Severity Of Chronic Pancreatitis Research Articles

Peculiarities of treatment of patients with comorbid pathology: chronic pancreatitis and hypothyroidism, taking into account SEPP1 gene polymorphism (RS7579)

Optimization of therapeutic regimens during the treatment of the polymorbid course of chronic pancreatitis combined with hypothyroidism is an important task of modern science.
 Aim: to treat patients with comorbid pathology: chronic pancreatitis and hypothyroidism, taking into account the polymorphism of the SEPP1 gene (RS7579)
 Materials and methods. During the research, we examined 128 people. Patients were divided into 3 groups. The first group included 48 patients with chronic pancreatitis, the second - 50 patients with chronic pancreatitis in combination with hypothyroidism, and the third - 30 practically healthy people.
 Results. Symptoms of maldigestion decreased in 72 % of the examined patients. Signs of nutritional deficiency have significantly decreased, and general well-being has improved. Multicomponent therapy also affected mood, sleep, and reduced irritability and symptoms of depression and anxiety disorders. A multisystemic polysyndromic approach to treatment led to improvements in both pancreatic and thyroid function. The effectiveness of the treatment strategy for patients with chronic pancreatitis was dependent on individual characteristics, such as the severity of chronic pancreatitis, the presence of primary hypothyroidism, the degree of selenium deficiency and concomitant symptoms, taking into account polymorphic variants of the SEPP1 (rs7579) gene. Selenoid deficiency decreased, especially in the group with a combination of chronic pancreatitis and hypothyroidism. The improvement in thyroid hormone activity included a 40.46 % decrease in blood TSH and a 2.5-fold increase in free T4.
 Conclusions. The program of complex therapy led to the normalization of the condition of patients with the G-allele genotype of the SEPP1 gene (rs7579), as evidenced by significant improvements in most of the analyzed indicators. The concentration of fecal elastase 1 and blood selenoprotein P significantly increased, and the level of serum pancreatic α-amylase significantly decreased in carriers of the AA genotype. Under the influence of therapy, there were also changes in the hormonal activity of the thyroid gland, a decrease in the concentration of total metabolites of NO, and an improvement in the health indicators of the cardiovascular system. However, for patients with the AA genotype of the SEPP1 (rs7579) gene, continuation of therapy remains important to achieve an optimal condition, in particular, to manage cholesterol levels and other cardiovascular risk factors

Efficiency of Complex Correction of Endotoxicosis in Chronic Pancreatitis During Renewal Treatment

Clinical manifestations and features of endogenous intoxication syndrome (EIS) in severe and critical conditions are described in the literature. EIS is one of the defining typical clinical and pathogenetic syndromes of the formation and severity of chronic pancreatitis (CP). The objective: to analyze the EIS parameters by CP in patients outside of exacerbation and their impact on the quality of patient’s life and the dynamics under the influence of the proposed treatment programs with the inclusion of ginkgo biloba drugs and bioregulatory therapy. Materials and methods. 100 patients with diagnosis of CP who had outpatient treatment took part in the study. The age of the patients ranged from 25 to 73 years old, the average age was 51.0±1.1 years. EIS was determined based on the concentration of medium molecular weight peptides with maximum absorption at the wavelength 254 nm and 280 nm and circulating immune complexes. Patients’ quality of life was assessed using the SF-36 questionnaire. The patients were divided into three 3 groups. The persons in the 1st group (n=34) received generally accepted treatment (GAT) in accordance with the clinical diagnosis and the protocol proposed by the Ministry of Health of Ukraine (Order No. 638 of 09/10/2014), the patients in the 2nd group (n=33) received GAT together with a course of ginkgo biloba (memoplant), the individuals in the 3rd group (n=33) received the GAT with a course of memoplant and bioregulatory therapy (BRT). Results. In the examined patients with CP a decrease in all indicators of the quality of life according to the SF-36 was found, the parameters of the role (33.7±3.4) and emotional (37.0±3.9) functioning scales decreased mostly, the average value of physical health was 51,1±7.2, psychological one – 45.1±3.9. An increase in EIS indicators was determined, which were reliably correlated with indicators of quality of life. In the patients who received GAT and ginkgo biloba the more significant dynamics of EIS regression were established at the levels of the studied indicators, however, their normalization to the control level was observed only in the 3rd group of patients who received an additional course of BRT (p<0.001). Conclusions. The results of the study determined a negative impact of EIS on parameters of quality of life according to the SF-36 in patients with CP, which justifies the necessity for the correction. A more severe EIS according to the levels of the studied indicators was found among people with excessive and reduced body weight (p<0.05), which indicates a more severe course of the inflammatory process. According to the dynamics of EIS the indicators in patients with CP it is possible to claim a higher efficiency of therapy with additional prescription to the generally accepted treatment of ginkgo biloba and a course of bioregulatory therapy.

