Uncomplicated Chronic Pancreatitis Research Articles

Possibilities of the early diagnosis and prognosis of complicated clinical forms of chronic pancreatitis

AIM: This study aimed to improve the methods for the diagnosis of complicated clinical forms of chronic pancreatitis (CP) by evaluating the clinical significance of the polymorphisms of the genes of cationic trypsinogen (PRSS1), pancreatic secretory trypsin inhibitor (SPINK1), transmembrane regulator of cystic fibrosis (CFTR), and alcohol dehydrogenase (ADH) in patients with complicated and uncomplicated forms of CP.
 MATERIALS AND METHODS: The study was carried out on the clinical base of the Department of Hospital Surgery, Ryazan State Medical University, Center for Surgery of Liver, Pancreas, and Biliary Tract in Ryazan in 20142019. A total of 108 patients of both genders aged 2565 years were examined. Of these patients, 38 were surgically treated for complicated CP, 20 had complicated CP without surgery, and 50 had uncomplicated CP (control group). A comparative clinical study with the control group of patients was performed, and the genotype was simultaneously determined on days 1 and 10 under controlled laboratory parameters. DNA was isolated from the leukocytes of the whole blood by using a DNA-expressing blood reagent (OOO NPF Litekh, Russia) for further analysis.
 RESULTS: No polymorphism of cationic trypsinogen PRSS1 gene and cystic fibrosis-2 CFTR2 gene was found. The predictive value of these polymorphisms was insignificant. For the polymorphism of CFTR1 cystic fibrosis-1 gene, the odds ratio was 0.444, but this finding was not significant. Among patients with the complicated clinical forms of CP, mutations were observed in the PRSS1 cationic trypsinogen gene (c2 = 6.453, p = 0.012) and ADH (c2=14.176, p = 0.001). Conversely, they were not detected in the CFTR-1 gene (c2 = 0.873, p = 0.351), CFTR-2 (c2 was not determined), and SPINK1 (c2 = 0.873, p = 0.351). The polymorphisms of the ADH and PRSS1 genes of cationic trypsinogen were associated with more evident structural changes in the parenchyma and ductal system of the pancreas. They also had a higher likelihood of complications, severe disease course, and a lower efficiency of conservative treatment. The polymorphism of the ADH gene increased the risk of the development of the cystic form of CP (c2 = 5.898, p = 0.016).
 CONCLUSION: The polymorphism of ADH and cationic trypsinogen genes should be determined and used for the complex diagnosis of CP to specify indications for the surgical treatment of patients with CP.

Endoscopic treatment of chronic pancreatitis: European Society of Gastrointestinal Endoscopy (ESGE) Guideline - Updated August 2018.

ESGE suggests endoscopic therapy and/or extracorporeal shockwave lithotripsy (ESWL) as the first-line therapy for painful uncomplicated chronic pancreatitis (CP) with an obstructed main pancreatic duct (MPD) in the head/body of the pancreas. The clinical response should be evaluated at 6 - 8 weeks; if it appears unsatisfactory, the patient's case should be discussed again in a multidisciplinary team and surgical options should be considered.Weak recommendation, low quality evidence.ESGE suggests, for the selection of patients for initial or continued endoscopic therapy and/or ESWL, taking into consideration predictive factors associated with a good long-term outcome. These include, at initial work-up, absence of MPD stricture, a short disease duration, non-severe pain, absence or cessation of cigarette smoking and of alcohol intake, and, after initial treatment, complete removal of obstructive pancreatic stones and resolution of pancreatic duct stricture with stenting.Weak recommendation, low quality evidence.ESGE recommends ESWL for the clearance of radiopaque obstructive MPD stones larger than 5 mm located in the head/body of the pancreas and endoscopic retrograde cholangiopancreatography (ERCP) for MPD stones that are radiolucent or smaller than 5 mm. Strong recommendation, moderate quality evidence.ESGE suggests restricting the use of endoscopic therapy after ESWL to patients with no spontaneous clearance of pancreatic stones after adequate fragmentation by ESWL.Weak recommendation, moderate quality evidence.ESGE suggests treating painful dominant MPD strictures with a single 10-Fr plastic stent for one uninterrupted year if symptoms improve after initial successful MPD drainage. The stent should be exchanged if necessary, based on symptoms or signs of stent dysfunction at regular pancreas imaging at least every 6 months. ESGE suggests consideration of surgery or multiple side-by-side plastic stents for symptomatic MPD strictures persisting beyond 1 year after the initial single plastic stenting, following multidisciplinary discussion. Weak recommendation, low quality evidence.ESGE recommends endoscopic drainage over percutaneous or surgical treatment for uncomplicated chronic pancreatitis (CP)-related pseudocysts that are within endoscopic reach.Strong recommendation, moderate quality evidence.ESGE recommends retrieval of transmural plastic stents at least 6 weeks after pancreatic pseudocyst regression if MPD disruption has been excluded, and long-term indwelling of transmural double-pigtail plastic stents in patients with disconnected pancreatic duct syndrome.Strong recommendation, low quality evidence.ESGE suggests the temporary insertion of multiple side-by-side plastic stents or of a fully covered self-expandable metal stent (FCSEMS) for treating CP-related benign biliary strictures.Weak recommendation, moderate quality evidence.ESGE recommends maintaining a registry of patients with biliary stents and recalling them for stent removal or exchange.Strong recommendation, low quality evidence.

