Significant variation in histopathological assessment of endoscopic resections for Barrett's neoplasia suggests need for consensus reporting: propositions for improvement.

Endoscopic resection (ER) is an important diagnostic step in management of patients with early Barrett's esophagus (BE) neoplasia. Based on ER specimens, an accurate histological diagnosis can be made, which guides further treatment. Based on depth of tumor invasion, differentiation grade, lymphovascular invasion, and margin status, the risk of lymph node metastases and local recurrence is judged to be low enough to justify endoscopic management, or high enough to warrant invasive surgical esophagectomy. Adequate assessment of these histological risk factors is therefore of the utmost importance. Aim of this study was to assess pathologist concordance on these histological features on ER specimens and evaluate causes of discrepancy. Of 62 challenging ER cases, one representative H&E slide and matching desmin and endothelial marker were digitalized and independently assessed by 13 dedicated GI pathologists from 8 Dutch BE expert centers, using an online assessment module. For each histological feature, concordance and discordance were calculated. Clinically relevant discordances were observed for all criteria. Grouping depth of invasion categories according to expanded endoscopic treatment criteria (T1a and T1sm1 vs. T1sm2/3), ≥1 pathologist was discrepant in 21% of cases, increasing to 45% when grouping diagnoses according to the traditional T1a versus T1b classification. For differentiation grade, lymphovascular invasion, and margin status, discordances were substantial with 27%, 42%, and 32% of cases having ≥1 discrepant pathologist, respectively. In conclusion, histological assessment of ER specimens of early BE cancer by dedicated GI pathologists shows significant discordances for all relevant histological features. We present propositions to improve definitions of diagnostic criteria.

Compact acousto-optic multimode interference device in (Al,Ga)As.

Multimode interference (MMI) devices are key components in modern integrated photonic circuits. Here, we present acoustically tuned optical switches on an (Al,Ga)As platform that enable robust, compact and fast response systems improving on recently demonstrated technology. The device consists of a 2 × 2 MMI device fine-tuned in its center region by a focused surface acoustic wave (SAW) beam working in the low GHz range. In this way, we can tune the refractive index profile over a narrow modulation region and thus control the optical switching behaviour via the applied SAW intensity. Direct tuning of the MMI device avoids losses and phase errors inherent to arrayed waveguide based switches, while also reducing the dimensions of the photonic circuit.

Residual disease after neoadjuvant chemoradiotherapy for oesophageal cancer: locations undetected by endoscopic biopsies in the preSANO trial.

BACKGROUND: Active surveillance has been proposed for patients with oesophageal cancer in whom there is a complete clinical response after neoadjuvant chemoradiotherapy (nCRT). However, endoscopic biopsies have limited negative predictive value in detecting residual disease. This study determined the location of residual tumour following surgery to improve surveillance and endoscopic strategies. METHODS: The present study was based on patients who participated in the prospective preSANO trial with adenocarcinoma or squamous cell carcinoma of the oesophagus or oesophagogastric junction treated in four Dutch hospitals between 2013 and 2016. Resection specimens and endoscopic biopsies taken during clinical response evaluations after nCRT were reviewed by two expert gastrointestinal pathologists. The exact location of residual disease in the oesophageal wall was determined in resection specimens. Endoscopic biopsies were assessed for the presence of structures representing the submucosal layer of the oesophageal wall. RESULTS: In total, 119 eligible patients underwent clinical response evaluations after nCRT followed by standard surgery. Residual tumour was present in endoscopic biopsies from 70 patients, confirmed on histological analysis of the resected organ. Residual tumour was present in the resection specimen from 27 of the other 49 patients, despite endoscopic biopsies being negative. Of these 27 patients, residual tumour was located in the mucosa in 18, and in the submucosa beneath tumour-free mucosa in eight. One patient had tumour in muscle beneath tumour-free mucosa and submucosa. CONCLUSION: Most residual disease after nCRT missed by endoscopic biopsies was located in the mucosa. Active surveillance could be improved by more sampling and considering submucosal biopsies.

