Search

© 2019 American Society for Surgery of the Hand Purpose: Current evidence on predictors of outcomes after distal radius fracture is often based on retrospective analyses or may be confounded by fracture type. Using data from the Wrist and Radius Injury Surgical Trial (WRIST), a 24-site randomized study of distal radius fracture treatment, in which all fractures are severe enough to warrant surgery, we set out to perform a secondary data analysis to explore predictors of better or worse hand outcomes. Methods: The primary outcome measure was the Michigan Hand Outcomes Questionnaire (MHQ) summary score 12 months after treatment. We used a regression tree analysis with recursive partitioning to identify subgroups of participants who experienced similar outcomes (ie, MHQ score) and to determine which baseline or treatment factors they had in common. Results: Factors most predictive of 12-month MHQ score were pain at enrollment, education, age, and number of comorbidities. Specifically, participants who had a high school education or less and also reported severe pain had the lowest MHQ scores. Conversely, participants with less pain and more education and who were age 87 years or younger with one or no comorbid condition had the highest MHQ scores. Treatment type or radiographic measurements assessed on post-reduction films did not affect 12-month outcomes. Conclusions: These results identified patient characteristics that can be used by surgeons to identify subgroups of patients who may experience similar hand outcomes. Type of study/level of evidence: Prognostic III.

This study was undertaken to evaluate radiation dosimetry for the prostate-specific membrane antigen targeted [68Ga]Ga-P16-093 radiopharmaceutical, and to initially assess agent performance in positron emission tomography (PET) detection of the site of disease in prostate cancer patients presenting with biochemical recurrence. Under IND 133,222 and an IRB-approved research protocol, we evaluated the biodistribution and pharmacokinetics of [68Ga]Ga-P16-093 with serial PET imaging following intravenous administration to ten prostate cancer patients with biochemical recurrence. The recruited subjects were all patients in whom a recent [68Ga]Ga-PSMA-11 PET/X-ray computed tomography (CT) exam had been independently performed under IND 131,806 to assist in decision-making with regard to their clinical care. Voided urine was collected from each subject at ~ 60 min and ~ 140 min post-[68Ga]Ga-P16-093 injection and assayed for Ga-68 content. Following image segmentation to extract tissue time-activity curves and corresponding cumulated activity values, radiation dosimetry estimates were calculated using IDAC Dose 2.1. The prior [68Ga]Ga-PSMA-11 PET/CT exam (whole-body PET imaging at 60 min post-injection, performed with contrast-enhanced diagnostic CT) served as a reference scan for comparison to the [68Ga]Ga-P16-093 findings. [68Ga]Ga-P16-093 PET images at 60 min post-injection provided diagnostic information that appeared equivalent to the subject’s prior [68Ga]Ga-PSMA-11 scan. With both radiopharmaceuticals, sites of tumor recurrence were found in eight of the ten patients, identifying 16 lesions. The site of recurrence was not detected with either agent for the other two subjects. Bladder activity was consistently lower with [68Ga]Ga-P16-093 than [68Ga]Ga-PSMA-11. The kidneys, spleen, salivary glands, and liver receive the highest radiation exposure from [68Ga]Ga-P16-093, with estimated doses of 1.7 × 10−1, 6.7 × 10−2, 6.5 × 10−2, and 5.6 × 10−2 mGy/MBq, respectively. The corresponding effective dose from [68Ga]Ga-P16-093 is 2.3 × 10−2 mSv/MBq. [68Ga]Ga-P16-093 provided diagnostic information that appeared equivalent to [68Ga]Ga-PSMA-11 in this limited series of ten prostate cancer patients presenting with biochemical recurrence, with the kidneys found to be the critical organ. Diminished tracer appearance in the urine represents a potential advantage of [68Ga]Ga-P16-093 over [68Ga]Ga-PSMA-11 for detection of lesions in the pelvis.

Introduction This study was performed to estimate the human radiation dosimetry for [ 68 Ga]Ga-HBED-CC (PSMA-11) ( 68 Ga PSMA-11). Methods Under an RDRC-approved research protocol, we evaluated the biodistribution and pharmacokinetics of 68 Ga PSMA-11 with serial PET imaging following intravenous administration to nine prostate cancer patients in whom clinical [ 11 C]acetate PET/CT exams had been independently performed under Expanded Access IND 118,204. List-mode imaging was performed over the initial 0–10min post-injection with the pelvis in the field-of-view. Whole-body images were acquired, pelvis-to-head, at 15, 60, and 90-min post-injection. Additional images of the pelvis were acquired at 40-min and 115-min, and voided urine collected from each subject at 48-min and 120-min post-injection. Radiation dosimetry estimates were calculated from these data using the OLINDA software package. Results Renal uptake was high and relatively invariant, ranging from 11% to 14% of the injected dose between 15 and 90-min post-injection. Radioactivity collected in the voided urine accounted for 14% of the injected dose over a period of 120-min. Lymph nodes and skeletal metastases suspicious for prostate cancer recurrence were detected in a greater number of patients using 68 Ga PSMA-11 than using 11 C-acetate. Conclusion Kidneys are the critical organ following 68 Ga PSMA-11 administration, receiving an estimated dose of 0.413mGy/MBq. Advances in knowledge and implications for patient care This study confirms that the kidneys will be the critical organ following intravenous administration of 68 Ga PSMA-11, and provided data consistent with the expectation that 68 Ga PSMA-11 will be superior to [ 11 C]acetate for defining sites of recurrence in prostate cancer patients presenting with biochemical relapse.

