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.

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.

From digital voices to vaccine choices: increasing female vaccine acceptance in Sudan through social listening.

The early COVID-19 vaccine rollout in Sudan experienced a gender disparity in vaccine uptake, with women accounting for less than 40% of vaccinations after four months of vaccine access. Initial analysis revealed that demand generation approaches were not sufficiently tailored to address the challenges and concerns of women. Using real-time social media monitoring, also known as social listening, to understand this inequity, we used an analytical tool called "Talkwalker" to track public sentiment and engagement regarding vaccination on social media platforms. The data captured subsequently informed a gender-responsive messaging campaign on social media that directly addressed specific concerns of Sudanese women. Within one week of the campaign's onset in September 2021, we observed a 144% increase in women's COVID-19 related social media engagement. Subsequent campaigns further enhanced women's engagement from 31% to between 35%-47%. Two subsequent campaigns in January and February/March 2022 were complemented with in-person activities, such as group meetings with community members and home visits by health promoters. Women's vaccination rates increased by 9% while the first two campaigns were live. System constraints hindered data linkages for the third campaign. These findings demonstrate the value of integrating real-time feedback with large-scale social media campaigns and the potential of linking online and offline strategies to further refine interventions, particularly in a conflict-prone and low-income country context. Our experience reinforces the notion that "one size does not fit all" when it comes to health-related communication. Responses should be tailored, contextualized, and person-centered, particularly in addressing concerns unique to women.

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.

Quantitative Edge Analysis of Pancreatic Margins in Patients with Chronic Pancreatitis: A Correlation with Exocrine Function.

BACKGROUND: Many efforts have been made to improve accuracy and sensitivity in diagnosing chronic pancreatitis (CP), obtaining quantitative assessments related to functional data. Our purpose was to correlate a computer-assisted analysis of pancreatic morphology, focusing on glandular margins, with exocrine function-measured by fecal elastase values-in chronic pancreatitis patients. METHODS: We retrospectively reviewed chronic pancreatitis patients who underwent fecal elastase assessment and abdominal MRI in our institute within 1 year. We identified 123 patients divided into three groups based on the fecal elastase value: group A with fecal elastase > 200 µg/g; group B with fecal elastase between 100 and 200 µg/g; and group C with fecal elastase < 100 µg/g. Computer-assisted quantitative edge analysis of pancreatic margins was made on non-contrast-enhanced water-only Dixon T1-weighted images, obtaining the pancreatic margin score (PMS). PMS values were compared across groups using a Kruskal-Wallis test and the correlation between PMS and fecal elastase values was tested with the Spearman's test. RESULTS: A significant difference in PMS was observed between the three groups (p < 0.0001), with a significant correlation between PMS and elastase values (r = 0.6080). CONCLUSIONS: Quantitative edge analysis may stratify chronic pancreatitis patients according to the degree of exocrine insufficiency, potentially contributing to the morphological and functional staging of this pathology.

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.

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.

Immunoglobulin G4-Related Disease Responder Index Correlates With the Risk of 1-Year Relapse in Type 1 Autoimmune Pancreatitis.

OBJECTIVES: Type 1 autoimmune pancreatitis (AIP) is a manifestation of immunoglobulin G4-related diseases (IgG4-RD). To evaluate the activity of the disease, the IgG4-RD responder index (RI) has been created. This study evaluated the IgG4-RD RI as prognostic factor of 1-year disease relapse. METHODS: Patients diagnosed with type 1 AIP between January 2012 and December 2016, with available magnetic resonance imaging and IgG4 dosage, were enrolled. Immunoglobulin G4-RD RI was calculated at baseline (time 0), and at 3 to 6 and 12 to 18 months after the end of steroid therapy (time 1 and time 2, respectively). RESULTS: Thirty-three patients were included in the study. Immunoglobulin G4-RD RI was 8.9 (standard deviation [SD], 3.8) at time 0, 2.4 (SD, 3.1) at time 1 (P < 0.0001 vs time 0), and 4.2 (SD, 3.9) at time 2 (P = 0.02 vs time 1). Fourteen patients who relapsed within 1 year showed a higher mean value of IgG4-RD RI at time 0 (10.9; SD, 4.3) versus 19 who did not (7.4; SD, 2.6; P = 0.012). This difference was observed also at time 2 (6.8 vs 2.1; P = 0.002). CONCLUSIONS: Immunoglobulin G4-RD RI correlates with type 1 AIP disease activity, and it predicts disease relapse within 1 year.