ANTECEDENTES: Se ha propuesto un seguimiento activo para los pacientes con cáncer de esófago en los que se logra una respuesta clínica completa tras quimiorradioterapia neoadyuvante (neoadjuvant chemoradiotherapy, nCRT). Sin embargo, las biopsias endoscópicas tienen un valor predictivo limitado para detectar la enfermedad residual. En este estudio se evaluó la localización del tumor residual tras la cirugía para poder determinar estrategias de seguimiento y endoscópicas. MÉTODOS: Este estudio se basa en pacientes que participaron en el ensayo prospectivo preSANO (adenocarcinoma o carcinoma escamoso del esófago o unión esofagogástrica en cuatro hospitales de los Países Bajos entre 2013 y 2016). Los especímenes quirúrgicos, así como las biopsias endoscópicas efectuadas durante las evaluaciones de la respuesta clínica después de nCRT fueron revisadas por dos patólogos gastrointestinales expertos. En los especímenes de resección, se determinó la localización exacta de la enfermedad residual en la pared del esófago. Se evaluaron las biopsias endoscópicas para identificar estructuras que constituyeran la capa submucosa de la pared del esófago. RESULTADOS: En total, 119 pacientes elegibles fueron sometidos a evaluaciones de la respuesta clínica tras nCRT seguida de cirugía estándar. Se detectó tumor residual en las biopsias endoscópicas de 70 pacientes, luego confirmadas en la histología de la pieza extirpada. Se identificó tumor residual en la pieza de resección de 27 de los otros 49 pacientes, a pesar de que las biopsias endoscópicas fueron negativas. En estos 27 pacientes, 18 presentaban tumor residual en la mucosa y ocho pacientes en la submucosa mas allá de una mucosa libre de tumor. Un paciente tenía tumor en el músculo más allá de una mucosa y submucosa libres de tumor. CONCLUSIÓN: La mayoría de los casos de enfermedad residual tras nCRT que no se detectaron en las biopsias endoscópicas, se localizaban en la mucosa. El seguimiento activo podría mejorar con la toma de más muestras y considerando las biopsias submucosas.

Frequency and power stabilization of a terahertz quantum-cascade laser using near-infrared optical excitation.

We demonstrate a technique to simultaneously stabilize the frequency and output power of a terahertz quantum-cascade laser (QCL). This technique exploits frequency and power variations upon near-infrared illumination of the QCL with a diode laser. It does not require an external terahertz optical modulator. By locking the frequency to a molecular absorption line, we obtain a long-term (one-hour) linewidth of 260 kHz (full width at half maximum) and a root-mean-square power stability below 0.03%. With respect to the free-running case, this stabilization scheme improves the frequency stability by nearly two orders of magnitude and the power stability by a factor of three.

Wideband, high-resolution terahertz spectroscopy by light-induced frequency tuning of quantum-cascade lasers.

Near-infrared optical excitation enables wideband frequency tuning of terahertz quantum-cascade lasers. In this work, we demonstrate the feasibility of the approach for molecular laser absorption spectroscopy. We present a physical model which explains the observed frequency tuning characteristics by the optical excitation of an electron-hole plasma. Due to an improved excitation configuration as compared to previous work, we observe a single-mode continuous-wave frequency coverage of as much as 40 GHz for a laser at 3.1 THz. This represents, for the same device, a ten-fold improvement over the usually employed tuning by current. The method can be readily applied to a large class of devices.

Management of psychogenic non-epileptic seizures: a multidisciplinary approach.