We evaluated which lesions are detected and missed on [Patients undergoing radical prostatectomy were enrolled in this prospective observational study. Patients underwent [On whole mount analysis 30 cancerous lesions were found in a total of 15 patients, including 4, 15, 4, 1 and 6 which were Grade Group 1, 2, 3, 4 and 5, respectively. PSMA-positron emission tomography detected 100% of primary/index lesions and 8 of 11 (82%) secondary lesions. All Grade Group 3-5 lesions were detected vs 12 of 15 Grade Group 2 lesions. When comparing Grade Group 2 vs 3-5, lesion size was similar (p=0.48) but the standardized uptake value was lower for Grade Group 2 vs 3-5 (5.3 vs 7.9, p=0.03). The 3 missed lesions showed 10% or less of pattern 4 and a Gleason pattern 4/5 volume of less than 0.1 cmPSMA positron emission tomography detected 100% of primary/index lesions in this study. The 3 missed secondary lesions were small and had a low percent of pattern 4. This argues for further study to better understand what defines clinically significant prostate cancer, which would assist in determining whether small lesions that become challenging to detect by [

[(68)Ga]Ga-DOTA-NOC was produced under an Expanded Access IND for 174 clinical PET/CT studies to evaluate patients with neuroendocrine tumors. Production employed either the TiO2-based EckertZiegler (EZAG) (68)Ge/(68)Ga-generator (with fractionated elution), or the SiO2-based ITG (68)Ge/(68)Ga-generator. In both cases, [(68)Ga]Ga-DOTA-NOC was reliably produced, without pre-synthesis purification of the(68)Ga generator eluate, using readily-implemented manual synthesis procedures. [(68)Ga]Ga-DOTA-NOC radiochemical purity averaged 99.2±0.4%. Administered (68)Ga dose averaged 181±22 MBq, and administered peptide mass averaged 43.2±5.2µg (n=47) and 23.9±5.7µg (n=127), respectively, using the EZAG and ITG generators. At dose expiration, (68)Ge breakthrough in the final product averaged 2.7×10(-7)% and 5.4×10(-5%) using the EZAG and ITG generators, respectively.

e19182 Background: Mortality within 30 days of chemotherapy is recognised as an important quality assurance measure. There is limited data regarding mortality within 30 days of immunotherapy and whether the same standards should apply. In contrast to chemotherapy, immunotherapy has a favourable toxicity profile and a higher chance of durable responses. We assess 3 years of data from two regional cancer centres in Queensland, Australia. Methods: Retrospective review of patients treated with checkpoint inhibitor immunotherapy at Cairns Hospital and Gold Cold University Hospital between June 2016 and June 2019. Results: 533 patients received immunotherapy and 59 (11.1%) died within 30 days of treatment. 25 patients died within 30 days of their first treatment (4.7%). Anti-PD-L1/PD-1 was more common than anti-CTLA-4 and combination treatment (84.7% v 1.7% v 13.6%). Median age was 65 years (range 37 – 87). Most patients were treated for non-small cell lung cancer (51%) and melanoma (36%). Poor prognostic features were prevalent: ECOG 3-4 (30%), brain metastases (34%), 3 sites of metastases (59%), and raised LDH (80%). Grade 3+ toxicity was uncommon (3.4%) and there were no treatment-related mortalities. Most patients died due to progressive disease. 67% died in hospital and 25% received acute treatment within 48 hours of their death. Most patients were known to palliative care (85%). Resuscitation plans were documented in 55% before their final treatment. Discussion regarding very poor prognosis was documented in 44%. Conclusions: Thirty-day mortality rates were similar to published data relating to chemotherapy and mortality within 30 days of initiating therapy was low. While there were few significant immune-related toxicities, a quarter of patients received acute treatment within 48 hours of their death. Most patients had documented resuscitation plans and were known to palliative care.

2084 Background: The Teleoncology model of care, as developed and implemented across health services in Far North Queensland (Australia), improves access to specialist oncology services, including telehealth supervised administration of Oncology drugs for patients in rural/remote towns. There is limited published data regarding the safety of checkpoint inhibitor immunotherapy when it is administered via Teleoncology. Aim: Evaluate safety of immunotherapy administration via Teleoncology, including immune-related adverse events (irAE), treatment delays, hospital admissions and interhospital transfers, in comparison to a retrospective control population. Methods: Retrospective review of all patients treated with immunotherapy via Teleoncology as part of Cairns and Hinterland Hospital and Health Service (CHHHS) and the Townsville Teleoncology Network (TTN) between January 2015 and April 2019. A retrospective cohort treated at Townsville Cancer Centre over the same time period was used as a control group. Results: Fifty-one patients received a total of 624 cycles of immunotherapy (all single agent anti-PD-1/L-1) via Teleoncology. The control population included 142 patients who received 1697 cycles of immunotherapy. Baseline characteristics were well matched between groups. Compared to the control population, patients treated via telehealth did not have statistically significant differences in the rate of Grade 3+ irAE (13.7% v 8%), hospital admissions (13.7% v 7.4%) or protocol suspensions due to immune toxicity (16% v 10%). One patient with Grade 3+ irAE required interhospital transfer for investigation and management, which occurred within 24 hours of presentation to hospital. There were no treatment-related mortalities in either group. Conclusions: Checkpoint inhibitor immunotherapy can safely be delivered using the Teleoncology model of care in rural and remote centres. The incidence of toxicity for single agent immunotherapy was predictably low and not significantly different between groups, however the numbers in this retrospective study were small. The time to recognition and management of immune mediated toxicity in rural and remote centres is an important factor that was not assessed in this study and will be considered in future work.

Purpose To characterize the distribution of absorbed radiation dose after glass microsphere radioembolization for hepatocellular carcinoma (HCC) using yttrium-90 ( 90 Y) positron emission tomography/computed tomography (PET/CT). Materials and Methods In this retrospective study, 64 90 Y PET/CT scans performed after treatment were evaluated following 90 Y glass-bead radioembolization in patients with advanced HCC. The intended dose to the target volume ranged from 83–129 Gy. Three-dimensional "dose maps" were created from reconstructed PET images using a voxel-based S-value transformation. Liver parenchyma and liver tumors were contoured on cross-sectional imaging and aligned with the created dose maps. Results There were 113 tumors examined as part of 64 lobar treatments. The average tumor size was 4.8 cm ± 4.0 with an average tumor dose of 173 Gy ± 109. The average dose to the nontumor parenchyma within the target volume was 93.4 Gy ± 32.6, with on average 50% of the parenchymal voxels receiving > 79 Gy ± 23 and 10% receiving > 173 Gy ± 55. The average and median tumor-to-parenchymal weighted dose ratios were 2.2 and 1.9, respectively. Conclusions Using recommended dosimetry and administration techniques for lobar glass microsphere radioembolization, high doses to target tumors as well as background parenchyma were achieved on average with modest preferential uptake within tumors. There was wide variation in measured tumor and parenchymal doses after hepatic radioembolization for HCC, suggesting the need for continued development of patient-specific dosimetry.

