The effect of steroid therapy on pancreatic exocrine function in autoimmune pancreatitis.

BACKGROUND/OBJECTIVES: Autoimmune pancreatitis (AIP) is a steroid-responsive inflammatory disease of the pancreas. Few studies investigated pancreatic exocrine function (PEF) in patients suffering from AIP and no definitive data are available on the effect of steroids in PEF recovery. Aim of the study is the evaluation of severe pancreatic insufficiency (sPEI) prevalence in AIP at clinical onset and after steroid treatment. METHODS: 312 Patients with diagnosis of AIP between January 1st, 2010 and December 31st, 2020 were identified in our prospectively maintained register. Patients with a pre-steroid treatment dosage of fecal elastase-1 (FE-1) were included. Changes in PEF were evaluated in patients with available pre- and post-treatment FE (between 3 and 12 months after steroid). RESULTS: One-hundred-twenty-four patients were included, with a median FE-1 of 122 (Q1-Q3: 15-379) µg/g at baseline. Fifty-nine (47.6 %) had sPEI (FE-1<100 µg/g). Univariable analysis identified type 1 AIP, radiological involvement of the head of the pancreas (diffuse involvement of the pancreas or focal involvement of the head), weight loss, age and diabetes as associated with a greater risk of sPEI. However, at multivariable analysis, only the involvement of the head of the pancreas was identified as independent risk factor for sPEI. After steroids, mean FE-1 changed from 64 (15-340) to 202 (40-387) µg/g (P = 0.058) and head involvement was the only predictor of improvement of sPEI. CONCLUSION: The inflammatory involvement of the head of the pancreas is associated with PEF severity, as well as PEF improvement after treatment with steroids in patients with AIP.

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.

An update on improving long-term outcomes for patients with chronic pancreatitis post-surgery.

INTRODUCTION: Chronic pancreatitis is a common inflammatory disease that severely impairs patients' quality of life, mainly due to abdominal pain which is the most frequent symptom. Current guidelines suggest medical therapy as the first line intervention based on a stepwise use of analgesics (i.e. NSAIDs followed by weak opioids and later by strong oppioids), which is rarely effective in improving pain and often leads to opioid addiction. Interventional procedures are therefore frequently needed. Endoscopic therapy is suggested as the second line of intervention, aiming at decompressing the main pancreatic duct via structure dilatation and ductal stone removal. Endoscopic therapy is usually effective in reducing pain in the short term, but its effects frequently decrease with time and multiple procedures are often required. Surgery is usually reserved as a last resource when medical and endoscopic therapy have failed. Pancreatic surgery is burdened with non negligible morbidity and mortality but is effective in reducing pain and improving quality of life in chronic pancratitis with long lasting effects. AREAS COVERED: Surgical treatment of chronic pancreatitis is based on resection of inflammatory head mass or decompression of the ductal system, alone or in combination, which can be performed using different techniques. In this paper we reviewed the current evidence on the long-term outcomes of this type of surgery in terms of pain relief, quality of life, exocrine end endocrine function, and long-term mortality. EXPERT OPINION: Quality of current evidence on this field is on average poor; a consensus to define clinically significant outcomes is needed in order to correctly design prospective studies that will enable gastroenterologists to understand which patients, and when, will benefit most from surgery and should therefore be referred to surgeons.

Endoscopic Ultrasound-Guided Gastroenterostomy versus Enteral Stenting for Malignant Gastric Outlet Obstruction: A Retrospective Propensity Score-Matched Study.