PATHOGENETIC RATIONALE FOR COMBINATION THERAPY OF PATIENTS WITH CHRONIC PANCREATITIS

Актуальность. Для хронического панкреатита характерен дисбаланс провоспалительных и противовоспалительных цитокинов, отражающий наличие хронического системного воспаления. Его выраженность определяет функциональное состояние микробно-тканевого комплекса кишечника. Восстановление нормального функционирования микробно-тканевого комплекса кишечника уменьшает выраженность воспалительных изменений поджелудочной железы.Цель – изучить клиническую эффективность комплексной терапии хронического панкреатита с применением средств коррекции функционального состояния микробно-тканевого комплекса кишечника.Материал и методы. Анализируемая выборка включала 117 пациентов с хроническим панкреатитом с умеренным болевым синдромом, умеренными экзокринными и эндокринными нарушениями, без осложнений. Средний возраст составил 43,9 ± 11,6 года (40,9 ± 13,5 года – у мужчин, 48,6 ± 11,7 года – у женщин). Больные хроническим панкреатитом были разделены на 2 группы; в основной группе пациентов в стандартную схему терапии дополнительно включен пребиотический комплекс Эубикор по 6 г в день.Результаты. На фоне комплексной терапии хронического панкреатита с применением средств коррекции функционального состояния микробно-тканевого комплекса кишечника отмечено статистически значимое (p < 0,05) снижение представительства патогенной и условно-патогенной микрофлоры кишечника при значимом росте главной микрофлоры кишечника, уменьшение показателей цитокинов TNF-α (с 74,32 ± 11,22 до 31,34 ± 8,92 нг/мл) и IL-1β (с 25,32 ± 4,36 до 10,52 ± 3,52 нг/мл), статистически значимое снижение уровня кортизола (с 456,53 ± 68,99 до 382,61 ± 60,24 нмоль/л). Положительная клиническая динамика, улучшение качества жизни наблюдались на фоне достоверной коррекции метаболических изменений.Заключение. Терапевтическая тактика при хроническом панкреатите должна включать применение препаратов, восстанавливающих функционирование микробно-тканевого комплекса кишечника и положительно влияющих на метаболический и гормональный балансы.

Rapid Progression of Multifocal Hepatic Epithelioid Hemangioendothelioma

A 60-year-old woman with past medical history of chronic pancreatitis and bilioenteric anastomosis was referred to our institution for routine unenhanced pancreatic MR evaluation. Besides the expected findings of uncomplicated chronic pancreatitis, the study revealed several focal lesions distributed through the liver, suggestive of metastases. They were hypointense in T1 imaging and remarkably hyperintense in T2-weighted images (Fig. 1). Blood tests where mostly unexceptional, only revealing elevated gammaglutamyl transferase [88 U/L (normal: 5--36 U/L)]. A liver biopsy was performed and, despite the obtention of only a small amount of diagnostic material, it was still possible to exclude carcinomatous, neuroendocrine and hepatocytary origin and to detect positivity for CD34, a marker present in tumors of hematopoietic or endothelial lineage.1 PET-CT was also realized for staging, demonstrating multiple slightly hypermetabolic liver lesions and significant hypermetabolism centered in the left aryepiglottic fold. After biopsy the neck lesion was diagnosed as squamous-cell carcinoma, non-related to the liver lesions. Neck MRI staging revealed invasion of the ipsilateral piriform sinus and

Endoscopic therapy in chronic pancreatitis: current perspectives.