The performance of a commercially produced (62)Zn/(62)Cu microgenerator system, and an associated kit-based radiopharmaceutical synthesis method, was evaluated for clinical site production of [(62)Cu]Cu-ETS (ethylglyoxal bis(thiosemicarbazonato)copper(II)), an investigational agent for PET perfusion imaging. Using 37 generators, containing 1.84±0.23 GBq (62)Zn at 9:00 AM on the day of clinical use, a total of 45 patient doses of [(62)Cu]Cu-ETS (672±172 MBq) were delivered without difficulty. (62)Cu elution yields were high (approximately 90%), accompanied by extremely low (62)Zn breakthrough (

2572 Background: Immunosuppressive factors such as regulatory T cells (Tregs) and myeloid-derived suppressive cells (MDSCs) limit the efficacy of immunotherapies. Histone deacetylase (HDAC) inhibitors have been shown to have immunomodulatory effects. We have previously reported that HDAC inhibitors have synergistic antitumor effects in combination with PD-1 inhibition in tumor models by inhibiting the function of Tregs and MDSCs. Thus, we conducted a Phase Ib clinical study with the HDAC inhibitor vorinostat and the PD-1 inhibitor pembrolizumab in patients (pts) with metastatic urothelial, renal and prostate carcinoma. Methods: The primary objective was to evaluate the safety and tolerability of this combination strategy. The phase I portion consisted of two dose levels of vorinostat (100 and 200 mg, PO daily 2 weeks ON and one week OFF) and a fixed, standard dose of pembrolizumab (200 mg IV every 21 days). Patients were assigned to three cohorts: Cohort A (previously treated, anti-PD1/PD-L1 naïve urothelial and renal cancer pts = 15), Cohort B (previously treated, anti-PD1/PD-L1 resistant urothelial and renal cancer pts = 14), and Cohort C (prostate cancer pts = 14). Results: Dose levels 1 (4 enrolled, 3 evaluable) and 2 (4 enrolled, 3 evaluable) were completed without DLTs and 200 mg was the Phase II recommended dose for vorinostat. The most common resolved grade 3/4 toxicities were acute kidney injury (n = 1), anemia (n = 1), diarrhea (n = 1), and hypothyroidism (n = 1) in the dose expansion cohorts. We have enrolled 43 pts (37 evaluable) in the dose expansion cohorts. For Cohort A, B, and C the median PFS were 2.8 months, 5.2 months, and 3.5 months. Two PR were observed including the dose escalation phase. Two PCA pts have achieved undetectable PSA. We have performed several correlative studies including flow cytometry and gene expression analysis on peripheral blood mononuclear cells, PDL-1 staining and PSMA PET scans in a subset of pts. Conclusions: The results from this phase Ib suggest that the combination of vorinostat and pembrolizumab is relatively well tolerated and may be active in a subset of immune checkpoint resistant UC/RCC pts and immune checkpoint naïve PCA pts. Clinical trial information: NCT02619253.

e16567Background: Assessment of TP using 62Cu-ETS PET/CT has been demonstrated in pts with RCC (Fletcher et al, J Nuc Med 2015; 56:56-62, Logan et al, ASCO 2014; abstr 11110) compared to 15O-water ...

Purpose Routine assessment was made of tumor metabolic activity as measured by 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in Stage I non–small-cell lung cancer (NSCLC). This report describes PET correlates prospectively collected after stereotactic body radiotherapy (SBRT) for patients with medically inoperable NSCLC. Methods and Materials 14 consecutive patients with medically inoperable Stage I NSCLC were enrolled. All patients received SBRT to 60–66 Gy in three fractions. Patients underwent serial planned FDG-PET/computed tomography fusion imaging before SBRT and at 2, 26, and 52 weeks after SBRT. Results With median follow-up of 30.2 months, no patients experienced local failure. One patient developed regional failure, 1 developed distant failure, and 1 developed a second primary. The median tumor maximum standardized uptake value (SUV max ) before SBRT was 8.70. The median SUV max values at 2, 26, and 52 weeks after SBRT were 6.04, 2.80, and 3.58, respectively. Patients with low pre-SBRT SUV were more likely to experience initial 2-week rises in SUV, whereas patients with high pre-SBRT SUV commonly had SUV declines 2 weeks after treatment ( p = 0.036). Six of 13 patients had primary tumor SUV max >3.5 at 12 months after SBRT but remained without evidence of local disease failure on further follow-up. Conclusions A substantial proportion of patients may have moderately elevated FDG-PET SUV max at 12 months without evidence of local failure on further follow-up. Thus, slightly elevated PET SUV max should not be considered a surrogate for local treatment failure. Our data do not support routine serial FDG-PET/computed tomography for follow-up of patients receiving SBRT for Stage I NSCLC.

Background Pulmonary nodules are spherical radiographic opacities that measure up to 30 mm in diameter. Nodules are extremely common in clinical practice and challenging to manage, especially small, "subcentimeter" nodules. Identification of malignant nodules is important because they represent a potentially curable form of lung cancer. Methods We developed evidence-based clinical practice guidelines based on a systematic literature review and discussion with a large, multidisciplinary group of clinical experts and other stakeholders. Results We generated a list of 29 recommendations for managing the solitary pulmonary nodule (SPN) that measures at least 8 to 10 mm in diameter; small, subcentimeter nodules that measure Conclusion Patients with pulmonary nodules should be evaluated by estimation of the probability of malignancy, performance of imaging tests to characterize the lesion(s) better, evaluation of the risks associated with various management alternatives, and elicitation of patient preferences for treatment.

Purpose Surgical resection is standard therapy in stage I non–small-cell lung cancer (NSCLC); however, many patients are inoperable due to comorbid diseases. Building on a previously reported phase I trial, we carried out a prospective phase II trial using stereotactic body radiation therapy (SBRT) in this population. Patients and Methods Eligible patients included clinically staged T1 or T2 (≤ 7 cm), N0, M0, biopsy-confirmed NSCLC. All patients had comorbid medical problems that precluded lobectomy. SBRT treatment dose was 60 to 66 Gy total in three fractions during 1 to 2 weeks. Results All 70 patients enrolled completed therapy as planned and median follow-up was 17.5 months. The 3-month major response rate was 60%. Kaplan-Meier local control at 2 years was 95%. Altogether, 28 patients have died as a result of cancer (n = 5), treatment (n = 6), or comorbid illnesses (n = 17). Median overall survival was 32.6 months and 2-year overall survival was 54.7%. Grade 3 to 5 toxicity occurred in a total of 14 patients. Among patients experiencing toxicity, the median time to observation was 10.5 months. Patients treated for tumors in the peripheral lung had 2-year freedom from severe toxicity of 83% compared with only 54% for patients with central tumors. Conclusion High rates of local control are achieved with this SBRT regimen in medically inoperable patients with stage I NSCLC. Both local recurrence and toxicity occur late after this treatment. This regimen should not be used for patients with tumors near the central airways due to excessive toxicity.

