Stage Shift Research Articles

Su1054 Prevalent Round Stage Shift in the National Bowel Cancer Screening Programme in Wales; Data From the First 3 Years in At a Single Screening Centre

Introduction Colorectal cancer screening is based on early detection of cancers and removal of premalignant polyps though this adenoma to carcinoma sequence is thought to progress over several years. The Bowel Screening Programme in Wales based on guaiac FOBt and colonoscopy for individuals resting positive began roll-out in October 2008, with the aim of reducing mortality through cancer detection at an early stage. The aim of this study was to investigate whether screen detected cancers in Cardiff and the Vale of Glamorgan demonstrated any shift in the stage of cancer during the first three years of screening (initial prevalent round). Methods Data was collected prospectively to compare the staging of colorectal cancer diagnosed in the BCSP with cancers diagnosed in the non-screening population in the same geographical region from 1st October 2008 to 31st December 2011. All information was cross checked with Cancer Registry data. Results Screen detected cancer was found in 69 individuals (44 male, 25 female), with a positive predictive value of colonoscopy (after positive FOB testing) of 8.7%. Complete clinical staging was available for all 69 individuals; two patients did not undergo surgical resection due to the presence of metastases after radiological staging. There were 696 non-screening detected cancers during the same time period. For the purposes of this analysis, polyp cancers (cancer that was removed by endoscopic means at the time of colonoscopy/flexible sigmoidoscopy) were included in Duke’s stage A, except for one polyp cancer that required subsequent surgical resection and was staged as Duke’s C1. The results are shown in table 1. Three-quarters of cancers diagnosed in the BCSP were Dukes A or B, compared to 44.1% in the non-screening population. Of Duke’s D cancers, only 2.8% were diagnosed through screening, with 27% diagnosed in the non screening population (p Conclusion This data strongly supports significant stage shift of colorectal cancer even within the initial prevalent round in this single Bowel Cancer Screening centre in Wales that the benefits of screening may be demonstrable in outcomes at a relatively early stage of the programme. Disclosure of Interest None Declared.

1351 INVERSE STAGE MIGRATION OF CLINICALLY LOCALIZED PROSTATE CANCER STILL CONTINUES AND IS MOST PRONOUNCED IN ELDER PATIENTS

INTRODUCTION AND OBJECTIVES: We recently demonstrated an inverse migration of clinical and pathological disease stages of men with newly diagnosed prostate cancer (PCa) in an unscreened European cohort (Budaus et al. BJUI 2011). Purpose of the current study was to evaluate the further trend stratified by age groups. METHODS: Radical prostatectomy (RP) was performed in 10584 patients between the years 2005 and 2011 at a single tertiarycare center. Year of surgery, age at surgery, D’Amico risk categories, pathological stage and pathological Gleason Score were descriptively evaluated with trends and proportions over time. Year of surgery (2005-2007, 2008-2009, 2010-2011) and age at surgery ( 60, 61-70, 71 years) were categorized accordingly. RESULTS: Median age at surgery (mean) increased from 62,83 (64) to 63,51 (65) years between 2005 and 2011. According to the D’Amico risk categories, a shift towards intermediate and high risk categories was most pronounced in men 71 years with an increase in high risk cancers from 21% in 2008-2009 to 29% in 2010-2011 (Figure 1). Accordingly, histopathological outcome demonstrated the most significant increase in locally advanced tumors ( pT3a) in men 71 years with a proportion of 35% in 2008-2009 to 42% in 2010-2011 (Figure 2). Disease characteristics of younger men ( 60 years) did not change significantly over all time strata. CONCLUSIONS: According to our data, inverse stage migration still continues since 2009 with a shift towards worse disease characteristics in a contemporary RP cohort. However, this observed trend is mainly attributed to a significant stage shift in elder patients. A change of treatment paradigm in Gleason 3 3 or 3 4 prostate cancer towards a more conservative approach in elder men might have caused this trend. Source of Funding: None

Intellectual disabilities and power spectra analysis during sleep: a new perspective on borderline intellectual functioning