Lobularity rather than hyperechoic foci/stranding on endoscopic ultrasonography is associated with more severe histological features in chronic pancreatitis.

Endoscopic ultrasonography (EUS) findings of the pancreatic parenchyma, such as hyperechoic foci/stranding and lobularity, may be associated with the severity of chronic pancreatitis (CP). However, the correlation between parenchymal EUS findings and histology remains unclear. We designed a large-scale retrospective study analyzing over 200 surgical specimens to elucidate the association between parenchymal EUS findings and histological features. Clinical data of 221 patients with pancreatobiliary tumors who underwent preoperative EUS and pancreatic surgery between January 2010 and November 2020 were reviewed to investigate the association between parenchymal EUS findings and histological features at the pancreatic body. None of these patients met the definition of CP. Of the 221 patients, 87 (39.4%), 89 (40.2%), and 45 (20.4%) had normal EUS findings, hyperechoic foci/stranding without lobularity, and hyperechoic foci/stranding with lobularity, respectively. In the multivariate analyses, parenchymal EUS findings significantly correlated with histological CP findings of fibrosis, inflammation, and atrophy (hyperechoic foci/stranding without lobularity vs hyperechoic foci/stranding with lobularity, odds ratio [95% confidence interval]: 4.1 [2.2-7.9] vs 31.3 [9.3-105.6], Ptrend <0.001; 3.9 [1.9-8.2] vs 21.8 [8.0-59.4], Ptrend <0.001; and 4.0 [2.0-7.8] vs 22.9 [7.0-74.5], Ptrend <0.001, respectively). Further, a trend toward higher histological grade was observed in the following order: normal findings, hyperechoic foci/stranding without lobularity, and hyperechoic foci/stranding with lobularity. Endoscopic ultrasonography findings of the pancreatic parenchyma may be associated with the histological conditions in CP, such as pancreatic fibrosis, inflammation, and atrophy. Lobularity reflects more severe histological conditions than does hyperechoic foci/stranding.

Chronic pancreatitis and the intestinal microbiome in adults and children: Not only SIBO but also gut dysbiosis has clinical significance

Chronic pancreatitis is accompanied by both small intestinal bacterial overgrowth and dysbiosis of the gut microbiota. The most typical changes in the gut microbiota in chronic pancreatitis are a decrease in microbial diversity, an increase in the abundance of Proteobacteria, a decrease in the abundance of Bacteroidetes, Actinobacteria, and Firmicutes, especially butyrate-producing bacteria such as Faecalibacterium, a significant association with infectious pathways (KEGG analysis]), concomitant metabolic disorders (diabetes mellitus) and exocrine pancreatic insufficiency. Changes in the gut microbiota in children with chronic pancreatitis are like those in adults and are characterized by a decrease in α-diversity and the loss of shortchain fatty acid producers: butyrate-producing Faecalibacterium, Subdoligranulum, and Eubacterium, propionate-producing Phascolarctobacterium, acetate- and lactate-producing Collinsella, and probiotic Bifidobacterium. Dysbiotic changes in the gut microbiome, including a decrease in the abundance of commensal symbionts, are significantly associated with the severity of chronic pancreatitis. The most important factor influencing the intestinal microbiota is the pancreatic exocrine function, a decrease which leads to a switch from enterotype 1 (Bacteroides predominance) to enterotype 2 (Prevotella predominance) and a decrease in phylogenetic diversity (α-diversity index). Modulation of the dysbiotic gut microbiota can be carried out with probiotics, prebiotics, bacterial metabolites such as butyrate, pancreatic enzymes and should become a full-fledged therapeutic option in patients with chronic pancreatitis.