Comparison between EUS-guided fine-needle aspiration cytology and EUS-guided fine-needle biopsy histology for the evaluation of pancreatic neuroendocrine tumors.

BACKGROUND/OBJECTIVES: Studies comparing EUS-guided fine-needle aspiration (EUS-FNA) with EUS-guided fine-needle biopsy (EUS-FNB) for the evaluation of pancreatic neuroendocrine tumors (pNETs) are lacking. We aimed at comparing EUS-FNA with EUS-FNB in terms of Ki-67 proliferative index (PI) estimation capability, cellularity of the samples, and reliability of Ki-67 PI/tumor grading compared with surgical specimens. METHODS: Patients diagnosed with pNETs on EUS and/or surgical specimens were retrospectively identified. Specimens were re-evaluated to assess Ki-67 PI feasibility, sample cellularity by manual counting, and determination of Ki-67 PI value. Outcomes in the EUS-FNA and EUS-FNB groups were compared. Kendall rank test was used for Ki-67 PI correlation between EUS and surgical specimens. Subgroup analysis including small (≤20 mm), non-functioning pNETs was performed. RESULTS: Three-hundred samples from 292 lesions were evaluated: 69 EUS-FNA cytology and 231 EUS-FNB histology. Ki-67 PI feasibility was similar for EUS-FNA and EUS-FNB (91.3% vs. 95.7%, p = 0.15), while EUS-FNB performed significantly better in the subgroup of 179 small pNETs (88.2% vs. 96.1%, p = 0.04). Rate of poor cellulated (<500 cells) specimens was equal between EUS-FNA and EUS-FNB. A significant correlation for Ki-67 PI values between EUS and 92 correspondent surgical specimens was found in both groups, but it was stronger with EUS-FNB (tau = 0.626, p < 0.0001 vs. tau = 0.452, p = 0.031). Correct grading estimation was comparable between the two groups (p = 0.482). CONCLUSION: Our study showed stronger correlation for Ki-67 values between EUS-FNB and surgical specimens, and that EUS-FNB outperformed EUS-FNA in the evaluation of small pNETs. EUS-FNB should become standard of care for grading assessment of suspected pNETs.

Rituximab as Maintenance Therapy in Type 1 Autoimmune Pancreatitis: An Italian Experience.

OBJECTIVE: Rituximab (RTX) has been proposed for the induction of remission and maintenance therapy in relapsing type 1 autoimmune pancreatitis (AIP). The aim of the study was to describe the use of RTX as maintenance therapy for patients with type 1 AIP. METHODS: Patients with type 1 AIP based on the International Consensus Diagnostic Criteria and treated with RTX were selected from our database. Two doses of RTX (1000 mg each) were administered 15 days apart and repeated after 6 months. RESULTS: Eighteen patients were treated with RTX as maintenance therapy. Of these, the involvement of other organs was observed in 16 patients (89%). Eight of the 18 patients (44%) relapsed during follow-up. Median time to relapse after the last infusion was 30 months (range, 12-35 months). No disease relapse was observed in the first year after the last infusion. Probability of disease relapse was 80% between 1 and 3 years from initial treatment. No adverse effects were observed. CONCLUSIONS: Rituximab seems be safe and effective for maintenance therapy of type 1 AIP during the first year after completing RTX infusion. However, the probability of disease relapse is high within 1 and 3 years from the last infusion.