The role of sleep in cognitive processes has been confirmed by a growing number of reports for all ages of life. Analysing sleep electroencephalogram (EEG) spectra may be useful to study cortical organisation in individuals with Borderline Intellectual Functioning (BIF), as seen in other disturbances even if it is not considered a disease. The aim of this study was to determine if the sleep EEG power spectra in children with BIF could be different from typically developing children. Eighteen BIF (12 males) (mean age 11.04; SD ± 1.07) and 24 typical developing children (14 men) (mean age 10.98; SD ± 1.76; P = 0.899) underwent an overnight polysomnography (PSG) recording in the Sleep Laboratory of the Clinic of Child and Adolescent Neuropsychiatry, after one adaptation night. Sleep was subdivided into 30-s epochs and sleep stages were scored according to the standard criteria and the power spectra were calculated for the Cz-A2 channel using the sleep analysis software Hypnolab 1.2 (SWS Soft, Italy) by means of the Fast Fourier Transform and the power spectrum was calculated for frequencies between 0.5 and 60 Hz with a frequency step of 1 Hz and then averaged across the following bands delta (0.5-4 Hz), theta (5-7 Hz), alpha (8-11 Hz), sigma (11-15 Hz), and beta (16-30 Hz), gamma (30-60 Hz) for S2, SWS and REM (Rapid Eye Movement) sleep stages. BIF have a reduced sleep duration (total sleep time; P < 0.001), and an increased rate of stage shifts (P < 0.001) and awakenings (P < 0.001) and WASO (wakefulness after sleep onset) % (P < 0.001); the stage 2% (P < 0.001), and REM% (P < 0.001) were lower and slow-wave sleep percentage was slightly higher (P < 0.001). All children with BIF had an AHI (apnoea-hypopnea index) less than 1 (mean AHI = 0.691 ± 0.236) with a mean oxygen saturation of 97.6% and a periodic leg movement index (PLMI) less than 5 (mean PLMI = 2.94 ± 1.56). All sleep stages had a significant reduction in gamma frequency (30-60 Hz) (P < 0.001) and an increased delta frequency (0.5-4.0 Hz) (P < 0.001) power in BIF subjects compared with typically developing children. Our findings shed light on the importance of sleep for cognition processes particularly in cognitive borderline dysfunction and the role of EEG spectral power analysis to recognize sleep characteristics in BIF children.

Hemostatics for nephron-sparing surgery

Owing to the increase in incidental diagnosis, approximately 60% of renal tumors are detected clinically at the T1N0M0 stage, showing a downward shift in tumor stage and size [1]. This means that i...

Who dies from prostate cancer in a Western country? A multicenter analysis.

211 Background: In the last 30 years, a major shift in initial staging has occurred for men with prostate cancer (CaP) in many Western countries, with the incidence of detectable metastases at diagnosis decreasing from more than half the cases in the 1970s to currently less than 10%. Still, prostate cancer is the second killing neoplasm in men. We used two prospective databases of patients with castration-resistant prostate cancer (CRPC) to describe the natural history of metastatic CRPC in the modern era. Methods: The outcome of 190 men with CaP treated for metastatic disease from 2007-2011 was studied. Characteristics of patients who died from CaP were analyzed. Results: After a median follow-up of 6.8 years, 112 patients had died from CaP and 109 were assessable for presence of metastasis at initial diagnosis. Of these 109 pts, 53 (49%) had detectable metastasis at diagnosis: 43 pts (81%), 6 pts (11%) and 17 pts (32%) had bone, visceral; and lymph nodes metastases, respectively. Overall, 10 pts (19%) had more than one metastatic site. Median time to CRPC was 16 months (range: 3-122 months) and median overall survival was 5 years (CI 95%: 4.6 – 6.6 years) for these pts with detectable metastasis at diagnosis. Among patients with localized CaP at diagnosis (n=56; 51%), 23 pts (41%) had T stage ≥ 3, 23 pts (41%) had a Gleason score ≥ 8. Their median PSA was 15 ng/ml (4-400). Overall, 39 pts (70%) were classified as having a high-risk CaP. 13 patients (23%) dying from CaP had an initial Gleason score ≤ 6. The median overall survival was 7 years (CI 95%: 6.1 – 9.1 years). Conclusions: In the modern era, approximately half of the patients eventually dying from CaP had detectable metastases at diagnosis. The paradigm of patients progressing from localized disease to metastatic disease and eventually death is represented only in the other half. Further efforts should be made to conduct clinical trials in patients with newly diagnosed metastatic prostate cancer.