Вплив ендотоксикозу на вегетативний статус пацієнтів з хронічним панкреатитом

Актуальність. Одними з визначальних типових клініко-патогенетичних синдромів формування і тяжкості перебігу хронічного панкреатиту (ХП) є синдроми ендогенної інтоксикації (СЕІ) та вегетативної дисфункції (ВД). Досліджень гематологічних індексів запалення та інтоксикації, а особливо у співставленні із параметрами вегетативного статусу при ХП нами знайдено не було, що й мотивувало до проведення даної науково-дослідної роботи. Мета дослідження: встановити взаємозв’язки гематологічних індексів запалення та інтоксикації і параметрів вегетативного статусу пацієнтів із хронічним панкреатитом. Матеріали та методи. Було обстежено 69 пацієнтів з діагнозом ХП, які лікувалися амбулаторно. Визначали наступні гематологічні індекси: лейкоцитарний індекс інтоксикації (ЛІІ), індекс адаптації (ІА) з подальшим визначенням типу неспецифічної адаптаційної реакції, лімфоцитарно-гранулоцитарний індекс (ІЛГ). Вивчались кореляційні зв’язки ЛІІ з параметрами психо-емоційного стану (нейротизмом, реактивною (РТ) та особистісною (ОТ) тривожністю згідно з опитувальниками Айзенка, Спілбергера-Ханіна), ВД за даними опитувальника Вейна, тривалістю захворювання. Результати. У 63% пацієнтів з хронічним панкреатитом встановлено наявність ендогенної інтоксикації легкого та середнього ступеня тяжкості за індексом Кальфа-Каліфа, що робить необхідним застосування препаратів, спрямованих на її корекцію. Встановлено достовірні кореляційні зв’язки між ЛІІ та особистісною тривожністю (прямий слабкий r=0,23, p&lt;0,05), нейротизмом (прямий середньої сили r=0,41, p&lt;0,05), вегетативною дисфункцією (прямий слабкий r=0,1, p&lt;0,05), тривалістю захворювання (прямий слабкий r=0,15, p&lt;0,05), структурним станом підшлункової залози за УЗД-проявами у балах (прямий слабкий r=0,29, p&lt;0,05), рівнем α-амілази панкреатичної (прямий середньої сили r=0,30, p&lt;0,05). Отримані результати довели наявність достовірних взаємовпливів параметрів запалення та ендотоксикозу з показниками вегетативного статусу і стану підшлункової залози. Це робить необхідним призначення хворим з ХП протизапальних і вегетотропних засобів для посилення протокольного лікування. Висновки. Серед пацієнтів з ХП сприятливі адаптаційні реакції спостерігались лише у 36% обстежених, несприятливі – у 25%, проміжні – у 39%, а середнє значення індекса адаптації становило – 0,48±0,18, що відповідає верхній межі реакції орієнтування. Це мотивує до додаткового призначення таким пацієнтам з ХП вегетотропних і адаптогенних препаратів. Лише у 10% пацієнтів з хронічним панкреатитом загальна імунна відповідь не має відхилень від адекватної імунної реакції, у 48% обстежених спостерігається нездатність імунної системи завершити запалення, у 42% – переважання аутоімунного компоненту інтоксикації, що потребує посилити протизапальну терапію біорегуляційними препаратами з метою гармонійного завершення запалення.

