Type 1 Autoimmune Pancreatitis in Europe: Clinical Profile and Response to Treatment.

BACKGROUND & AIMS: Autoimmune pancreatitis (AIP) is an immune-mediated disease of the pancreas with distinct pathophysiology and manifestations. Our aims were to characterize type 1 AIP in a large pan-European cohort and study the effectiveness of current treatment regimens. METHODS: We retrospectively analyzed adults diagnosed since 2005 with type 1 or not-otherwise-specified AIP in 42 European university hospitals. Type 1 AIP was uniformly diagnosed using specific diagnostic criteria. Patients with type 2 AIP and those who had undergone pancreatic surgery were excluded. The primary end point was complete remission, defined as the absence of clinical symptoms and resolution of the index radiologic pancreatic abnormalities attributed to AIP. RESULTS: We included 735 individuals with AIP (69% male; median age, 57 years; 85% White). Steroid treatment was started in 634 patients, of whom 9 (1%) were lost to follow-up. The remaining 625 had a 79% (496/625) complete, 18% (111/625) partial, and 97% (607/625) cumulative remission rate, whereas 3% (18/625) did not achieve remission. No treatment was given in 95 patients, who had a 61% complete (58/95), 19% partial (18/95), and 80% cumulative (76/95) spontaneous remission rate. Higher (≥0.4 mg/kg/day) corticosteroid doses were no more effective than lower (<0.4 mg/kg/day) doses (odds ratio, 0.428; 95% confidence interval, 0.054-3.387) and neither was a starting dose duration >2 weeks (odds ratio, 0.908; 95% confidence interval, 0.818-1.009). Elevated IgG4 levels were independently associated with a decreased chance of complete remission (odds ratio, 0.639; 95% confidence interval, 0.427-0.955). Relapse occurred in 30% of patients. Relapses within 6 months of remission induction were independent of the steroid-tapering duration, induction treatment duration, and total cumulative dose. CONCLUSIONS: Patients with type 1 AIP and elevated IgG4 level may need closer monitoring. For remission induction, a starting dose of 0.4 mg/kg/day for 2 weeks followed by a short taper period seems effective. This study provides no evidence to support more aggressive regimens.

The Impact of the Angulus Biopsy on the Detection of Staging and the Grading of Chronic Gastritis.

There is a generally recognized need for a morphological assessment of the individual risk of developing gastric cancer in a patient with chronic gastritis, according to the OLGA system (Operative Link for Gastritis Assessment). At the same time, the role of assessing the biopsy from the incisura angularis remains controversial. The aim of our study was to assess the value of incisura angularis biopsy in staging gastritis according to the OLGA system by examining the atrophic and inflammatory changes in the antrum, incisura angularis, and body. MATERIALS AND METHODS: A total of 718 patients (576 women and 142 men) aged 20 to 84 years were examined. Most of the patients were in the age group of 50 to 70 years (54.6%). Depending on the detection of H. pylori and autoimmune gastritis markers, all patients were divided into three groups. The first group included 380 patients with H. pylori gastritis without signs of autoimmune gastritis. The second group consisted of 209 patients with autoimmune gastritis, in whom no infection was detected during the examination, and there were no indications of H. pylori eradication. The third group consisted of 129 patients with chronic gastritis of combined etiology (autoimmune and H. pylori). Endoscopy biopsies were taken according to the updated Sydney System. Histological assessments of the grade and the stage of gastritis were carried out according to the standard OLGA-based protocol. Then, the same assessments were evaluated without taking into account histological changes in the incisura angularis. RESULTS: When assessing the severity of inflammatory changes in the gastric mucosa according to the OLGA system, grade II (72.3%) was most often detected in all groups of patients. A severe degree of activity of chronic gastritis was most often observed in the group of patients with H. pylori gastritis (6.1%). These indicators practically did not change if the assessment did not take the angulus biopsy into account. When assessing the severity of atrophy of the glands in the gastric mucosa in patients of the first group, mild stages of atrophy prevailed. Without taking into account the angulus biopsy, a decrease in the stage of atrophy was observed in 27 cases (7.11%), and in only 4 cases did stage IV change to stage III, while in 23 cases, discrepancies were noted only within groups with a mild stage of atrophy. There were no transitions from stage III to stage II. In the group of patients with autoimmune gastritis, pronounced stages of atrophy prevailed-in more than 77%. Without taking into account the angulus biopsy, a decrease in the stage of atrophy was observed in eight cases (3.83%), and in three (1.4%) patients, stage III was changed to stage II. In the group of patients with combined etiology (autoimmune + H. pylori), severe stages of atrophy also prevailed (70.5%). A decrease in the stage of atrophy without taking into account the angulus biopsy was only observed in three patients (2.32%), of which two cases concerned patients with mild stages of atrophy. Thus, in general, severe stages of atrophy of the gastric mucosa (stages III and IV according to the OLGA staging system) were detected in 313 patients (43.59%). If the assessment of the atrophy stage did not take into account changes in the angulus biopsy, then severe stages of atrophy (III and IV according to OLGA) were detected in 310 patients (43.17%). In total, changes in the assessment of the atrophy stage occurred in 38 patients (5.29%), and this was more often observed in patients with stages I and II of atrophy. CONCLUSIONS: Accounting for histological changes in the incisura angularis does not significantly affect the assessment of the grade and stage of chronic gastritis according to the OLGA system, regardless of the etiology of atrophic gastritis.