Time structure of leg movement activity during sleep in attention-deficit/hyperactivity disorder and effects of levodopa

To evaluate the leg movement (LM) time structure (periodicity and night distribution) during sleep in children with attention-deficit/hyperactivity disorder (ADHD) and their eventual changes after treatment with levodopa (L-DOPA). One group of ADHD patients (n=18) and another group of normal controls (n=17) were recruited; those with ADHD were randomized to L-DOPA or placebo therapy. At baseline (both groups) and after therapy (only patients) subjects underwent full-night polysomnography (PSG) and the leg motor pattern was evaluated with advanced tools of analysis particularly able to detect and describe LM time structure (periodicity and distribution). With respect to controls ADHD children showed prolonged sleep latency, increased number of stage shifts, awakenings, and percentage of sleep stage 1. Arousal index was higher in ADHD and also their PLMS index was slightly but considerably higher than controls; however, their periodicity was low and not different from controls. Only sleep latency was significantly reduced by L-DOPA treatment with all the other parameters (sleep scoring and LM activity) remaining substantially unmodified. LMs during sleep in children with ADHD do not show a highly periodic character and are not considerably modified by L-DOPA treatment; this finding has potential implications for drug treatment that might target the most prominent changes observed in our study including arousals and sleep structure disruption.

Computed Tomography Screening for Lung Cancer: Has It Finally Arrived? Implications of the National Lung Screening Trial

The National Lung Screening Trial (NLST) has provided compelling evidence of the efficacy of lung cancer screening using low-dose helical computed tomography (LDCT) to reduce lung cancer mortality. The NLST randomized 53,454 older current or former heavy smokers to receive LDCT or chest radiography (CXR) for three annual screens. Participants were observed for a median of 6.5 years for outcomes. Vital status was available in more than 95% of participants. LDCT was positive in 24.2% of screens, compared with 6.9% of CXRs; more than 95% of all positive LDCT screens were not associated with lung cancer. LDCT detected more than twice the number of early-stage lung cancers and resulted in a stage shift from advanced to early-stage disease. Complications of LDCT screening were minimal. Lung cancer-specific mortality was reduced by 20% relative to CXR; all-cause mortality was reduced by 6.7%. The major harms of LDCT are radiation exposure, high false-positive rates, and the potential for overdiagnosis. This review discusses the risks and benefits of LDCT screening as well as an approach to LDCT implementation that incorporates systematic screening practice with smoking cessation programs and offers opportunities for better determination of appropriate risk cohorts for screening and for better diagnostic prediction of lung cancer in the setting of screen-detected nodules. The challenges of implementation are considered for screening programs, for primary care clinicians, and across socioeconomic strata. Considerations for future research to complement imaging-based screening to reduce the burden of lung cancer are discussed.

Influence of Glucose Concentrations on Biofilm Formation, Motility, Exoprotease Production, and Quorum Sensing in Aeromonas hydrophila

Aeromonas hydrophila recently has received increased attention because it is opportunistic and a primary human pathogen. A. hydrophila biofilm formation and its control are a major concern for food safety because biofilms are related to virulence. Therefore, we investigated biofilm formation, motility inhibition, quorum sensing, and exoprotease production of this opportunistic pathogen in response to various glucose concentrations from 0.05 to 2.5% (wt/vol). More than 0.05% glucose significantly impaired (P < 0.05) quorum sensing, biofilm formation, protease production, and swarming and swimming motility, whereas bacteria treated with 0.05% glucose had activity similar to that of the control (0% glucose). A stage shift biofilm assay revealed that the addition of glucose (2.5%) inhibited initial biofilm formation but not later stages. However, addition of quorum sensing molecules N-3-butanoyl-DL-homoserine lactone and N-3-hexanoyl homoserine lactone partially restored protease production, indicating that quorum sensing is controlled by glucose concentrations. Thus, glucose present in food or added as a preservative could regulate acyl-homoserine lactone quorum sensing molecules, which mediate biofilm formation and virulence in A. hydrophila.

