Pancreatic sphincterotomy to manage intraductal papillary mucinous neoplasm-related recurrent pancreatitis: are we ready for a controlled trial?

pancreatic sphincterotomya and efficacy oh recurrent pancreatitis in IPM

Pseudo solid-appearing pancreatic serous microcystic adenomas: Histologic diagnosis with the EUS core biopsy fork-tip needle

Background and Objectives: Despite rarely, serous cystic adenoma (SCA) can assume a pseudo-solid aspect mimicking other pancreatic neoplasm as neuroendocrine tumor. EUS-FNA cytology has low diagnostic accuracy due to the scant cellularity of the collected samples. Histological diagnosis is usually made after resection. Recently, end-cutting needles for EUS-fine-needle biopsy (EUS-FNB), which obtain tissue cores by penetrating the lesions, have been developed. We aimed to assess the capability of EUS-FNB with SharkCore (TM) needles in the preoperative diagnosis of serous cystic adenoma pseudo-solid-appearing on imaging (Sa-SCA). Materials and Methods: Between January 2016 and January 2018, data from consecutive adult patients, who were referred for EUS-FNB of a solid pancreatic lesion and were diagnosed with having SCA, were retrieved from a single-center institutional database. Results: Two patients were excluded because of microcystic aspect at EUS. Histological diagnosis of SCA was made by EUS-FNB in the remaining 7 patients (5 females; mean age of 62.5 years). Lesions (mean size of 19.8 mm) were hypervascular on cross-sectional imaging, slightly hyperdense magnetic resonance imaging with T2-weighted images can, and negative at Ga-68-somatostatin receptor positron emission tomography and (18)fluoro-deoxyglucose positron emission tomography. EUS-FNB samples were judged adequate for a definitive diagnosis in all cases, achieving specimens suitable for histological evaluation and several ancillary stains. Histochemical positivity for periodic acid-Schiff (PAS) and PAS with diastase digestion was observed in 7/7 cases. Immunohistochemical positivity for alpha-inhibin (7/7), GLUT1 (6/6), MUC6 (5/5), and negativity for synaptophysin (7/7) and chromogranin A (2/2) favored SCA diagnosis. Conclusions: In the case of preoperative workup suspected for Sa-SCA, a "forward acquiring" needle could improve the rate of preoperative histological diagnosis

Preliminary experience with pancreatic sphincterotomy as treatment for intraductal papillary mucinous neoplasm-associated recurrent pancreatitis

\u2002Pancreatic intraductal papillary mucinous neoplasms (IPMN) are cystic tumors of the pancreas characterized by a malignant potential. IPMN have been associated with recurrent pancreatitis (RP). Obstruction of the main pancreatic duct by thick mucus has been postulated to be the cause of pancreatitis. In a few isolated reports, pancreatic sphincterotomy (PS) has been reported to reduce the frequency of pancreatitis. The aim of this study was to assess the efficacy of PS in patients with IPMN-associated RP

Azathioprine Maintenance Therapy to Prevent Relapses in Autoimmune Pancreatitis

Steroids are used to induce remission in autoimmune pancreatitis (AIP). Low-dosage steroid therapy or immunosuppressant (IMs) has been proposed as maintenance therapy to prevent AIP relapse. Few and conflicting data have been published on the efficacy of azathioprine (AZA) in preventing AIP relapse. The aim of this study was to evaluate the indication and efficacy of AZA as maintenance therapy to prevent disease relapse in AIP

STRAS: a new high time resolution aerosol sampler for PIXE analysis

The joint use of hourly resolution sampling and analyses with accelerated ion beams such as Particle Induced X-ray Emission (PIXE) technique has allowed the measurement of hourly temporal patterns of particulate matter (PM) composition at many sites in different parts of the world. The demand within the scientific community for this type of analysis has been continuously increasing in recent years, but hourly resolution samplers suitable for PIXE analysis are now discontinued and/or suffer from some technical limitations. In this framework, a new hourly sampler, STRAS (Size and Time Resolved Aerosol Sampler), was developed for the collection of PM10, PM2.5 or PM1. It allows automatic sequential sampling of up to 168 hourly samples (1 week), it is mechanically robust, compact, and easily transportable. To increase PIXE sensitivity, each sample is concentrated on a small surface area on a polycarbonate membrane. The comparison between the elemental concentrations retrieved by STRAS samples and samples collected using a standard sequential sampler operated in parallel shows a very good agreement; indeed, if both the samplers use the same kind of membrane, the concentrations of all detected elements are in agreement within 10 %

CFTR function is impaired in a subset of patients with pancreatitis carrying rare CFTR variants

