Solid-state continuous time crystal in a polariton condensate with a built-in mechanical clock.

Time crystals (TCs) are many-body systems that display spontaneous breaking of time translation symmetry. We demonstrate a TC by using driven-dissipative condensates of microcavity exciton-polaritons, spontaneously formed from an incoherent particle bath. The TC phases are controlled by the power of a continuous-wave nonresonant optical drive exciting the condensate and the interaction with cavity phonons. Those phases are, for increasing power, Larmor-like precession of the condensate pseudo-spins-a signature of continuous TC; locking of the frequency of precession to self-sustained coherent phonons-stabilized TC; and doubling of TC's period by phonons-a discrete TC with continuous excitation. These results establish microcavity polaritons as a platform for the investigation of time-broken symmetry in nonhermitian systems.

Asynchronous locking in metamaterials of fluids of light and sound.

Lattices of exciton-polariton condensates represent an attractive platform for the study and implementation of non-Hermitian bosonic quantum systems with strong non-linear interactions. The possibility to actuate on them with a time dependent drive could provide for example the means to induce resonant inter-level transitions, or to perform Floquet engineering or Landau-Zener-Stückelberg state preparation. Here, we introduce polaromechanical metamaterials, two-dimensional arrays of µm-sized traps confining zero-dimensional light-matter polariton fluids and GHz phonons. A strong exciton-mediated polariton-phonon interaction induces a time-dependent inter-site polariton coupling J(t) with remarkable consequences for the dynamics. When locally perturbed by continuous wave optical excitation, a mechanical self-oscillation sets-in and polaritons respond by locking the energy detuning between neighbor sites at integer multiples of the phonon energy, evidencing asynchronous locking involving the polariton and phonon fields. These results open the path for the coherent control of dissipative quantum light fluids with hypersound in a scalable platform.

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.

Polariton-driven phonon laser.

Efficient generation of phonons is an important ingredient for a prospective electrically-driven phonon laser. Hybrid quantum systems combining cavity quantum electrodynamics and optomechanics constitute a novel platform with potential for operation at the extremely high frequency range (30-300 GHz). We report on laser-like phonon emission in a hybrid system that optomechanically couples polariton Bose-Einstein condensates (BECs) with phonons in a semiconductor microcavity. The studied system comprises GaAs/AlAs quantum wells coupled to cavity-confined optical and vibrational modes. The non-resonant continuous wave laser excitation of a polariton BEC in an individual trap of a trap array, induces coherent mechanical self-oscillation, leading to the formation of spectral sidebands displaced by harmonics of the fundamental 20 GHz mode vibration frequency. This phonon "lasing" enhances the phonon occupation five orders of magnitude above the thermal value when tunable neighbor traps are red-shifted with respect to the pumped trap BEC emission at even harmonics of the vibration mode. These experiments, supported by a theoretical model, constitute the first demonstration of coherent cavity optomechanical phenomena with exciton polaritons, paving the way for new hybrid designs for quantum technologies, phonon lasers, and phonon-photon bidirectional translators.

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.

Granular dot-like staining with MLH1 immunohistochemistry is a clone-dependent artefact.

Immunohistochemistry (IHC) for DNA mismatch repair proteins MLH1, PMS2, MSH2, and MSH6 is used for microsatellite instability (MSI) screening in colorectal carcinoma (CRC) and endometrial carcinoma (EC). Loss of PMS2, with retained MLH1 staining occurs in germline mutations of PMS2 gene, and is an indication for genetic testing. We report a pitfall of immunohistochemical interpretation in an EC, initially regarded as MLH1-positive and PMS2-negative. Review of the MLH1-IHC (M1-clone) revealed a granular, dot-like, nuclear staining. On repeating the MLH1-IHC with a different clone (ES05-clone), complete negativity was noted, and on molecular testing, MLH1 promotor methylation was detected. The dot-like pattern was therefore adjudged a clone-dependent artefact. On reviewing the archived MLH1-IHC slides, we observed the same dot-like pattern in two CRCs; in both cases the M1-clone had been used. Awareness of this artefact may prevent reporting errors, and unnecessary referrals for germline mutation testing.

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.

Adherence to pre-set benchmark quality criteria to qualify as expert assessor of dysplasia in Barrett's esophagus biopsies - towards digital review of Barrett's esophagus.

Background: Dysplasia assessment of Barrett's esophagus biopsies is associated with low observer agreement; guidelines advise expert review. We have developed a web-based review panel for dysplastic Barrett's esophagus biopsies. Objective: The purpose of this study was to test if 10 gastrointestinal pathologists working at Dutch Barrett's esophagus expert centres met pre-set benchmark scores for quality criteria. Methods: Ten gastrointestinal pathologists twice assessed 60 digitalized Barrett's esophagus cases, enriched for dysplasia; then randomised (7520 assessments). We tested predefined benchmark quality criteria: (a) percentage of 'indefinite for dysplasia' diagnoses, benchmark score ≤14% for all cases, ≤16% for dysplastic subset, (b) intra-observer agreement; benchmark score ≥0.66/≥0.39, (c) percentage agreement with 'gold standard diagnosis'; benchmark score ≥82%/≥73%, (d) proportion of cases with high-grade dysplasia underdiagnosed as non-dysplastic Barrett's esophagus; benchmark score ≤1/78 (≤1.28%) assessments for dysplastic subset. Results: Gastrointestinal pathologists had seven years' Barrett's esophagus-experience, handling seven Barrett's esophagus-cases weekly. Three met stringent benchmark scores; all cases and dysplastic subset, three met extended benchmark scores. Four pathologists lacked one quality criterion to meet benchmark scores. Conclusion: Predefined benchmark scores for expert assessment of Barrett's esophagus dysplasia biopsies are stringent and met by some gastrointestinal pathologists. The majority of assessors however, only showed limited deviation from benchmark scores. We expect further training with group discussions will lead to adherence of all participating gastrointestinal pathologists to quality criteria, and therefore eligible to join the review panel.

