Hereditary pancreatitis in a young adult: Acute to chronic

This report investigates an unusual case of recurrent pancreatitis. A 22-year-old female was admitted to the emergency room for severe abdominal pain, nausea, and weight loss. She reported having these symptoms since she was a toddler. The clinician ordered fecal pancreatic elastase-1, fat-soluble vitamins, molecular studies, and imaging of the pancreas by computed tomography. The screening test result for fecal pancreatic elastase-1 revealed severe pancreatic exocrine insufficiency, and the concentrations of fat-soluble vitamins were also low. Imaging showed scattered calcifications in the pancreas. These findings supported a diagnosis of chronic pancreatitis. Due to the rarity of chronic pancreatitis in young adults, molecular studies were performed. The patient was found to be homozygous for a mutation in the SPINK1 gene, which is associated with hereditary pancreatitis. This case report discusses hereditary pancreatitis and highlights data on the utilization of fecal pancreatic elastase-1 to assess pancreatic exocrine insufficiency.     

Analysis of exocrine pancreatic function in cystic fibrosis: one mild CFTR mutation does not exclude pancreatic insufficiency

BACKGROUND: Cystic fibrosis (CF) is the most common cause of exocrine pancreatic insufficiency in childhood. The aim of the present study is to evaluate the correlation between genotype and exocrine pancreatic insufficiency in CF patients. The special emphasis was put on the analysis of mild CFTR mutations. DESIGN: The study comprised 394 CF patients and 105 healthy subjects (HS). Elastase-1 concentrations were measured in all subjects. RESULTS: Severe pancreatic insufficiency was associated with the presence of two CFTR gene mutations (DeltaF508, N1303K, CFTR dele 2,3 (21kb), G542X, 1717-1G-A, R533X, W1282X, 621GT, 2183AAG, R560T, 2184insA and DeltaI507, G551D, 895T) and mild insufficiency with the presence of at least one mutation (R117H, 3171insC, A155P2, 138insL, 296 + 1G-A, E92GK, E217G, 2789 + 5G-A. 3849 + 1kbC-T/3849 + 1kbC-T) genotype resulted in high elastase-1-values. However, in case of patients with genotype DeltaF508/3849 + 10kbC-T, 1717-1GA/3849 + 10kbC-T as well as with DeltaF508/R334W, both high and low elastase-1 concentrations were found. Low E1 values were found in a patient with DeltaF508/R347P genotype. CONCLUSION: Patients who carry two 'severe' mutations develop pancreatic insufficiency, whereas those who carry at least one 'mild' usually remain pancreatic sufficient. However, the presence of one mild mutation does not exclude pancreatic insufficiency.     

Cationic trypsinogen mutations and pancreatitis

The discovery of PRSS 1 mutations in hereditary pancreatitis and analysis of how the genotype affects the presentation and progression of hereditary pancreatitis has led to a better understanding of the pathophysiology of the disease. Patients with hereditary pancreatitis present with symptoms at an early age and have a significant lifetime risk for the development of endocrine and exocrine insufficiency, albeit at a later stage than patients with either idiopathic or alcoholic chronic pancreatitis. There are distinct phenotypic differences between hereditary pancreatitis and with other types of pancreatitis. As many as 80% of patients with symptomatic hereditary pancreatitis have an underlying causative PRSS1 mutation; there are, however, few significant phenotypic differences between these PRSS1 mutations. TheR122H mutation is the most common PRSS1 mutation observed, and patients with the R122H mutation present earlier. This, however, does not necessarily translate into a more aggressive disease with respect to complications of chronic pancreatitis. Indeed, the age of presentation of symptoms may be a poor surrogate for predicting outcome, as inherited disorders of trypsinogen may cause subclinical attacks of pancreatitis, which ultimately lead to pancreatic destruction and dysfunction. All patients, irrespective of whether they carry a PRSS1 mutation, are at significant risk of developing pancreatic ductal adenocarcinoma. The risk appears to be insignificant below the age of 40 years, but it increases incrementally thereafter. Significantly, the risk of pancreatic cancer is not related to PRSS1 mutation type and does not appear to be related to the mode of inheritance. The role of SPINK1 mutations in modifying the expression of PRSS1mutations is unclear but appears to be of clinical importance. It is unlikely that they act as causative mutations per se, at least in the Western form of the disease. Additionally, they do not appear to have an impact on the penetrance of PRSS1 gene mutations in hereditary pancreatitis.     

A modified mutagenic PCR-RFLP method for K-ras codon 12 and 13 mutations detection in NSCLC patients.

