A pleiotropy scan to discover new susceptibility loci for pancreatic ductal adenocarcinoma.

Pleiotropic variants (i.e., genetic polymorphisms influencing more than one phenotype) are often associated with cancer risk. A scan of pleiotropic variants was successfully conducted ten years ago in relation to pancreatic ductal adenocarcinoma susceptibility. However, in the last decade, genetic association studies performed on several human traits have greatly increased the number of known pleiotropic variants. Based on the hypothesis that variants already associated with a least one trait have a higher probability of association with other traits, 61,052 variants reported to be associated by at least one genome wide association study (GWAS) with at least one human trait were tested in the present study consisting of two phases (discovery and validation), comprising a total of 16,055 pancreatic ductal adenocarcinoma (PDAC) cases and 212,149 controls. The meta-analysis of the two phases showed two loci (10q21.1-rs4948550 (P=6.52×10-5) and 7q36.3-rs288762 (P=3.03×10-5) potentially associated with PDAC risk. 10q21.1-rs4948550 shows a high degree of pleiotropy and it is also associated with colorectal cancer risk while 7q36.3-rs288762 is situated 28,558 base pairs upstream of the Sonic Hedgehog (SHH) gene, which is involved in the cell differentiation process and PDAC etiopathogenesis. In conclusion, none of the single nucleotide polymorphisms (SNPs) showed a formally statistically significant association after correction for multiple testing. However, given their pleiotropic nature and association with various human traits including colorectal cancer, the two SNPs showing the best associations with PDAC risk merit further investigation through fine mapping and ad hoc functional studies.

Liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) methods for the therapeutic drug monitoring of cytotoxic anticancer drugs: An update.

In the era of precision medicine, there is increasing evidence that conventional cytotoxic agents may be suitable candidates for therapeutic drug monitoring (TDM)- guided drug dosage adjustments and patient's tailored personalization of non-selective chemotherapies. To that end, many liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) assays have been developed for the quantification of conventional cytotoxic anticancer chemotherapies, that have been comprehensively and critically reviewed. The use of stable isotopically labelled internal standards (IS) of cytotoxic drugs was strikingly uncommon, accounting for only 48 % of the methods found, although their use could possible to suitably circumvent patients' samples matrix effects variability. Furthermore, this approach would increase the reliability of cytotoxic drug quantification in highly multi-mediated cancer patients with complex fluctuating pathophysiological and clinical conditions. LC-MS/MS assays can accommodate multiplexed analyses of cytotoxic drugs with optimal selectivity and specificity as well as short analytical times and, when using stable-isotopically labelled IS for quantification, provide concentrations measurements with a high degree of certainty. However, there are still organisational, pharmacological, and medical constraints to tackle before TDM of cytotoxic drugs can be more largely adopted in the clinics for contributing to our ever-lasting quest to improve cancer treatment outcomes.

All-in-Fiber Electrochemical Sensing.

Electrochemical sensors have found a wide range of applications in analytical chemistry thanks to the advent of high-throughput printing technologies. However, these techniques are usually limited to two-dimensional (2D) geometry with relatively large minimal feature sizes. Here, we report on the scalable fabrication of monolithically integrated electrochemical devices with novel and customizable fiber-based architectures. The multimaterial thermal drawing technique is employed to co-process polymer composites and metallic glass into uniform electroactive and pseudoreference electrodes embedded in an insulating polymer cladding fiber. To demonstrate the versatility of the process, we tailor the fiber microstructure to two configurations: a small-footprint fiber tip sensor and a high-surface-area capillary cell. We demonstrate the performance of our devices using cyclic voltammetry and chronoamperometry for the direct detection and quantification of paracetamol, a common anesthetic drug. Finally, we showcase a fully portable pipet-based analyzer using low-power electronics and an "electrochemical pipet tip" for direct sampling and analysis of microliter-range volumes. Our approach paves the way toward novel materials and architectures for efficient electrochemical sensing to be deployed in existing and novel personal care and surgical configurations.

Long-term outcomes after pancreatoduodenectomy for ampullary cancer: The influence of the histological subtypes and comparison with the other periampullary neoplasms.