556 A Prospective Review of Risk Factors, Clinical Presentation and Management Outcomes for Chronic Pancreatitis

Abstract Aim and objectives: To identify the risk factors, symptoms, and severity of Chronic pancreatitis (CP) on admission. To determine the relationship between pancreatic duct diameter and severity of pain and to assess extent of pain relief achieved by medical, endoscopic, and surgical intervention. Method 75 patients with CP were admitted over 2 years. Data collected included etiology, symptoms, pain scores and CT/MRCP findings. Patients were classified into mild, moderate, and severe category according to Cambridge classification. Type and response to treatment was recorded. Statistical correlation of the pancreatic duct diameter and pain severity as well as the comparison of pain scores after medical, surgical and endoscopy was performed using Chi square test (p value &amp;lt;0.05) Results Median age of presentation of CP was 43 years. Male: female ratio was 3:1. Alcohol was the etiology in 66 %, 99% presented with pain, 65 % belonged to severe category. There was no statistical correlation between pain severity and duct diameter. Pain relief following medical management was 66 %, endoscopic - 73% and surgical - 83 %. There was no correlation between Cambridge classification and pain severity. There was no statistical difference between pain relief offered by either of the three modalities. However, there was a statistically significant correlation between duct diameter and type of intervention. Conclusions There is no consensus on the best treatment modality for CP as pain relief was equivalent amongst all the modalities. Therefore, the choice of intervention for patients suffering from chronic pancreatitis should be based on imaging characteristics and symptomology.

2792 A Retrospective Study of Probiotic Use in Patients With Chronic Pancreatitis

INTRODUCTION: Chronic pancreatitis is a debilitating condition that develops following recurrent episodes of pancreatitis. It increases morbidity, decreases quality of life and leads to high utilization of medical resources. There is no definitive medical treatment. Studies have shown that gut microbiota may play a role in pancreatitis as bacterial and endotoxin translocation can contribute to severity. Bacteria such as lactobacillus, and bifidobacterium have been noted to be lower in chronic pancreatitis while enterobacteriaceae species were identified at higher levels in those. Probiotics can increase concentrations of bifidobacteria, lactobacilli and streptococci, preventing overgrowth of non-commensals. We are focused on researching new strategies to prevent disease progression and decrease length of hospital stay. METHODS: Retrospective chart review of a database of 86 chronic pancreatitis patients and probiotic use. All patients were cohorted based on severity of disease as rated on EUS using a scale of 1-5 with grades 1-3 grouped as “non-severe” and 4-5 as “severe.” We chose a null of 0.05 with a 95% confidence interval for statistical significance. Relative risk assessments were conducted on the rate of severe chronic pancreatitis in users of probiotics versus negative control. RESULTS: Our initial results revealed that 34% of patients had used probiotics since diagnosis of chronic pancreatitis on EUS. The rate of severe pancreatitis for the cohort of probiotic users was 0.241, and that for negative control was 0.298. A relative risk assessment for our population found a relative risk of 0.81 (95% CI, [0.379-1.727]; P = 0.2922) for the rate of severe chronic pancreatitis given exposure to probiotics. The result suggested a potential effect from probiotics on decreasing the risk of having severe chronic pancreatitis but was not statistically significant. CONCLUSION: There was no significant association between probiotic use and severity of chronic pancreatitis. We cannot exclude that probiotics may have a protective or therapeutic immunomodulatory effect on the microbiome of patients with chronic pancreatitis. This study is limited to a chart review in order to determine the extent of probiotic use in patients and cannot verify compliance with probiotics. We cannot report a correlation between probiotic use and severity of chronic pancreatitis.