Evidence from many investigators has shown that mutations in the first exon of K- ras gene occur at elevated frequencies in lung, pancreatic and colon carcinoma and seem to be of prognostic importance. The aim of this study was to develop an effective method for the detection of K- ras mutations in codons 12 and 13 in non-small-cell lung cancer (NSCLC) patients in order to investigate correlation with clinical outcome. DNA was extracted from tumour and neighbouring non-neoplastic lung tissues from 70 patients and screened for codon 12 and 13 mutations. We applied a mutagenic PCR-restriction fragment length polymorphism for both codon 12 and 13 mutation detection. Codon 12 mutation was identified in 20% of NSCLC patients, whereas no codon 13 mutation was detected. As expected, the respective non-neoplastic tissues exhibited no mutations. We observed an increased codon 12 mutation prevalence in adenocarcinoma comparing to other types of carcinomas. Follow-up for 29 patients with a mean time of 12 months indicates an increased relapse rate in NSCLC patients with the K- ras codon 12 mutation. Furthermore, a trend towards increased percentage of mutant samples was observed in the advanced stage group of patients. We provide evidence that our approach is a fast and reliable method for screening K- ras exon 1 mutations in tumour samples from NSCLC patients.     

Clinical significance of serum pancreatic enzymes in the quiescent phase of chronic pancreatitis

The most commonly used serum enzymes in pancreatic diseases are total amylase, pancreatic isoamylase, lipase and trypsin. To determine which of these enzymes is the most useful in the diagnosis of clinically quiescent chronic pancreatitis and which enzyme best reflects exocrine functional reserve, we studied 22 healthy control subjects, 44 patients with gastrointestinal, liver and biliary tract diseases, and 25 patients with chronic pancreatitis. On the basis of duodenal intubation, the latter were divided into two subgroups: one group of 13 patients with slight to moderate secretion deficiency and another of 12 patients with severe exocrine insufficiency. Of the enzymes studied, lipase, trypsin and pancreatic isoamylase are equally suitable for the evaluation of function in severe chronic pancreatitis, but not for the early diagnosis of the disease. Results for total amylase are not reliable so that its use in the study of chronic pancreatitis is not advisable.     

The prognostic value of immunologic indices in chronic pancreatitis]

Analysis of clinical and immunologic parallels in 200 patients with chronic pancreatitis has revealed that lymphocyte autosensitization to pancreatic tissue in the lymphocyte blastogenesis test (LBGT) is in high correlation with the frequency of the disease recurrences, and the severity of pancreatic exocrine insufficiency with the immune complex level. This permits recommending LBGT with pancreatic tissue antigen for the prediction of the condition recurrences, and measurements of the immune complexes level for the prediction of the developing exocrine pancreatic insufficiency.     

Elevated fasting cholecystokinin levels in pancreatic exocrine impairment: evidence to support feedback regulation

Previous studies have suggested that intraduodenal protease suppression of pancreatic exocrine secretion may be mediated through cholecystokinin (CCK) release. Our study compares basal plasma immunoreactive CCK concentrations in normal human subjects with those obtained in patients with chronic pancreatitis. Fasting plasma samples were collected from 18 normal subjects and from 18 patients with chronic pancreatitis. Eight patients had mild to moderate pancreatic exocrine impairment, and 10 had severe exocrine insufficiency. Venous plasma immunoreactive CCK concentrations were measured with two distinct peptide region-specific antibodies. Basal plasma CCK concentration in controls was 14.3 +/- 1.3 fmol/ml (mean +/- SEM), a value significantly less than that obtained in all patients with chronic pancreatitis, 30.1 +/- 4.0 fmol/ml (p less than 0.001). Patients with mild to moderate impairment had a fasting plasma CCK concentration of 32.8 +/- 7.9 fmol/ml (vs. control p less than 0.01), and those with severe disease 27.9 +/- 3.6 fmol/ml (vs. control p less than 0.001). In five patients with mild to moderate impairment of exocrine function and pancreatic extract-responsive abdominal pain, there was a 39 +/- 11% decrease in basal CCK levels during extract therapy (p less than 0.05). Results of this study indicate that pancreatic exocrine impairment is associated with elevated basal CCK levels, which may reflect a failure to provide feedback downmodulation of CCK release.     