BACKGROUND: Ampullary carcinoma (AC) is histologically classified as intestinal (In-AC), pancreaticobiliary (Pb-AC) or mixed-AC. The prognostic role of AC subtypes has been debated and remains unclear. The aims of this study were to evaluate outcomes after pancreatoduodenectomy (PD) for each subtype of AC and to compare these with pancreatic ductal adenocarcinoma [PDAC] and distal cholangiocarcinoma [DCC]. METHODS: PDs performed for AC between 2010 and 2018 were retrospectively evaluated. Histological subtype was obtained for all patients. One-year, 3-year and 5-year disease-free-survival (DFS) and overall survival (OS) rates were calculated. Kaplan-Meier survival analysis was performed to compare Pb-AC, In-AC and mixed-AC. Comparison with PDs performed for PDAC and DCC during the same period was also performed. RESULTS: A total of 97 patients undergoing PD for AC were evaluated: 34 (35.1%) In-AC, 54 (55.7%) Pb-AC and 9 mixed-AC (9.3%). DFS and OS rates for Pb-AC were significantly lower compared to In-AC (p < 0.05 and p < 0.01), but similar to mixed-AC (p = 0.3 and p = 0.4). Adjuvant therapy was not associated with increased survival, regardless of the histological subtype (p > 0.05). During the same period, 337 and 53 PDs for PDAC and DCC, respectively, were performed. In-AC was associated with significantly better outcomes compared to PDAC and DCC (p < 0.001); DFS and OS rates for Pb-AC and mixed AC were significantly higher compared to PDAC (p < 0.001), but similar to DCC (p > 0.05). CONCLUSIONS: Pb-AC has significantly worse survival compared to In-AC. Moreover, mixed-AC should be considered as Pb-AC. Pb-AC and mixed-AC seem to have better prognosis compared to PDAC, but similar to DCC.

The Number of Metastatic Lymph Nodes is a Useful Predictive Factor for Recurrence after Surgery for Nonmetastatic Nonfunctional Neuroendocrine Neoplasm of the Pancreas.

Nodal involvement (actually categorized as positive or negative) is an important prognostic factor after surgery for pancreatic neuroendocrine neoplasms (pNENs). We aim to evaluate the predictive role of the number of nodal metastases after pancreatic resection for pNENs. We analyzed from a prospectively maintained database all pancreatic resections for nonmetastatic nonfunctioning pNENs performed in our institution from 2011 to 2016. According to the number of nodal metastases, enhancing the actual categorization, we distinguished the following: N0, no nodal metastases; N1, 1-3 metastatic lymph nodes; and N2, metastases in 4 or more regional lymph nodes. Recurrence and disease-free survival (DFS) were evaluated. The predictive value in terms of recurrence for each clinicopathological data, including the number of metastatic lymph nodes, was calculated. Univariate and multivariate analyses were conducted. 77 patients underwent pancreatic surgery for pNENs. N0, N1, and N2 resections were found in 52 (67.5%), 16 (20.8%), and 9 (11.7%) cases, respectively. Mean follow-up of the entire cohort was 48 (±25) months. The recurrence rate was 11.8%, and the mean time of recurrence was 12 (±14) months. DFS was 83.7 months (76.0 - 91.5). At a univariate analysis, factors associated with recurrence were mitotic count (OR 1.19, p = 0.001), Ki67 value (OR 1.06, p = 0.001), the presence of nodal metastases (OR 11.54, p = 0.002), and metastases in 4 or more regional lymph nodes (N2) (OR 30.19, p = 0.002). At a multivariate analysis, only mitotic count (OR 1.51, p = 0.005) and N2 resection (OR 134.74, p = 0.002) were found to be predictive factors of recurrence. The number of metastatic lymph nodes and mitotic count is the most significant predictive factors of recurrence after pancreatic surgery for nonmetastatic nonfunctioning pNENs.

Aptamer-based Field-Effect Biosensor for Tenofovir Detection.

During medical treatment it is critical to maintain the circulatory concentration of drugs within their therapeutic range. A novel biosensor is presented in this work to address the lack of a reliable point-of-care drug monitoring system in the market. The biosensor incorporates high selectivity and sensitivity by integrating aptamers as the recognition element and field-effect transistors as the signal transducer. The drug tenofovir was used as a model small molecule. The biointerface of the sensor is a binary self-assembled monolayer of specific thiolated aptamer and 6-mercapto-1-hexanol (MCH), whose ratio was optimized by electrochemical impedance spectroscopy measurements to enhance the sensitivity towards the specific target. Surface plasmon resonance, performed under different buffer conditions, shows optimum specific and little non-specific binding in phosphate buffered saline. The dose-response behavior of the field-effect biosensor presents a linear range between 1 nM and 100 nM of tenofovir and a limit of detection of 1.2 nM. Two non-specific drugs and one non-specific aptamer, tested as stringent control candidates, caused negligible responses. The applications were successfully extended to the detection of the drug in human serum. As demonstrated by impedance measurements, the aptamer-based sensors can be used for real-time drug monitoring.