Endoscopic therapy in chronic pancreatitis (CP) aims to provide pain relief and to treat local complications, by using the decompression of the pancreatic duct and the drainage of pseudocysts and biliary strictures, respectively. This is the reason for using it as first-line therapy for painful uncomplicated CP. The clinical response has to be evaluated at 6–8 weeks, when surgery may be chosen. This article reviews the main possibilities of endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS) therapies. Endotherapy for pancreatic ductal stones uses ultrasound wave lithotripsy and sometimes additional stone extractions. The treatment of pancreatic duct strictures consists of a single large stenting for 1 year. If the stricture persists, simultaneous multiple stents are applied. In case of unsuccessful ERCP, the EUS-guided drainage of the main pancreatic duct (MPD) or a rendezvous technique can solve the ductal strictures. EUS-guided celiac plexus block has limited efficiency in CP. The drainage of symptomatic or complicated pancreatic pseudocysts can be performed transpapillarily or transgastrically/transduodenally, preferably by EUS guidance. When the biliary stricture is symptomatic or progressive, multiple plastic stents are indicated. In conclusion, as in many fields of symptomatic treatment, endoscopy remains the first choice, either by using ERCP or EUS-guided procedures, after consideration of a multidisciplinary team with endoscopists, surgeons, and radiologists. However, what is crucial is establishing the right timing for surgery.

Small intestinal bacterial overgrowth in patients with chronic pancreatitis.

To assess the prevalence of small intestinal bacterial overgrowth (SIBO) in chronic pancreatitis (CP), and analyze factors related with SIBO in CP. SIBO is to be considered a factor that worsens symptoms and nutritional status in patients with CP. However, the few studies evaluating the rate of SIBO in CP patients used nonuniform and nonstandardized procedures, and reported a wide range of positivity (0% to 92%). Those studies often investigated CP patients with previous resection surgery (cause of SIBO per se). CP patients and controls evaluated for SIBO by the H2 glucose breath test with a standard protocol. For CP patients, the relationship between test results, abdominal symptoms, and clinical and biochemical variables was analyzed. A total of 43 CP patients and 43 controls were enrolled. Of the CP patients, 8 had advanced disease (defined by M-ANNHEIM index) and none had undergone previous surgery. The glucose breath test positivity rate was higher in the CP patients than in the controls (21% vs. 14%), albeit without a significant difference (P=0.57). Mean fasting H2 excretion and mean H2 excretion at 120 minutes also had a trend toward higher levels in CP patients. There were no clinical differences between CP patients with or without SIBO, but there were nutritional differences for lower levels of vitamin D and higher levels of folate in these patients with SIBO. Our findings suggest that SIBO is not uncommon in uncomplicated CP patients. The lack of a significant difference compared with controls might be due to the study being underpowered. SIBO in CP patients does not seem to be related to peculiar clinical features, but it might affect nutritional status.

Importance of small intestinal bacterial overgrowth in chronic pancreatitis

Importance of small intestinal bacterial overgrowth in chronic pancreatitis

Small Intestine Bacterial Overgrowth Is not Related with Disease Severity and Symptoms in Patients with Chronic Pancreatitis

