodynamic and metabolic changes in patients with increased oxygen extraction fraction (OEF) in the hemisphere distal to an occluded carotid artery who remain free of stroke. Methods —Ten patients with increased OEF and no interval stroke underwent repeated positron emission tomography examinations 12 to 59 months after the initial examination. Quantitative regional measurements of cerebral blood flow, cerebral blood volume, cerebral rate of oxygen metabolism (CMRO 2 ), and OEF were obtained. Regional measurements of the cerebral rate of glucose metabolism (CMRGlc) were made on follow-up in 5 patients. Statistical significance ( P t tests and linear regression analysis. Results —The ipsilateral/contralateral OEF ratio declined from a mean of 1.16 to 1.08 ( P =0.022). Greater reductions were seen with longer duration of follow-up ( P =0.023, r =0.707). The cerebral blood flow ratio improved from 0.81 to 0.85 ( P =0.021). No change in cerebral blood volume or CMRO 2 was observed. CMRGlc was reduced in the ipsilateral hemisphere ( P =0.001 compared with normal), but the CMRO 2 /CMRGlc ratio was normal. Conclusions —Increased OEF improves in patients with carotid occlusion and no interval stroke. This improvement in OEF is due to an improvement in collateral blood flow.

Technical advances in accessing the lateral cranial base have permitted disease in this area previously deemed inoperable to be resected. The procedures required to effect an oncologically adequate resection are often long and accompanied by the potential for serious, even life-threatening, complications. Although it has been demonstrated that such disease can be extirpated, the question of whether such heroic surgery improves long-term survival remains unanswered. We retrospectively reviewed the records of 25 patients who underwent a combination of frontotemporal craniotomy with other, more conventional, anterolateral procedures (eg, infratemporal fossa approach, maxillectomy, orbitectomy, mandibulopharyngectomy) to resect stage IV malignant disease of the lateral to midcranial base between 1983 and 1990. Perioperative deaths occurred in 2 patients, 1 patient died of unrelated causes free of disease, and 2 patients were lost to follow-up, leaving 20 patients with a minimum 5-year evaluation. Five (25%) of the 20 patients we monitored were free of disease. Of those patients in whom recurrent disease developed, local control was achieved in about 50%; however in 80% of those with recurrence, metastatic disease developed. Surgical treatment of selected stage IV malignant disease of the lateral to midcranial base appears to have provided long-term disease-free survival to 25% of patients in this series who would otherwise have had little hope of survival. (Otolaryngol Head Neck Surg 1999;120:17-24.)

✓ This 52-year-old woman developed crystal deposition disease involving the cervical vertebrae. She presented with symptomatic spinal cord compression secondary to extensive calcified lesions in the posterior elements of the cervical spine. Surgical decompression with posterior fusion was performed. Histological examination showed hardened deposits of calcium carbonate involving the soft tissue, and dissolution of the vertebral bone trabeculae. There was no inflammatory response to these deposits. One year postoperatively the patient developed severe pulmonary disease associated with the collagen-vascular disorder, scleroderma (calcinosis, Raynaud's phenomenon, esophageal hypomotility, sclerodactyly, and telangiectasia [CREST] syndrome). Calcium carbonate deposition disease represents an unusual clinical entity that is possibly associated with scleroderma or other collagen-vascular diseases, and it is distinct from ligamentum flavum calcification, calcium pyrophosphate deposition disease, and hydroxyapatite deposition disease.