Low frequency of p53 and ras mutations in bile of patients with hepato-biliary disease: a prospective study in more than 100 patients

The diagnosis of biliary disease, namely malignant disorders, is frequently hampered by the inconclusive cytology. We investigated prospectively the frequency of molecular changes in p53 and ras compared with cytology in patients with primary or secondary hepato-biliary disease. We investigated 118 consecutive patients, aged 24-89 with the following clinical diagnoses: choledocho/cholecystolithiasis (28), cholangiocellular carcinoma (21), gall bladder tumor (8), liver metastasis (3), autoimmune disease (8), chronic pancreatitis (16), pancreatic carcinoma (11), papillary disease (4), hepatic cirrhosis (6), cholangitis (2), anomalies (2), and normal (9). Bile was aspirated during routine endoscopic retrograde cholangio pancreatography (ERCP) or percutaneous transhepatic cholangiography (PTC). DNA was prepared freshly from a native aliquot. p53 mutations were detected by polymerase chain reaction (PCR) for exons 5 through 8 followed by TGGE. PCR for ras mutations was performed as RFLP-PCR with sequencing. In four cases, mutations in p53 could be found in exons 6 and 7. Twenty-two samples showed ras mutations; ras mutations were found in choledocholithiasis (4/28), bile duct (5/21), gall bladder (3/8) and pancreatic (1/11) carcinoma, liver metastasis (3/3), ulcerative colitis (2/3), PSC (1/2), and chronic pancreatitis (1/16). Cytology was clearly positive in seven cases, suspicious in three other, inconclusive in six, and negative in the rest. The molecular analysis resulted in a sensitivity of 33% and specificity of 87%, respectively, for the diagnosis of a malignant condition. PCR for p53 and ras mutations may aid the diagnosis of primary and secondary (metastatic) hepatobiliary disease if a malignant condition of the bile ducts and the liver is suspected and cytology is inconclusive or negative. However, the incidence of p53 and ras mutations in bile seems less frequent than in other malignant conditions of the gastrointestinal tract and the pancreas and lower than in tissue, leaving a poor sensitivity and specificity. Nevertheless, the presence of a p53 and/or ras mutation per se supports a clinical suspicion of malignancy, even when the conventional cytology is negative or inconclusive.     

急性胰腺炎患者胰腺外分泌功能不全识别及护理的研究进展

急性胰腺炎发病率逐年上升。急性胰腺炎后近1/3患者发生胰腺外分泌功能不全,导致患者出现消化吸收障碍、营养不良等症状。该文回顾国内外文献,对护理人员关注急性胰腺炎患者胰腺外分泌功能不全的重要性、胰腺外分泌功能不全的识别与监测、护理措施等方面进行综述,为护理人员的相关临床工作提供科学依据。     

Chronic pancreatitis

Chronic pancreatitis is the progressive and permanent destruction of the pancreas resulting in exocrine and endocrine insufficiency and, often, chronic disabling pain. The etiology is multifactorial. Alcoholism plays a significant role in adults, whereas genetic and structural defects predominate in children. The average age at diagnosis is 35 to 55 years. Morbidity and mortality are secondary to chronic pain and complications (e.g., diabetes, pancreatic cancer). Contrast-enhanced computed tomography is the radiographic test of choice for diagnosis, with ductal calcifications being pathognomonic. Newer modalities, such as endoscopic ultrasonography and magnetic resonance cholangiopancreatography, provide diagnostic results similar to those of endoscopic retrograde cholangiopancreatography. Management begins with lifestyle modifications (e.g., cessation of alcohol and tobacco use) and dietary changes followed by analgesics and pancreatic enzyme supplementation. Before proceeding with endoscopic or surgical interventions, physicians and patients should weigh the risks and benefits of each procedure. Therapeutic endoscopy is indicated for symptomatic or complicated pseudocyst, biliary obstruction, and decompression of pancreatic duct. Surgical procedures include decompression for large duct disease (pancreatic duct dilatation of 7 mm or more) and resection for small duct disease. Lateral pancreaticojejunostomy is the most commonly performed surgery in patients with large duct disease. Pancreatoduodenectomy is indicated for the treatment of chronic pancreatitis with pancreatic head enlargement. Patients with chronic pancreatitis are at increased risk of pancreatic neoplasm; regular surveillance is sometimes advocated, but formal guidelines and evidence of clinical benefit are lacking.     