Surface trap mediated electronic transport in biofunctionalized silicon nanowires.

Silicon nanowires (SiNWs), fabricated via a top-down approach and then functionalized with biological probes, are used for electrically-based sensing of breast tumor markers. The SiNWs, featuring memristive-like behavior in bare conditions, show, in the presence of biomarkers, modified hysteresis and, more importantly, a voltage memory component, namely a voltage gap. The voltage gap is demonstrated to be a novel and powerful parameter of detection thanks to its high-resolution dependence on charges in proximity of the wire. This unique approach of sensing has never been studied and adopted before. Here, we propose a physical model of the surface electronic transport in Schottky barrier SiNW biosensors, aiming at reproducing and understanding the voltage gap based behavior. The implemented model describes well the experimental I-V characteristics of the device. It also links the modification of the voltage gap to the changing concentration of antigens by showing the decrease of this parameter in response to increasing concentrations of the molecules that are detected with femtomolar resolution in real human samples. Both experiments and simulations highlight the predominant role of the dynamic recombination of the nanowire surface states, with the incoming external charges from bio-species, in the appearance and modification of the voltage gap. Finally, thanks to its compactness, and strict correlation with the physics of the nanodevice, this model can be used to describe and predict the I-V characteristics in other nanostructured devices, for different than antibody-based sensing as well as electronic applications.

Nano-fabricated memristive biosensors for biomedical applications with liquid and dried samples.

Nanowire based platforms are widely reported for sensing applications and for their potential in the bio-detection field. In the present work, memristive nanowire devices are implemented for label-free sensing in liquid samples as well as in dried samples via leveraging the modification of the hysteresis in the devices electrical response as a consequence of the surface modification. First, pH sensing in liquid conditions is demonstrated. In addition, the memristive devices are bio-functionalized using antibodies for Prostate Specific Antigen (PSA) as case of study. In this way, the nanowires are converted to memristive biosensors paving the way for future molecular diagnostics applications in general, and for detection of prostate cancer disease in particular.

Study on the bio-functionalization of memristive nanowires for optimum memristive biosensors.

Semiconductor nanowires are emerging as promising building blocks for biosensors enabling direct electrical detection of various biomolecules. In this framework, two-terminal Schottky-barrier silicon (Si) nanowire arrays that exhibit memristive electrical response, so-called memristive devices, are bio-functionalized and converted to memristive biosensors for bio-detection purposes. A comparative analysis of three bio-functionalization strategies is proposed here in order to design and develop optimum memristive biosensors to be implemented in label-free sensing applications. The surface of the device is modified with an anti-free-Prostate Specific Antigen (PSA) antibody as the case of study via: (a) direct adsorption on the device surface, (b) a bio-affinity approach using biotin-streptavidin combination and (c) covalent attachment using (3-glycidyloxypropyl)trimethoxysilane (GPTES). The optimum memristive biosensor is defined via the calibration and comparative study of the biosensors' electrical response under controlled environmental conditions (humidity and temperature) in order to maximize the performance of the biosensor. In addition, it is demonstrated that the direct passive adsorption strategy presents double the performance of the other two methods. The uptake of biological molecules on the nanostructure surface is verified by atomic force microscopy and confocal microscopy. Scanning electron microscopy reveals the details of the surface morphology of the nanofabricated structures before and after bio-functionalization for the three methods applied. The system shows potential for general application in molecular diagnostics, and, in particular, for the early detection of prostate cancer.

Continuous monitoring of Naproxen by a cytochrome P450-based electrochemical sensor.