BACKGROUND: Endoscopic ultrasound-guided gastroenterostomy (EUS-GE) using lumen apposing metal stent has emerged as a minimally invasive treatment for the management of malignant gastric outlet obstruction (mGOO). We aimed to compare EUS-GE with enteral stenting (ES) for the treatment of mGOO. METHODS: Patients who underwent EUS-GE or ES for mGOO between June 2017 and June 2023 at two Italian centers were retrospectively identified. The primary outcome was stent dysfunction. Secondary outcomes included technical success, clinical failure, safety, and hospital length of stay. A propensity score-matching analysis was performed using multiple covariates. RESULTS: Overall, 198 patients were included (66 EUS-GE and 132 ES). The stent dysfunction rate was 3.1% and 16.9% following EUS-GE and ES, respectively (p = 0.004). Using propensity score-matching, 45 patients were allocated to each group. The technical success rate was 100% for both groups. Stent dysfunction was higher in the ES group compared with the EUS-GE group (20% versus 4.4%, respectively; p = 0.022) without differences in clinical efficacy (p = 0.266) and safety (p = 0.085). A significantly shorter hospital stay was associated with EUS-GE compared with ES (7.5 ± 4.9 days vs. 12.5 ± 13.0 days, respectively; p = 0.018). Kaplan-Meier analyses confirmed a higher stent dysfunction-free survival rate after EUS-GE compared with ES (log-rank test; p = 0.05). CONCLUSION: EUS-GE offers lower rates of stent dysfunction, longer stent patency, and shorter hospital stay compared with ES.

EUS-FNA versus EUS-FNB in Pancreatic Solid Lesions ≤ 15 mm.

A small tumor size may impact the diagnostic performance of endoscopic ultrasound-guided tissue acquisition (EUS-TA) for diagnosing solid pancreatic lesions (SPLs). We aimed to compare the diagnostic yield of EUS-guided fine-needle aspiration (FNA) and biopsy (FNB) in SPLs with a diameter ≤ 15 mm. Consecutive patients who underwent EUS-TA for SPLs ≤ 15 mm between January 2015 and December 2022 in a tertiary referral center were retrospectively evaluated. The primary endpoint was diagnostic accuracy. The final diagnosis was based on surgical pathology or disease evolution after a minimum follow-up of 6 months. Inadequate samples were all considered false negatives for the study. Secondary outcomes included sample adequacy, factors impacting accuracy, and safety. We included 368 patients (52.4% male; mean age: 60.2 years) who underwent FNA in 72 cases and FNB in 296. The mean size of SPLs was 11.9 ± 2.6 mm. More than three passes were performed in 5.7% and 61.5% of patients in the FNB and FNA groups, respectively (p < 0.0001). FNB outperformed FNA in terms of diagnostic accuracy (89.8% vs. 79.1%, p = 0.013) and sample adequacy (95.9% vs. 86.1%, p < 0.001). On multivariate analysis, using FNA (OR: 2.10, 95% CI: 1.07-4.48) and a final diagnosis (OR: 3.56, 95% CI: 1.82-6.94) of benign conditions negatively impacted accuracy. Overall, the adverse event rate was 0.8%, including one pancreatitis in the FNA group and one pancreatitis and one bleeding in the FNB group, all mild and conservatively managed. EUS-TA for SPLs ≤ 15 mm has a high diagnostic yield and safety. This study suggests the superiority of FNB over FNA, with better performance even with fewer passes performed.

Clinical features and long-term outcomes of patients with type 2 autoimmune pancreatitis.

OBJECTIVES: Type 2 is a rare form of autoimmune pancreatitis (AIP). Despite being considered a benign disease, only few studies with limited sample size and short follow-up have been published on type 2 AIP. The aim of this observational study was to evaluate long-term outcomes, such as the risk of relapse, pancreatic insufficiency and cancer in a large type 2 AIP cohort with long follow-up. METHODS: Patients with definitive or probable diagnosis of type 2 AIP by International Consensus Diagnostic Criteria (ICDC) present in our prospectively maintained database since 1995 at 31.12.2021 were identified. All patients were clinically evaluated during the year 2022. Clinical, radiological, serological, and pathological data were evaluated. RESULTS: Eighty-eight out of 420 patients present in the database (21%) were diagnosed with type 2 AIP (mean age 33.5 ± 13.5 years). According to the ICDC, 21 patients (23.8%) had a definitive and 67 (76.2%) a probable diagnosis of type 2 AIP. The mean follow-up was 9.2 ± 7.1 years (range 1-27 years). No differences were observed when comparing patients with definitive and probable type 2 AIP diagnosis. Concomitant IBD was reported in 77 patients (87.5%). The probability of disease relapse was lower in patients treated with steroids versus surgery (at 5 years 13% vs. 33%; p = 0.038) but this difference was not statistically significant at multivariable analysis. The risk of endocrine or severe exocrine insufficiency was low (5% and 25%). Four extra-pancreatic malignancies (5%) were diagnosed, none pancreatic. One patient died in a car accident. CONCLUSIONS: Type 2 AIP has benign long-term clinical outcomes. Mortality and cancer rates are low and no specific follow-up is needed after radiological remission.