The International League against Epilepsy (ILAE) proposed a diagnostic scheme for psychogenic non-epileptic seizure (PNES). The debate on ethical aspects of the diagnostic procedures is ongoing, the treatment is not standardized and management might differ according to age group. The objective was to reach an expert and stakeholder consensus on PNES management. A board comprising adult and child neurologists, neuropsychologists, psychiatrists, pharmacologists, experts in forensic medicine and bioethics as well as patients' representatives was formed. The board chose five main topics regarding PNES: diagnosis; ethical issues; psychiatric comorbidities; psychological treatment; and pharmacological treatment. After a systematic review of the literature, the board met in a consensus conference in Catanzaro (Italy). Further consultations using a model of Delphi panel were held. The global level of evidence for all topics was low. Even though most questions were formulated separately for children/adolescents and adults, no major age-related differences emerged. The board established that the approach to PNES diagnosis should comply with ILAE recommendations. Seizure induction was considered ethical, preferring the least invasive techniques. The board recommended looking carefully for mood disturbances, personality disorders and psychic trauma in persons with PNES and considering cognitive-behavioural therapy as a first-line psychological approach and pharmacological treatment to manage comorbid conditions, namely anxiety and depression. Psychogenic non-epileptic seizure management should be multidisciplinary. High-quality long-term studies are needed to standardize PNES management.

Loss of SRY-box2 (SOX2) expression and its impact on survival of patients with oesophageal adenocarcinoma.

BACKGROUND: Oesophageal adenocarcinoma (OAC) is a highly aggressive malignancy with poor survival, which is highly variable amongst patients with comparable conventional prognosticators. Therefore molecular biomarkers are urgently needed to improve the prediction of survival in these patients. SRY (sex determining region Y)-box 2, also known as SOX2, is a transcription factor involved in embryonal development of the gastrointestinal tract as well as in carcinogenesis. The purpose of this study was to see whether SOX2 expression is associated with survival in patients with OAC. METHODS: SOX2 was studied by immunohistochemistry in patients who had undergone potentially curative oesophagectomy for adenocarcinoma. Protein expression of SOX2 was evaluated using tissue microarrays from resection specimens, and results were analysed in relation to the clinical data by Cox regression analysis. SOX2 was evaluated in two independent OAC cohorts (Rotterdam cohort and a multicentre UK cohort). RESULTS: Loss of SOX2 expression was independently predictive of adverse overall survival in the multivariable analysis, adjusted for known factors influencing survival, in both cohorts (Rotterdam cohort: hazard ratio (HR) 1·42, 95 per cent c.i. 1·07 to 1·89, P = 0·016; UK cohort: HR 1·54, 1·08 to 2·19, P = 0·017). When combined with clinicopathological staging, loss of SOX2 showed an increased effect in patients with pT1-2 tumours (P = 0·010) and node-negative OAC (P = 0·038), with an incrementally adverse effect on overall survival for stage I OAC with SOX2 loss (HR 3·18, 1·18 to 8·56; P = 0·022). CONCLUSION: SOX2 is an independent prognostic factor for long-term survival in OAC, especially in patients with stage I OAC.

Active surveillance in clinically complete responders after neoadjuvant chemoradiotherapy for esophageal or junctional cancer.

Neoadjuvant chemoradiotherapy (nCRT) followed by surgery is standard of care for locally advanced esophageal cancer in many countries. After nCRT up to one third of all patients have a pathologically complete response in the resection specimen, posing an ethical imperative to reconsider the necessity of standard surgery in all operable patients after nCRT. An active surveillance strategy following nCRT, in which patients are subjected to frequent clinical investigations after the completion of neoadjuvant therapy, has been evaluated in other types of cancer with promising results. In esophageal cancer, both patients who are cured by neoadjuvant therapy alone as well as patients with subclinical disseminated disease at the time of completion of neoadjuvant therapy may benefit from such an organ sparing approach. Active surveillance is currently applied in selected patients with esophageal cancer who refuse surgery or are medically unfit for major surgery after completion of nCRT, but this strategy is not (yet) adopted as an alternative to standard surgery or definitive chemoradiation. The available literature is scarce, but suggests that long-term oncological outcomes after active surveillance are noninferior compared to standard surgical resection, providing justification for comparison of both treatments in a phase III trial. This review gives an overview of the current knowledge regarding active surveillance after completion of nCRT in esophageal cancer and outlines future research perspectives.

A multicentre comparative prospective blinded analysis of EUS and MRI for screening of pancreatic cancer in high-risk individuals.