Context Small intestine bacterial overgrowth (SIBO) is considered as a factor possibly worsening symptoms and nutritional status in patients with chronic pancreatitis (CP) and pancreatic exocrine insufficiency (PEI) not responding to treatment. However, few studies evaluated the rate of SIBO in CP patients (range of positivity ranging 0-92%), employed different substrates and non-standardized procedures, and often investigated CP patients with previous resective surgery (cause of SIBO per se) . Objective To assess the prevalence of SIBO in CP patients without history of resective surgery as compared with a control group. Secondary aim is to analyze factors related with SIBO in CP patients. Methods CP patients and controls (outpatients with upper-GI unspecific symptoms; exclusion criteria CP, IBD, celiac disease or previous surgery), had SIBO evaluated by H 2 glucose breath test (GBT) with a standard protocol according to Rome consensus conference. Positivity rate, basal, peak over basal (HOB) and H 2 values at 120 minutes were evaluated. For CP patients, relation between GBT results, abdominal symptoms, nutritional and clinical variables was analyzed. Results Twenty-six CP patients and 22 controls were enrolled. Of the 26 patients (alcoholic aetiology in 11), 13 had PEI, 5 advanced CP (defined by M-ANNHEIM severity index) and none had previous resective surgery. GBT positivity rate was 5/26 (19.2%) in cases and 3/21 (13.6%) in controls (P=0.71). Mean H 2 basal excretion (9.78 ppm in CP vs . 5.47 ppm in controls; P=0.13), HOB (4.6 ppm in CP vs . 4.52 ppm in controls; P=0.95) and H 2 at 120 minutes (4.86 in CP vs . 2.20 in controls; P=0.08) were not different between the two groups. Diagnosis of SIBO in the CP group was not correlated with presence of PEI, severity of disease, abdominal symptoms, pancreatic enzymes and proton pump inhibitors therapy. Conclusion The rate of SIBO seems similar in CP patients without previous resective surgery and controls. CP patients with SIBO did not have more severe disease, more symptoms or worse nutritional status. These findings do not suggest a relevant impact of SIBO on the clinical course and management of uncomplicated CP but our findings deserve confirmation in a larger cohort.

Endoscopic treatment of chronic pancreatitis: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline

Clarification of the position of the European Society of Gastrointestinal Endoscopy (ESGE) regarding the interventional options available for treating patients with chronic pancreatitis. Systematic literature search to answer explicit key questions with levels of evidence serving to determine recommendation grades. The ESGE funded development of the Guideline. For treating painful uncomplicated chronic pancreatitis, the ESGE recommends extracorporeal shockwave lithotripsy/endoscopic retrograde cholangiopancreatography as the first-line interventional option. The clinical response should be evaluated at 6 - 8 weeks; if it appears unsatisfactory, the patient's case should be discussed again in a multidisciplinary team. Surgical options should be considered, in particular in patients with a predicted poor outcome following endoscopic therapy (Recommendation grade B). For treating chronic pancreatitis associated with radiopaque stones ≥ 5 mm that obstruct the main pancreatic duct, the ESGE recommends extracorporeal shockwave lithotripsy as a first step, combined or not with endoscopic extraction of stone fragments depending on the expertise of the center (Recommendation grade B). For treating chronic pancreatitis associated with a dominant stricture of the main pancreatic duct, the ESGE recommends inserting a single 10-Fr plastic stent, with stent exchange planned within 1 year (Recommendation grade C). In patients with ductal strictures persisting after 12 months of single plastic stenting, the ESGE recommends that available options (e. g., endoscopic placement of multiple pancreatic stents, surgery) be discussed in a multidisciplinary team (Recommendation grade D).For treating uncomplicated chronic pancreatic pseudocysts that are within endoscopic reach, the ESGE recommends endoscopic drainage as a first-line therapy (Recommendation grade A).For treating chronic pancreatitis-related biliary strictures, the choice between endoscopic and surgical therapy should rely on local expertise, patient co-morbidities and expected patient compliance with repeat endoscopic procedures (Recommendation grade D). If endoscopy is elected, the ESGE recommends temporary placement of multiple, side-by-side, plastic biliary stents (Recommendation grade A).

A note of caution for the doctor on duty: take the acute attack in chronic pancreatitis seriously!