Diagnostic Endoscopic Ultrasound in Pancreatology: Focus on Normal Variants and Pancreatic Masses.

Background: Endoscopic ultrasound (EUS) is a main tool in gastroenterology for both diagnosis and exclusion of pancreatic pathology. It allows minimally invasive assessment of various diseases or anatomic variations affecting the pancreas also with the help of new Doppler technologies, elastography, contrast-enhanced imaging including post hoc image processing with quantification analyses, three-dimensional reconstruction, and artificial intelligence. EUS also allows interventional direct access to the pancreatic parenchyma and the retroperitoneal space, to the pancreatic duct, pancreatic masses, cysts, and vascular structures. Summary: This review aimed to summarize new developments of EUS in the field of pancreatology. We highlight the role of EUS in evaluating pancreatic pathology by describing normal anatomic variants like pancreas divisum, pancreatic lipomatosis, pancreatic fibrosis in the elderly and characterizing pancreatic masses, both in the context of chronic pancreatitis and within healthy pancreatic parenchyma. EUS is considered the optimal imaging modality for pancreatic masses of uncertain dignity and allows both cytological diagnosis and histology, which is essential not only for neoplastic conditions but also for tailoring therapy for benign inflammatory conditions. Key Messages: EUS plays an indispensable role in pancreatology and the development of new diagnostic and interventional approaches to the retroperitoneal space and the pancreas exponentially increased over the last years. The development of computer-aided diagnosis and artificial intelligence algorithms hold the potential to overcome the obstacles associated with interobserver variability and will most likely support decision-making in the management of pancreatic disease.

Endoscopic Ultrasound in Pancreatology: Focus on Inflammatory Diseases and Interventions.

Background: Endoscopic ultrasound (EUS) is a main tool in pancreatology for both diagnosis and therapy. It allows minimally invasive differentiation of various diseases, with a minimal degree of inflammation or anatomic variations. EUS also enables interventional direct access to the pancreatic parenchyma and the retroperitoneal space, the pancreatic duct, the pancreatic masses, cysts, vascular structures for diagnostic and therapeutic purposes. Summary: This review aimed to summarize the new developments of EUS in the field of pancreatology, with special interest on inflammation and interventions. EUS enables way to perform pseudocyst drainage, necrosectomy, transenteral drainage and transenteric access of the main pancreatic duct, or the direct visualization or therapy of vascular structures adjacent to the pancreas. Key Messages: EUS has a deep impact on pancreatology, and the development of new diagnostic and interventional approaches to the retroperitoneal space and the pancreas has increased in the last years exponentially, allowing minimal invasive diagnostics and therapy and avoiding surgery and percutaneous therapy.

Pancreatic steatosis and metabolic pancreatic disease: a new entity?