This paper reports the characterization of an electrochemical biosensor for the continuous monitoring of Naproxen based on cytochrome P450. The electrochemical biosensor is based on the drop-casting of multi-walled carbon-nanotubes (MWCNTs) and microsomal cytochrome P4501A2 (msCYP1A2) on a graphite screen-printed electrode (SPE). The proposed biosensor was employed to monitor Naproxen (NAP), a well-known anti-inflammatory compound, through cyclic voltammetry. The dynamic linear range for the amperometric detection of NAP had an upper limit of 300 µM with a corresponding limit of detection (LOD) of 16 ± 1 µM (S/N=3), which is included in NAP physiological range (9-300 µM). The MWCNT/msCYP1A2-SPE sensor was also calibrated for NAP detection in mouse serum that was previously extracted from mice, showing a slightly higher LOD (33 ± 18 µM). The stability of the msCYP1A2-based biosensor was assessed by longtime continuous cyclic voltammetric measurements. The ability of the sensor to monitor drug delivery was investigated by using a commercial micro-osmotic pump. Results show that the MWCNT/msCYP1A2-SPE sensor is capable of precisely monitoring the real-time delivery of NAP for 16 h. This work proves that the proposed electrochemical sensor might represent an innovative point-of-care solution for the personalization of drug therapies, as well as for pharmacokinetic studies in both animals and humans.

Social and ethical determinants of sexuality: gender and health.

The aim of this paper is to expand concepts of gender and explore how behaviours associated with sexual identity affect health risks, as well as the right to sexual expression for sexual minorities and persons with disabilities, to promote safe sexual behaviour and reduce the incidence of sexually transmitted diseases, through the internationally sanctioned Sexual and Reproductive Health concept. During the XX century the multiple meanings of sexuality have been progressively recognized and its physical and psychological health dimension have become a reality, enshrined in United Nations (UN) documents. Countries have begun to adapt their legislations to this new reality and Conventions today guarantee equal sexual and reproductive rights to persons with disabilities, while the nature of variant sexual behaviours is being debated. Sexual and reproductive health is today an acknowledged goal for every individual and the right to equality for persons with variant behaviours and disabilities, as well as the coexistence of diverse meanings of sexuality an established fact. Healthy and safe sexual behaviour should become an important goal for all societies and cultures.

Social and ethical determinants of human sexuality: 1. The need to reproduce.

Aims of this study was to review the many and diverse factors conditioning human sexual behavior; starting with the first and still most important: the need to reproduce and to analyse these factors and how they have changed over time in order to better understand the interplay between the major determinants of human sexuality. For this aim the authors made a literature review of relevant scientific papers and books, including religious websites. At the dawn of humanity, sexuality was focused on reproduction; this, however, did not exclude other important meanings in sexual relationships, since non-conceptive copulations have been a constant aspect of human behavior, becoming an almost unique feature of genus homo. In this respect, the characteristics of a female continuously accessible to her male set the stage for a trend towards monogamy and created the substrate for closed families. Anthropologists have justified conceptive sexuality because sexual activity is costly in terms of energy consumption; for this reason, in the early days, restricting sexual activity made sense for the survival of the species. Traditional ethical considerations and ancient norms by the three major monotheistic religions have favored conceptive sexuality, restricting sexual activity to sanctioned unions and insisting that the major scope of sexuality is procreation. In spite of this, among humans sexuality has always had a wider meaning to the point that for millennia, humans have tried to separate its unitive and procreative meanings. Today much has changed since reproduction can be achieved without intercourse, further separating it from sexual activity. In humans sexuality always possessed multiple meanings, first and foremost reproduction and the creation of a bond between a man and one or several women.

Estimating diagnostic accuracy of tests for latent tuberculosis infection without a gold standard among healthcare workers.

The evaluation of diagnostic accuracy of new in vitro diagnostic assays for tuberculosis infection has been hampered by the lack of a standard reference test. The aim of this study was to compare sensitivity and specificity of interferon gamma assays for latent tuberculosis infection by assessing the association of test results with tuberculosis occupational exposure and by using latent class analysis. We analysed data from 115 healthcare workers on whom tuberculin skin test (TST) and the following in vitro tests were performed: in-house ELISPOT for RD1 proteins, T.SPOT-TB and Quantiferon-TB Gold. Results of all tests were associated with increased occupational risk of exposure to Mycobacterium tuberculosis, but only TST was associated with Bacillus Calmette-Guerin (BCG) vaccination. Sensitivity/specificity (95% confidence intervals) estimated by a latent class model were: 99.9%/64.2% (53.0-74.1) for TST, 95.3% (61.8-99.6)/87.5% (78.0-93.2) for in-house ELISPOT, 96.7% (69.3-99.7)/85.6%(75.3-92.0) for T.SPOT-TB, and 76.3% (55.9-89.1)/93.6% (85.4-97.3) for Quantiferon. The estimated specificity of in vitro assays was higher than that of TST also among individuals who were not BCG-vaccinated. In conclusion, when used in healthcare workers, in vitro assays may provide a significant increase of specificity for tuberculosis infection compared to TST, even among non vaccinated individuals, at the cost of some sensitivity.

