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Surveillance costs and appropriateness of surgery of "low-risk" BD-IPMNs are relevant issues. In this study we evaluated the rate of correct indication for pancreatectomy defined as high grade dysplasia (HGD) at histology in 961 patients who underwent surveillance for a median of 5.1 years. Undertreatment and overtreatment were defined as invasive cancer and low grade dysplasia (LGD) at histology, respectively. Of the 66 patients (6.9%) who were operated, only 16 (23.8%) had a HGD while 40 (59.7%) had a LGD and 10 (14.9%) an invasive cancer, without differences regarding timing of surgery. The mean surveillance cost was € 194.9 ± 107.6 per patient-year, with a median cost of € 277.1 ± 148.2 in the correct surgery group compared with € 222.7 ± 111.6 and € 197 ± 102.7 in the overtreatment and undertreatment groups. The surveillance mean cost from diagnosis to surgery was € 854.8. Rate of appropriate surgery in BD-IPMNs under surveillance is low.

Background: The cost-effectiveness of minimally invasive distal pancreatectomy (MIDP) is still a matter of debate. This study compares the cost-effectiveness of open (ODP), laparoscopic (LDP) and robotic distal pancreatectomy (RDP).Methods: Pubmed, Web of Science and Cochrane Library databases were searched. Studies comparing cost-effectiveness of ODP and MIDP were included.Results: A total of 1052 titles were screened and 16 articles were included in the study, 2431 patients in total. LDP resulted the most cost-efficient procedure, with a mean total cost of 14,682 +/- 5665 V and the lowest readmission rates. ODP had lower surgical procedure costs, 3867 +/- 768 V. RDP was the safest approach regarding hospital stay costs (5239 +/- 1741 V), length of hospital stay, morbidity, clinically relevant pancreatic fistula and reoperations.Conclusion: In this meta-analysis MIDP resulted as the most cost-effective approach. LDP seems to be protective against high costs, but RDP seems to be safer. (C) 2021 Elsevier Inc. All rights reserved.

Drug-induced pancreatitis is a gastrointestinal adverse effect concerning about 2% of drugs. The majority of cases are mild to moderate but severe episodes can also occur, leading to hospitalization or even death. Unfortunately, the mechanisms of this adverse reaction are still not clear, hindering its prevention, and the majority of data available of this potentially life-threatening adverse effect are limited to case reports leading to a probable underestimation of this event. In particular, in this editorial, special attention is given to thiopurine-induced pancreatitis (TIP), an idiosyncratic adverse reaction affecting around 5% of inflammatory bowel disease (IBD) patients taking thiopurines as immunosuppressants, with a higher incidence in the pediatric population. Validated biomarkers are not available to assist clinicians in the prevention of TIP, also because of the inaccessibility of the pancreatic tissue, which limits the possibility to perform dedicated cellular and molecular studies. In this regard, induced pluripotent stem cells (iPSCs) and the exocrine pancreatic differentiated counterpart could be a great tool to investigate the cellular and molecular mechanisms underlying the development of this undesirable event. This particular type of stem cells is obtained by reprogramming adult cells, including fibroblasts and leukocytes, with a set of transcription factors known as the Yamanaka's factors. Maintaining unaltered the donors' genetic heritage, iPSCs represent an innovative model to study the mechanisms of adverse drug reactions in individual patients' tissues not easily obtainable from human probands. Indeed, iPSCs can differentiate under adequate stimuli into almost any somatic lineage, opening a new world of opportunities for researchers. Several works are already available in the literature studying liver, central nervous system and cardiac cells derived from iPSCs and adverse drug effects. However, to our knowledge no studies have been performed on exocrine pancreas differentiated from iPSCs and drug-induced pancreatitis, so far. Hence, in this editorial we focus specifically on the description of the study of the mechanisms of TIP by using IBD patient-specific iPSCs and exocrine pancreatic differentiated cells as innovative in vitro models.

Aims Intraductal tubulopapillary neoplasm (ITPN) of the pancreas is a recently recognized pancreatic tumor entity. Here we aimed to determine the most important features with a systematic review coupled with an integrated statistical approach. Methods and results PubMed, SCOPUS, and Embase were searched for studies reporting data on pancreatic ITPN. The clinicopathological, immunohistochemical, and molecular data were summarized. Then a comprehensive survival analysis and a comparative analysis of the molecular alterations of ITPN with those of pancreatic ductal adenocarcinoma (PDAC) and intraductal papillary mucinous neoplasm (IPMN) from reference cohorts (including the International Cancer Genome Consortium- ICGC dataset and The Cancer Genome Atlas, TCGA program) were conducted. The core findings of 128 patients were as follows: (i) Clinicopathological parameters: pancreatic head is the most common site; presence of an associated adenocarcinoma was reported in 60% of cases, but with rare nodal metastasis. (ii) Immunohistochemistry: MUC1 (>90%) and MUC6 (70%) were the most frequently expressed mucins. ITPN lacked the intestinal marker MUC2; unlike IPMN, it did not express MUC5AC. (iii) Molecular landscape: Compared with PDAC/IPMN, the classic pancreatic drivers KRAS, TP53, CDKN2A, SMAD4, GNAS, and RNF43 were less altered in ITPN (P < 0.001), whereas MCL amplifications, FGFR2 fusions, and PI3KCA mutations were commonly altered (P < 0.001). (iv) Survival analysis: ITPN with a "pure" branch duct involvement showed the lowest risk of recurrence. Conclusion ITPN is a distinct pancreatic neoplasm with specific clinicopathological and molecular characteristics. Its recognition is fundamental for its clinical/prognostic implications and for the enrichment of potential targets for precision oncology.