Abstract 2237: Diclofenac as a dual inhibitor of cyclooxygenase and aldo-keto-reductase 1B10 inhibits pancreatitis-enhanced carcinogenesis in LSL-Kras G12D -Pdx-1-Cremice

Abstract Diclofenac is one of non-steroid anti-inflammatory drugs and is recently identified as a competitive inhibitor of aldo-keto reductase family 1B10 (AKR1B10). AKR1B10 is an NADPH-dependent enzyme that exhibits lipid substrate specificity, especially for farnesyl and geranylgeranyl involved in protein prenylation (such as for Kras) and plays an oncogenic role in pancreatic carcinogenesis. In the present study, we determined the chemopreventive effects and mechanism of diclofenac on inhibiting pancreatitis-carcinogenesis in LSL-KrasG12D/Pdx1-Cre mice (called Pankras mice), particularly on Kras prenylation. Pancreatitis was induced by single i.p. injection of Cearulein (250ug/Kg body weight) for 5-week old mice, and one week after caerulein treatment, Pankras mice were fed an AIN-93M diet or a diet with 5 or 20ppm diclofenac (n=12 mice/group) for 7 months. The results showed that Diclofenac significantly reduced the severity of chronic pancreatitis, as measured by the extent of acini loss, inflammatory cell infiltration and stromal fibrosis. The progression of low-grade mPanIN I to high-grade mPanIN II/III and to invasive carcinoma was significantly suppressed and the tumor incidence significantly reduced to 50% and 17% in the mice treated with either 5ppm or 20 diclofenac compared to 86% in Pankras mice. Inhibition of membrane-bound mutant Kras (prenylated) and its transmitted phosphorylation of mitogen-activated protein kinase's kinase/extracellular signal-regulated kinases were demonstrated in pancreatic tissues by western blot assay. Analysis of the eicosanoid profile revealed a significant reduction of prostaglandin E2. These results indicate that diclofenac is a highly potential agent for preventing chronic pancreatitis and carcinogenesis, mainly via targeting mutant Kras and inflammation (Supported by NIH R01 CA164041). Citation Format: Jie Liao, Leyu Sun, Haonan Li, Rong Xia, Xiaoming You, Dandan Xu, Guang-Yu Yang. Diclofenac as a dual inhibitor of cyclooxygenase and aldo-keto-reductase 1B10 inhibits pancreatitis-enhanced carcinogenesis in LSL-KrasG12D-Pdx-1-Cremice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2237.

Abstract 1250: Inhibition of pancreatic carcinogenesis by t-CUPM, a dual inhibitor of c-Raf and soluble epoxide hydrolase

Abstract Mutant Kras activated Raf-MAPK/ERK pathway and chronic pancreatitis are the most common pathogenic events involved in human pancreatic carcinogenesis. The soluble epoxide hydrolase (sEH), a pro-inflammatory enzyme, generally inactivates anti-inflammatory epoxyeicosatrienoic acids (EETs). Herein, we have synthesized a novel compound of trans-4-{4-[3-(4-chloro-3-trifluoromethyl-phenyl)-ureido]-cyclohexyloxy}-pyridine-2-carboxylic acid methylamide (t-CUPM) via modifying the central phenyl ring of sorafenib and confirmed its dual inhibition of sEH and c-Raf by recombinant kinase activity assay. Pharmacokinetic analysis revealed that oral dosing of t-CUPM resulted in the higher blood levels than that of sorafenib throughout the complete time course (48 h). The effect of t-CUPM on the development of pancreatitis and pancreatic intraepithelial neoplasia (mPanIN) was determined in the LSL-KrasG12D/Pdx1-Cre mice. The results showed that t-CUPM significantly reduced the severity of chronic pancreatitis, as measured for the extents of acini loss, inflammatory cell infiltration and stromal fibrosis. The progression of low-grade mPanIN I to high grade mPanIN II/III was significantly suppressed by t-CUPM treatment. Inhibition of mutant Kras-transmitted phosphorylations of MEK/ERK was demonstrated in pancreatic tissues and in vitro pancreatic cancer cells by Western blot assay. qPCR analysis revealed that t-CUPM treatment resulted in significantly decreasing the levels of inflammatory cytokines including TNF-α, MCP-1, as well as VCAM-1, and the levels of Shh and GLI1 (Hedgehog pathway). Analysis of eicosanoid profile revealed a significant increase of the EET/DHET ratio that further confirmed sEH inhibition by t-CUPM. These results indicate that simultaneous inhibition of sEH and c-Raf by t-CUPM is important in preventing chronic pancreatitis and carcinogenesis. (supported by NIH R01CA172431) Note: This abstract was not presented at the meeting. Citation Format: Jie Liao, Wanying Zhang, Sung Hee Hwng, Haonan Li, Aaron T. Wecksler, Ke Ma, Bruce D. Hammock, Guang-Yu Yang. Inhibition of pancreatic carcinogenesis by t-CUPM, a dual inhibitor of c-Raf and soluble epoxide hydrolase. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1250. doi:10.1158/1538-7445.AM2014-1250