Overweight and obesity are some of the most important health challenges. Many diseases are related to these metabolic disorders, and, among them, the pancreatic fat accumulation, also called "pancreatic steatosis" or "nonalcoholic fatty pancreas", seems to have an emerging role in different conditions. There are different method to evaluate the fat content in the pancreas, such as histology, different imaging techniques and endoscopic ultrasound, but there is no gold standard for the correct diagnosis and for the identification of "inter/intralobular" and "intra-acinar" pancreatic fat. However, the fat storage in the pancreas is linked to chronic inflammation and to several conditions, such as acute and chronic pancreatitis, type 2 diabetes mellitus and pancreatic cancer. In addition, pancreatic fat accumulation has also been demonstrated to play a role in surgical outcome after pancreatectomy, in particular for the development of postoperative pancreatic fistula. Different possible therapeutic approaches have been proposed, but there is still a lack of evidence. The aim of this review is to report the current evidence about the relationship between the obesity, the pancreatic fat accumulation and its potential role in pancreatic diseases.

A Clinical and Pathophysiological Overview of Intestinal and Systemic Diseases Associated with Pancreatic Disorders: Causality or Casualty?

The relationship between chronic intestinal disease, including inflammatory bowel disease (IBD) and celiac disease (CelD), and pancreatic disorders has been little investigated. Although an increased risk of acute pancreatitis (AP), exocrine pancreatic insufficiency with or without chronic pancreatitis, and chronic asymptomatic pancreatic hyperenzymemia have been described in these patients, the pathogenetic link remains unclear. It may potentially involve drugs, altered microcirculation, gut permeability/motility with disruption of enteric-mediated hormone secretion, bacterial translocation, and activation of the gut-associated lymphoid tissue related to chronic inflammation. In addition, the risk of pancreatic cancer seems to be increased in both IBD and CelD patients with unknown pathogenesis. Finally, other systemic conditions (e.g., IgG4-related disease, sarcoidosis, vasculitides) might affect pancreatic gland and the intestinal tract with various clinical manifestations. This review includes the current understandings of this enigmatic association, reporting a clinical and pathophysiological overview about this topic.

Secondary Tumors of the Pancreas: A Multicenter Analysis of Clinicopathological and Endosonographic Features.

Many tumors may secondarily involve the pancreas; however, only retrospective autopic and surgical series are available. We retrospectively collected data from all consecutive patients with histologically confirmed secondary tumors of the pancreas referred to five Italian centers between 2010 and 2021. We described clinical and pathological features, therapeutic approach and treatment outcomes. EUS characteristics of the lesions and the tissue acquisition procedures (needle, passages, histology) were recorded. A total of 116 patients (males/females 69/47; mean age 66.7) with 236 histologically confirmed pancreatic metastases were included; kidney was the most common primary site. EUS was performed to confirm the diagnosis in 205 lesions which presented as predominantly solitary (59), hypoechoic (95) and hypervascular (60), with a heterogeneous (n = 54) pattern and well-defined borders (n = 52). EUS-guided tissue acquisition was performed in 94 patients with an overall accuracy of 97.9%. Histological evaluation was possible in 88.3% of patients, obtaining final diagnosis in all cases. When cytology alone was performed, the final diagnosis was obtained in 83.3% of cases. A total of 67 patients underwent chemo/radiation therapy, and surgery was attempted in 45 (38.8%) patients. Pancreatic metastases are a possible event in the natural history of solid tumors, even long after the diagnosis of the primary site. EUS-guided fine needle biopsy may be suggested to implement the differential diagnosis.

Chronic pancreatitis and nutritional support.

Malnutrition in patients with chronic pancreatitis is common, but its evaluation is often missed in clinical practice. Pancreatic exocrine insufficiency is the single most important cause of malnutrition; therefore, it needs to be screened for and treated appropriately. Specific diet regimens in patients suffering from chronic pancreatitis are rarely reported in the literature. Patients suffering from chronic pancreatitis have a higher demand for energy but a lower caloric intake secondary to pancreatic exocrine insufficiency, combined with the malabsorption of liposoluble vitamin and micronutrients, which needs be corrected by appropriate dietary counselling. Diabetes is frequently observed in chronic pancreatitis and classified as type 3c, which is characterized by low levels of both serum insulin and glucagon; therefore, there is a tendency towards hypoglycaemia in patients treated with insulin. Diabetes contributes to malnutrition in chronic pancreatitis. Strategies to treat exocrine and endocrine insufficiency are important to achieve better control of the disease.