The outbreak of COVID-19, initially developed in China in early December 2019, has rapidly spread to other countries and represents a public health emergency of international concern. COVID-19 has caused great concern about respiratory symptoms, but it is worth noting that it can also affect the gastrointestinal tract. However, the data on pancreatic involvement during SARS-CoV-2 infection are limited. The prevalence and severity of pancreatic damage and acute pancreatitis, as well as its pathophysiology, are still under debate. Moreover, the possible implication of pancreatic damage as an apparent adverse effect of COVID-19 therapies or vaccines are issues that need to be addressed. Finally, the COVID-19 pandemic has generated delays and organizational consequences for pancreatic surgery, an element that represent indirect damage from COVID-19. This narrative review aims to summarize and analyze all the aspects of pancreatic involvement in COVID-19 patients, trying to establish the possible underlying mechanisms and scientific evidence supporting the association between COVID-19 and pancreatic disease.

The safety of minimally invasive procedures during COVID pandemic remains hotly debated, especially in a country, like Italy, where minimally invasive techniques have progressively and pervasively entered clinical practice, in both the hepatobiliary and pancreatic community. A nationwide snapshot of the management of HPB minimally invasive surgery activity during COVID-19 pandemic is provided: a survey was developed and conducted within AICEP (Italian Association of HepatoBilioPancreatic Surgeons) with the final aim of conveying the experience, knowledge, and opinions into a unitary report enabling more efficient crisis management. Results from the survey (81 respondents) show that, in Italian hospitals, minimally invasive surgery maintains its role despite the COVID-19 pandemic, with the registered reduction of cases being proportional to the overall reduction of the HPB surgical activity. Respondents agree that the switch from minimally invasive to open technique can be considered as a valid option for cases with a high technical complexity. Several issues merit specific attention: screening for virus positivity should be universally performed; only expert surgical teams should operate on positive patients and specific technical measures to lower the biological risk of contamination during surgery must be followed. Future studies specifically designed to establish the true risks in minimally invasive surgery are suggested. Furthermore, a standard and univocal process of prioritization of patients from Regional Healthcare Systems is advisable. Electronic supplementary material The online version of this article (10.1007/s13304-020-00815-5) contains supplementary material, which is available to authorized users.

Intraductal papillary mucinous neoplasms are common lesions with the potential of harbouring/developing a pancreatic cancer. An accurate evaluation of intraductal papillary mucinous neoplasms with high-resolution imaging techniques and endoscopic ultrasound is mandatory in order to identify patients worthy either of surgical treatment or surveillance. In this review, the diagnosis and management of patients with intraductal papillary mucinous neoplasms are discussed with a specific focus on current guidelines. Areas of uncertainty are also discussed, as there are controversies related to the optimal indications for surgery, surveillance protocols and surveillance discontinuation.

Introduction: Pancreatic Neuroendocrine Tumor (Pan-NET) clinical outcome shows a high variability among patients within the same World Health Organization (WHO) category. To date, there is a lack of markers to predict recurrence after resection, which makes it difficult to identify patients with higher risk of progression. Aim(s): To evaluate morphologic and clinicopathological features of surgically resected Pan-NET. Materials and methods: Surgical specimens of 150 Pan-NET patients were evaluated for the following diagnostic and prognostic tools: Tumor stage, Ki-67, parenchymal infiltration, neural and vascular invasion, tumor necrosis or sclerosis and tumor deposits. These data were correlated with Overall Survival (OS) and stage I-II-III Disease-Free Survival (DFS). Results: Overall, 76 (50.7%) patients showed localized (stage I-II), 22 (14.7%) locally advanced (stage III), and 52 (34.7%) metastatic disease (stage IV). Tumor size >2 cm (p