Painless chronic pancreatitis.

BACKGROUND: Painless chronic pancreatitis (CP) is a rare form of the disease. AIM: To evaluate the prevalence and the characteristics of this overlooked form of pancreatitis. METHODS: Patients with a diagnosis of CP and absence of pain were selected, excluding patients suffering from autoimmune pancreatitis. Clinical data, imaging features, and exocrine and endocrine function were therefore analyzed. RESULTS: Among 781 patients observed between 2010 and 2016, 74 patients with painless CP (9.5%) were selected. Mean age at diagnosis was 60.8 (SD 10.8) years. 38(51%) individuals did not report any symptom, 36(49%) were affected by symptoms other than pain. Pancreatic calcifications were diagnosed in 70 patients (95%), main pancreatic duct dilation in 55(74%), and pancreatic atrophy in 39(53%).Thirty-six patients (55%) had severe exocrine pancreatic insufficiency(EPI). Diabetes was observed in 34 out of 72 patients (47%). During a mean follow-up of 2.9 (SD 2.8) years, only a mild pancreatitis was diagnosed in a 71-year old female. No patient underwent endoscopic treatment or surgery, developed pancreatic cancer or died. CONCLUSIONS: In a tertiary center painless CP is observed in 10% of cases, and it is frequently associated with EPI. The probability of onset of pain is very low in a short-term follow-up.

Autoimmune pancreatitis not otherwise specified (NOS): Clinical features and outcomes of the forgotten type.

BACKGROUND: Autoimmune pancreatitis (AIP) is a well-recognized fibroinflammatory disease of the pancreas. Despite the significant number of studies published on AIP type 1 and 2, no studies have been focused on AIP type not otherwise specified (NOS) and therefore very little is known about clinical features and long-term outcomes of these patients. The aim of this study was to investigate clinical and radiological features of AIP type NOS-patients. METHODS: Patients classified as AIP type NOS at clinical onset included in our database prospectively maintained since 1995 were evaluated. Epidemiological, clinical data were collected and analyzed. RESULTS: Forty-six patients were included in the study. The clinical onset was mainly characterized by weight loss, jaundice and acute pancreatitis. Eight patients (17.4%) were reclassified as AIP type 2 during follow-up because of the development of ulcerative colitis. Seven patients (15.2%) experienced relapse after steroid treatment but only one (2.2%) needed immunosuppressive drugs because of recurrent relapses. CONCLUSIONS: AIP type NOS shares clinical features similar to AIP type 2 and a relevant proportion of patients was reclassified as AIP type 2 during follow-up because of the development of ulcerative colitis. The risk of relapse is low but not irrelevant.

Residual pancreatic function after pancreaticoduodenectomy is better preserved with pancreaticojejunostomy than pancreaticogastrostomy: A long-term analysis.

BACKGROUND: Pancreatico-enteric anastomosis after pancreaticoduodenectomy can be performed using either a pancreaticojejunostomy (PJ) or pancreaticogastrostomy (PG). Differences in surgical outcomes are still a matter of debate, and less is known about long-term functional outcomes. METHODS: Twelve years after the conclusion of a comparative study evaluating the surgical outcomes of PJ and PG (Bassi et al., Ann Surg 2005), available patients underwent morphological and functional pancreatic assessment: pancreatic volume and duct diameter measured by MRI, impaired secretion after secretin, fecal fat, fecal elastase-1 (FE-1), serum vitamin D and endocrine function. Quality of life and symptom scores were evaluated with the EORTC QLQ-C30 questionnaire. RESULTS: Only 34 patients were available for assessment. No differences were found in terms of BMI variation, endocrine function, quality of life or symptoms. Exocrine function was more severely impaired after PG than after PJ (fecal fats 26.6 ±â€¯4.1 vs 18.2 ±â€¯3.6 g/day; FE-1 121.4 ±â€¯6.7 vs 170.2 ±â€¯25.5 µg/g, vitamin D 18.1 ±â€¯1.8 vs. 23.2 ±â€¯3.1 ng/mL). MRI assessment identified a lower pancreatic volume (26 ±â€¯3.1 vs. 36 ±â€¯4.1 cm3) and a more dilated pancreatic duct (4.6 ±â€¯0.92 vs. 2.4 ±â€¯0.18 mm) in patients with PG compared to those with PJ. CONCLUSION: Compared to PJ, PG is associated with a more severely impaired exocrine function long-term, but they result similar endocrine function and quality of life. In patients with a long life expectancy, this should be taken into account.