Experimental Pain and Opioid Analgesia in Volunteers at High Risk for Obstructive Sleep Apnea

BackgroundObstructive sleep apnea (OSA) is characterized by recurrent nocturnal hypoxia and sleep disruption. Sleep fragmentation caused hyperalgesia in volunteers, while nocturnal hypoxemia enhanced morphine analgesic potency in children with OSA. This evidence directly relates to surgical OSA patients who are at risk for airway compromise due to postoperative use of opioids. Using accepted experimental pain models, we characterized pain processing and opioid analgesia in male volunteers recruited based on their risk for OSA.MethodsAfter approval from the Intitutional Review Board and informed consent, we assessed heat and cold pain thresholds and tolerances in volunteers after overnight polysomnography (PSG). Three pro-inflammatory and 3 hypoxia markers were determined in the serum. Pain tests were performed at baseline, placebo, and two effect site concentrations of remifentanil (1 and 2 µg/ml), an μ-opioid agonist. Linear mixed effects regression models were employed to evaluate the association of 3 PSG descriptors [wake after sleep onset, number of sleep stage shifts, and lowest oxyhemoglobin saturation (SaO2) during sleep] and all serum markers with pain thresholds and tolerances at baseline, as well as their changes under remifentanil.ResultsForty-three volunteers (12 normal and 31 with a PSG-based diagnosis of OSA) were included in the analysis. The lower nadir SaO2 and higher insulin growth factor binding protein-1 (IGFBP-1) were associated with higher analgesic sensitivity to remifentanil (SaO2, P = 0.0440; IGFBP-1, P = 0.0013). Other pro-inflammatory mediators like interleukin-1β and tumor necrosis factor-α (TNF-α) were associated with an enhanced sensitivity to the opioid analgesic effect (IL-1β, P = 0.0218; TNF-α, P = 0.0276).ConclusionsNocturnal hypoxemia in subjects at high risk for OSA was associated with an increased potency of opioid analgesia. A serum hypoxia marker (IGFBP-1) was associated with hypoalgesia and increased potency to opioid analgesia; other pro-inflammatory mediators also predicted an enhanced opioid potency.Trial Registration: ClinicalTrials.gov NCT00672737.

Sleep and neurocognitive functioning in children with eczema

Sleep disruption in childhood is associated with clearly defined deficits in neurocognition and behaviour. Childhood eczema is also a potent cause of sleep disruption though it is unknown whether it too results in neurocognitive deficits. To test this hypothesis, neurocognitive (WISC-IV), parental-reported sleep quality (Sleep Disturbance Scale of Children (SDSC)) and overnight polysomnographic (PSG) data were collected in 21 children with eczema and 20 healthy controls (age range 6–16years). Children with eczema had worse sleep quality on both PSG (notably increased nocturnal wakefulness, a higher number of stage shifts and a longer latency to REM onset) and parental report. In addition, they demonstrated significant neurocognitive deficits (especially verbal comprehension, perceptual reasoning and to a lesser extent working memory) with a composite Full Scale IQ 16 points lower than controls. Parental reported sleep problems but not PSG parameters were correlated with reduced neurocognitive performance. However, hierarchical regression analyses revealed that eczema status was predictive while sleep fragmentation (parental or PSG) was not predictive of neurocognitive performance. As this is the first study to systematically examine neurocognitive functioning in children with eczema and given the finding of significant deficits it merits replication especially given the prevalence of the condition. The unanswered question is whether these cognitive deficits normalise with effective eczema treatment and if this is mediated by improvements in sleep architecture.

Epilepsia nocturna frontal infradiagnosticada en la infancia como un trastorno del sueño: estudio de una serie

