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.

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.

Fecal elastase-1 is useful in the detection of steatorrhea in patients with pancreatic diseases but not after pancreatic resection.

BACKGROUND: Fecal elastase-1(FE-1) has been suggested as an alternative to steatorrhea quantification to evaluate pancreatic insufficiency, but its diagnostic performance has not been compared with steatorrhea in chronic pancreatitis or after pancreatic resection. METHODS: The relationship between steatorrhea and FE-1 was studied in patients with chronic pancreatic disorders or pancreatic resection. Student's t test and ANOVA were used for statistical analysis, accepting 0.05 as limit for significance. RESULTS: Eighty-two patients were studied (42 non-operated; 40 previously submitted to pancreatic resection). Fat output was higher in operated than non-operated patients (29.2 ± 3.1 vs 9.9 ± 2.2 g/day, p < 0.001) FE-1 was more severely reduced in operated patients (202 ± 32.3 µg/g in non operated vs 68.6 ± 18.2 in operated patients; p < 0.001). Steatorrhea was significantly more severe in operated patients across different levels of FE-1. The relationship between FE-1 and steatorrhea was described by a power regression model, with a regression line significantly different in operated and non-operated patients (p < 0.001). A steatorrhea of 7 g (upper limit of normal range) was calculated by this regression line when FE-1 is 15 µg/g in non-operated, but as high as 225 µg/g in operated patients. CONCLUSION: FE-1 is useful to identify pancreatic insufficiency. Steatorrhea is anticipated in non-operated patients only when FE-1 is below the limit for a confident measurement of our assay. In operated patients, steatorrhea may be present even if FE-1 is only slightly reduced, that suggests a role for non pancreatic factors. FE1 is not useful to identify operated patients at risk of malabsorption.

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.

Ablation Difficulty Score: Proposal of a new tool to predict success rate of percutaneous ablation for hepatocarcinoma.

PURPOSE: Identify the factors related to failure ablation after percutaneous ultrasound guided single electrode radiofrequency ablation (RFA) for hepatocarcinoma (HCC) and propose a score for improving patient selection and treatment allocation. METHODS: From 2010 to 2020 585 HCC nodules treated with RFA were prospectively collected. Ablation Difficulty Score (ADS) was built-up according to clinical and radiological factors related to failure ablation identified by Cox-logistic regression analysis. The study population was stratified in low risk (ADS 0), intermediate risk (ADS 1), and high risk (ADS ≥ 2) of failure ablation. RESULTS: Overall ablation success rate was 85.5%. Morbidity and mortality rates were 3.5% and 0.0%. According to per nodule analysis the following factors resulted related to failure ablation: size > 20 mm (p = 0.002), sub-capsular location (p = 0.008), perivascular location (p = 0.024), isoechoic appearance (p = 0.008), and non-cirrhotic liver (p = 0.009). The ablation success rate was 93.5% in ADS 0, 85.8% in ADS 1 and 71.3% in ADS ≥ 2 (p < 0.001). The 1-year local tumor progression (LTP) free survival was 90.2% in ADS 0, 80.6% in ADS 1, and 72.3% in ADS ≥ 2 (p = 0.009). Nodule's size > 20 mm (p = 0.014), isoechoic appearance (p = 0.012), perivascular location (p = 0.012) resulted related to lower LTP free survival. CONCLUSION: Ablation Difficulty Score could be a simple and useful tool for guiding the treatment decision making of HCC. RFA in high risk nodules (ADS ≥ 2) should be carefully evaluated and reserved for patients not suitable for surgery or liver transplantation.

Azathioprine Maintenance Therapy to Prevent Relapses in Autoimmune Pancreatitis.

