Citations

In this work, we have proposed an on-line computer-aided diagnostic system called “UroImage” that classifies a Transrectal Ultrasound (TRUS) image into cancerous or non-cancerous with the help of non-linear Higher Order Spectra (HOS) features and Discrete Wavelet Transform (DWT) coefficients. The UroImage system consists of an on-line system where five significant features (one DWT-based feature and four HOS-based features) are extracted from the test image. These on-line features are transformed by the classifier parameters obtained using the training dataset to determine the class. We trained and tested six classifiers. The dataset used for evaluation had 144 TRUS images which were split into training and testing sets. Three-fold and ten-fold cross-validation protocols were adopted for training and estimating the accuracy of the classifiers. The ground truth used for training was obtained using the biopsy results. Among the six classifiers, using 10-fold cross-validation technique, Support Vector Machine and Fuzzy Sugeno classifiers presented the best classification accuracy of 97.9% with equally high values for sensitivity, specificity and positive predictive value. Our proposed automated system, which achieved more than 95% values for all the performance measures, can be an adjunct tool to provide an initial diagnosis for the identification of patients with prostate cancer. The technique, however, is limited by the limitations of 2D ultrasound guided biopsy, and we intend to improve our technique by using 3D TRUS images in the future.

Exendin-(9,39) is a competitive antagonist of glucagon-like peptide-1 (GLP-1) at its receptor. However, it is unclear if it has direct and unique effects of its own. We tested the hypothesis that exendin-(9,39) and GLP-1-(9,36)amide have direct effects on hormone secretion and β-cell function as well as glucose metabolism in healthy subjects. Glucose containing [3-3H]glucose was infused to mimic the systemic appearance of glucose after a meal. Saline, GLP-1-(9,36)amide, or exendin-(9,39) at 30 pmol/kg/min (Ex 30) or 300 pmol/kg/min (Ex 300) were infused in random order on separate days. Integrated glucose concentrations were slightly but significantly increased by exendin-(9,39) (365 ± 43 vs. 383 ± 35 vs. 492 ± 49 vs. 337 ± 50 mmol per 6 h, saline, Ex 30, Ex 300, and GLP-1-[9,36]amide, respectively; P = 0.05). Insulin secretion did not differ among groups. However, insulin action was lowered by exendin-(9,39) (25 ± 4 vs. 20 ± 4 vs. 18 ± 3 vs. 21 ± 4 10−4 dL/kg[min per μU/mL]; P = 0.02), resulting in a lower disposition index (DI) during exendin-(9,39) infusion (1,118 ± 118 vs. 816 ± 83 vs. 725 ± 127 vs. 955 ± 166 10−14 dL/kg/min2 per pmol/L; P = 0.003). Endogenous glucose production and glucose disappearance did not differ significantly among groups. We conclude that exendin-(9,39), but not GLP-1-(9,36)amide, decreases insulin action and DI in healthy humans.

Objective Autoimmune pancreatitis (AIP) is a treatable form of chronic pancreatitis that has been increasingly recognised over the last decade. We set out to better understand the current burden of AIP at several academic institutions diagnosed using the International Consensus Diagnostic Criteria, and to describe long-term outcomes, including organs involved, treatments, relapse frequency and long-term sequelae. Design 23 institutions from 10 different countries participated in this multinational analysis. A total of 1064 patients meeting the International Consensus Diagnostic Criteria for type 1 (n=978) or type 2 (n=86) AIP were included. Data regarding treatments, relapses and sequelae were obtained. Results The majority of patients with type 1 (99%) and type 2 (92%) AIP who were treated with steroids went into clinical remission. Most patients with jaundice required biliary stent placement (71% of type 1 and 77% of type 2 AIP). Relapses were more common in patients with type 1 (31%) versus type 2 AIP (9%, p<0.001), especially those with IgG4-related sclerosing cholangitis (56% vs 26%, p<0.001). Relapses typically occurred in the pancreas or biliary tree. Retreatment with steroids remained effective at inducing remission with or without alternative treatment, such as azathioprine. Pancreatic duct stones and cancer were uncommon sequelae in type 1 AIP and did not occur in type 2 AIP during the study period. Conclusions AIP is a global disease which uniformly displays a high response to steroid treatment and tendency to relapse in the pancreas and biliary tree. Potential long-term sequelae include pancreatic duct stones and malignancy, however they were uncommon during the study period and require additional follow-up. Additional studies investigating prevention and treatment of disease relapses are needed.

Spontaneous intracerebral hemorrhage (sICH) represents a devastating clinical event with high mortality and morbidity rates. Only few patients with sICH are treated with neurosurgical evacuation of the hematoma, and the majority of them need only a good conservative medical approach. The goal of medical treatment is to avoid secondary neurological and systemic complications. Venous thromboembolism (VTE) represents one of the most feared complications of sICH, and it is a potential cause of death. The balance between the benefit of VTE prevention and the risk of hematoma enlargement and/or rebleeding with the use of pharmacologic thromboprophylaxis remains controversial because of the lack of consistent evidences in the literature. The efficacy of mechanical prophylaxis is also uncertain. Consequently, until now there are no clear guidelines and scientific evidences available for physicians in this field. The aim of this review is to analyze the available literature and guidelines about pharmacological VTE prophylaxis in patients with nonsurgical sICH.