INTRODUCTION. We present a series of children who underwent a video-polysomnographic recording at our Sleep and Epilepsy Unit, who received a diagnosis of nocturnal frontal lobe epilepsy (NFLE). AIMS. To describe electroclinical and video polygraphic features of paediatric NFLE that differentiate this condition from other sleep disorders that overlap and mimic the sleep motor and autonomic events of NFLE. PATIENTS AND METHODS. The inclusion criterion was that the patients have their first video-EEG-PSG recording in our laboratory. RESULTS. Twenty-four out of 190 children were diagnosed with NFLE (group 1); while 166 had other sleep disorders (group 2). Among children diagnosed with NFLE, seven were referred for sleep-disordered breathing, seven for parasomnias, two for insomnia, two for hypersomnia, and one for periodic limb movements, while five were referred for epilepsy. In group 1, perinatal history was normal in most cases (21 out of 24) and a familiar history of epilepsy was found in four cases. Sleep-disordered breathing was diagnosed as a comorbid condition in four children. Standard EEG was normal in 21 cases. Interictal EEG showed epileptic discharges in four cases, while ictal EEG was expressed by a rhythmic theta activity preceded by an arousal and/or a short background desynchronization, movement artifacts, and autonomic changes. All seizures, repeated highly stereotyped motor events, were followed by stage shifts and/or a postural change and, by short awakenings. CONCLUSIONS. We found a high percentage of children with NFLE, often misdiagnosed or associated with other sleep disorders, which may be a trigger for nocturnal seizures.

The Changing Natural History of Metastatic Prostate Cancer

Since 1941, the understanding of prostate cancer pathogenesis and therapy has undergone a significant transformation. Rigorous translational research has identified multiple mechanisms underlying castration resistance, the fatal clinical state of the disease. Therapeutic approaches targeting these mechanisms in metastatic castration-resistant prostate cancer have now been clinically validated in the clinic including high-potency androgen signaling inhibition, novel cytotoxic chemotherapy, and bone-targeted therapies. Despite these advances, cure remains an elusive goal. The natural history of metastatic prostate cancer has evolved particularly in the last 2 decades in step with improved management of age-associated comorbidities, improved imaging, and the expansion of novel therapies, thus providing new opportunities and challenges. It is also important to note that the advent of prostate-specific antigen testing caused a stage shift in the disease spectrum, thus leading to earlier interventions and potentially positively impacting survival. The optimal sequencing and combinations of available therapies, predictive biomarkers, and better understanding of mechanisms of resistance remain high priority. Further refinement of the clinical niche for novel therapies in hormone-sensitive and castration-resistant disease through rationally designed clinical trials incorporating molecular, clinical, and imaging biomarkers and quality-of-life correlatives is of paramount importance.

The Assessment of the Rice Growing Stage Shift under Climate Change in Northern Part of Iwate, and important Matters to Obtain for Stable and Higher Rice Yields

The Assessment of the Rice Growing Stage Shift under Climate Change in Northern Part of Iwate, and important Matters to Obtain for Stable and Higher Rice Yields

Design and Implementation of Encoder for (15, k) Binary BCH Code Using VHDL and eliminating the fan-out

In this paper we have designed and implemented(15, k) a BCH Encoder on FPGA using VHDL for reliable data transfers in AWGN channel with multiple error correction control. The digital logic implementation of binary encoding of multiple error correcting BCH code (15, k) of length n=15 over GF (2 4 ) with irreducible primitive polynomial x 4 +x+1 is organized into shift register circuits. Using the cyclic codes, the reminder b(x) can be obtained in a linear (15-k) stage shift register with feedback connections corresponding to the coefficients of the generated polynomial. Three encoder are designed using VHDL to encode the single, double and triple error correcting BCH code (15, k) corresponding to the coefficient of generated polynomial. Information bit is transmitted in unchanged form up to k clock cycles and during this period parity bits are calculated in the LFSR then the parity bits are transmitted from k+1 to 15 clock cycles. Total 15-k numbers of parity bits with k information bits are transmitted in 15 code word. Here we have implemented (15, 5, 3), (15, 7, 2) and (15, 11, 1) BCH code encoder on Xilinx Spartan 3 FPGA using VHDL and the simulation & synthesis are done using Xilinx ISE 13.3. BCH encoders are conventionally implemented by linear feedback shift register architecture. Encoders of long BCH codes may suffer from the effect of large fan out, which may reduce the achievable clock speed. The data rate requirement of optical applications require parallel implementations of the BCH encoders. Also a comparative performance based on synthesis & simulation on FPGA is presented. Keywords: BCH, BCH Encoder, FPGA, VHDL, Error Correction, AWGN, LFSR cyclic redundancy checking, fan out .