Background and aims: Therapy and prognosis of pancreatic neuroendocrine tumors (PanNETs) are strictly related to the Ki-67 index, which defines tumor grading. The criterion standard for the assessment of grading of PanNETs is EUS-guided FNA (EUS-FBAFNA) or EUS-guided fine-needle biopsy sampling (EUS-FNB). Because data on diagnostic accuracy of EUS-FNA and EUS-FNB are heterogeneous, we aimed to analyze the variability in concordance between EUS grading and surgical grading. Methods: The MEDLINE, SCOPUS, and EMBASE databases were searched until November 2021 to identify studies reporting the concordance rate between EUS grading and surgical grading. The study was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Pooled events were calculated using a random-effects model and expressed in terms of pooled prevalence rates. A multivariate meta-regression was performed to find possible sources of heterogeneity. Where available, individual data were analyzed. Results: Twenty-six studies with 864 patients undergone EUS-FNA or EUS-FNB and surgical resection for PanNETs were included. The pooled estimate rate for the overall concordance of EUS grading and surgical grading was 80.3% (95% confidence interval, 75.6-85.1). Undergrading (EUS grading< surgical grading) was significantly more frequent with respect to overgrading (14.7% vs 3.5%, P< .001). Individual data analysis showed that among nonconcordant patients, the median Ki-67 difference was 3% (interquartile range, 2-6.15). The type of World Health Organization classification adopted and the median lesion diameter were significantly associated with heterogeneity at meta-regression. Conclusions: EUS is an accurate technique in defining grading in patients with PanNETs, but a margin of error still exists, which should be the focus of future studies to minimize the risk of over- and/or undertreatment.

Background Several studies have suggested a survival benefit of neoadjuvant therapy (NAT) for pancreatic ductal adenocarcinoma (PDAC) in the pancreatic head. Data concerning NAT for PDAC located in pancreatic body or tail are lacking. Methods Post hoc analysis of an international multicenter retrospective cohort of distal pancreatectomy for PDAC in 34 centers from 11 countries (2007–2015). Patients who underwent resection after NAT were matched (1:1 ratio), using propensity scores based on baseline characteristics, to patients who underwent upfront resection. Median overall survival was compared using the stratified log-rank test. Results Among 1236 patients, 136 (11.0%) received NAT, most frequently FOLFIRINOX (25.7%). In total, 94 patients receiving NAT were matched to 94 patients undergoing upfront resection. NAT was associated with less postoperative major morbidity (Clavien–Dindo ≥ 3a, 10.6% vs. 23.4%, P = 0.020) and pancreatic fistula grade B/C (9.6% vs. 21.3%, P = 0.026). NAT did not improve overall survival [27 (95% CI 14–39) versus 31 months (95% CI 19–42), P = 0.277], as compared with upfront resection. In a sensitivity analysis of 251 patients with radiographic tumor involvement of splenic vessels, NAT (n = 37, 14.7%) was associated with prolonged overall survival [36 (95% CI 18–53) versus 20 months (95% CI 15–24), P = 0.049], as compared with upfront resection. Conclusion In this international multicenter cohort study, NAT for resected PDAC in pancreatic body or tail was associated with less morbidity and pancreatic fistula but similar overall survival in comparison with upfront resection. Prospective studies should confirm a survival benefit of NAT in patients with PDAC and splenic vessel involvement.

Matrix assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) of intact proteins is mostly performed using time-of-flight (TOF) based mass spectrometers, operated in linear mode. Linear MALDI-TOF systems provide limited mass resolving power and mass accuracy, which complicates assigning identities to the peaks in the MSI datasets. In this work we report ultra-high mass resolution MALDI-MSI based on 15T Fourier transform ion cyclotron resonance (FTICR) mass spectrometry for the analysis of intact proteins directly from non-embedded and OCT-embedded mouse and human (control and type 2 diabetes) pancreas so that small endocrine compartments (islets of Langerhans) may be analyzed in control and pathological tissues. Sample preparation methods, in terms of increased sensitivity while limiting lateral diffusion of analytes, have been investigated. By combining protein localization, high mass accuracy, and the clearly resolved isotope patterns we were able to assign protein identities with additional confidence, including proteins of similar average mass and with interspersed isotopomers. These capabilities allowed us to ascertain the presence of many protein adducts that, with a low resolving power instrument, could be misinterpreted as distinct protein ions. (C) 2017 Published by Elsevier B.V

Currently, advances in surgical techniques, improvements in perioperative care, new formulations of intermediate and long-acting insulin and of modern pancreatic enzyme preparations have allowed obtaining good short and long-term results and quality of life, especially in high-volume centres in performing total pancreatectomy (TP).Thus, the surgeon’s fear in performing TP is not justified and total pancreatectomy can be considered a viable option in selected patients in high-volume centres. The aim of this review was to define the current indications for this procedure, in particular for upfront TP, considering not only the pancreatic disease, but also the surgical approach (open, mini-invasive) and the relationship with vascular resection.