OBJECTIVE The cerebral hemodynamic and metabolic effects of aneurysmal subarachnoid hemorrhage are complex. To investigate the impact of surgical retraction, we analyzed position emission tomography (PET) studies that measured the regional cerebral metabolic rate for oxygen, regional oxygen extraction fraction, and regional cerebral blood flow in four patients before and after right frontotemporal craniotomies for clipping of ruptured anterior circulation aneurysms. METHODS Preoperative studies were conducted 1 day before surgery and postoperative studies 6 to 17 days after surgery. No patient had hydrocephalus or intracerebral hematoma. At the time of the second PET study, none of the patients had signs of clinical vasospasm. Regional measurements were obtained from the right ventrolateral frontal and anterior temporal regions corresponding to the area of retraction and compared to the same regions in the opposite hemisphere. To establish a quantitative means to differentiate between hemodynamic and metabolic changes related to arterial vasospasm and those caused by brain retraction, we studied a second group of preoperative patients, who had undergone PET during angiographic and clinical vasospasm. RESULTS There was a 45% reduction in regional cerebral metabolic rate for oxygen (1.87 +/- 0.22 to 1.04 +/- 0.28 ml 100 g-1 min-1) and 32% reduction in regional oxygen extraction fraction (0.41 +/- 0.04 to 0.28 +/- 0.03) in the region of retraction but no change in the opposite hemisphere (paired t test; P = 0.042 and 0.003, respectively). There was no change in regional cerebral blood flow in any region. Brain retraction produced a focal area of tissue injury at the site of retractor blade placement, as compared to more diffuse vascular territory changes produced by vasospasm. CONCLUSION This reduction in the cerebral metabolic rate of oxygen and the oxygen extraction fraction indicates a primary reduction in metabolism and uncoupling of flow and metabolism (luxury perfusion). Similar findings of luxury perfusion have been reported after ischemic stroke and traumatic brain injury. Further studies will be necessary to fully understand the clinical and pathophysiological significance of these observations.

Introduction and Objective: Existing epidemiologic data do not support an association between circulating levels of sex steroid hormones and risk of prostate cancer. Although it has been suggested that the combined action of androgens and estrogens'specifically their balance'may play a key role in prostate carcinogenesis, epidemiologic studies to evaluate this hypothesis are sparse, have assessed a limited number of sex steroid hormones, and have provided inconsistent results. We investigated associations between serum sex hormones'with a particular focus on estrogen metabolites'and risk of aggressive prostate cancer. Study Population, Design and Methods: In a case-control study nested within the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, we measured 15 parent serum estrogens (estrone and estradiol) and estrogen metabolites, including those in the C-2, -4, or 16 hydroxylation pathways, using a liquid chromatography-tandem mass spectrometry (LC/MS/MS) assay. Cases (n=195) were defined as non-Hispanic white men diagnosed with aggressive prostate cancer (stage III or IV and/or Gleason ≥7) between and 1994 and 2009 who were 55–70 years at diagnosis. Controls (n=195) were non-Hispanic white men who were free from prostate cancer for the duration of follow-up and frequency-matched to cases by age at study entry (5-yr intervals), time since baseline screen (1-yr time windows) and year of blood draw. Only cases and controls included in a previous study that measured serum androgens and sex-hormone binding globulin (SHBG) were eligible. Logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (95%CI). Results: Individual parent estrogens and individual estrogen metabolites were unrelated to risk of aggressive prostate cancer; with the exception of a non-linear inverse relationship between cancer and levels of methylated catechols, namely 2- and 4-methoxyestrone. However, there was an increased risk of aggressive prostate cancer associated with an increasing ratio of 2:16 hydroxyestrone (fourth vs. first quartile: OR 2.44, 95% CI 1.34–4.45, p trend=0.001) and a strong trend of decreasing prostate cancer risk with an increasing ratio of estradiol to testosterone (fourth vs. first quartile: OR 0.27, 95% CI 0.12–0.59, p trend=0.003). Conclusion: We observed a strong protective effect of higher serum estradiol to testosterone levels in relation to risk of aggressive prostate cancer. Men with higher concentrations of methylated catechols in the 2- and 4-hydroxylation pathway may have a reduced risk of aggressive prostate cancer, while those with higher ratios of 2:16 hydroxyestrone may be at increased risk. These findings suggest a role for sex steroid hormone metabolism in prostate carcinogenesis. Citation Format: Amanda Black, Paul F. Pinsky, Robert L. Grubb, III, Roni T. Falk, Ann W. Hsing, Lisa W. Chu, Tamra E. Meyer, Tim Veenstra, Xia Xu, Kai Yu, Louise A. Brinton, Robert N. Hoover, Michael B. Cook. Estrogen metabolism in relation to the risk of aggressive prostate cancer. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr A53.