Positron emission tomography (PET oxygen-15 labeled water or PET [15O]H2O) was used to identify changes in regional cerebral blood flow (rCBF) in response to acute vagus nerve stimulation (VNS) in four subjects with treatment-resistant major depression (TRMD). Four 90-s PET [15O]H2O scans were performed on each subject in an off-on sequence (2 VNS de-activated; 2 VNS activated). PET images were aligned, normalized for global uptake, and resampled to standard atlas space. Statistical t-images were used to evaluate change. VNS-induced increases in rCBF were found in the bilateral orbitofrontal cortex, bilateral anterior cingulate cortex, and right superior and medial frontal cortex. Decreases were found in the bilateral temporal cortex and right parietal area. Regions of change were consistent with brain structures associated with depression and the afferent pathways of the vagus nerve.

Background Diagnostic tests, particularly diagnostic imaging modalities such as computed tomography (CT) and positron emission tomography (PET), have the potential to make important contributions to improved patient care and medical decision making. The expense of these tests is justified to the extent that they improve diagnostic and treatment decisions, and ultimately health outcomes. Clinical studies evaluating the accuracy of diagnostic tests and assessing their influence on decision making are essential to setting health policy and directing patient care. Purpose We present the design and participant baseline characteristics of the Department of Veterans Affairs Cooperative Study 027 (Prospective Study of the Diagnostic Accuracy of 18F-Fluorodeoxyglucose (FDG) – Positron Emission Tomography (PET) Imaging in the Management of Patients with Solitary Pulmonary Nodules (SNAP). Methods SNAP is a prospective, multi-site diagnostic trial to evaluate the efficacy of PET and CT for characterizing solitary pulmonary nodules. The study incorporated an assessment of the impact of these imaging modalities on clinical decision making. Results Between January 1999 and June 2001, 10 SNAP sites enrolled 532 participants with a mean age of 66 years (SD ± 11.3), of whom 97.3% were male. A history of smoking was claimed by 93.6% of participants, with 45.7% of all participants smoking at time of enrollment. Those still smoking had an average exposure of 56.8 pack-years, while those who had quit smoking prior to enrollment had an exposure of 58.1 pack-years. Limitations The study design reduced most common biases, but some degree of selection bias and verification bias remained. We sought to minimize verification bias by use of a dual reference standard. Conclusion SNAP is a diagnostic test study that was designed to minimize bias and to assess a test's impact on clinical decision making, providing the kind of information most needed by clinicians and health policy makers.

This study was undertaken to demonstrate the feasibility of whole-body (62)Cu-ethylglyoxal bis(thiosemicarbazonato)copper(II) ((62)Cu-ETS) PET/CT tumor perfusion imaging in patients with metastatic renal carcinoma and to validate (62)Cu-ETS as a quantitative marker of tumor perfusion by direct comparison with (15)O-water perfusion imaging.PET/CT imaging of 10 subjects with stage IV renal cell cancer was performed after intravenous administration of (15)O-water (10-min dynamic list-mode study) with the heart and at least 1 tumor in the PET field of view, followed 10 min later by intravenous (62)Cu-ETS (6-min list-mode study). Whole-body (62)Cu imaging was then performed from 6 to 20 min at 2-3 min/bed position. Blood flow (K1) was quantified with both agents for normal and malignant tissues in the 21.7-cm dynamic field of view. The required arterial input functions were derived from the left atrium and, in the case of (62)Cu-ETS, corrected for partial decomposition of the agent by blood with data from an in vitro analysis using a sample of each patient's blood. This imaging protocol was repeated at an interval of 3-4 wk after initiation of a standard clinical treatment course of the antiangiogenic agent sunitinib.All subjects received the scheduled (62)Cu-ETS doses for the dynamic and subsequent whole-body PET/CT scans, but technical issues resulted in no baseline (15)O-water data for 2 subjects. Direct comparisons of the perfusion estimates for normal tissues and tumor metastases were made in 18 paired baseline and treatment studies (10 subjects; 8 baseline studies, 10 repeated studies during treatment). There was an excellent correlation between the blood flow estimates made with (62)Cu-ETS and (15)O-water for normal tissues (muscle, thyroid, myocardium) and malignant lesions (pulmonary nodules, bone lesions); the regression line was y = 0.85x + 0.15, R(2) = 0.83, for the 88 regions analyzed.(62)Cu-ETS provided high-quality whole-body PET/CT images, and (62)Cu-ETS measures of blood flow were highly and linearly correlated with (15)O-water-derived K1 values (mL(-1) ⋅ min(-1) ⋅ g). This tracer is suitable for use as a PET tracer of tumor perfusion in patients with metastatic renal cell carcinoma.

The anterolateral thigh flap is an extremely versatile flap first described in 1984. The flap is based on either a septocutaneous or musculocutaneous perforator of the descending branch of the lateral circumflex femoral system. It can be designed as a skin and subcutaneous flap, fasciocutaneous, or musculocutaneous flap. Furthermore, it can be harvested as a sensate flap by taking the lateral cutaneous nerve of the thigh. Technique for harvesting the flap is described in detail. Complications include flap failure and donor site morbidity. Due to its versatility, the anterolateral thigh flap is particularly useful for upper extremity reconstruction.

The key to achieving an excellent result following rhinoplasty lies in a strong fundamental knowledge of nasal anatomy. The purpose of this study was to analyze the anatomic and histologic relationship of the nose to the alar-facial crease. Fifteen cadaver noses were dissected and a total of thirty lower lateral cartilages were measured. Two fresh cadaver noses were fixed in neutral buffer formalin and embedded in paraffin. They were then sectioned into 6-mu coronal and sagittal sections and stained with hematoxylin and eosin, Eosin von Geison, and safranin to evaluate for collagen, elastin and muscle, respectively. Measurements of the lower lateral cartilages showed the average lateral crural height was 23.5 mm (+/- 2.5 mm), lateral crus width was 11.7 mm (+/- 1.5 mm), lateral domal width was 5.7 mm (+/- 0.9 mm), and intercrural distance was 20.2 mm (+/- 3.2 mm). No statistical differences were noted between male and female cadaver measurements. Histologic sections showed the area of the alar-facial crease to have a greater quantity of elastin fibers compared with muscle, collagen, or cartilage. These elastin fibers were predominantly orientated vertically (anterior-posterior) rather than horizontally (cephalo-caudad). This study demonstrates a higher ratio of elastin to collagen fibers in the region of the alar-facial crease.