Postoperative pancreatic fistula (POPF), the major driver of morbidity and mortality following pancreatectomy, is caused by an abnormal communication between the pancreatic ductal epithelium and another epithelial surface containing pancreas-derived, enzyme-rich fluid. There is a strong correlation between the amylase content in surgically-placed drains early in the postoperative course and the development of POPF. A simple and cheap method to determine the amylase content from the drain effluent has been eagerly advocated. Here, we developed an amylase optical biosensor, based on a surface plasmon resonance (SPR) plastic optical fiber (POF), metallized with a 60 nm layer of gold and interrogated with white light. The sensor was made specific by coupling it with an anti-amylase antibody. Each surface derivatization step was optimized and studied by XPS, contact angle, and fluorescence. The POF-biosensor was tested for its response to amylase in diluted drain effluents. The volume of sample required was 50 µL and the measurement time was 8 min. The POF-biosensor showed selectivity for amylase, a calibration curve log-linear in the range of 0.8–25.8 U/L and a limit of detection (LOD) of ~0.5 U/L. In preliminary tests, the POF-biosensor allowed for the measurement of the amylase content of diluted surgically-placed drain effluents with an accuracy of &gt, 92% with respect to the gold standard. The POF-biosensor allows for reliable measurement and could be implemented to allow for a rapid bedside assessment of amylase value in drains following pancreatectomy.

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Background: The Blumgart anastomosis is a method of pancreaticojejunostomy after pancreaticoduodenectomy (PD) which combines the principle of duct-to-mucosa anastomosis with an invagination technique of the pancreas. Methods: Retrospective study involving consecutive patients who underwent pancreaticoduodenectomy for pancreatic head cancer. Data predictive of pancreatic fistula and postoperative outcomes were collected. The patients were divided into three groups and were compared based on the type of pancreatic anastomosis performed: Blumgart anastomosis (BA), duct-to-mucosa anastomosis (DtoM), and invagination pancreaticojejunostomy (PJ). The primary endpoint was to determine the occurrence of clinically relevant postoperative pancreatic fistula (CR-POPF). The secondary endpoints were to determine whether postoperative pancreatic fistula grade C (POPF C) and/or severe complications occurred as well as to determine the reoperation rate and 30- and 90-day mortality. A propensity score matching analysis was used. Results: Using propensity score matching (PSM), the occurrence of CR-POPF was not significantly different between the BA (21.6%) and the other pancreatic anastomoses (all 31.1%, DtoM = 27.0%; PJ = 35.1%). However, the BA significantly reduced (1) severe complications (0 versus 35.1%; P < 0.001) and 90-day mortality (0% versus 12.2%; P = 0.028) with respect to all anastomoses; (2) severe complications (0% versus 29.7%; P < 0.001), POPF grade C (0% versus 16.2%; P = 0.025), and reoperation (2.7% versus 16.2%; P = 0.056) with respect to DtoM; and (3) severe complications (0% versus 40.5%; P < 0.001) and 90-day mortality (0% versus 13.5%; P = 0.054) with respect to PJ. Conclusions: Applying the PSM analysis for the first time, the present study seemed to suggest that the BA succeeded in minimizing severe complications after PD.

Background We predicted cancer mortality statistics for 2021 for the European Union (EU) and its five most populous countries plus the UK. We also focused on pancreatic cancer and female lung cancer. Materials and methods We obtained cancer death certifications and population data from the World Health Organization and Eurostat databases for 1970-2015. We predicted numbers of deaths and age-standardised (world population) rates for 2021 for total cancers and 10 major cancer sites, using a joinpoint regression model. We calculated the number of avoided deaths over the period 1989-2021. Results We predicted 1 267 000 cancer deaths for 2021 in the EU, corresponding to age-standardised rates of 130.4/100 000 men (−6.6% since 2015) and 81.0/100 000 for women (−4.5%). We estimated further falls in male lung cancer rates, but still trending upward in women by +6.5%, reaching 14.5/100 000 in 2021. The breast cancer predicted rate in the EU was 13.3/100 000 (−7.8%). The rates for stomach and leukaemias in both sexes and for bladder in males are predicted to fall by >10%; trends for other cancer sites were also favourable, except for the pancreas, which showed stable patterns in both sexes, with predicted rates of 8.1/100 000 in men and 5.6/100 000 in women. Rates for pancreatic cancer in EU men aged 25-49 and 50-64 years declined, respectively, by 10% and 1.8%, while for those aged 65+ years increased by 1.3%. Rates fell for young women only (−3.4%). Over 1989-2021, about 5 million cancer deaths were avoided in the EU27 compared with peak rates in 1988. Conclusion Overall cancer mortality continues to fall in both sexes. However, specific focus is needed on pancreatic cancer, which shows a sizeable decline for young men only. Tobacco control remains a priority for the prevention of pancreatic and other tobacco-related cancers, which account for one-third of the total EU cancer deaths, especially in women, who showed less favourable trends.