Dear Sir, Three different typical pain profiles have been described during the evolution of chronic pancreatitis: Repeated episodes of acute pancreatitis in the early stages. Spontaneous lasting pain relief in association with severe pancreatic insufficiency in the late stage of uncomplicated chronic pancreatitis. Persistent severe pain (or frequent recurrent episodes of pain), usually in association with local complications such as pseudocysts and ductal hypertension or extrapancreatic complications such as partial obstruction of the common bile duct, peptic ulcer and opiate addiction [1]. Pain has been attributed to increased intrapancreatic pressure, pancreatic ischaemia, pancreatic fibrosis leading to increased intraductal pressure in the chronically inflamed organ and to the presence of pancreatic pseudocysts causing compression of adjacent structures. Immunohistological reports have shown that the amount of neurotransmitters is increased in afferent pancreatic nerves, and a correlation between pain and immune cell infiltration of the nerves has been found (‘neurogenic inflammation’) [1]. Faced with the large number of publications concerning this fascinating theory, we felt that acute inflammation occurring at different stages of the disease has been rather neglected as a cause of pain. Therefore, we reviewed retrospectively the data of 21 patients (17 male, four female; age 48.2 ± 11.2 years, mean ± SD), who were admitted to our department from 2003 to 2006 with an acute attack of chronic pancreatitis. The diagnosis of chronic pancreatitis was made on the basis of abnormal morphology, i.e. pancreatic calcifications in all cases [2]. The aetiology of the disease was alcohol-related in 17 patients (16 male, one female) and unknown in four patients (one male, three female). All patients had their amylase and lipase levels measured on admission, with two exceptions, and all underwent contrast-enhanced computed tomography (CT), which is the gold standard for the differentiation between interstitial and necrotizing pancreatitis. The CT was performed within 96 h after admission and the findings were scored according to Balthazar et al. [3, 4]. None of our patients had acute respiratory and/or renal failure on admission (arterial pO2 < 60 mmHg; serum creatinine >2 mg dL−1 after rehydration). Only one (patient 14) required a stay on the intensive care unit. Mean hospital stay was 13.6 days (range 3–90 days). It is generally believed that the increase in pancreatic enzymes during an acute attack of chronic pancreatitis is low or even nonexistent, as the pancreas in this state is unable to release enough pancreatic enzymes into the bloodstream. Amylase and lipase were normal in 36% and 24%, respectively, of the attacks; however, they were increased to three times the upper limit of normal, which is generally considered to be diagnostic for acute pancreatitis, in 20% and 60% of the attacks. In all cases CT showed substantial changes: interstitial pancreatitis in 20 examinations (74%), necrotizing pancreatitis in seven (26%). However, interstitial pancreatitis was severe in 11 patients (Balthazar score E4), and usually one-third of such patients will already have organ failure (Table 1) [5]. Enzyme elevation and the CT findings were not significantly correlated (Mantel–Haenszel chi-square, 0.51 and 0.94). To our knowledge, this is the first conservative assessment of the severity of acute attacks of chronic pancreatitis. However, there are three surgical studies (two very old, one recent) which state that pancreatic necroses were found in 7–11% of patients who had undergone surgery for chronic pancreatitis [6–8]. These reports and our results support the necrosis–fibrosis sequence in the development of chronic pancreatitis [9]. Apart from the small contribution that this study makes to our understanding of acute attacks in chronic pancreatitis and their possible importance for the development of the disease, it also has some implications for the doctor on duty. First, similar to acute pancreatitis, the degree of enzyme elevation is not an indication of the severity of the disease [10]. Secondly, acute (necrotizing) pancreatitis is frequent in chronic pancreatitis patients hospitalized with acute pain on admission. Thus, the acute attack in chronic pancreatitis is not harmless. It should be taken seriously, ensuring that the guidelines laid down for acute pancreatitis are followed [11]. No conflict of interest was declared.

The patient with slightly elevated pancreatic enzymes and abdominal complaints

Abdominal complaints in combination with slightly elevated serum pancreatic enzymes represent a classical clinical challenge. These symptoms may be due to coincidental unrelated harmless disorders, benign pancreatic alterations which are fairly easily treatable such as mild acute pancreatitis or uncomplicated chronic pancreatitis. However, serious, often insidious diseases such as pancreatic tumours may also present with this constellation as their first signs. Diagnostic procedures need to be stratified according to acuteness and severity of symptoms. While patients with acute onset of symptoms and severe complaints need immediate and combined laboratory and imaging investigations to allow adequate therapy, chronic and mild complaints usually justify a stepwise diagnostic approach consecutively using abdominal ultrasound, CT/MRI and endoscopic ultrasound as imaging procedures and reserving ERCP for cases which remain unclear or in which interventional therapy is needed. Diagnosis and follow-up are often particularly demanding in patients with cystic tumours of the pancreas. In chronic pancreatitis patients pain therapy and adequate control of pancreatic exocrine insufficiency may pose major problems. Patients with refractory pain may ultimately require surgical intervention. Another important indication for surgery in chronic pancreatitis is suspicion of cancer that cannot be ruled out by dedicated diagnostic procedures. This also applies to cystic tumours of the pancreas, which have a high risk of malignant transformation or may even already represent pancreatic cancer at the time of diagnosis.