The finding of a solitary pulmonary nodule on a chest radiograph is a common problem in pulmonary medicine and is seen in about 1 in 500 chest radiographs. Of the benign lesions, 80% are infectious granulomas, 10% are hamartomas, and the remaining 10% are caused by a variety of rarer disorders including noninfectious granulomas and other benign tumors. The prevalence of malignancy ranges from 10% to 68% in the literature. Because of the high prevalence of malignancy and the poor survival for lung cancer, early detection, characterization, and directed treatment are important. Positron emission tomography with 18-Fluorodeoxyglucose (FDG-PET) can play an important role in the evaluation and management of solitary pulmonary nodules. This includes improved characterization of solitary pulmonary nodules with very high negative predictive value and improved staging information when performed in association with CT, especially for nodal staging and identification of unsuspected stage IV disease. PET also provides additional information for management of solitary pulmonary nodules by esitimating the probability of malignancy. Copyright 2002, Elsevier Science (USA). All rights reserved.

Accurate diagnosis of coronary heart disease has the potential to contribute substantially to cost-effective delivery of health services. Recent work by Fleischmann et al (JAMA 1998;280:913-20) represents an effort to summarize the accuracy of exercise echocardiography and exercise single photon emission computed tomography (SPECT).A critique of the previous work was constructed, obtaining the 44 articles used. These articles were reviewed and summarized with established techniques for meta-analysis. The studies summarized by Fleischmann et al were found to be significantly heterogeneous (echocardiography and SPECT, both P.001). In the SPECT cohort, combination of different radioisotopes and reading techniques, and inclusion of reports using experimental techniques, were sources of heterogeneity. In the echocardiography cohort, experimental techniques and an individual series were identified. When the sample was stratified for sources of heterogeneity, it was found that there was no significant difference in diagnostic accuracy between the echocardiography and SPECT techniques used in current clinical practice. Meta-regression with summary receiver operating characteristic curve techniques, after adjustment of the model for multicolinearity and outliers, revealed that there were no significant differences between SPECT as used in current clinical practice and echocardiography.The report by Fleischmann et al contains serious flaws that limit its validity and generalizability.

Myxoma is a rare benign tumor composed of stellate or spindle-shaped cells in a loose myxoid stroma. Few cases involving the hand have previously been described. We present a rare case of recurrent myxoma in the intermetacarpal space and detail the clinical behavior of this indolent tumor.

PURPOSE Solitary pulmonary nodules (SPNs) are commonly identified by chest radiographs and computed tomography (CT). Biopsies are often performed to evaluate the nodules further. An accurate, noninvasive diagnostic test could avoid the morbidity and costs of invasive tissue sampling. We evaluated the ability of fluorine-18 deoxyglucose positron emission tomography (FDG-PET) to discriminate between benign and malignant pulmonary nodules in a prospective, multicenter trial. METHODS Eighty-nine patients who had newly identified indeterminate SPNs on chest radiographs and CT were evaluated with FDG-PET. PET data were analyzed semiquantitatively by calculating standardized uptake values (SUVs) as an index of FDG accumulation and also by a visual scoring method. PET results were compared with pathology results. RESULTS Sixty SPNs were malignant and 29 were benign. Using SUV data, PET had an overall sensitivity and specificity for detection of malignant nodules of 92% and 90%. Visual analysis provided a slightly higher, but not statistically significant, sensitivity of 98% and lower specificity of 69%. For SPNs < or = 1.5 cm (34 of 89), the sensitivity and specificity of SUV and visual analysis were 80% and 95% and 100% and 74%, respectively. CONCLUSION FDG-PET can accurately characterize indeterminate SPNs. PET imaging provides a noninvasive method to evaluate indeterminate SPNs, which can reduce the need for invasive tissue biopsy.

This article will briefly review measures of accuracy for diagnostic tests. We will present valid, methodologically rigorous prospective clinical trial design features that avoid bias and that can generate high-quality evidence on the diagnostic accuracy of PET and its impact on diagnostic decision-making and therapeutic efficacy. Knowledge of the principles of Evidence-based Medicine, and an understanding of the key elements of designing a methodologically rigorous, prospective clinical trial will permit avoidance of the previous study design limitations and weaknesses of the existing literature on diagnostic imaging modalities. Published results of studies that are valid, obtained rapidly, and generalizable, will provide important support for the paradigm shift away from informal, opinion-driven decision-making in health care, toward a process that is evidence-based, rationale and considerate of our available resources and their most effective use in patient care.

Background [F-18]Fluorodeoxyglucose (FDG)-positron emission tomography (PET) can measure the metabolic activity of tissues; FDG-PET may be able to predict response to chemotherapy by identifying changes in tumor metabolism. Measurement of response to treatment may help improve survival in the management of advanced head and neck cancer. We evaluated this particular use of FDG-PET in patients participating in a neoadjuvant organ-preservation protocol using taxol and carboplatin and compared pathologic response after chemotherapy with changes in tumor metabolism measured by FDG-PET. Methods Serial FDG-PET studies (n = 56) were performed in patients (n = 28) with stage III/IV head and neck cancer participating in a neoadjuvant organ-preservation protocol. The FDG-PET studies were performed before and after chemotherapy. All patients had tissue biopsies before and after chemotherapy. Patients were classified as pathologic complete response (PCR) or residual disease (RD) based on tissue biopsies. Visual analysis of PET scans was performed to identify patients with complete response by PET, and these findings were compared with pathology results. Metabolic changes were also evaluated using standardized uptake ratios (SUR) of FDG. Results The sensitivity and specificity of PET for residual cancer after therapy was 90% (19/21) and 83% (5/6), respectively. Two patients had initially negative biopsies and positive PET studies for persistent disease. Pathology review and rebiospy led to confirmation of the PET results in these cases, giving a sensitivity of 90% for initial tissue biopsy. Conclusions In this preliminary analysis, FDG-PET was accurate in classifying response to chemotherapy in most patients. Fluorodeoxyglucose-PET may identify residual viable tumor when it is otherwise undetectable. © 1997 John Wiley & Sons, Inc. Head Neck19: 666–674, 1997.