Background Local ablation of pancreatic cancer has been suggested as an option to manage locally advanced pancreatic cancer (LAPC) although no robust evidence has been published to date to support its application. The aim of this study is to compare overall survival (OS) and progression-free survival (PFS) in patients receiving both radiofrequency ablation (RFA) and conventional chemoradiotherapy (CHRT) with patients receiving CHRT only. Methods This is a multicentre prospective randomized controlled trial (RCT). Patients with LAPC diagnosed by the Pancreas-Ablation-Team-Verona were randomly assigned to open RFA (Group A) or CHRT (Group B). Survival analyses were performed using the Kaplan-Meier method and compared using the log-rank test. Statistical significance was set at p Results One hundred LAPC patients were enrolled from January 2014 to August 2016. 33% of patients in Group A did not receive the designated procedure because of intraoperative findings of liver (18.7%) or peritoneal metastases (43.8%), or technical contraindications (37.5%). We did not observe any statistically significant survival benefit from RFA compared to CHRT, neither in terms of OS (medians of 14.2 months and 18.1 months, respectively, p = 0.639) nor PFS (medians of 8 months and 6 months respectively, p = 0.570). Mortality was nil and RFA-related morbidity was 15.6%. In 13% of subjects, conversion to surgery occurred (2 after RFA and 11 after CHRT). Conclusions This is the first RCT evaluating the impact of upfront RFA in the multimodal treatment of LAPC. Compared to CHRT, RFA alone did not provide any advantage in terms of OS or PFS. It could be considered as a therapeutic option for LAPC within a multimodal context and after neoadjuvant therapies.

INTRODUCTION : There is increasing evidence to support the efficacy of endoscopic ultrasound (EUS)-guided through-the-needle biopsy (TTNB) technique as a means of sampling pancreatic cystic lesions (PCLs). Results provide evidence demonstrating the benefits of this procedure over standard EUS fine-needle aspiration (FNA), thus supporting a push for its widespread implementation in clinical practice. Though this technique has demonstrated advantages, achieving these advantages in clinical practice is contingent upon careful considerations to ensure safety and efficacy. AREAS COVERED : The purpose of this review is to assess the level of evidence supporting the use of through-the-needle biopsy, revise its main technical and procedural characteristics, and to develop suggested guidelines outlining the safe assimilation of this device in clinical practice. EXPERT OPINION : EUS-TTNB enables more definitive and accurate diagnosis of PCLs by providing higher quality histological samples. However, EUS-TTNB is not appropriate for all PCLs. Selection of suitable patients as well as morphology and risk factors of the cystic lesion is a crucial component of achieving the described benefits of this procedure while minimizing risks of adverse effects. Subjects with weak or absent indications for this procedure are susceptible to a range of complications and may even result in fatality.

The use of cosolvents and high hydrostatic pressure (HHP) has been described as an efficient means to modulate the stability of enzymes and their catalytic activity. Cosolvents and pressure can lead to increased reaction rates without affecting the stability of the enzyme. Here, we studied the combined effects of one of the most used organic cosolvents, dimethyl sulfoxide (DMSO), and HHP to reveal their combined effect on the kinetic constants of an α-chymotrypsin-catalyzed peptide hydrolysis reaction. The Michaelis constant and the turnover number of the reaction respond differently to the two variables, and we observed an opposite effect of hydrostatic pressure and the dipolar cosolvent DMSO on the kinetic parameters. The results could be rationalized by determining the volume diagram of the reaction at the different solution conditions. In our case, the use of high hydrostatic pressure in concert with DMSO does not lead to an improvement of the enzymatic activity. However, the advantages of DMSO and HHP to increase the temperature stability of the enzyme and to increase the solubility of more hydrophobic substrates could still be useful.

Purpose of review The aim of this review is to give an overview of recently published articles covering preoperative carbohydrate loading in surgical patients. Recent findings Between January 1, 2017, and December 31, 2019, 26 publications addressing the effect of carbohydrate load were retrieved through a systematic search. Seventeen were randomized clinical trials, three prospective observational studies and six retrospective series with case-control comparison. Most of the studies were underpowered, addressed surrogate endpoints, and variability among dose and timing of carbohydrate (CHO) treatment was high. The most recent literature endorses preoperative carbohydrate loading up to 2 h before operations as a safe treatment. The new evidence confirm that this strategy is effective in reducing perioperative insulin resistance and the proportion of hyperglycemia episodes, and improving patient well-being and comfort but without affecting surgery-related morbidity. Summary Further properly designed randomized clinical trials, addressing more clinically relevant endpoints such as length of hospitalization and morbidity rate, are warrant.