ABSTRACT Introduction Peyronie’s disease (PD) is characterized by fibrotic plaque formation within the tunica albuginea, leading to penile deformity, angulation, painful erections, and often, erectile dysfunction. There is limited knowledge of its etiology and pathophysiology. Currently, there is no standardization for reporting the evaluation and treatment outcomes. No consensus exists on the ideal management of PD. Aim The aim of this study is to review the use of radiation therapy (RT) for the treatment of PD. Methods This study used a review of the literature and informed expert opinion. Main Outcome Measures The main outcome measures are the reported improvement with regard to pain, curvature, plaque size, and erectile function as well as a review of the safety profile of RT. Results Radiation has been used for the empirical treatment of PD with mixed results throughout the literature. Low-dose RT in the early stages of PD seems to be effective in patients with painful erections not improving with time or with the use of oral or intralesional therapies. Comparison with other current medical therapies is difficult due to the absence of criteria for therapeutic success and the absence of randomized, controlled trials. Multiple studies have demonstrated varied results in terms of curvature reduction, plaque volume, and sexual functioning. The absence of the use of validated means of measuring penile deformity and sexual function, the limited relevance of plaque and pain improvement combined with the potential negative consequences of radiation on erectile tissue structure and function lead us to make a recommendation that RT not be used for the management of PD. Conclusions In clinical practice, mixed success for RT has led to the recommendation against its use as a treatment modality for PD.

Background and Purpose The use of intermittent reperfusion versus straight occlusion during neurovascular procedures is controversial. This experiment studied the effects of intermittent reperfusion and single occlusion on intracellular brain pH (pH i ), regional cerebral or cortical blood flow, and nicotinamide adenine dinucleotide (NADH) fluorescence during temporary focal ischemia. Methods Twenty fasted rabbits under 1.0% halothane anesthesia were divided into four groups: (1) nonischemic controls, (2) 60 minutes of uninterrupted focal ischemia, (3) 2×30-minute periods of focal ischemia separated by a 5-minute reperfusion, and (4) 4×15-minute periods of focal ischemia separated by three 5-minute reperfusion periods. Focal ischemia was produced by occlusion of both the middle cerebral and ipsilateral anterior cerebral arteries. After the final occlusion, there was a 3-hour reperfusion period in all groups. Regional cerebral and cortical blood flow, brain pH i , and NADH fluorescence were measured with in vivo panoramic fluorescence imaging. Results During occlusion, regional cerebral and cortical blood flows and NADH fluorescence values were not different among the groups. Brain pH i was significantly lower in the 4×15-minute group compared with the 1×60-minute group (6.57±0.02 versus 6.73±0.06; P <.03) but not significant when compared with the 2×30-minute group. During the short reperfusion periods, all parameters returned to normal except for NADH fluorescence levels, which remained elevated. During the postischemic final reperfusion period, there was a mild brain alkalosis of approximately 7.1 in all groups. There were no significant differences in NADH fluorescence among groups during the final reperfusion. Regional cerebral and cortical blood flow returned to near normal values in all groups. Conclusions This study demonstrates that intermittent reperfusion during temporary focal ischemia has different effects on the intracytoplasmic and the intramitochondrial compartments: worsening of brain cytoplasmic pH i but no significant differences in the oxidation/reduction level of mitochondrial NADH.

Abstract In the Breast International Group (BIG) and North Central Cancer Treatment Group (NCCTG) co-led phase III adjuvant breast cancer trial, ALTTO (Adjuvant Lapatinib and/or Trastuzumab Treatment Optimisation), two central laboratories, the European Institute of Oncology (IEO; Milan, Italy) and Mayo Clinic (Rochester, MN), are responsible for confirming the human epidermal growth factor receptor-2 (HER2), estrogen receptor α(ER), and progesterone receptor status of the primary breast tumors for the Rest of World (excluding China, which conducts a separate central review) and North American patients, respectively, prior to patient study entry. As of December 2009, discordance in HER2 and ER testing between local and central laboratories was observed by both central laboratories. For IEO, 14.5% of 8,037 HER2 cases locally positive [by either immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH)] were not able to be confirmed as centrally positive; whereas for Mayo, 5.8% of 412 HER2 cases locally positive were not able to be confirmed as centrally positive (Table 1). Central and local IHC ER discordance was 12.1% and 11.7% for 9,021 IEO screened cases and 419 Mayo screened cases, respectively (Table 2). In particular, IEO observed more false-positive (locally positive/centrally negative) HER2 findings than Mayo and Mayo observed more false-positive ER findings than IEO. Purpose: Motivated by the above findings, we launched a ring study to assess whether the central lab results of a subset of local/central discordant ALTTO cases could be confirmed in the other central lab. Methods: IEO and Mayo exchanged and retested a subset of FFPE breast tumors collected in ALTTO. IEO sent 20 HER2 false-positive, 5 ER false-positive, and 5 ER false-negative (locally negative/centrally positive) ALTTO breast tumors to Mayo. Mayo sent 5 HER2 false-positive, 20 ER false-positive, and 5 ER false-negative ALTTO breast tumors to IEO. IEO and Mayo performed IHC for ER according to their own methodology: DAKO cocktail of ER 1D5 and 2.123 monoclonal antibodies and monoclonal ER 1D5 antibody, respectively. The two laboratories performed IHC for HER2 according to the HercepTest® manufacturers’ instructions (Dako, Carpenteria, CA) and FISH for HER2 using the PathVysion HER2 DNA probe kit and the HER2/centromere 17 probe mixture (Abbott Molecular, Des Plaines, IL). Results: IEO and Mayo confirmed the central HER2-negative result in 100% of 25 cases. Analyses of ER are ongoing and ER results will be presented. Conclusions: In this subset of patients, enrollment ineligibility did not change when HER2 testing was performed by either IEO or Mayo Clinic central laboratories. Table 1. HER2 Local/Central Lab Results Table 2. ER Local/Central Lab Results Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-10-36.