Chronic Asymptomatic Pancreatic Hyperenzymemia: A Long-term Follow-up.

OBJECTIVES: Chronic asymptomatic pancreatic hyperenzymemia (CAPH) was described as a benign disease. However, we already described clinically relevant findings requiring surgery or follow-up in half of the subjects. The aim of this study was to evaluate the long-term outcome of CAPH in terms of symptoms and evolution toward chronic pancreatitis. METHODS: Subjects previously enrolled in the first phase of the study (from 2005 to 2010) were reinvestigated from December 2013 to January 2017 with a phone call ± magnetic resonance cholangiopancreatography with secretin stimulation. RESULTS: A total of 133 subjects were eligible for the follow-up study (75 males, 58 females; age, 48.4 [standard deviation {SD}, 14] years); 24 (18%) of them dropped out. During a mean follow-up of 9.3 (SD, 5.2) years after the first diagnosis of CAPH, no episode of acute pancreatitis or abdominal pain was reported. Sixty-three subjects (58%) of 109 underwent magnetic resonance cholangiopancreatography with secretin stimulation with a mean follow-up of 5.7 [SD, 3.1] years (range, 1-11 years). Secretin stimulation-MRCP resulted unchanged in 54 (90%) of 60 subjects, worsened in 3 (5%) and improved in 3 (5%). Two subjects died from causes unrelated to pancreatic disease. CONCLUSIONS: Excluding subjects with a pancreatic disease at index magnetic resonance imaging, CAPH is a benign condition.

Patterns of Recurrence after Resection for Pancreatic Neuroendocrine Tumors: Who, When, and Where?

BACKGROUND/AIMS: Pancreatic neuroendocrine tumors (pan-NENs) represent an increasingly common indication for pancreatic resection, but there are few data regarding possible recurrence after surgery. The aim of the study was to describe the frequency, timing, and patterns of recurrence after resection for pan-NENs with consequent implications for postoperative follow-up. METHODS: We performed a retrospective analysis of pan-NENs resected between 1990 and 2015 at The Pancreas Institute, University of Verona Hospital Trust. Predictors of recurrence were assessed. Survival analysis was conducted using the Kaplan-Meier and conditional survival (CS) methods. RESULTS: The cohort consisted of 487 patients with a median follow-up of 71 months. Recurrence developed in 12.3%: 54 (11.1%) liver metastases, 11 (2.3%) local recurrence, 10 (2.1%) nodal recurrence, and 8 (1.6%) metastases in other organs. Thirty-one (6.4%) died due to disease recurrence. Size > 21 mm, G3 grade, nodal metastasis, and vascular infiltration were independent predictors of overall recurrence. Recurrence occurred either during the first year of follow-up (n = 9), or after 10 years (n = 4). CS analysis revealed that nonfunctioning G1 pan-NEN ≤20 mm without nodal metastasis or vascular invasion had a negligible risk of developing recurrence. In the present series, after 5 years of follow-up without developing recurrence, tumor recurrence occurred only in the form of liver metastases. CONCLUSIONS: Recurrence of pan-NENs is rare and is predicted by tumor size, nodal metastasis, grading, and vascular invasion. Patients with G1 pan-NEN without nodal metastasis and vascular invasion may be considered cured by surgery. After 5 years without recurrence, follow-up should focus on excluding the development of liver metastases.