Screening for Familial Ovarian Cancer: A Ray of Hope and a Light to Steer by

Screening for Familial Ovarian Cancer: A Ray of Hope and a Light to Steer by

S91 Improved Lung Cancer Survival and Reduced Emergency Diagnoses Resulting from an Early Diagnosis Campaign in Leeds 2011

BackgroundLung cancer survival in the UK lags behind other developed nations, and excess early deaths following diagnosis suggest advanced disease at presentation. Patients diagnosed with lung cancer following emergency presentation...

An observational clinical and video-polysomnographic study of the effects of clonazepam in REM sleep behavior disorder

To analyze the differences in sleep structure and nocturnal motor activity between drug-free REM sleep behavior disorder (RBD) patients and those under therapy with clonazepam, and to evaluate the long-term longitudinal changes under continued therapy with clonazepam. Fifty-seven consecutive iRBD patients were recruited (52 men and 5 women, mean age 68.8±6.03years). Forty-two patients were not taking any medication at the time of the evaluation (iRBD-Clo) while 15 were taking clonazepam (0.5-1mg) at bedtime (iRBD+Clo). The Clinical Global Impression-Severity (CGI-S) scale was obtained. Sleep was video-polysomnographically recorded and the RBD severity scale (RBDSS) obtained. The chin EMG amplitude was quantitatively assessed and the Atonia Index computed. Disease duration was significantly longer in iRBD+Clo patients who also showed a lower rate of stage shifts, higher sleep efficiency and lower percentage of wakefulness after sleep onset and of sleep stage 1, and an increased percentage of sleep stage 2. The longitudinal long-term follow up study in a subgroup of 13 patients showed moderately increased total sleep time, sleep efficiency, sleep stage 2, slow-wave sleep and decreased wakefulness after sleep onset and sleep stage 1, under clonazepam treatment. The CGI scale clearly tended to improve after treatment, but no common trend was evident for RBDSS or Atonia Index. This study provides evidence of important objective effects of clonazepam on NREM sleep in RBD; this data might be very important for the development of new and effective treatments for this condition.

Ovarian cancer: role of ultrasound in preoperative diagnosis and population screening

Ovarian cancer: role of ultrasound in preoperative diagnosis and population screening

Computer‐aided detection should be used routinely to assist screening mammogram interpretation

Computer‐aided detection should be used routinely to assist screening mammogram interpretation

Virtual Surgical Planning: A Novel Aid to Robot-Assisted Laparoscopic Partial Nephrectomy

Incidental detection of small renal masses has significantly increased over the last two decades with the advent of cross-sectional imaging. The shift in stage has been met with a shift in treatment modality because the preservation of renal parenchyma can prevent adverse outcomes. Robot-assisted laparoscopic partial nephrectomy (RALPN) needs significant surgeon expertise, and preoperative planning is imperative. Between December 2010 and September 2011, virtual surgical planning (VSP) was used in consecutive patients with renal tumors that were suspicious for renal-cell carcinoma who were undergoing RALPN by a single surgeon. Three-dimensional (3D) reconstructions were examined and manipulated preoperatively, and an operative plan formulated. Intraoperative anatomy and preoperative 3D reconstructions were compared in real time. A total of 10 patients underwent RALPN with preoperative VSP. Average patient age at intervention was 54.6 years and average tumor size was 4.3 cm (range 1.7-7.5 cm). Tumor laterality was evenly distributed. Nephrometry score ranged from 5A to 10P, and final tumor pathology results revealed malignancy in 80%. No complications occurred intraoperatively, and an excellent correlation was noted between preoperative 3D reconstruction and intraoperative anatomy. All patients underwent a successful partial nephrectomy with no positive margins on final pathology results. Mean length of surgery was 232.9 minutes (range 156-435 min), and mean estimated blood loss was 370 mL (range 75-1800 mL). Warm ischemia time ranged from 20 to 50 minutes (mean 33.9 min). Data regarding postoperative renal function were available for six patients with an average loss of function of 9.5% (range 2%-17%). The implementation of this novel technology has significantly improved our ability to plan RALPN preoperatively. Tumor depth and complexity of tumor resection are assessed and the appropriate operative intervention and approach planned. Tumor proximity to vascular structures and collecting system were reliably predicted and therefore anticipated. Overall, these advantages created a safer surgical endeavor.