Association of Fat Consumption With Clinical Manifestations, Diagnosis and Severity of Chronic Pancreatitis

Association of Fat Consumption With Clinical Manifestations, Diagnosis and Severity of Chronic Pancreatitis

Pancreatic Secretory Trypsin Inhibitor 1 Reduces the Severity of Chronic Pancreatitis in Mice Over-Expressing Interleukin-1β in the Pancreas

Pancreatic Secretory Trypsin Inhibitor 1 Reduces the Severity of Chronic Pancreatitis in Mice Over-Expressing Interleukin-1β in the Pancreas

M1367 Factors Associated to the Severity of Chronic Pancreatitis at Diagnosis: Alcohol, Tobacco, or Both?

M1367 Factors Associated to the Severity of Chronic Pancreatitis at Diagnosis: Alcohol, Tobacco, or Both?

Magnetic Resonance Cholangiopancreatography Reports in the Evaluation of Chronic Pancreatitis: A Need for Quality Improvement

Background: Numerous publications from academic centers suggest that magnetic resonance cholangiopancreatography (MRCP) can diagnose early chronic pancreatitis (CP) and assess pancreatic secretory reserve/function. However, the rigorous composite interpretation methods and quantitative secretory dynamics reported in these studies are not routinely measured in clinical practice.Therefore, the utility of routine MRCP reports in the clinical setting is unknown. Study Design: Cross-sectional study of patients referred to a tertiary center who underwent both MRCP and endoscopic pancreas function testing (ePFT) for assessment of chronic pancreatitis and abdominal pain. Aims: To compare MRCP and sMRCP reports to a reference standard pancreas function test for diagnosis of chronic pancreatitis. Methods: Source population: patients seen within a pancreas clinic at a tertiary referral center. MRCP and sMRCP reports were reviewed to record pancreas duct (dilation, side-branch changes), parenchyma enhancement (T1, T2 signal) and physiologic response (duodenal filling, pancreas duct response) to secretin. ePFT was categorized based on previously published data (normal peak bicarbonate >80 mEq/l). Referent values were calculated for MRCP and sMRCP using secretin ePFT as gold standard. Results: A total of 69 patients were identified (mean age 43.5 ± 12; 65.2% female). 28 (40.6%) patients had abnormal ePFT based on their peak bicarbonate level. The mean bicarbonate values in the abnormal PFT and normal PFT groups were 59 ± 13.9 and 95.3 ±12.6 mEq/l, respectively. Peak bicarbonate decreased with severity of chronic pancreatitis on MRCP (p = 0.0016). There was fair agreement of MRCP and ePFT (κ 0.335 [0.113,0.557]). The pre-stimulation pancreas duct changes reported were found to be the only predictor of abnormal pancreas function (p = 0.002). The post-stimulation findings of duodenal filling (p = 0.47), T2 enhancement (p = 0.21) or change in pancreas duct caliber (p = 0.3) reported did not improve MRCP agreement with ePFT. Overall diagnostic accuracy, sensitivity and specificity were 70, 85 and 46%, respectively, for MRCP reports using ePFT as the gold standard. Conclusions: Pancreas ductal features described on routine MRCP reports correlate with abnormal pancreas function. Current MRCP reports should be standardized to include all radiologie information available in hopes of predicting early chronic pancreatitis.