Background: MRI is a useful imaging modality to assess the presence of pancreatic neuroendocrine tumors (PNETs), allowing repeat monitoring examinations in multiple endocrine neoplasia type 1 (MEN-1) patients. Objectives: We aimed to compare the diagnostic accuracy of conventional MRI sequences to identify which sequence better depicts the presence of PNETs in MEN-1 patients. Method: We performed a retrospective analysis of consecutive MEN-1 patients who underwent a conventional MRI protocol to monitor previously proven PNETs. MRI sequences T1-w chemical shift (CS), T2-w HASTE, fat-suppressed (FS) T2-w HASTE, diffusion-weighted imaging (DWI), and pre- and post-contrast FS T1-w sequences were independently analyzed by 2 experienced radiologists using a 3-grade score (no lesion, uncertain lesion, and certain lesion); lesion size and signal intensity were recorded. A Friedman ANOVA and a Wilcoxon pairwise test for the post hoc analysis were used. The sensitivity of each sequence was measured, and the results were analyzed with the χ2 test. Results: We included 21 patients with a total of 45 PNETs proven by histology, endoscopic ultrasonography-guided fine-needle aspiration, CT, and nuclear medicine studies. A statistically significant (p < 0.01) difference was observed in the detection performance of each MRI sequence, particularly between DWI (91%) and T2-w FS (85%) sequences in comparison to the others (T1-w CS, T2-w, and pre- and post-contrast FS T1-w, ≤56% for all); no significant (p = 0.5) difference was found between the detection performance of DWI and T2-w FS sequences. No correlation was observed between the qualitative score of each sequence and lesion tumor size. Conclusions: DWI and T2-w FS sequences proved to be the most accurate in the detection of PNETs, thus suggesting a role for an abbreviated MRI protocol without contrast medium administration for monitoring MEN-1 patients.

Tumorigenesis of biliopancreatic lesions is linked to specific alterations in key genes. Pancreatic neoplasms are well characterized at the genomic level. For example, exome and genome sequencing analyses revealed that pancreatic adenonocarcinomas are characterized by mutations manly in KRAS, TP53, CDKN2A/p16, and SMAD4 genes. Nevertheless, the pre-operative diagnosis and the management of patients with biliopancreatic lesion are still a clinical challenge, involving not only the endoscopic ultrasound-guided fine-needle aspiration procedure but also the appropriate biomolecular assessment of these lesions. The aim of the present chapter is to provide an overview of the current knowledge of the biology of biliopancreatic lesions as detected by molecular techniques.

The gastrointestinal system may be affected by COVID-19 infection with an incidence variable from 3% up to 79%. Several works show that the pan-creas, both in its exocrine and endocrine function, can be affected by this viral infection, although this organ has been poorly analyzed in this current epidemic context. This mini-review aims to provide a summary of available studies on exocrine pancreas involvement during COVID-19 infection. A search through MEDLINE/PubMed was conducted on the topic in hand. With regard to exocrine function, some studies highlight the presence of an associated hyperenzymemia (hyperamylasemia, hyperlipasem-ia), while others describe isolated and rare cases of acute pancreatitis. More attention should be paid to pancreatic impairment in subjects with COVID-19, as this may prove to be one of the elements aggra-vating its clinical course. Indeed, acute pancreatitis, especially when presenting in severe forms with hy-perstimulation of the pro-inflammatory response, may represent a crucial factor in the progression of COVID-19, entailing both an increase in hospitaliza-tion days and in mortality rate.

Contrast-enhanced ultrasonography (CEUS) is increasingly being performed in Italy and Europe, particularly in the field of hepato-gastroenterology. Initially, it was mainly carried out to characterize focal hepatic lesions, but, since then, numerous studies have demonstrated its efficacy in the differential diagnosis of focal pancreatic pathologies (D’Onofrio et al. in Expert Rev Med Devices 7(2):257–273, 2010; Vidili et al. in J Ultrasound 22(1):41–51, 2019). The purpose of this paper is to provide Italian Medical Doctors with recommendations and thereby practical guidelines on the management of these patients. The present paper reports the final conclusions reached by the SIUMB guideline commission. This paper addresses particularly percutaneous ultrasound (US) examination (transabdominal US) and is drawn up specifically for publication.