Symptomatic diabetes mellitus in patients with chronic recurrent pancreatitis

Out of 279 patients with chronic recurrent cholepancreatitis 34 (12.2%) developed secondary diabetes mellitus. The secondary genesis of the diabetes was suggested in view of its origin in the presence of chronic pancreatitis and absence of hereditary predisposition, concomitant diseases promoting diabetes onset. The frequency of pancreatitis exacerbations and the degree of pancreatic exocrine insufficiency correlate with the occurrence of symptomatic diabetes. Diminished blood levels of insulin and C-peptide, inhibited response to pancreozymin registered in the patients may be indicative of symptomatic diabetes onset. Ketoacidosis was recorded in 9 patients, diabetic retinopathy in no patients. Ten patients out of 34 patients with chronic pancreatitis with secondary diabetes, 9 of which had episodes of ketoacidosis, received insulin. The sequence chronic cholecystitis-pancreatitis-diabetes was discussed in detail.     

The effect of small amounts of alcohol on the clinical course of chronic pancreatitis

OBJECTIVE: To investigate the hypothesis that an increasing intake of alcohol accelerates the course of chronic pancreatitis. PATIENTS AND METHODS: In this retrospective record analysis and subsequent prospective follow-up of 372 patients with chronic pancreatitis, we separately compared the clinical course of chronic pancreatitis among the following patients: those with early-onset idiopathic chronic pancreatitis and no alcohol intake (group A [n=25]) and those with late-onset idiopathic chronic pancreatitis and no alcohol intake (group B [n=41]), low alcohol intake (< 50 g/d) (group C [n=57]), and high alcohol intake (> or = 50 g/d) (group D [n=249]). From medical records, physical examinations, questionnaires, death certificates, or autopsy reports, we obtained information on sex, age, signs and symptoms (pain severity, calcification, endocrine and exocrine insufficiency), complications, surgery, and survival. RESULTS: Group D had the highest percentage of men (72%). At the onset of chronic pancreatitis, patients in group A were significantly younger than those in groups B, C, and D (P<.05), and severity of pain was significantly greater in patients in group A than in groups B, C, and D (P<.05). The percentage of patients who eventually developed endocrine or exocrine insufficiency was similar in all groups. Among patients in groups B, C, and D, an increasing intake of alcohol from zero to less than 50 g/d to more than 50 g/d was associated with earlier inception of disease (P<.001). Pain prevalence at onset was less in group B patients than in patients in groups C and D (P<.05). Intake of a large amount of alcohol (group D) shortened time to calcification and survival (P<.05). In addition, patients in group D had more complications (fistulas, pseudocysts, abscesses, and biliary obstruction) (P<.05) than those in groups A and B. More patients in group A underwent pancreatic surgery compared with patients in groups B and C. CONCLUSIONS: Among patients with onset of chronic pancreatitis after age 35 years, alcohol intake, even less than 50 g/d, induced earlier disease characterized by more frequent severe pain, calcification, and complications. Intake of large amounts of alcohol (> or = 50 g/d) reduced time to calcification and death.     

Neurological features and enzyme therapy in patients with endocrine and exocrine pancreas dysfunction due to CEL mutations

OBJECTIVE—To further define clinical features associated with the syndrome of diabetes and pancreatic exocrine dysfunction due to mutations in the carboxyl-ester lipase (CEL) gene and to assess the effects of pancreatic enzyme substitution therapy.RESEARCH DESIGN AND METHODS—Nine patients with CEL gene mutation, exocrine deficiency, and diabetes were treated and followed for 30 months.RESULTS—Treatment improved symptoms in seven of nine patients. Exocrine and endocrine function assessed by fecal elastase and A1C were not affected, although fecal lipid excretion was reduced. Vitamin E was low in all patients but increased with treatment (P < 0.001 at 30 months) and improved in five subjects. A predominantly demyelinating neuropathy was seen in a majority of patients, and carpal tunnel syndrome was common.CONCLUSIONS—Pancreatic enzyme substitution alleviated symptoms and malabsorption and normalized vitamin E levels. Glycemic control was not significantly affected. The CEL syndrome seems associated with a demyelinating neuropathology.We recently described the syndrome of diabetes and exocrine pancreas dysfunction due to mutations in the carboxyl-ester lipase (CEL) gene (1,2). In the present study, we assessed the effects of pancreatic enzyme substitution therapy (PEST) on the endocrine and exocrine pancreatic function of mutation carriers with exocrine insufficiency. In addition, neurological features associated with the syndrome were reviewed.     

Update of exocrine functional diagnostics in chronic pancreatitis

Diagnostics of pancreatic insufficiency rely mainly on tests of pancreatic exocrine function based on either measurement of pancreatic secretion or the secondary effects resulting from lack of digestive enzymes or imaging modalities. These methods have been developing rapidly over the last decades, and the aims of this review were to describe exocrine functional testing and imaging of the pancreas in chronic pancreatitis..     