Imaging of paraduodenal pancreatitis: A systematic review.

BACKGROUND: Paraduodenal pancreatitis (PP) represents a diagnostic challenge, especially in non-referral centers, given its potential imaging overlap with pancreatic cancer. There are two main histological variants of PP, the cystic and the solid, with slightly different imaging appearances. Moreover, imaging findings in PP may change over time because of disease progression and/or as an effect of its risk factors exposition, namely alcohol intake and smoking. AIM: To describe multimodality imaging findings in patients affected by PP to help clinicians in the differential diagnosis with pancreatic cancer. METHODS: The systematic review was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-analyses 2009 guidelines. A Literature search was performed on PubMed, Embase and Cochrane Library using (groove pancreatitis [Title/Abstract]) OR (PP [Title/Abstract]) as key words. A total of 593 articles were considered for inclusion. After eliminating duplicates, and title and abstract screening, 53 full-text articles were assessed for eligibility. Eligibility criteria were: Original studies including 8 or more patients, fully written in English, describing imaging findings in PP, with pathological confirmation or clinical-radiological follow-up as the gold standard. Finally, 14 studies were included in our systematic review. RESULTS: Computed tomography (CT) findings were described in 292 patients, magnetic resonance imaging (MRI) findings in 231 and endoscopic ultrasound (EUS) findings in 115. Duodenal wall thickening was observed in 88.8% of the cases: Detection rate was 96.5% at EUS, 91.0% at MRI and 84.1% at CT. Second duodenal portion increased enhancement was recognizable in 76.3% of the cases: Detection rate was 84.4% at MRI and 72.1% at CT. Cysts within the duodenal wall were detected in 82.6% of the cases: Detection rate was 94.4% at EUS, 81.9% at MRI and 75.7% at CT. A solid mass in the groove region was described in 40.9% of the cases; in 78.3% of the cases, it showed patchy enhancement in the portal venous phase, and in 100% appeared iso/hyperintense during delayed phase imaging. Only 3.6% of the lesions showed restricted diffusion. The prevalence of radiological signs of chronic obstructive pancreatitis, namely main pancreatic duct dilatation, pancreatic calcifications, and pancreatic cysts, was extremely variable in the different articles. CONCLUSION: PP has peculiar imaging findings. MRI is the best radiological imaging modality for diagnosing PP, but EUS is more accurate than MRI in depicting duodenal wall alterations.

The role of serological biomarkers in the diagnosis and management of autoimmune pancreatitis.

INTRODUCTION: Autoimmune pancreatitis (AIP) is a fibroinflammatory disease of the pancreas. Type 1 AIP is the pancreatic manifestation of a systemic IgG4-related disease and is associated with serum elevation of IgG4, tissue infiltration of IgG4-positive plasma cells, and multiorgan involvement. Although serum IgG4 elevation is considered a useful diagnostic tool, the concomitant presence of more diagnostic criteria is needed to achieve diagnosis. No other biomarkers have been approved in clinical practice in type 1 AIP. Type 2 AIP is a pancreatic-specific disease associated with inflammatory bowel disease. No specific biomarkers for type 2 AIP have been identified. AREAS COVERED: The role of serum IgG4 in the diagnosis, management and follow-up of patients with type 1 AIP. Moreover, data on other emerging biomarkers for type 1 and 2 AIP have been reported. EXPERT OPINION: The diagnosis of AIP is challenging in clinical practice, especially for focal forms without multiorgan involvement, where distinction from pancreatic cancer can be difficult. Despite the strong association with type 1 AIP, serum IgG4 should only be measured when the suspicion for the disease is high, considering its limited sensitivity. New biomarkers with high diagnostic yield for both type 1 and type 2 AIP are needed.

Identification of patients with branch-duct intraductal papillary mucinous neoplasm and very low risk of cancer: multicentre study.