Purpose: Pancreatic neuroendocrine neoplasms (PNENs) are a group of clinically rare and heterogeneous tumors of the pancreas. Currently there are no studies investigating the gender difference in PNEN susceptibility. Thus, the purpose of this study was aimed at examining how gender shapes risk factors, clinicopathological features, and comorbidities in PNENs. Methods: The study design consisted of an Italian multicenter, retrospective study. The study included all consecutive patients with PNENs followed at the participating centers. Two hundred and twenty-nine patients (105 males,124 females, age 54 ± 0.98 years) with PNENs were enrolled at the participating centers. The clinicopathological features (age, gender, BMI, histology, tumor size, tumor grade, distant metastasis, hormonal function, and diagnostic circumstances), comorbidities (cardiovascular diseases (CVD), pancreatitis, type 2 diabetes (T2DM), and potential risk factors (smoking and drinking) were included in the analysis. Results: Females were slightly prevalent (54.15%). PNENs were diagnosed at younger age in females compared to males (p = 0.04). The prevalence of CVD was significantly higher in males than in females (p = 0.006). In the female group, the presence of T2DM was significantly associated with higher tumor grade (p = 0.04) and metastatic disease (p = 0.02). The proportion of smokers and alcohol drinkers was significantly higher in the male group (p < 0.001). No significant gender differences were detected regarding the other parameters included in the analysis. Conclusions: This study has identified gender differences of PNENs in terms of age at diagnosis, associated comorbidities, and potential risk factors. A gender-tailored approach could become a potential strategy to better understand the natural history of PNENs and improve the effectiveness of PNENs clinical management.

The value of minimally invasive pancreatic surgery (MIPS) is still uncertain, despite the growing number of publications, including reviews and meta-analyses, and the quick diffusion of these procedures worldwide. The Italian Group of Minimally Invasive Pancreas Surgery (IGoMIPS) was created under the auspices of three Scientific Societies: Associazione Italiana Studio Pancreas (AISP), Associazione Italiana Chirurgia Epato-Bilio-Pancreatica (AICEP, former IT-IHPBA), and Società Italiana di Chirurgia Endoscopica (SICE). The main aim of IGoMIPS is to develop and implement a national registry for MIPS. IGoMIPS was founded on February 22, 2019 in Pisa. The IGoMIPS registry became operational in September 2019, following approval by the Ethic Committees of founding Institutions, inscription into the Registry of Patient Registries (RoPR), and a wrap-up meeting held in Bologna during the Annual Congress of the Italian Surgical Society. During this meeting IGoMIPS members approved that the Italian Registry will provide data to the European Registry, while retaining the right to analyze and publish Italian data. An audience survey was also conducted to obtain information on perceived value and current implementation of MIPS in founding Institutions. MIPS is performed in 94.7% of IGoMIPS centers, including pancreaticoduodenectomy in 42.1%. Robotic assistance was employed in 52.6% of Institutions. The annual volume of MIPS was 6–10 cases in 38.9% of the centers, 11–20 cases in 16.7%, 21–30 cases in 22.2%, and > 30 cases in 22.2%. The registry was felt to be extremely important for both safety improvement and educational purposes by 94.5% of the centers.

The burden of pancreatic cancer varies greatly across countries, with the number of deaths, incident cases, and disability-adjusted life years more than doubling in recent years, and with high-income countries having the highest incidence and mortality rates. We conducted this systematic review with meta-analysis with the goal of summarizing the current evidence on dietary fiber intake and its role in reducing the risk of pancreatic cancer, given the importance of identifying risk factors. This systematic review followed the guidelines of the Cochrane Collaboration and the Meta-analysis of Observational Studies in Epidemiology and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020. The structured literature search was conducted on PubMed/Medline and Scopus, combining free text words and medical subject headings. Our review contained 18 records at the end of the process. Our results show that dietary fiber intake reduces the risk of pancreatic cancer. When the analysis was differentiated according to the type of fiber considered, sub-grouped by gender (reduction of around 60% among women), and when case-control studies were conducted, the strength of the association increased. Clinicians and policymakers should improve interventions to raise the population’s awareness regarding the consumption of high-fiber diets, both in practice and in terms of public health policy.

No abstract available

Purpose: To assess the feasibility of automated stereotactic volumetric modulated arc therapy (SBRT-VMAT) planning using a simultaneous integrated boost (SIB) approach as a dose escalation strategy for SBRT in pancreatic cancer. Methods: Twelve patients with pancreatic cancer were retrospectively replanned. Dose prescription was 30Gy to the planning target volume (PTV) and was escalated up to 50Gy to the boost target volume (BTV) using a SIB technique in 5 fractions. All plans were generated by Pinnacle3 Autoplanning using 6MV dual-arc VMAT technique for flattened (FF) and flattening filter-free beams (FFF). An overlap volume (OLV) between the PRV duodenum and the PTV was defined to correlate with the ability to boost the BTV. Dosimetric metrics for BTV and PTV coverage, maximal doses for serial OARs, integral dose, conformation numbers, and dose contrast indexes were used to analyze the dosimetric results. Dose accuracy was validated using the PTW Octavius-4D phantom together with the 1500 2D-array. Differences between FF and FFF plans were quantified using the Wilcoxon matched-pair signed rank. Results: Full prescription doses to the 95% of PTV and BTV can be delivered to patients with no OLV. BTV mean dose was >90% of the prescribed doses for all patients at all dose levels. Compared to FF plans, FFF plans showed significant reduced integral doses, larger number of MUs, and reduced beam-on-times up to 51% for the highest dose level. Despite plan complexity, pre-treatment verification reported a gamma pass-rate greater than the acceptance threshold of 95% for all FF and FFF plans for 3%-2mm criteria. Conclusions: The SIB-SBRT strategy with Autoplanning was dosimetrically feasible. Ablative doses up to 50Gy in 5 fractions can be delivered to the BTV for almost all patients respecting all the normal tissue constraints. A prospective clinical trial based on SBRT strategy using SIB-VMAT technique with FFF beams seems to be justified.