4594 Background: The survival benefit with neoadjuvant chemotherapy for bladder cancer was established in 2003. However, adoption of this paradigm in clinical practice has been slow. We explored the use of neoadjuvant chemotherapy and identified predictors of its use in a contemporary cohort in the Veterans Health Administration (VA). Methods: Using the national VA Clinical Cancer Registry, all patients diagnosed with clinical stage T2-4, N0 or Nx, M0 bladder cancer from 1997 to 2007 were stratified into surgically (radical cystectomy [RC], n=1,211) and nonsurgically managed groups (n=2,125). Receipt of neoadjuvant chemotherapy was defined as chemotherapy treatment up to 6 months before RC as well as initial treatment only with chemotherapy (without subsequent surgery or radiation) in the nonsurgical group. Temporal trends in neoadjuvant chemotherapy use were evaluated with a chi square test. Predictors of neoadjuvant chemotherapy were examined using a multivariable logistic regression model incorporating demographic, socioeconomic, comorbid, pathologic and hospital factors. Results: 6.3% and 8.3% of patients received neoadjuvant chemotherapy in the surgical and non-surgical group, respectively. Analysis of temporal trends in chemotherapy use demonstrated an increase in neoadjuvant chemotherapy use over time (p

113 Background: Multiple definitions of high risk prostate cancer exist. Studies have primarily correlated these definitions with biochemical recurrence and not with survival. We applied six previously described high risk definitions to men treated with radical prostatectomy and evaluated their ability to predict survival outcomes in a multi-institutional cohort. Methods: The study population included 6477 men treated with radical prostatectomy between 1995 and 2005 and followed for a median of 67 months. The six high risk definitions were 1) preoperative PSA≥20ng/ml, 2) biopsy Gleason score 8-10, 3) clinical stage≥T2c, 4) clinical stage T3, 5) D’Amico definition, or 6) National Comprehensive Cancer Network definition. Survival was evaluated with the Kaplan-Meier method to generate unadjusted prostate cancer survival estimates. To control for the competing risks of age and comorbidity, multivariable Cox proportional hazard regression models were used to estimate the hazard ratio for prostate cancer specific mortality (PCSM) and overall mortality (OM) in high risk patients compared to low/intermediate risk. Results: High risk patients comprised between 0.7% (cT3) and 8.2% (D’Amico) of the study population. The 10-year Kaplan Meier prostate cancer survival estimates varied from 89.7% for PSA≥20 to 69.7% for cT3. On multivariable analysis controlling for age and comorbidity, high risk prostate cancer (of all definitions) had an increased risk of PCSM compared to low/intermediate risk with a hazard ratio (HR) ranging from 4.38 for PSA≥20 to 19.97 for cT3 (all p Conclusions: In a contemporary cohort of men with high risk prostate cancer treated with radical prostatectomy, the majority of men experienced long term prostate cancer survival. However, heterogeneity in survival outcomes existed based on the definition of high risk used. Clinical stage T3 and high Gleason score were most strongly associated with PCSM and OM.

73 Background: Analysis from population-based cancer registry data has suggested that being married is associated with improved survival in men with prostate cancer. However, a limitation of such analysis is the inability to control for PSA or medical comorbidity which may differ by marital status. We investigated the association between marital status and both prostate cancer specific mortality (PCSM) and overall mortality (OM) in men treated with radical prostatectomy. Methods: The study population included 3596 men treated with radical prostatectomy at a single institution between 1994 and 2004 and followed for a median of 72 months. Disease specific factors (PSA, clinical stage, and biopsy Gleason grade), comorbidity (validated ACE-27 comorbidity index), ethnicity, age, and marital status at time of treatment were retrieved from an institutional cancer registry. Differences between marital status groups were evaluated by Chi square or ANOVA. Multivariable Cox proportional hazard regression models were used to estimate the hazard ratio (HR) of PCSM and OM by marital status. Results: 86.9% of men were married, 5.3% divorced, 2.4% widowed, and 5.5% never married. Marital status was associated with differences in PSA (p Conclusions: Never married men had an increased risk of PCSM and OM. Factors associated with social isolation or unhealthy behaviors may have a detrimental effect on survival after prostatectomy. [Table: see text]

Cerebrospinal fluid fistula into the upper airway often results in meningitis. Closure of fistulas is usually effective using conventional surgical techniques to reconstruct the defect. We report a case of cerebrospinal fluid fistula into the sphenoid sinus and nasopharynx secondary to resection of a clivus chordoma that resisted conventional attempts at closure, including a rectus abdominus free flap. Closure of the fistula was accomplished with the use of a novel alloplast, biocompatible osteoconductive polymer. Follow-up for more than 1 year shows no evidence of rejection, infection, or recurrent cerebrospinal fluid rhinorrhea. (Arch Otolaryngol Head Neck Surg. 1994;120:459-461)