OBJECTIVE: Endoscopic ultrasonography (EUS) and MRI are promising tests to detect precursors and early-stage pancreatic ductal adenocarcinoma (PDAC) in high-risk individuals (HRIs). It is unclear which screening technique is to be preferred. We aimed to compare the efficacy of EUS and MRI in their ability to detect clinically relevant lesions in HRI. DESIGN: Multicentre prospective study. The results of 139 asymptomatic HRI (>10-fold increased risk) undergoing first-time screening by EUS and MRI are described. Clinically relevant lesions were defined as solid lesions, main duct intraductal papillary mucinous neoplasms and cysts ≥10 mm. Results were compared in a blinded, independent fashion. RESULTS: Two solid lesions (mean size 9 mm) and nine cysts ≥10 mm (mean size 17 mm) were detected in nine HRI (6%). Both solid lesions were detected by EUS only and proved to be a stage I PDAC and a multifocal pancreatic intraepithelial neoplasia 2. Of the nine cysts ≥10 mm, six were detected by both imaging techniques and three were detected by MRI only. The agreement between EUS and MRI for the detection of clinically relevant lesions was 55%. Of these clinically relevant lesions detected by both techniques, there was a good agreement for location and size. CONCLUSIONS: EUS and/or MRI detected clinically relevant pancreatic lesions in 6% of HRI. Both imaging techniques were complementary rather than interchangeable: contrary to EUS, MRI was found to be very sensitive for the detection of cystic lesions of any size; MRI, however, might have some important limitations with regard to the timely detection of solid lesions.

CT-Colonography vs. Colonoscopy for Detection of High-Risk Sessile Serrated Polyps.

OBJECTIVES: Sessile serrated polyps (SSPs) are suggested to be the precursors of 15-30% of all colorectal cancers (CRCs). Therefore, CRC screening modalities should also be designed to detect high-risk SSPs. We compared computed tomography colonography (CTC) with colonoscopy-based screening for the detection of high-risk SSPs in average-risk individuals. METHODS: Data from a randomized controlled trial that compared CTC with colonoscopy for population screening were used for the analysis. Individuals diagnosed at CTC with a lesion ≥10 mm in size were referred for colonoscopy. Individuals with only 6-9 mm lesions were offered surveillance CTC. This surveillance CTC was followed by a colonoscopy when a lesion ≥6 mm was detected. Yield of both was accumulated to mimic current American College of Radiology CTC referral strategy (referral of individuals with any lesion ≥6 mm). Per participant detection of ≥1 high-risk (dysplastic and/or ≥10 mm) SSP was compared with colonoscopy using multiple logistic regression analysis. RESULTS: In total, 8,844 individuals were invited to participate (in 2:1 allocation), of which 1,276 colonoscopy and 982 CTC invitees participated in the study. In the colonoscopy arm, 4.3% of individuals were diagnosed with ≥1 high-risk SSP, compared with 0.8% in the CTC arm (odds ratio (OR) 5.5; 95% confidence interval (CI) 2.6-11.6; P<0.001). In total, 3.1% of individuals in the colonoscopy arm were diagnosed with high-risk SSPs as most advanced lesion, compared with 0.4% in the CTC arm (OR 7.7; 95% CI 2.7-21.6; P<0.001). The current CTC strategy showed a marked lower detection for especially flat high-risk SSPs (17 vs. 0), high-risk SSP located in the proximal colon (32 vs. 1), and SSPs with dysplasia (30 vs. 1). CONCLUSIONS: In a randomized controlled setting, the detection rate of high-risk SSPs was significantly higher with colonoscopy than CTC. These results might have implications for CTC as a CRC modality for opportunistic screening in average-risk adults.

Tumour antigen expression in hepatocellular carcinoma in a low-endemic western area.