Pancreatic exocrine insufficiency and pancreatic enzyme replacement therapy in patients with advanced pancreatic cancer: A systematic review and meta-analysis.

BACKGROUND: Pancreatic cancer is the fourth leading cause of cancer mortality. Most patients are diagnosed with advanced pancreatic cancer, either at locally advanced or metastatic stages, and have a high rate of malnutrition and weight loss which are associated with poor outcomes. Pancreatic exocrine insufficiency is one of the causes of malnutrition and weight loss in these patients. The prevalence and clinical consequences of pancreatic exocrine insufficiency in advanced pancreatic cancer are poorly investigated with heterogeneous results. We sought to determine the prevalence and clinical consequences of pancreatic exocrine insufficiency and the effect of pancreatic enzyme replacement therapy in patients with advanced pancreatic cancer by systematic review and meta-analysis. METHODS: Scopus, Medline, and Embase were searched for cohort studies or randomised clinical trials reporting pancreatic exocrine insufficiency and/or the effect of pancreatic enzyme replacement therapy in patients with advanced pancreatic cancer. We considered pancreatic exocrine insufficiency as an abnormal result on direct and/or indirect pancreatic exocrine function tests. Pancreatic enzyme replacement therapy was evaluated by its effect on survival and quality of life in patients with advanced pancreatic cancer. RESULTS: A total of 11 studies were included; seven studies reported the prevalence of pancreatic exocrine insufficiency and seven the effect of pancreatic enzyme replacement therapy in advanced pancreatic cancer. The pooled prevalence of pancreatic exocrine insufficiency in advanced pancreatic cancer was 72% (95% confidence interval: 55-86%), being significantly higher when tumours were located in the pancreatic head (relative risk = 3.36, 1.07-10.54; p = 0.04) six studies investigated the impact of pancreatic enzyme replacement therapy on survival/quality of life. Pancreatic enzyme replacement therapy was associated with 3.8 months (95% confidence interval: 1.37-6.19) survival benefit. Patients receiving pancreatic enzyme replacement therapy had a trend towards a better quality of life.Conclusions The prevalence of pancreatic exocrine insufficiency in advanced pancreatic cancer is substantial and its treatment can improve the outcomes of these patients.

Pancreatic Cancer Malnutrition and Pancreatic Exocrine Insufficiency in the Course of Chemotherapy in Unresectable Pancreatic Cancer.

Background: Malnutrition and cachexia are common in patients with advanced pancreatic ductal adenocarcinoma (PDAC) and have a significant influence on the tolerance and response to treatments. If timely identified, malnourished PDAC patients could be treated to increase their capacity to complete the planned treatments and, therefore, possibly, improve their efficacy. Aims: The aim of this study is to assess the impact of nutritional status, pancreatic exocrine insufficiency (PEI), and other clinical factors on patient outcomes in patients with advanced PDAC. Methods: PAncreatic Cancer MAlnutrition and Pancreatic Exocrine INsufficiency in the Course of Chemotherapy in Unresectable Pancreatic Cancer (PAC-MAIN) is an international multicenter prospective observational cohort study. The nutritional status will be determined by means of Mini-Nutritional Assessment score and laboratory blood tests. PEI will be defined by reduced fecal elastase levels. MAIN OUTCOME: adherence to planned chemotherapy in the first 12 weeks following the diagnosis, according to patients' baseline nutritional status and quantified and reported as "percent of standard chemotherapy dose delivered." SECONDARY OUTCOMES: rate of chemotherapy-related toxicity, progression-free survival, survival at 6 months, overall survival, quality of life, and the number of hospitalizations. ANALYSIS: chemotherapy dosing over the first 12 weeks of therapy (i.e., percent of chemotherapy received in the first 12 weeks, as defined above) will be compared between well-nourished and malnourished patients. SAMPLE SIZE: based on an expected percentage of chemotherapy delivered of 70% in well-nourished patients, with a type I error of 0.05 and a type II error of 0.20, a sample size of 93 patients per group will be required in case of a percentage difference of chemotherapy delivered of 20% between well-nourished and malnourished patients, 163 patients per group in case of a difference of 15% between the groups, and 356 patients per group in case of a 10% difference. Centers from Russia, Romania, Turkey, Spain, Serbia, and Italy will participate in the study upon Local Ethics Committee approval. Discussion: PAC-MAIN will provide insights into the role of malnutrition and PEI in the outcomes of PDAC. The study protocol was registered at clinicaltrials.gov as NCT04112836.