BACKGROUND: Different surveillance strategies for patients with low-risk branch-duct (BD) intraductal papillary neoplasm (IPMN) have been described. The aim of this study was to describe the natural history of low-risk BD-IPMN, and to identify risk factors for the development of worrisome features (WF)/high-risk stigmata (HRS) and of pancreatic malignancies. METHODS: This was a multicentre retrospective study of patients with BD-IPMN who were under active surveillance between January 2006 and December 2015. Patients were eligible if they had a low-risk lesion and had a minimum follow-up of 24 months. Outcomes were development of WF/HRS or cytologically/histologically confirmed malignant IPMN. RESULTS: Of 837 patients included, 168 (20 per cent) developed WF/HRS. At the end of the observation time, 132 patients (79 per cent) with WF/HRS were still under surveillance without progression to pancreatic cancer. Factors associated with the development of WF or HRS in multivariable analysis included localized nodules (versus diffuse: hazard ratio (HR) 0.43, 95 per cent c.i. 0.26 to 0.68), cyst size 15-19 mm (versus less than 15 mm: HR 1.88, 1.23 to 2.87) or at least 20 mm (versus less than 15 mm: HR 3.25, 2.30 to 4.60), main pancreatic duct size over 3 mm (versus 3 mm or less: HR 2.17, 1.41 to 3.34), and symptoms at diagnosis (versus no symptoms: HR 2.29, 1.52 to 3.45). Surveillance in an endoscopy-oriented centre was also associated with increased detection of WF or HRS (versus radiology-oriented: HR 2.46, 1.74 to 3.47). CONCLUSION: Conservative management of patients with low-risk BD-IPMN is safe and feasible.

HLA-DRB1∗16 and -DQB1∗05 alleles are strongly associated with autoimmune pancreatitis in a cohort of hundred patients.

BACKGROUND/OBJECTIVES: Autoimmune diseases are often associated with human leukocyte antigen (HLA) haplotypes, indicating that changes in major histocompatibility complex (MHC)-dependent self-peptide or antigen presentation contribute to autoimmunity. In our study, we aimed to investigate HLA alleles in a large European cohort of autoimmune pancreatitis (AIP) patients. METHODS: Hundred patients with AIP, diagnosed and classified according to the International Consensus Diagnostic Criteria (ICDC), were prospectively enrolled in the study. Forty-four patients with chronic pancreatitis (CP) and 254 healthy subjects served as control groups. DNA was isolated from blood samples and two-digit HLA typing was performed with sequence-specific primer (SSP-) PCR. HLA allele association strength to AIP was calculated as odds ratio. RESULTS: We uncovered a strong enrichment of HLA-DQB1 homozygosity in type 1 and type 2 AIP patients. Moreover, a significantly increased incidence of the HLA-DRB1∗16 and HLA-DQB1∗05 alleles and a concomitant lack of the HLA-DRB1∗13 allele was detected in AIP type 1 and type 2 patients. In contrast, the HLA-DQB1∗02 allele was underrepresented in the 'not otherwise specified' (NOS) AIP subtype. We detected no significant difference in the HLA-DRB3, HLA-DRB4 and HLA-DRB5 allele frequency in our cohort. CONCLUSIONS: Although AIP type 1 and type 2 are characterized by distinct histopathological characteristics, both subtypes are associated with the same HLA alleles, indicating that the disease might rely on similar immunogenic mechanisms. However, AIP NOS represented another subclass of AIP.

The features and clinical outcomes of inflammatory bowel disease associated with autoimmune pancreatitis: A greater awareness is needed.