BACKGROUND: Identification of tumour antigens is crucial for the development of vaccination strategies against hepatocellular carcinoma (HCC). Most studies come from eastern-Asia, where hepatitis-B is the main cause of HCC. However, tumour antigen expression is poorly studied in low-endemic, western areas where the aetiology of HCC differs. METHODS: We constructed tissue microarrays from resected HCC tissue of 133 patients. Expression of a comprehensive panel of cancer-testis (MAGE-A1, MAGE-A3/4, MAGE-A10, MAGE-C1, MAGE-C2, NY-ESO-1, SSX-2, sperm protein 17), onco-fetal (AFP, Glypican-3) and overexpressed tumour antigens (Annexin-A2, Wilms tumor-1, Survivin, Midkine, MUC-1) was determined by immunohistochemistry. RESULTS: A higher prevalence of MAGE antigens was observed in patients with hepatitis-B. Patients with expression of more tumour antigens in general had better HCC-specific survival (P=0.022). The four tumour antigens with high expression in HCC and no, or weak, expression in surrounding tumour-free-liver tissue, were Annexin-A2, GPC-3, MAGE-C1 and MAGE-C2, expressed in 90, 39, 17 and 20% of HCCs, respectively. Ninety-five percent of HCCs expressed at least one of these four tumour antigens. Interestingly, GPC-3 was associated with SALL-4 expression (P=0.001), an oncofetal transcription factor highly expressed in embryonal stem cells. SALL-4 and GPC-3 expression levels were correlated with vascular invasion, poor differentiation and higher AFP levels before surgery. Moreover, patients who co-expressed higher levels of both GPC-3 and SALL-4 had worse HCC-specific survival (P=0.018). CONCLUSIONS: We describe a panel of four tumour antigens with excellent coverage and good tumour specificity in a western area, low-endemic for hepatitis-B. The association between GPC-3 and SALL-4 is a novel finding and suggests that GPC-3 targeting may specifically attack the tumour stem-cell compartment.

Preoperative chemoradiotherapy for esophageal or junctional cancer.

BACKGROUND: The role of neoadjuvant chemoradiotherapy in the treatment of patients with esophageal or esophagogastric-junction cancer is not well established. We compared chemoradiotherapy followed by surgery with surgery alone in this patient population. METHODS: We randomly assigned patients with resectable tumors to receive surgery alone or weekly administration of carboplatin (doses titrated to achieve an area under the curve of 2 mg per milliliter per minute) and paclitaxel (50 mg per square meter of body-surface area) for 5 weeks and concurrent radiotherapy (41.4 Gy in 23 fractions, 5 days per week), followed by surgery. RESULTS: From March 2004 through December 2008, we enrolled 368 patients, 366 of whom were included in the analysis: 275 (75%) had adenocarcinoma, 84 (23%) had squamous-cell carcinoma, and 7 (2%) had large-cell undifferentiated carcinoma. Of the 366 patients, 178 were randomly assigned to chemoradiotherapy followed by surgery, and 188 to surgery alone. The most common major hematologic toxic effects in the chemoradiotherapy-surgery group were leukopenia (6%) and neutropenia (2%); the most common major nonhematologic toxic effects were anorexia (5%) and fatigue (3%). Complete resection with no tumor within 1 mm of the resection margins (R0) was achieved in 92% of patients in the chemoradiotherapy-surgery group versus 69% in the surgery group (P<0.001). A pathological complete response was achieved in 47 of 161 patients (29%) who underwent resection after chemoradiotherapy. Postoperative complications were similar in the two treatment groups, and in-hospital mortality was 4% in both. Median overall survival was 49.4 months in the chemoradiotherapy-surgery group versus 24.0 months in the surgery group. Overall survival was significantly better in the chemoradiotherapy-surgery group (hazard ratio, 0.657; 95% confidence interval, 0.495 to 0.871; P=0.003). CONCLUSIONS: Preoperative chemoradiotherapy improved survival among patients with potentially curable esophageal or esophagogastric-junction cancer. The regimen was associated with acceptable adverse-event rates. (Funded by the Dutch Cancer Foundation [KWF Kankerbestrijding]; Netherlands Trial Register number, NTR487.).

Histological and Molecular Subclassification of Pancreatic and Nonpancreatic Periampullary Cancers: Implications for (Neo) Adjuvant Systemic Treatment.