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.

Hotspot DAXX, PTCH2 and CYFIP2 mutations in pancreatic neuroendocrine neoplasms.

Mutations in DAXX/ATRX, MEN1 and genes involved in the phosphoinositide-3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway have been implicated in pancreatic neuroendocrine neoplasms (pNENs). However, mainly mutations present in the majority of tumor cells have been identified, while proliferation-driving mutations could be present only in small fractions of the tumor. This study aims to identify high- and low-abundance mutations in pNENs using ultra-deep targeted resequencing. Formalin-fixed paraffin-embedded matched tumor-normal tissue of 38 well-differentiated pNENs was sequenced using a HaloPlex targeted resequencing panel. Novel amplicon-based algorithms were used to identify both single nucleotide variants (SNVs) and insertion-deletions (indels) present in >10% of reads (high abundance) and in <10% of reads (low abundance). Found variants were validated by Sanger sequencing. Sequencing resulted in 416,711,794 reads with an average target base coverage of 2663 ± 1476. Across all samples, 32 high-abundance somatic, 3 germline and 30 low-abundance mutations were withheld after filtering and validation. Overall, 92% of high-abundance and 84% of low-abundance mutations were predicted to be protein damaging. Frequently, mutated genes were MEN1, DAXX, ATRX, TSC2, PI3K/Akt/mTOR and MAPK-ERK pathway-related genes. Additionally, recurrent alterations on the same genomic position, so-called hotspot mutations, were found in DAXX, PTCH2 and CYFIP2. This first ultra-deep sequencing study highlighted genetic intra-tumor heterogeneity in pNEN, by the presence of low-abundance mutations. The importance of the ATRX/DAXX pathway was confirmed by the first-ever pNEN-specific protein-damaging hotspot mutation in DAXX. In this study, both novel genes, including the pro-apoptotic CYFIP2 gene and hedgehog signaling PTCH2, and novel pathways, such as the MAPK-ERK pathway, were implicated in pNEN.

Germline variant in MSX1 identified in a Dutch family with clustering of Barrett's esophagus and esophageal adenocarcinoma.

The vast majority of esophageal adenocarcinoma cases are sporadic and caused by somatic mutations. However, over the last decades several families have been identified with clustering of Barrett's esophagus and esophageal adenocarcinoma. This observation suggests that one or more hereditary factors may play a role in the initiation of Barrett's esophagus and esophageal adenocarcinoma in these families. A Dutch family with clustering of Barrett's esophagus and esophageal adenocarcinoma was identified. Normal DNA obtained from the proband diagnosed with Barrett's esophagus was analyzed with SNP array and exome sequencing. A custom-made panel consisting of potential germline variants was verified in the normal DNA of the affected family members. In addition, the respective tumors were analyzed for somatic loss of the wild type allele or the presence of an inactivating somatic mutation in the wild type allele. Exome sequencing revealed 244 candidate variants in the normal DNA of the proband, of which 212 variants were verified successfully. After the normal DNA of the affected family members was analyzed for the presence of the 212 potential germline variants and subsequently the respective tumors, only one potential germline variant in MSX1 (chr4: 4861985 T > G, c.359T > G, p.V120G, NM_002448) showed loss of the wild type allele in the tumor DNAs of the affected family members. A germline variant in MSX1 was identified in a Dutch family with clustering of Barrett's esophagus and esophageal adenocarcinoma. This finding indicates that the germline defect in MSX1 may be associated with Barrett's esophagus and cancer in this particular family.

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.

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.

Gonadal dysgenesis in disorders of sex development: Diagnosis and surgical management.

Recent studies on gonadal histology have improved the understanding of germ cell malignancy risk in patients with disorders of sex development (DSD), and evidence-based gonadal management strategies are gradually emerging. Especially in 46,XY DSD and 45,X/46,XY DSD, which are characterized by gonadal dysgenesis, the risk of germ cell malignancy is significantly increased. This paper summarized the progress over the past 10 years in malignancy risk assessment in patients with DSD, and its implications for optimal surgical handling of the involved gonads.

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.

A MicroRNA Panel in Pancreatic Cyst Fluid for the Risk Stratification of Pancreatic Cysts in a Prospective Cohort.

A subset of pancreatic cystic neoplasms are regarded as precursor lesions of pancreatic cancer, but only a minority of all pancreatic cystic neoplasms will undergo malignant transformation. MicroRNAs are increasingly recognized as molecular targets in carcinogenesis. Previously, a 9-microRNA (miR) signature was suggested to discriminate between high risk and low risk pancreatic cystic neoplasm. In this study, we aimed to validate this 9-miR panel in a prospective cohort. Total miR was isolated from pancreatic cyst fluid and expression of miR18a, miR24, miR30a-3p, miR92a, miR99b, miR106b, miR142-3p, miR342-3p, and miR532-3p was analyzed by singleplex Taqman MicroRNA Assay. A total of 62 patient samples were analyzed. During follow-up, 24 (38.7%) patients underwent resection, of which 6 (9.7%) patients showed at least high grade dysplasia. A logistic regression model presented a "predicted risk" score which significantly differed between low and high risk cysts, either including all patients or only those with histological confirmation of diagnosis. Using a set cut-off of 50%, the sensitivity of the model for the total cohort was 10.0%, specificity 100.0%, positive predicted value 100.0%, negative predicted value 85.2%, and diagnostic accuracy of 85.5%. Thus, while observing a significant difference between low and high risk cysts, clinical implementation of this biomarker panel is as yet unlikely to be beneficial in the management of pancreatic cysts.

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.