Score Name Description T-MSBL-FP Mixed L2/L1 RIDGE ADAS ADAS total score 0.683 6 0.076 0.663 6 0.068 0.681 6 0.063 MMSE MMSE score 0.678 6 0.030 0.671 6 0.037 0.681 6 0.042 RAVLT-Total Total score of the first 5 trials 0.592 6 0.070 0.554 6 0.062 0.561 6 0.057 RAVLT-T30 30 minute delay # of words recalled 0.534 6 0.079 0.480 6 0.073 0.492 6 0.071 RAVLT-Recog 30 minute delay recognition score 0.512 6 0.089 0.451 6 0.054 0.470 6 0.055 TRAILSA Trail making A score 0.471 6 0.070 0.446 6 0.069 0.466 6 0.068 TRAILSB Trail making B score 0.584 6 0.104 0.561 6 0.111 0.566 6 0.108 TRAILS(B-A) TRAILSB TRAILSA 0.511 6 0.126 0.467 6 0.126 0.477 6 0.123 Alzheimer’s Imaging Consortium Poster Presentations: IC-P P63

Objectives To develop a method for assessing absolute renal function (as well as morphology) in children, using gamma camera imaging of intravenously injected technetium-99m (99mTc) dimercaptosuccinic acid (DMSA). Methods Forty-five children (ages 1 week to 10 years; mean, 2.0 years) were imaged using a planar technique in which not only the appearance but the absolute amount of intravenously administered 99mTc DMSA taken up by the kidneys was calculated for each child and compared with contemporaneous determinations of creatinine clearance. Results There was a close correlation between the absolute DMSA uptake and creatinine clearance ( r = 0.752). Conclusions Renal function in children, expressed as creatinine clearance, can be accurately estimated by measuring absolute DMSA uptake with planar gamma camera imaging using 99mTc DMSA.

300 Background: Detection of advanced prostate cancer has historically relied on radionuclide bone scanning and cross-sectional imaging with varying degrees of sensitivity and specificity based on the clinical scenario. In the current era, use of NaF and Choline based whole body scans have led to increased detection, but access to these scan can be limited and expense can be prohibitive. Similar to choline based scanning, acetate is metabolically active in cancer, including prostate. Methods: Fifty-six men previously diagnosed with prostate cancer with PSA recurrences after some failed primary treatment, have undergone whole body C-11 Acetate PET scans at Indiana University since June of 2013. Patient demographics, prior treatments, PSA values, prior imaging, post-scan therapies, and therapeutic outcomes have been recorded prospectively and updated as follow-up information becomes available. Results: Analysis of these initial 56 men demonstrated 31/56 men had a C-11 Acetate PET scan that lead to further definitive loco-regional treatments, including salvage radiation therapy ( 12), salvage regional lymph node dissection (11) and salvage cryo-ablation (8), while 9/56 men had initiation of hormonal ablation, secondary to detection of systemic disease. The remainder of these men had negative scans and are currently under continued active surveillance without evidence of disease progression requiring either loco-regional or systemic therapy. Closer analysis of the 31 men who received loco-regional treatments revealed 10 men who benefited with clear PSA declines, 4 men who failed to demonstrate a benefit from the definitive loco-regional therapy and 17 of men are too early to determine at the time of analysis. Careful pathological analysis of the regional lymph dissections revealed the limit of detection of the C-11 Acetate PET scan of greater than or equal to 3mm. Correlations of SUV readings of detected prostate cancer lesions with PSA kinetics, suggest importance of both PSA doubling time and absolute PSA value cutoffs. Conclusions: The C-11 Acetate PET scan is a useful adjunct to current imagining techniques and provides additional clinical information to guide clinicians caring for prostate cancer patients.

Summary Background Plexiform neurofibromas are slow-growing chemoradiotherapy-resistant tumours arising in patients with neurofibromatosis type 1 (NF1). Currently, there are no viable therapeutic options for patients with plexiform neurofibromas that cannot be surgically removed because of their proximity to vital body structures. We undertook an open-label phase 2 trial to test whether treatment with imatinib mesylate can decrease the volume burden of clinically significant plexiform neurofibromas in patients with NF1. Methods Eligible patients had to be aged 3–65 years, and to have NF1 and a clinically significant plexiform neurofibroma. Patients were treated with daily oral imatinib mesylate at 220 mg/m 2 twice a day for children and 400 mg twice a day for adults for 6 months. The primary endpoint was a 20% or more reduction in plexiform size by sequential volumetric MRI imaging. Clinical data were analysed on an intention-to-treat basis; a secondary analysis was also done for those patients able to take imatinib mesylate for 6 months. This trial is registered with ClinicalTrials.gov, number NCT01673009. Findings Six of 36 patients (17%, 95% CI 6–33), enrolled on an intention-to-treat basis, had an objective response to imatinib mesylate, with a 20% or more decrease in tumour volume. Of the 23 patients who received imatinib mesylate for at least 6 months, six (26%, 95% CI 10–48) had a 20% or more decrease in volume of one or more plexiform tumours. The most common adverse events were skin rash (five patients) and oedema with weight gain (six). More serious adverse events included reversible grade 3 neutropenia (two), grade 4 hyperglycaemia (one), and grade 4 increases in aminotransferase concentrations (one). Interpretation Imatinib mesylate could be used to treat plexiform neurofibromas in patients with NF1. A multi-institutional clinical trial is warranted to confirm these results. Funding Novartis Pharmaceuticals, the Indiana University Simon Cancer Centre, and the Indiana University Herman B Wells Center for Pediatric Research.

We present the case of a 42-year-old woman with myotonic dystrophy and thymoma. She was treated with combination chemotherapy followed by external beam radiation, and remains in remission 19 months after thymoma was diagnosed. The myotonic dystrophy is unchanged. Only six cases of this nature have been reported in the literature, and this patient is the first to be successfully treated with combined modality therapy.