The benefit of adjuvant chemotherapy for resected pancreatic ductal adenocarcinoma (PDAC) has been confirmed in randomized controlled trials. For nonpancreatic periampullary cancers (NPPC) originating from the distal bile duct, duodenum, ampulla, or papilla of Vater, the role of adjuvant therapy remains largely unclear. This review describes methods for distinguishing PDAC from NPPC by means of readily available and recently developed molecular diagnostic methods. The difficulties of reliably determining the exact origin of these cancers pathologically also is discussed. The review also considers the possibility of unintentional inclusion of NPPC in the most important adjuvant trials on PDAC and the subsequent implications for interpretation of the results. The authors conclude that correct determination of the origin of periampullary cancers is essential for clinical management and should therefore be systematically incorporated into clinical practice and future studies.

Acoustically driven arrayed waveguide grating.

We demonstrate compact tunable phased-array wavelength-division multiplexers driven by surface acoustic waves (SAWs) in the low GHz range. The devices comprise two couplers, which respectively split and combine the optical signal, linked by an array of single-mode waveguides (WGs). Two different layouts are presented, in which multi-mode interference couplers or free propagating regions were separately employed as couplers. The multiplexers operate on five equally distributed wavelength channels, with a spectral separation of 2 nm. A standing SAW modulates the refractive index of the arrayed WGs. Each wavelength component periodically switches paths between the output channel previously asigned by the design and the adjacent channels, at a fixed applied acoustic power. The devices were monolithically fabricated on (Al,Ga)As. A good agreement between theory and experiment is achieved.

Spatial Patterns of Dissipative Polariton Solitons in Semiconductor Microcavities.

We report propagating bound microcavity polariton soliton arrays consisting of multipeak structures either along (x) or perpendicular (y) to the direction of propagation. Soliton arrays of up to five solitons are observed, with the number of solitons controlled by the size and power of the triggering laser pulse. The breakup along the x direction occurs when the effective area of the trigger pulse exceeds the characteristic soliton size determined by polariton-polariton interactions. Narrowing of soliton emission in energy-momentum space indicates phase locking between adjacent solitons, consistent with numerical modeling which predicts stable multihump soliton solutions. In the y direction, the breakup originates from inhomogeneity across the wave front in the transverse direction which develops into a stable array only in the solitonic regime via phase-dependent interactions of propagating fronts.

Human epidermal growth factor receptor 2 overexpression and amplification in endoscopic biopsies and resection specimens in esophageal and junctional adenocarcinoma.

Human epidermal growth factor receptor 2 (HER2) is overexpressed in a subset of esophageal adenocarcinomas. Frequently, biopsy material is used for evaluation of HER2 status. The aim of the study was to determine if HER2 expression in preoperative endoscopic biopsies is representative for the entire tumor. Preoperative endoscopic biopsies and matched resection specimens were collected from 75 patients who underwent esophagectomy for esophageal adenocarcinoma. Immunohistochemical staining (IHC) on HER2 and dual-color in situ hybridization (ISH) were performed. HER2 status was determined by following a clinical algorithm, first determining HER2 overexpression on immunohistochemistry and, when equivocal (2+), determining HER2 amplification on ISH. Seventy-one of 75 (95%) biopsies and 69/75 (92%) resection specimens could be analyzed due to technical failure. HER2 positivity was seen in 18/71 (25%) biopsies and in 15/69 (22%) resection specimens. Overall, HER2 status in the biopsy was concordant with HER2 status in the resection specimen in 94% of cases. Interobserver agreement on IHC scoring for all three observers was 83% in biopsies and 85% in resection specimens. HER2 positivity was detected in 22% of esophageal adenocarcinomas. Although interobserver agreement was moderate, HER2 status of a primary tumor can be reliably determined based on the endoscopically obtained pretreatment biopsy.

High-temperature, continuous-wave operation of terahertz quantum-cascade lasers with metal-metal waveguides and third-order distributed feedback.