Investigation of Oddi sphincter structure by optical coherence tomography in patients with biliary-type 1 dysfunction: a pilot in vivo study.

BACKGROUND: Type 1 sphincter of Oddi dysfunction is a clinical entity characterised by biliary-type pain, elevated liver biochemical tests, and common bile duct dilation. Sphincter fibrosis is a common finding in this type of dysfunction and may require in some cases a differential diagnosis with a malignant intra-papillary disease. Optical coherence tomography permits high-resolution, real-time imaging of the sphincter of Oddi microstructure by a probe inserted into the common bile duct through an ERCP catheter. No data exist on the evaluation of sphincter of Oddi fibrosis by optical coherence tomography during ERCP in vivo. OBJECTIVE: To assess the feasibility of optical coherence tomography investigation of the sphincter of Oddi structure and assess its potential for diagnosing type 1 sphincter of Oddi dysfunction. PATIENTS: Ten consecutive patients, five with biliary-type 1 sphincter of Oddi dysfunction and five with pancreatic head/mid-body adenocarcinoma not involving the papillary region, who underwent both endoscopic ultrasound and therapeutic ERCP, were investigated by optical coherence tomography immediately before biliary sphincterotomy or stenting. RESULTS: In all sphincter of Oddi dysfunction patients optical coherence tomography recognised a hyper-reflective intermediate, fibro-muscular layer, significantly thicker than in patients with non-pathological sphincter of Oddi (p<0.0001). CONCLUSIONS: Optical coherence tomography imaging recognised an increased thickness and reflectance of the fibro-muscular layer of the sphincter of Oddi, very likely determined by fibrosis, and was not time-consuming; it can be safely used during ERCP to confirm the diagnosis in difficult cases. Its use in clinical practice has one important limitation since it requires magnification in the post-procedure computer analysis to obtain images useful for diagnosis.

Characterization of regulatory T cells identified as CD4(+)CD25(high)CD39(+) in patients with active tuberculosis.

Forkhead box P3 (FoxP3) is a transcription factor whose expression characterizes regulatory T cells (T(reg)), but it is also present on activated T cells, thus hindering correct T(reg) identification. Using classical markers for T(reg) recognition, discordant results were found in terms of T(reg) expansion during active tuberculosis (TB) disease. Recently CD39 has been shown to be an accurate marker for T(reg) detection. The objectives of this study were: (i) to identify T(reg) expressing CD39 in patients with TB and to compare the results with those obtained by the standard phenotypic markers; (ii) to evaluate if T(reg) are expanded in vitro by exogenous interleukin (IL)-2 or by antigen-specific stimulation; and (iii) to characterize T(reg) function on the modulation of antigen-specific responses. We enrolled 13 patients with pulmonary TB and 12 healthy controls. T(reg) were evaluated by flow cytometry ex vivo and after antigen-specific in vitro stimulation using CD25, FoxP3, CD127 and CD39 markers. Results indicate that CD39(+) cells within the CD4(+)CD25(high) cells have T(reg) properties (absence of interferon-gamma production and transforming growth factor-beta1 release upon stimulation). Ex vivo analysis did not show significant differences between TB patients and controls of T(reg) by classical or novel markers. In contrast, a significantly higher percentage of T(reg) was found in TB patients after antigen-specific stimulation both in the presence or absence of IL-2. Depletion of CD39(+) T(reg) increased RD1-specific responses significantly. In conclusion, CD39 is an appropriate marker for T(reg) identification in TB. These results can be useful for future studies to monitor Mycobacterium tuberculosis-specific response during TB.

[Voluntary pregnancy termination over the first trimester. A five-year observation]. / Interruzione volontaria di gravidanza oltre il primo trimestre. Cinque anni di osservazione.