BACKGROUND Tibia fractures may require soft tissue coverage with transposed tissue and can develop nonunions. Tibial defects can be approached with a posterolateral approach or by elevating the previously transposed tissue. No literature has previously reported the efficacy or safety of the latter approach. The purpose of this study was to report the flap survival rate and complications from delayed elevation of transposed soft tissue as part of a protocol for the treatment of tibia nonunions. METHODS In a retrospective review of patients having local, regional, or free soft tissue transposition for the management of open type III B high-energy tibial fractures and also requiring secondary procedures on the same tibia for treatment of tibial nonunion and/or osteomyelitis that required flap elevation, 23 patients with 24 flaps were identified and studied. The 24 flaps were elevated a total of 72 times as part of a staged protocol for nonunion reconstruction by a single surgeon. Primary end point was flap survival. Mean follow-up after definitive soft tissue coverage was 23.7 months. Mean follow-up after injury was 28.9 months. RESULTS One flap failed after elevation. On a per elevation surgery basis, the flap survival rate was 98.6% (71 of 72). On a per flap basis, the flap survival rate was 95.8% (23 of 24). CONCLUSIONS This is the first report of the survival and complication rates for delayed elevation of soft tissue flaps for tibial nonunion reconstruction. A total of 95.8% of flaps survived elevation. Flap elevation seems to be an alternative to posterolateral tibial approaches for treatment of tibial nonunions.

Purpose Objective assessment of technical skills in hand surgery has been lacking. This article reports on an Objective Structured Assessment of Technical Skills format of a multiple bench-station evaluation of orthopedic surgery residents' technical skills for 3 common upper extremity surgeries. Methods Twenty-seven residents (6 postgraduate year [PGY] 2, 8 PGY 3, 8 PGY 4, and 5 PGY 5) participated in the examination. Each resident performed surgery on a cadaveric specimen at 3 stations, trigger finger release (TFR), open carpal tunnel release, and distal radius fracture fixation. A board-certified hand surgeon evaluated trainee performance at each station, using a procedure-specific detailed checklist, a validated global rating scale, and pass/fail assessment. A resident post-testing evaluation was collected. Results Construct validity with correlation between year in training and detailed checklist scores was demonstrated for TFR and carpal tunnel release; between year in training and global rating scores for TFR and distal radius fracture fixation; and between year in training and pass/fail assessment for TFR. Criterion validity was demonstrated by the correlation between global rating scale scores, detailed checklist scores, and pass/fail assessment for TFR, carpal tunnel release, and distal radius fracture fixation. Time to complete the surgery was not correlated with surgical performance. Residents rated the multiple-station Objective Structured Assessment of Technical Skills format as highly educational. Conclusions This study reports that a surgeon's ability to release a trigger finger does not correlate specifically to his or her ability to perform a carpal tunnel release or to perform plate fixation of a radius fracture. The results of this study would indicate that, for 3 different surgical simulations representing procedures of varying complexity, assessments by a single assessment tool is not adequate. To completely understand a resident's abilities, assessment by checklist (understanding the steps of the surgery), global rating scales (assessment of basic surgical skills in light of lesser or greater complexity surgeries), and pass/fail assessment (examination of adverse events) are all necessary components. Type of study/level of evidence Therapeutic II.

The use of standardized uptake values (SUVs) is now common place in clinical 2-deoxy-2-[ 18 F] fluoro-D-glucose (FDG) position emission tomography-computed tomography oncology imaging and has a specific role in assessing patient response to cancer therapy. Ideally, the use of SUVs removes variability introduced by differences in patient size and the amount of injected FDG. However, in practice there are several sources of bias and variance that are introduced in the measurement of FDG uptake in tumors and also in the conversion of the image count data to SUVs. In this article the overall imaging process is reviewed and estimates of the magnitude of errors, where known, are given. Recommendations are provided for best practices in improving SUV accuracy.

The rationale was to develop recommendations on the use of 18F-FDG PET in breast, colorectal, esophageal, head and neck, lung, pancreatic, and thyroid cancer; lymphoma, melanoma, and sarcoma; and unknown primary tumor. Outcomes of interest included the use of 18F-FDG PET for diagnosing, staging, and detecting the recurrence or progression of cancer. Methods: A search was performed to identify all published randomized controlled trials and systematic reviews in the literature. An additional search was performed to identify relevant unpublished systematic reviews. These publications comprised both retrospective and prospective studies of varied methodologic quality. The anticipated consequences of false-positive and false-negative tests when evaluating clinical usefulness, and the impact of 18F-FDG PET on the management of cancer patients, were also reviewed. Results and Conclusion:18F-FDG PET should be used as an imaging tool additional to conventional radiologic methods such as CT or MRI; any positive finding that could lead to a clinically significant change in patient management should be confirmed by subsequent histopathologic examination because of the risk of false-positive results. 18F-FDG PET should be used in the appropriate clinical setting for the diagnosis of head and neck, lung, or pancreatic cancer and for unknown primary tumor. PET is also indicated for staging of breast, colon, esophageal, head and neck, and lung cancer and of lymphoma and melanoma. In addition, 18F-FDG PET should be used to detect recurrence of breast, colorectal, head and neck, or thyroid cancer and of lymphoma.

CT and PET are widely used to characterize solitary pulmonary nodules (SPNs). However, most CT accuracy studies have been performed with outdated technology and methods, and previous PET studies have been limited by small sample sizes and incomplete masking. Our objective was to compare CT and PET accuracy in veterans with SPN.Between January 1999 and June 2001, we recruited 532 participants with SPNs newly diagnosed on radiography and untreated. The SPNs were 7-30 mm. All patients underwent (18)F-FDG PET and CT. A masked panel of 3 PET and 3 CT experts rated the studies on a 5-point scale. SPN tissue diagnosis or 2-y follow-up established the final diagnosis.A definitive diagnosis was established for 344 participants. The prevalence of malignancy was 53%. The average size was 16 mm. Likelihood ratios (LRs) for PET and CT results for combined ratings of either definitely benign (33% and 9% of patients, respectively) or probably benign (27% and 12%) were 0.10 and 0.11, respectively. LRs for PET and CT results for combined ratings of indeterminate (1% and 25%), probably malignant (21% and 39%), or definitely malignant (35% and 15%) were 5.18 and 1.61, respectively. Area under the receiver operating characteristic curve was 0.93 (95% confidence interval, 0.90-0.95) for PET and 0.82 (95% confidence interval, 0.77-0.86) for CT (P0.0001 for the difference). PET inter- and intraobserver reliability was superior to CT.Definitely and probably benign results on PET and CT strongly predict benign SPN. However, such results were 3 times more common with PET. Definitely malignant results on PET were much more predictive of malignancy than were these results on CT. A malignant final diagnosis was approximately 10 times more likely than a benign final diagnosis in participants with PET results rated definitely malignant.