Pancreatic function after endoscopic and surgical occlusion of the pancreatic duct in patients with chronic pancreatitis

Complex monitoring of pancreatic function was done after 18 endoscopic or surgical occlusions of the pancreatic duct in 15 patients with chronic pancreatitis. The indirect function tests (starch tolerance test, Lipiodol test and fat loading) as well as the direct tests (secretin-pancreozymin and Lundh tests) demonstrated only moderate pancreatic insufficiency. Overall values of the Lundh test performed before and after the treatment in 10 cases did not change significantly. The surgical procedure decreased pancreatic function somewhat more effectively, but the symptom-free "burned-out" state was only rarely achieved. Even glucose tolerance slightly diminished after treatment. The uneven results of obstruction therapy were attributed to the recovered exocrine function of the pancreas. Patients with severe pancreatic insufficiency or proximal resection of the pancreas seem to be better candidates for such treatments.     

超声引导下细针穿刺胰腺腺癌基因诊断

目的：探讨超声引导下细针穿刺与基因检测相结合早期诊断胰腺癌的临床应用。方法：应用超声引导下细针穿刺技术对３８例可疑胰腺癌及其邻近器官占位性病变患者进行穿刺活检,同进采用聚合酶链反应－限制性酶切片段长度多态性技术,对所取得的标本ｃ－ｋｉ－ｒａｓ基因第１２密友子突变进行检测。应用于胰腺癌的诊断。结果：２２例胰腺癌中有２１例有ｃ－ｋｉ－ｒａｓ基因第１２密友子突变,多为ＧＧＴ变成ＧＡＴ、ＧＣＴ、ＧＴＴ,阳     

Octreotide-induced acute pancreatitis in a patient with acquired immunodeficiency syndrome

Unremitting diarrhea is a common problem in patients with AIDS. We have reported the case of such a patient who was treated with the somatostatin analogue octreotide for chronic diarrhea and who had acute pancreatitis as a consequence of this therapy. We postulate that the possible mechanism for the pathogenesis of this pancreatic damage was octreotide-induced prevention of pancreatic exocrine secretion. We believe this acted as a "physiologic gallstone", inducing an attack of acute pancreatitis.     

Determination of lipase concentrations by enzyme immunoassay in secretin-caerulein test

Conclusions Lipase determination by enzyme immunoassay is a reliable method. The determination in serum and duodenal juice can be performed by this test. Serum lipase determination separates normal subjects from patients with exocrine pancreatic insufficiency. An early stage of chronic pancreatitis can be suspected by an increased ratio of secretin-stimulated serum lipase. Lipase concentration in duodenal juice indicates different stages of decreased exocrine pancreatic function. It is a change of standardization of the secretin ceruletid test because duodenal juice can be stored and the results of different laboratories can be compared.     

Idiopathic pancreatitis related to CFTR: complex inheritance and identification of a modifier gene.

Idiopathic chronic pancreatitis (ICP) is the leading cause of nonalcoholic chronic pancreatitis. This study examined a series of patients with ICP to determine the prevalence and role of mutations of the cystic fibrosis gene (CFTR) and of a trypsin inhibitor gene (PSTI). Genetic testing was done in 39 patients with ICP. In this series, 17 patients had CFTR mutations and 9 had PSTI mutations. Pancreatitis risk was increased 14-fold by having the N34S PST1 mutation, 40-fold by having two abnormal copies of CFTR, and 600-fold by having both. In patients with two CFTR mutations, extrapancreatic clinical findings and nasal bioelectric responses suggested reduced residual CFTR protein function. Thus, pancreatitis risk showed complex inheritance and was highest in individuals who have abnormalities in both the pancreatic ducts (CFTR) and acini (PSTI). These findings indicate that PSTI is a modifier gene for CFTR-related ICP and have implications for the classification, diagnosis, and pathogenesis of pancreatitis.     

口服胰功肽测定胰腺外分泌功能在消化系疾病的应用

本文通过对30例正常人,110例消化系疾病患者口服一定量的 N—苯甲酰—L—酪氨酰—对氨基苯甲酸(下称 BT—PABA)做胰腺外分泌功能试验.发现肝硬化、慢性肝炎、慢性胃炎及消化系溃疡患者的 BT—PABA 排出率与正常人比较无显著差异.肝硬变并肾功能损害者、胰腺癌及急、慢性胰腺炎患者的 PABA 排出率低于正常人。此实验对鉴别急、慢性胰腺炎及胰腺炎恢复过程的动态观察有一定价值。