AIM: The law for legalising abortion was approved by the Italian Government in May 1978. In regulating legal abortion this law identifies two different scenarios: one where legal abortion is performed within 90 days of gestational age, and the second where it can be performed beyond this term but within 120 days: ''when pregnancy or delivery can cause a severe damage to the woman's life, in case of severe pathologies, as fetal relevant anomalies or malformations which can cause a severe damage to the woman's physical or psychological health''. Since during the last years an increase of requests for voluntary pregnancy termination (VPT) over 90 days of gestational age has been observed in Italy, it was decided to carry out a retrospective study on the reasons for requesting such an operation. METHODS: All interventions for VPT over 90 days of gestational age performed in the Department of Obstetrics and Gynecology in the University of Rome ''La Sapienza'' between January 2003 and December 2007 have been re-assessed, analysing age of women, obstetric anamnesis, reasons for VPT request, gestational age, mode of intervention, complications due to intervention and days of inpatient admission. RESULTS: During five years 255 women demanded to terminate a pregnancy over the first trimester. In all cases requested have been authorized following a psychological consult assessing a severe damage on psychological health by the Clinical Psychology Service of ''La Sapienza'' University, that in all cases was subsequent to a diagnosis of fetal anomalies, ascertained by a genetic test and/or ultrasound scan. Anomalies were genetic in 112 of cases (43.2%) and morphological, both single and multiple, in 143 of cases (56.8%). In most of the cases (65%) these anomalies have been assessed by ultrasound scan, while in 35% by cariotype analysis. CONCLUSION: After the legalisation in 1978, cases of abortion have constantly increased. More detailed data would be helpful to better understand and face this event.

Endoscopic ultrasound-guided application of a new internally gas-cooled radiofrequency ablation probe in the liver and spleen of an animal model: a preliminary study.

BACKGROUND AND STUDY AIMS: In a previous study, a new flexible bipolar hybrid cryotherm probe was applied with success to the pancreas of a living pig. Here we evaluated feasibility, efficacy, and safety of its application to the porcine liver and spleen. MATERIAL AND METHODS: Ten applications to the liver and nine to the spleen were performed in 19 pigs. Power input (16-18 W) and simultaneous cooling with CO(2) (standardized pressure: 675 psi) as the cryogenic agent were investigated. Application time varied from 120 seconds to 900 seconds. The ablation area was measured by endoscopic ultrasound (EUS) after ablation (T0), and before euthanasia (T1). Gross pathology (T2) and histology after necropsy represented the gold standard. The interval from treatment to euthanasia was 1 or 2 weeks. RESULTS: For both organs the correlation between EUS and gross pathology was good (correlation coefficient R(liver) = 0.71; R(spleen) = 0.73). EUS tended to overestimate the area of the ablated zone. EUS observed a time-dependent ablation area: we demonstrated a positive trend of lesion size (T1) over time in liver tissue (R = 0.51 (P = 0.1)). In the spleen we found a clear correlation of lesion area T2 and application time (R = 0.75, P = 0.01). There were no complications. CONCLUSIONS: Selective EUS-guided transgastric cryotherm ablation of the liver and spleen in a pig model is feasible and safe. The new bipolar probe creates a time-dependent ablation area without any complications, and opens a field of new potential indications of RF-ablative therapies.

Endoscopic ultrasound-guided application of a new hybrid cryotherm probe in porcine pancreas: a preliminary study.

BACKGROUND AND STUDY AIMS: Open, laparoscopic, or percutaneous radiofrequency (RF) ablation of the pancreas is still dangerous, whereas endoscopic ultrasound (EUS)-guided ablation might reduce risk because it is less invasive and provides real-time monitoring. We aimed to demonstrate the feasibility of transluminal RF ablation and to evaluate the efficacy and safety of a new flexible bipolar ablation probe combining RF and cryotechnology. METHODS: 14 ablations were performed in 14 pigs. Energy input (16 W) and simultaneous cryogenic cooling with carbon dioxide (650 psi) were standardized. Application time range was 120 - 900 seconds. Ablation area was measured by EUS immediately after ablation (area T0), and before euthanasia (area T1). Macroscopic findings (area T2) and histological findings after necropsy served as gold standard. The interval from application to euthanasia was either 1 or 2 weeks. RESULTS: The correlation between EUS findings (area T1) and macroscopic appearance (area T2) was good ( R = 0.89). The correlation between the T2 ablation area and the application time showed a fitted ratio of 2.3 ( P < 0.0001) with a 1-week interval and 0.2 ( P = 0.01) with a 2-week interval. No pig died because of the procedure. Two pigs showed histochemical pancreatitis, which was clinically overt in one. Necropsy additionally revealed one burn to the gastric wall and four gut adhesions. CONCLUSIONS: Selective transluminal RF ablation of the pancreas under EUS control in a living pig model is feasible. The new flexible bipolar probe creates an ablation area with extent related to the duration of application, and with fewer complications than conventional RF ablation techniques.