Currently, different competing waveguide and resonator concepts exist for terahertz quantum-cascade lasers (THz QCLs). We examine the continuous-wave (cw) performance of THz QCLs with single-plasmon (SP) and metal-metal (MM) waveguides fabricated from the same wafer. While SP QCLs are superior in terms of output power, the maximum operating temperature for MM QCLs is typically much higher. For SP QCLs, we observed cw operation up to 73 K as compared to 129 K for narrow (≤ 15 µm) MM QCLs. In the latter case, single-mode operation and a narrow beam profile were achieved by applying third-order distributed-feedback gratings and contact pads which are optically insulated from the intended resonators. We present a quantitative analytic model for the beam profile, which is based on experimentally accessible parameters.

Effects of spin-dependent interactions on polarization of bright polariton solitons.

We report on the spin properties of bright polariton solitons supported by an external pump to compensate losses. We observe robust circularly polarized solitons when a circularly polarized pump is applied, a result attributed to phase synchronization between nondegenerate TE and TM polarized polariton modes at high momenta. For the case of a linearly polarized pump, either σ+ or σ- circularly polarized bright solitons can be switched on in a controlled way by a σ+ or σ- writing beam, respectively. This feature arises directly from the widely differing interaction strengths between co- and cross-circularly polarized polaritons. In the case of orthogonally linearly polarized pump and writing beams, the soliton emission on average is found to be unpolarized, suggesting strong spatial evolution of the soliton polarization. The observed results are in agreement with theory, which predicts stable circularly polarized solitons and unstable linearly polarized solitons.

The colorectal cancer screening program in the local health unit n. 6 of Livorno: evaluation of the screening activity in the period 2000-2011.

INTRODUCTION: The colorectal cancer screening program in the Local Health Unit n. 6 of Livorno is running since July 2000 and is meant to residents, aged between 50 and 70, who are invited to perform the test for faecal occult blood every 2 years. The aim of this work is an evaluation of the screening activity in the period 2000-2011. METHODS: The evaluation is based on the analysis of the main quality indicators formulated by GISCoR (Italian Group for Colorectal screening). RESULTS: The screening activity extension reached 93% in 2006 and 100% in 2009. The compliance level was maintained above the acceptable GISCoR value (> 45%) with a maximum of 54.9%. Values around 80% were recorded for the compliance to colonoscopy. The detection rate (DR) for cancer and advanced adenoma showed, as expected, the highest values in the early years and then move on values consistently lower than the regional average. In 2011, the raw DR for cancer was 0.9 x 1000 and the raw DR for advanced adenoma 5.3 x 1000. The distribution by stage at diagnosis of screen-detected carcinomas shows that 58.1% of these were identified at stage I while the proportion of cases in stage III+ is 19.5%. CONCLUSIONS: The overall analysis shows a good performance of the program. The proportion of colonoscopies performed on the total number of positive subjects remains a critical point of the system. The distribution by stage of screen-detected cancers shows an excellent diagnostic anticipation of the screening program.

Acceleration-induced spectral beats in strongly driven harmonic oscillators.

The harmonic modulation of coherent systems gives rise to a wealth of physical phenomena, e.g., the AC-Stark effect and Mollow triplets, with important implications for coherent control and frequency conversion. Here, we demonstrate a novel regime of temporal coherence in oscillators harmonically driven at extreme energy modulation amplitudes relative to the modulation quantum. The studies were carried out by modulating a confined exciton-polariton Bose-Einstein condensate (BEC) by an acoustic wave. Features of the new regime are the appearance, in the spectral domain, of a comb of resonances termed acceleration beats with energy spacing tunable by the modulation amplitude and, in the time domain, of temporal correlations at time scales much shorter than the acoustic period, which also depend on the modulation amplitude. These features are quantitatively accounted for by a theoretical framework, which associates the beats with accelerated energy-change rates during the harmonic cycle. These observations are underpinned by the high sensitivity of the BEC energy to the acoustic driving, which simultaneously preserves the BEC's temporal coherence. The acceleration beats are a general feature associated with accelerated energy changes: analogous features are thus also expected to appear under highly accelerated motion e.g., in connection with Cherenkov and Hawking radiation.