Protection Against Chronic Pancreatitis and Pancreatic Fibrosis in Mice Overexpressing Pancreatic Secretory Trypsin Inhibitor

Mutations in the gene encoding for pancreatic secretory trypsin inhibitor (PSTI) can contribute to chronic pancreatitis. In the current study, we tested whether overexpression of PSTI-I in mice protects against chronic pancreatitis and pancreatic fibrosis. Rat PSTI-I expression was targeted to pancreatic acinar cells in transgenic mice. Chronic pancreatitis was achieved by intraperitoneal injection of cerulein for 10 weeks. Pancreatitis severity was assessed by histological grading of inflammatory infiltrate, atrophy, and fibrosis; quantitation of myeloperoxidase (MPO) activity; quantitative morphometric analysis of collagen content; and measurements of type I collagen, fibronectin, and transforming growth factor beta mRNA expression. Cerulein administration to nontransgenic mice produced histological evidence of inflammatory infiltrate, glandular atrophy, and parenchymal fibrosis and increased collagen production, MPO activity, and collagen I and fibronectin mRNA levels. In cerulein-treated PSTI transgenic mice, there were significant reductions in inflammatory infiltrate, MPO activity, fibrosis, and collagen I and fibronectin mRNA levels. Transgenic mice treated with cerulein had significantly less collagen than nontransgenic mice. The severity of chronic pancreatitis and pancreatic fibrosis is significantly reduced in mice expressing rat PSTI-I. We propose that pancreatic trypsin inhibitors play a protective role in the pancreatic response to repeated injurious events.

A prospective, quantitative assessment of the effect of ethanol and other variables on the endosonographic appearance of the pancreas

Background & Aims: Studies comparing endosonography with endoscopic pancreatography, histological examination, and functional assays show that the number of endosonographic abnormalities (or “criteria”) increases with the severity of chronic pancreatitis. However, it is unclear to what extent such variables as demographics, body habitus, and routine exposure to such pancreatic toxins as ethanol and cigarette smoke can affect pancreatic endosonography. The aim of the study is to quantify the effects of these variables precisely. Methods: Pancreatic endosonography was performed by a single operator in consecutive patients referred for any indication. The relationship between 8 possible endosonographic criteria and these variables was studied. Results: One thousand one hundred fifty-seven patients were studied (93% of eligible patients). Number of criteria correlated most strongly with ethanol ingestion ( r = 0.273; P = 0.0001) and smoking history ( r = 0.201; P = 0.0001). It did not correlate with age or body mass index. The strongest independent predictors of severe pancreatic abnormalities (≥5 criteria) were heavy ethanol ingestion (odds ratio [OR], 5.1; 95% confidence interval [CI], 3.1–8.5), male sex (OR, 1.8; 95% CI, 1.3–2.55), clinical suspicion of pancreatic disease (OR, 1.7; 95% CI, 1.2–2.3), and heavy smoking (OR, 1.7; 95% CI, 1.2–2.4). Severe endosonographic abnormalities were found in only 2 of 51 patients (3.9%) with no risk factors or symptoms of pancreatic disease. Conclusions: Several variables can affect the endosonographic appearance of the pancreas independently. Severe abnormalities may be asymptomatic. The clinical, functional, and histological significance of endosonographic abnormalities requires clarification.

Role of CFTR mutations in evolution and severity of chronic pancreatitis

Role of CFTR mutations in evolution and severity of chronic pancreatitis

4560 Assessment of chronic pancreatitis by using endoscopic ultrasonography and fine-needle aspiration cytology compared with ercp and pancreatic function tests.