Background: Many affected by pancreatitis harbor rare variants of the cystic fibrosis (CF) gene, CFTR, which encodes an epithelial chloride/bicarbonate channel. We investigated CFTR function and the effect of CFTR modulator drugs in pancreatitis patients carrying CFTR variants. Methods: Next-generation sequencing was performed to identify CFTR variants. Sweat tests and nasal potential difference (NPD) assays were performed to assess CFTR function in vivo. Intestinal current measurement (ICM) was performed on rectal biopsies. Patient-derived intestinal epithelial monolayers were used to evaluate chloride and bicarbonate transport and the effects of a CFTR modulator combination: elexacaftor, tezacaftor and ivacaftor (ETI). Results: Of 32 pancreatitis patients carrying CFTR variants, three had CF-causing mutations on both alleles and yielded CF-typical sweat test, NPD and ICM results. Fourteen subjects showed a more modest elevation in sweat chloride levels, including three that were provisionally diagnosed with CF. ICM indicated impaired CFTR function in nine out of 17 non-CF subjects tested. This group of nine included five carrying a wild type CFTR allele. In epithelial monolayers, a reduction in CFTR-dependent chloride transport was found in six out of 14 subjects tested, whereas bicarbonate secretion was reduced in only one individual. In epithelial monolayers of four of these six subjects, ETI improved CFTR function. Conclusions: CFTR function is impaired in a subset of pancreatitis patients carrying CFTR variants. Mutations outside the CFTR locus may contribute to the anion transport defect. Bioassays on patient-derived intestinal tissue and organoids can be used to detect such defects and to assess the effect of CFTR modulators.</p

CFTR function is impaired in a subset of patients with pancreatitis carrying rare CFTR variants

Background: Many affected by pancreatitis harbor rare variants of the cystic fibrosis (CF) gene, CFTR, which encodes an epithelial chloride/bicarbonate channel. We investigated CFTR function and the effect of CFTR modulator drugs in pancreatitis patients carrying CFTR variants. Methods: Next-generation sequencing was performed to identify CFTR variants. Sweat tests and nasal potential difference (NPD) assays were performed to assess CFTR function in&nbsp;vivo. Intestinal current measurement (ICM) was performed on rectal biopsies. Patient-derived intestinal epithelial monolayers were used to evaluate chloride and bicarbonate transport and the effects of a CFTR modulator combination: elexacaftor, tezacaftor and ivacaftor (ETI). Results: Of 32 pancreatitis patients carrying CFTR variants, three had CF-causing mutations on both alleles and yielded CF-typical sweat test, NPD and ICM results. Fourteen subjects showed a more modest elevation in sweat chloride levels, including three that were provisionally diagnosed with CF. ICM indicated impaired CFTR function in nine out of 17 non-CF subjects tested. This group of nine included five carrying a wild type CFTR allele. In epithelial monolayers, a reduction in CFTR-dependent chloride transport was found in six out of 14 subjects tested, whereas bicarbonate secretion was reduced in only one individual. In epithelial monolayers of four of these six subjects, ETI improved CFTR function. Conclusions: CFTR function is impaired in a subset of pancreatitis patients carrying CFTR variants. Mutations outside the CFTR locus may contribute to the anion transport defect. Bioassays on patient-derived intestinal tissue and organoids can be used to detect such defects and to assess the effect of CFTR modulators

Development of synthetic ADAMTS7 selective inhibitors potentially useful for the treatment of cardiovascular diseases

ADAMTS (A Disintegrin And Metalloproteinase with Thrombospondin Motifs) family belongs to the superfamily of Metzincins and comprises 19 secreted zinc metalloproteinases. An altered homeostasis of ADAMTS enzymes is associated to pathological conditions, rendering these proteases an attractive pharmacological target. In particular, in vivo studies confirmed that ADAMTS7 is involved in both Coronary Artery Disease (CAD) and atherosclerosis. Overall, recent findings revealed the role of ADAMTS7 as promising target for intervention and its inhibition as a potential pharmacological approach. So far, no selective ADAMTS7 inhibitors have been reported. My Thesis project focused on the synthesis of potent and selective hydroxamate-based ADAMTS7 inhibitors, starting from the already published ADAMTS7 inhibitor EDV33. The optimization process led to the synthesis of new compounds, which were tested for enzymatic activity and selectivity by a fluorometric assay by Dr. Santamaria (Imperial College London, UK). The optimized compounds displayed a good activity on the target enzyme and a significant improvement in selectivity. Even though further modifications have to be done in order to develop a SAR study and achieve a high affinity and selectivity for ADAMTS7, final compounds reported in this Thesis showed promising results, thus representing a good starting point for future optimizations

Aggiornamento delle linee guida della pancreatite acuta

Commento sulle linee guida pancreatiche acut