OBJECTIVES: Steroids are used to induce remission in autoimmune pancreatitis (AIP). Low-dosage steroid therapy or immunosuppressant (IMs) has been proposed as maintenance therapy to prevent AIP relapse. Few and conflicting data have been published on the efficacy of azathioprine (AZA) in preventing AIP relapse. The aim of this study was to evaluate the indication and efficacy of AZA as maintenance therapy to prevent disease relapse in AIP. METHODS: Patients suffering from AIP diagnosed according to the ICDC in type 1, type 2, and not otherwise specified (NOS) were divided in those treated with AZA (AZA+ group) as maintenance therapy and not treated with maintenance therapy (AZA- group). Exclusion criteria were: previous pancreatic surgery, other autoimmune diseases as indication for AZA treatment, and use of IMs different from AZA. Drug safety, clinical and instrumental outcome of AZA+ patients were evaluated. RESULTS: A total of 23 patients (18 Males and 5 Females, mean age 54±11 years) in AZA+ group and 97 (58 Males and 39 Females, mean age 45±18 years) in AZA- group were compared. In AZA+ group, patients were significantly older (P=0.043), type 1 AIP was more frequently diagnosed (87 vs. 51%, P=0.006), sIgG4 higher (758±625 vs. 311±409 mg/dl, P<0.001), other organ involvement (OOI) more frequently observed (83 vs. 48%, P=0.002), with higher frequency of relapse before AZA treatment (78 vs. 14%, P<0.001). Three patients in AZA+ group required drug discontinuation because of adverse events. Twenty patients were therefore evaluated for outcome. Six out of 20 patients (30%) relapsed after 24±15 months (5 in pancreas and 1 on biliary tract). They were retreated with steroids and continued AZA. Two out of 6 patients (33%) had a second relapse,after respectively 11 months (in pancreas and kidney) and 22 months (in kidney). CONCLUSIONS: AZA is an effective and safe treatment to prevent AIP relapses.

Clinical and Morphological Features of Paraduodenal Pancreatitis: An Italian Experience With 120 Patients.

OBJECTIVES: This study aimed to evaluate the clinical and radiological features and clinical outcomes of paraduodenal pancreatitis (PP). METHODS: A final diagnosis of PP was based on surgical specimens in resected patients and on imaging in nonoperated patients. Clinical, radiological, and pathological data were collected and reevaluated. RESULTS: We studied 120 patients, 97.5% of whom were drinkers and 97.5% were smokers. Symptoms at clinical onset were acute pancreatitis in 78 patients (65%) and continuous pain in 68 patients (55.8%). Other symptoms were vomiting (36.7%), weight loss (25.8%), and jaundice (11.7%). Cystic variant was diagnosed in 82 patients (68.0%), and solid variant was diagnosed in 38 patients (32.0%). Pure and diffuse forms were observed in 22 (18.3%) and 98 (81.7%) patients, respectively. Pancreatic calcifications were present at clinical onset in 5.0% of the patients and in 61.0% at the end of follow-up. Somatostatin analogs were used in 13 patients (10.8%), and 81 patients (67.0%) underwent surgery. CONCLUSIONS: The clinical profile of PP was found to be middle-aged men who were heavy drinkers and smokers with painful pancreatitis and was associated with vomiting and weight loss. In nonresponders, alcohol withdrawal and medical therapy can be proposed as a first-line treatment, and surgery as a second-line treatment.

Role of Amylase-α2A Autoantibodies in the Diagnosis of Autoimmune Pancreatitis.