Background: Previous studies showed that endoscopic ultrasonography (EUS) can sensitively detect structural inflammatory changes of the pancreas. However, little is known about the specificity and clinical impact of EUS findings in chronic pancreatitis (cP). Therefore, we studied the morphology of the pancreas in patients with cP by using EUS techniques and fine-needle aspiration cytology (FNA), and we compared the EUS results to ERCP and pancreatic function tests. Materials/Methods: 37 patients with clinical symptoms and laboratory tests suggestive of cP (48±13 years) were prospectively studied. Patients with malignancy or major concomitant disease were excluded. EUS was carried out 10±3 days after the resolution of clinical signs of pancreatitis, and FNA was performed during EUS in 24 patients. EUS criteria for cP included the presence of echointense septae and echoreduced foci (=pseudolobularity), ductal irregularities, and calcifications. ERCP served as reference in all patients using the Cambridge classification. The clinical work-up also included fecal elastase and urine pancreolaureate tests. Results: 31 patients had cP, while 6 had normal findings during ERCP. EUS showed morphologic abnormalities in 32 patients, while ERCP revealed pathologic findings in only 31 patients. The combination of EUS/FNA versus ERCP reached a sensitivity of 100% with a specificity of 83%. Based on the presence of pseudolobularity alone, EUS reached a sensitivity of 96% with a specificity of only 72% for the presence of chronic pancreatitis, while the positive predictive value (PPV) was 93%, and the negative predictive value (NPV) was 83%. Based on 3 EUS criteria including ductal irregularities, the specificity decreased to 46%, while the sensitivity reached 97%. Compared with pancreatic function tests, EUS reached a sensitivity of only 86% with a specificity of 73%. EUS was in agreement with the severity of chronic pancreatitis in 6/8 patients with grade I, in 11/13 patients with grade II, and in 10/10 patients with grade III. Conclusions: EUS is a highly sensitive tool to detect morphologic abnormalities of the pancreas. However, the EUS findings are unspecific, which is probably due to postinflammatory organ abnormalities that may resolve completely over time. FNA improves the specificity and should thus be performed routinely during EUS. The association between morphologic findings and pancreatic function is poor.

Endoscopic manometry of the sphincter of Oddi and the pancreatic and biliary ducts in patients with chronic pancreatitis.

Sphincter of Oddi activity and the common bile duct (CBD) and pancreatic duct (PD) pressures were measured by means of endoscopic manometry in 15 patients (11 men and 4 women aged 18-77 (median, 40) years) with various degrees of chronic pancreatitis. Eleven of the 15 patients studied had an abnormal manometric pattern: elevated base-line pressures were seen in 8 patients, elevated duct pressures in 6 patients, abnormal peristalsis in 6 patients, and discoordination in 4 patients. There was no relation between the severity of chronic pancreatitis as shown by endoscopic retrograde pancreatography and the pancreatic function test and the manometric findings. However, a positive correlation between the sphincter of Oddi base-line pressure and the pancreatic duct pressure was found. It is concluded that manometric abnormalities are common findings in patients with chronic pancreatitis. Whether this is primary or secondary to the inflammatory process is still uncertain.

Plasma lipase, C-peptide reactivity and human pancreatic polypeptide responses after ingestion of elemental diet in patients with chronic pancreatitis.

Plasma lipase, C-peptide reactivity (CPR) and human pancreatic polypeptide (HPP) responses after ingestion of elemental diet were studied in 27 patients with chronic pancreatitis. These subjects were classified into 3 groups according to ERP findings; minimum or mild (MIP, n = 17), moderate (MOP, n = 6) and advanced (ADP, n = 4). Basal plasma lipase levels in the MIP and MOP patients were significantly higher than that in the controls (P < 0.05). Plasma CPR response (sigma delta CPR) in MIP cases were significantly higher than that in controls (P < 0.05). Also, plasma HPP (response (sigma delta HPP) in MIP cases were significantly higher than that in controls (P < 0.05). Plasma CPR and HPP responses correlated with the severity of chronic pancreatitis. Fourteen of the 17 MIP patients (82%) showed higher levels of basal lipase or sigma delta HPP in comparison to the respective normal ranges. This study suggested that the ED test may be more sensitive for detection of mild chronic pancreatitis and that it may be useful for evaluating exocrine and endocrine pancreatic functions in various stages of chronic pancreatitis.