Chronic Pancreatitis: Challenges and Advances in Pathogenesis, Genetics, Diagnosis, and Therapy

Chronic pancreatitis (CP) is characterized by progressive pancreatic damage that eventually results in significant impairment of exocrine as well as endocrine functions of the gland. In Western societies, the commonest association of chronic pancreatitis is alcohol abuse. Our understanding of the pathogenesis of CP has improved in recent years, though important advances that have been made with respect to delineating the mechanisms responsible for the development of pancreatic fibrosis (a constant feature of CP) following repeated acute attacks of pancreatic necroinflammation (the necrosis-fibrosis concept). The pancreatic stellate cells (PSCs) are now established as key cells in fibrogenesis, particularly when activated either directly by toxic factors associated with pancreatitis (such as ethanol, its metabolites or oxidant stress) or by cytokines released during pancreatic necroinflammation. In recent years, research effort has also focused on the genetic abnormalities that may predispose to CP. Genes regulating trypsinogen activation/inactivation and cystic fibrosis transmembrane conductance regulator (CFTR) function have received particular attention. Mutations in these genes are now increasingly recognized for their potential 'disease modifier' role in distinct forms of CP including alcoholic, tropical, and idiopathic pancreatitis. Treatment of uncomplicated CP is usually conservative with the major aim being to effectively alleviate pain, maldigestion and diabetes, and consequently, to improve the patient's quality of life. Surgical and endoscopic interventions are reserved for complications such as pseudocysts, abscess, and malignancy.

Etiology and natural history of chronic pancreatitis.

Chronic pancreatitis (CP) is a rare but serious disease with high morbidity and mortality. Its exact etiology remains uncertain, but several associated conditions have been identified. Geographical distribution of CP can be linked to alcoholism, especially in countries with high-protein, high-fat diets. In Afro-Asiatic countries with protein malnutrition, however, CP is frequently observed in children and young nonalcoholic adults from the poorest segments of these societies. To analyze the natural history of CP, besides etiology three additional main factors have to be considered, namely clinical pattern and therapy (surgery), pancreatic function (endocrine and exocrine), and morphology. During progress of the disease clinical picture, morphology and pancreatic function have typical correlative changes. Basically, from this viewpoint, three typical models of the disease can be distinguished: (1) early stage of uncomplicated CP; (2) late stage of uncomplicated CP, and (3) complicated CP, a disease stage which is characterised by local complications (chiefly pseudocysts and duct obstruction). The main concept of the natural history of CP bases on the thesis that CP burns itself out with spontaneous relief of pain, i.e. persistent freedom from pain occurs parallel with severe pancreatic dysfunction in the late stage of the disease. In the clinical picture and long-term course, nonalcoholic CP differs in certain essential respects from alcoholic CP; however, the two forms do not differ essentially as regards mortality and survival.

Parapancreatic biliary and intestinal obstruction in chronic obstructive pancreatitis: Is prophylactic bypass necessary?

Prophylactic bypass of the common duct and duodenum at the time of pancreatojejunostomy for chronic pancreatitis (triple bypass) has been recommended. If the subsequent development of parapancreatic obstruction were sufficiently frequent, such a recommendation would deserve more widespread application. In a group of 80 patients with otherwise uncomplicated chronic pancreatitis who underwent pancreatojejunostomy for control of pain, remote postoperative parapancreatic obstruction occurred in only 5 of 62 patients (8 percent) during an average follow-up of 6 years. Prophylactic bypass of the common duct and duodenum at the time of pancreatojejunostomy is not warranted. However, the overall 13.7 percent incidence of parapancreatic obstruction in patients undergoing operation for chronic pancreatitis is sufficiently high to remind the prudent surgeon that long-term postoperative evaluation of these patients is necessary.