ABSTRACT: The prevalence of inflammatory bowel disease (IBD) has been described in 5% to 40% of autoimmune pancreatitis (AIP) patients. The aim of our study was to evaluate the prevalence, endoscopic features, and outcome of IBD in association with AIP.A retrospective analysis including all consecutive patients with AIP and a histological diagnosis of IBD from 2010 to 2020 was performed. Demographical data, AIP, and IBD features, as well as clinical course, were recorded.Among 267 AIP patients, 45 were diagnosed with ulcerative colitis (UC) (27 men, mean age 31.6), all with a diagnosis of type 2 AIP. The most frequent presentation of AIP was acute pancreatitis (55.5%). Both diffuse (51.1%) and focal (48.9%) pancreatic involvement were observed. The AIP relapse rate was 11.1% over a mean follow-up of 55 months. In 69% of patients, the interval time between the diagnosis of AIP and UC was <1 year. When UC was present at AIP onset, UC was in clinical remission in 50% of patients. Fecal calprotectin levels, when available, were elevated in 86.6% of these patients. Mostly, mild-moderate pancolitis was initially diagnosed (55.5%). During follow-up, escalation therapy for UC was required in 40% of patients after a mean time of 45 months. Two patients (4.4%) underwent colectomy.The prevalence of UC in AIP patients was 17%. Mild pancolitis with a low rate of colectomy was found. Greater awareness is needed to avoid a delayed diagnosis of UC, and the dosage of fecal calprotectin levels could have a role in this setting.

Pancreatic Enzyme Replacement Therapy in Patients Undergoing First-Line Gemcitabine Plus nab-paclitaxel for Advanced Pancreatic Adenocarcinoma.

BACKGROUND: The clinical consequences of pancreatic exocrine insufficiency and its treatment in advanced pancreatic ductal adenocarcinoma (PDAC) are poorly investigated. This retrospective study aims at investigating the pancreatic enzyme replacement therapy (PERT) use and its impact on survival and maldigestion-related symptoms in advanced PDAC patients undergoing chemotherapy. METHODS: A retrospective analysis was conducted on advanced PDAC patients, treated with first-line gemcitabine plus nab-paclitaxel at two academic institutions (March 2015-October 2018). Data were correlated with overall survival (OS) using Cox regression model. Kaplan-Meier curves were compared using Log-Rank test. RESULTS: Data from 110 patients were gathered. PERT was administered in 55 patients (50%). No significant differences in baseline characteristics with those who did not receive PERT were found. Median OS for the entire group was 12 months (95% CI 9-15). At multivariate analysis, previous surgical resection of the primary tumor, (HR 2.67, p=0.11), weight gain after 3 months (HR 1.68, p=0.07) and PERT (HR 2.85, p ≤ 0.001) were independent predictors of OS. Patients who received PERT reported an improvement of maldigestion-related symptoms at 3 months more frequently than patients who did not (85.2% vs 14.8%, p ≤ 0.0001). CONCLUSION: PERT is associated with significantly prolonged survival and maldigestion-related symptoms alleviation in advanced PDAC patients.

The Role of EUS-Guided FNA and FNB in Autoimmune Pancreatitis.

Autoimmune pancreatitis (AIP) is an increasingly recognized disease classified into two different subtypes based on histology. According to the International Diagnostic Criteria (ICDC), the diagnosis is achieved using a combination of different criteria. In patients presenting with a typical imaging appearance, the diagnosis may be straightforward, and steroid treatment is recommended, even without histological confirmation. In patients with atypical imaging or mass-forming appearance, the differential diagnosis with pancreatic cancer is challenging and crucial for treatment strategy. Endoscopic ultrasound (EUS)-guided tissue acquisition has been proposed to achieve a histological diagnosis. Fine-needle aspiration (FNA) was first proposed to aspirate cells from pancreatic lesions. Despite excellent results in terms of sensitivity for pancreatic cancer, the data are disappointing regarding the diagnosis of AIP. The recent development of new needles allowing fine-needle biopsy (FNB) has been associated with improved diagnostic accuracy based on preserving the tissue architecture, which is necessary to detect the typical histological features of AIP. However, the published literature on the role of EUS-guided FNA and FNB is limited and mainly focused on type 1 AIP. The present study aimed to review the available literature on the role of EUS-guided FNA and FNB in the diagnosis of AIP.