Pancreatic organogenesis is a multistep process that requires the cooperation of several signaling pathways. In this context, the role of pancreatic mesenchyme is important to define the epithelium development, nevertheless, the precise space&ndash, temporal signaling activation still needs to be clarified. This study reports a dissection of the pancreatic embryogenesis, highlighting the molecular network surrounding the epithelium&ndash, mesenchyme interaction. To investigate this crosstalk, pancreatic epithelium and surrounding mesenchyme, at embryonic day 10.5, were collected through laser capture microdissection (LCM) and characterized based on their global gene expression. We performed a bioinformatic analysis to hypothesize crosstalk interactions, validating the most promising genes and verifying the precise localization of their expression in the compartments, by RNA in situ hybridization (ISH). Our analyses pointed out also the c-Met gene, a very well-known factor involved in stimulating motility, morphogenesis, and organ regeneration. We also highlighted the potential crosstalk between Versican (Vcan) and Syndecan4 (Sdc4) since these genes are involved in pancreatic tissue repair, strengthening the concept that the same signaling pathways required during pancreatic embryogenesis are also involved in tissue repair. This finding leads to novel strategies for obtaining functional pancreatic stem cells for cell replacement therapies.

Pancreatic duct variations are usually diagnosed incidentally, in particular when using magnetic resonance cholangiopancreatography (MRCP), the most accurate imaging modality for depicting the pancreatic ductal system. However, the frequency and the embryologic development of pancreatic variants have not been well investigated. The purpose of this prospective study was to investigate the frequency of pancreatic ductal variants, providing potential explanations of their embryologic basis. The pancreatic ductal anatomies of 202 patients with mean ± standard deviation (SD) age of 54 ± 27 years, 56% females, who underwent MRCP for different indications between April 2018 and March 2019, were prospectively collected. Normal pancreatic ductal variants were identified in 196 cases (97%), and variants of pancreas divisum in six cases (3%). In the type C variant of the normal pancreatic anatomy, found in 3% of the cases, the dorsal duct was joined to the ventral duct while the accessory duct did not communicate with the dorsal duct. Unlike the classic type C variant, in our cases, the accessory pancreatic duct (APD) was long (mean ± SD of 58 ± 8.5 mm) and originated in the lower portion of the pancreatic head, caudally to the duct of Wirsung. This was a new subtype of the type C variant or a new variant, which could be called "pancreas divisum inversus"; the APD could be called the isolated duct of Santorini. Reporting this new variant could increase knowledge regarding the pancreatic anatomy in order to avoid misdiagnosis and to help in better understanding pancreatic diseases and their relative treatment. Clin. Anat., 33:646-652, 2020. © 2019 Wiley Periodicals, Inc.

Background and Objective: EUS-guided fine-needle biopsy has become the standard for tissue sampling. A new 20G ProCore™ (PC) needle has been developed to overcome the limitations of tissue acquisition of the smaller needles (22G, 25G) and the rigidity of the larger one (19G). The aim of this study is to assess the performance of the 20G PC needle. Materials and Methods: Patients who underwent EUS-guided tissue acquisition with the 20G PC needle of pancreatic and extra-pancreatic mass lesions were retrospectively identified at three Italian centers (Bologna, Fermo, and Palermo). Diagnostic adequacy, accuracy, and tissue core acquisition were the outcome measures. All the cases were performed without rapid on-site evaluation. Results: A total of 384 patients with pancreatic (62.2%) and extra-pancreatic lesions were included in the study. For pancreatic lesions, adequacy, accuracy, sensitivity, and specificity were 92.4%, 91.5%, 90.8%, and 100%, respectively, with a number needed to misdiagnose (NNM) of 11.8. The tissue core was obtained in 72% of cases. Transduodenal approach was performed in 150 pancreatic lesions; adequacy, accuracy, and tissue core acquisition were 88.7%, 90%, and 66%, respectively (NNM 10). For extrapancreatic lesions, adequacy, accuracy, sensitivity, specificity, and tissue core sampling were 95.3%, 95.3%, 92.6%, 100%, and 84.5% (NNM 21.3). Conclusions: The 20G PC needle showed high diagnostic adequacy and accuracy, regardless the access route.