OBJECTIVES: Several serological markers have been reported in autoimmune pancreatitis (AIP) patients. However, only serum IgG4 (sIgG4) is available in clinical practice for AIP diagnosis. Antiamylase α antibodies (AMY-α Abs) have been proposed to diagnose AIP. This study evaluates the utility of AMY-α Abs and sIgG4 for AIP diagnosis. METHODS: Twenty-five AIP patients, 84 disease control groups (31 chronic pancreatitis, 30 acute pancreatitis, 23 pancreatic adenocarcinoma), and 59 healthy donors were prospectively studied. The AMY-α Abs were determined by homemade enzyme-linked immunosorbent assay and sIgG4 by nephelometry. RESULTS: Increased sIgG4 were detected to be present in 52% of AIP, 5% in control groups, and 0% in healthy donors, and AMY-α Abs, respectively, in 76%, 36%, and 2%. sIgG4 was elevated in 92% of the 13 patients with type 1 AIP, but in none of 3 with type 2 and of 8 with not otherwise specified AIP. The AMY-α Abs were present in 79%, 67%, and 75% of type 1, type 2, and not otherwise specified AIP, respectively. Sensitivity and specificity of AMY-α Abs were 76% and 78%, and of sIgG4 50% and 94%. By combining the 2 serological markers, sensitivity was 41%, and specificity was 99%. CONCLUSIONS: The AMY-α Abs may help to diagnosis of AIP and to differentiate AIP subtypes.

Impedance pH Monitoring: Intra-observer and Inter-observer Agreement and Usefulness of a Rapid Analysis of Symptom Reflux Association.

BACKGROUND/AIMS: Symptom reflux association analysis is especially helpful for evaluation and management of proton pump inhibitor (PPI) re-fractory patients. An accurate calculation requires manual editing of 24-hour multichannel intraluminal impedance-pH (MII-pH) tracings after automatic analysis. Intra- and inter-observer agreement as well as reliability of rapid editing confined to the time around symptomatic episodes are unknown. Aim of this study was to explore these topics in a prospective multicenter study. METHODS: Forty consecutive patients who were off PPI therapy underwent MII-pH recordings. After automatic analysis, their tracings were anonymized and randomized. Three experienced observers, each one trained in a different European center, independently per-formed manual editing of 24-hour tracings on 2 separate occasions. Values of symptom index and symptom association proba-bility for acid and non acid reflux were transformed into binary response (i.e., positive or negative). RESULTS: Intra-observer agreement on symptom reflux association was 92.5% to 100.0% for acid and 85.0% to 97.5% for non-acid reflux. Inter-observer agreement was 100.0% for acid and 82.5% to 95.0% for non-acid reflux. Values for symptom index and symptom association probability were similar. Concordance between 24-hour and rapid (2 minutes-window before each symp-tomatic episode) editings for symptom reflux association occured in 39 to 40 patients (acid) and in 37 to 40 (non-acid), de-pending on the observer. CONCLUSIONS: Intra- and inter-observer agreement in classifying patients with or without symptom reflux association at manual editing of 24-hour tracings was high, especially for acid reflux. Classifying patients according to a rapid editing showed excellent con-cordance with the 24-hour one and can be adopted in clinical practice.

Esophageal motility and symptoms in restricting and binge-eating/purging anorexia.

BACKGROUND: Esophageal symptoms are common in anorexia nervosa, but it is not known whether they are associated with motility disorders, with different forms of the disease, and whether they respond to nutritional rehabilitation. METHODS: To clarify these points, 23 patients with anorexia nervosa (12 binge-eating/purging, "purgers"; 11 restricting type, "restricters") were studied by esophageal manometry before and after 22 weeks rehabilitation. Manometric parameters of 35 age and sex-matched patients were used as controls. Patients with anorexia also filled questionnaires on eating disorder psychopathology, psychopathological distress and esophageal, gastric and colonic symptoms before and after 4 and 22 weeks of a rehabilitation program. RESULTS: Symptoms were more severe in patients than in controls. Gastric and colonic, but not esophageal symptoms improved with treatment. LES basal pressure was higher in restricters (restricters 32.1±4.6; purgers 14.9±2.2; controls 17.1±1.1 mmHg, p<0.005), but still within normal range; this difference disappeared after treatment. Postdeglutitive body waves were normally propagated. Their amplitude was significantly higher in anorexia than in controls. No correlation was found between results of psychopathological tests (improved after treatment), esophageal symptoms and manometry. CONCLUSIONS: In anorexia, esophageal symptoms are frequent and severe. They are not adequately explained by psychological or manometric derangements.