The purpose of this research was to evaluate two sources of error in the performance of computerized tomography (CT) and magnetic resonance imaging (MRI) of the abdomen/pelvis. The sources of error assessed were inter- and intra-observer reliability. Thirty abdomen/pelvis CT scans were randomly selected from each of three hospitals (university, VA, military) with different CT scanners. Two radiologists were recruited from each site to be CT observers. Forty-five abdomen/pelvis MRI scans were randomly selected from two institutions with different MRI scanners. Four observers were recruited to read the MRI scans. All scans were read blind without clinical information or patient identification. Overall inter-observer and intra-observer diagnostic agreement was significantly higher for MRI compared to CT. Inter-observer diagnostic agreement rates were also significantly higher for MRI when the etiologies of neoplastic vascular and metabolic/toxic were assigned. Observer experience in CT (range: 5-9 yr) or MRI (range: 2-4 yr) was not statistically associated with improved diagnostic agreement. This research addresses many of the criticisms of the MRI literature and compares MRI favorably to CT.

To determine the relationship between the metabolic activity measured by 2-[(18)F]-fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET) and computed tomography (CT)-derived tumour growth rates for stage 1 lung cancer.Stage I lung cancer patients at our institution who underwent FDG PET, and who had at least two pre-treatment chest CT examinations (n=51), were retrospectively identified. Metabolic activity was defined by maximum lesion standardized uptake value (SUV) and maximum lesion-to-mean background activity (LBR). Growth rates were determined from serial CT volume measurements and the doubling time (DT) was calculated. Tumour growth rates were divided into rapid (DT180 days), intermediate (DT=180-270 days), and slow (DT270 days) groups.Rapid, moderate, and slow DT were seen in 22, 19, and 10 patients, respectively. Means (standard deviations) of SUV in the three groups (from rapid to slow growth rate) were 8.2 (4.8), 5.5 (4.5), and 2.2 (1.1), respectively and of LBR were 22.7 (10.1), 15.1 (12.6), and 6 (2.6), respectively. There was a significant relationship between SUV and DT (p0.05), as well as between LBR and DT (p0.05).For stage I lung tumours, there is a significant relationship between growth rates, as measured by serial CT examinations, and the initial pre-treatment metabolic activities, as measured by FDG uptake. This suggests that in patients in whom it is difficult to decide on the aggressiveness on treatment, FDG-PET may be used as additional prognostic tool for determining management.

Summary Purpose To investigate the utility of positron emission tomography (PET) in patients treated with stereotactic body radiotherapy (SBRT) for stage I non-small-cell lung cancer (NSCLC) on prospective institutional trials. Patients and methods Fifty-eight patients with medically inoperable stage I NSCLC who participated in prospective phase I and II trials of SBRT, had ≥2 years of follow-up, and received FDG-PET imaging are the focus of this evaluation. Fifty-seven of 58 patients received pre-SBRT FDG-PET to confirm stage I status. All patients received stereotactic body frame immobilization and treatment with 7–10 photon beams. SBRT total doses ranged from 24 to 72 Gy in three fractions. No elective nodal irradiation was undertaken. Regular follow-up with planned CT imaging was performed on all patients. Post-SBRT FDG-PET was not mandated by protocol and was typically ordered upon concern for disease recurrence. Thirty-eight post-SBRT PET studies were performed in 28 patients at a median 17.3 months following SBRT. Results With a median follow-up of 42.5 months, the 3-year actuarial overall survival and local control for this select subset of our SBRT experience were 48.9% and 74.8%, respectively. Pre-SBRT FDG-PET SUV did not predict 3-year overall survival or local control. Fourteen of 57 patients eventually failed in nodal stations by CT and/or PET. Isolated first site of failure was nodal in 6 patients (10%). Out of 28 patients with post-SBRT PET, 4 (14%) had delayed PET imaging (22–26 months after SBRT) showing moderate hypermetabolic activity (SUV 2.5–5.07), but no evidence of local, nodal, or distant recurrence by clinical examination and conventional imaging performed 20–26 months following these concerning PET findings. Conclusions Isolated nodal recurrence following PET-staged I NSCLC treated with SBRT is uncommon. Moderate post-SBRT PET hypermetabolic activity may persist 2 years following treatment without definite evidence of recurrence. Further study is needed to confirm these results in larger populations with longer follow-up.

Purpose The anterolateral thigh free flap (ALTF) first was reported in 1984 and has been used in large series with success for a multitude of clinical purposes. We describe our results with the ALTF in upper-extremity and hand reconstruction. Methods From 1996 to 2003 there were 15 patients who had reconstruction of the hand and upper extremity using the ALTF. The parameters used to assess the outcome of our series included the success rate of the flap as measured by flap survival rate and adequacy of skin coverage, ability to close the donor site primarily or necessity of a skin graft, complications associated with the flap, donor site, and non-flap-related complications such as pulmonary embolism. Results Of the 15 patients with an ALTF, 3 (20%) had a musculocutaneous perforator and 12 (80%) had a septocutaneous perforator. Two patients had a neurotized ALTF reconstruction. There were 4 complications related to the flap with 1 complete flap failure. The overall flap survival rate was 93%. The donor site was closed primarily in 8 patients (53%) and with a skin graft in 7 patients (47%). One donor site breakdown occurred. Conclusions Our results show many advantages of the ALTF for upper-extremity reconstruction. Because of its versatility the ALTF is suited ideally for upper-extremity reconstruction and should be considered as part of the reconstructive ladder.

Testicular circulatory isolation (TCI) holds promise as a method to avoid drug-induced infertility in male patients about to receive cancer chemotherapy. Complete exclusion of blood flow to the testicle is essential to the success of this technique. We have compared the hand-held Doppler probe and radionuclide angiography (technetium-99m pertechnetate) as monitors of testicular blood flow in 10 patients subjected to unilateral TCI. When Doppler evaluation indicated that testicular circulation had been interrupted, the radionuclide angiogram uniformly confirmed and quantified this conclusion. These results validate the hand-held Doppler as an appropriate tool for assessing testicular blood flow in patients undergoing TCI. © 1993 Wiley-Liss, Inc.