Clinical profile of early-onset and late-onset idiopathic chronic pancreatitis in South India

Background and Aim

Idiopathic chronic pancreatitis (ICP) is the most common form of chronic pancreatitis reported in India. There is paucity of literature on the prevalence and profiles of early- and late-onset forms of ICP in India.

Material and Methods

We compared the profile of early- and late-onset ICP in a patient population attending a tertiary care hospital in South India.

Results

Pain was the characteristic feature as more than 90 % with both early-onset and late-onset ICP had pain as the most significant symptom. Onset of pain was at age 14.9?±?7.7 years in early-onset and at 38.1?±?9.9 in late-onset ICP (p?<?0.001). There was considerable delay between onset of pain in early onset as compared to late-onset ICP. Diabetes was seen in 41.4 % in early-onset as compared to 69.1 % in late-onset ICP (p?<?0.001). Pancreatic exocrine insufficiency was seen in 34.4 % in early-onset as compared to 53.2 % in late-onset ICP (p?<?0.001). Increased prevalence of exocrine insufficiency and diabetes was observed in late-onset as compared to early-onset ICP. Univariate analysis showed that alcohol use, smoking, age, and family history of diabetes were significantly associated with diabetes. Multivariate analysis showed strong associations for diabetes with smoking (odds ratio (OR)?=?4.2), calcification (OR?=?7.7), as well as family history and age >40 years.

Conclusions

There were differences between early-onset and late-onset ICP in southern Indian patients. Diabetes was strongly associated with smoking and pancreatic calcification.     

慢性胰腺炎胰腺钙化与烟酒关系初探

目的 探讨国内慢性胰腺炎(CP)患者烟酒摄入量与发生胰腺钙化间的关系.方法 按入院时有无胰腺钙化分为两组进行比较分析,再将无胰腺钙化者出院后有无新发胰腺钙化分为新发组和持续无钙化组.Logistic回归或Cox比例风险模型进行逐步回归分析胰腺钙化的风险因素.结果 1997年1月到2007年7月共收治并成功随访449例CP患者,248例有胰腺钙化;201例无胰腺钙化,其中13例出院后新发生胰腺钙化.入院时胰腺钙化者的发病年龄小、病史长、糖尿病和腹泻发生率高.首发年龄≤40岁、酒精摄入量>20 g/d、糖尿病和腹泻为胰腺钙化风险因素;过量饮酒为无胰腺钙化CP 患者新发生钙化的唯一风险因素(OR 3.2).结论 饮酒增加CP患者胰腺钙化风险,建议戒酒;吸烟的作用需进一步研究.     

Cigarette smoking accelerates progression of alcoholic chronic pancreatitis

BACKGROUND: Smoking is a recognised risk factor for pancreatic cancer and has been associated with chronic pancreatitis and also with type II diabetes. AIMS: The aim of this study was to investigate the effect of tobacco on the age of diagnosis of pancreatitis and progression of disease, as measured by the appearance of calcification and diabetes. PATIENTS: We used data from a retrospective cohort of 934 patients with chronic alcoholic pancreatitis where information on smoking was available, who were diagnosed and followed in clinical centres in five countries. METHODS: We compared age at diagnosis of pancreatitis in smokers versus non-smokers, and used the Cox proportional hazards model to evaluate the effects of tobacco on the development of calcification and diabetes, after adjustment for age, sex, centre, and alcohol consumption. RESULTS: The diagnosis of pancreatitis was made, on average, 4.7 years earlier in smokers than in non-smokers (p = 0.001). Tobacco smoking increased significantly the risk of pancreatic calcifications (hazard ratio (HR) 4.9 (95% confidence interval (CI) 2.3-10.5) for smokers v non-smokers) and to a lesser extent the risk of diabetes (HR 2.3 (95% CI 1.2-4.2)) during the course of pancreatitis. CONCLUSIONS: In this study, tobacco smoking was associated with earlier diagnosis of chronic alcoholic pancreatitis and with the appearance of calcifications and diabetes, independent of alcohol consumption.     

Increased angiogenin expression in obstructive chronic pancreatitis surrounding pancreatic cancer but not in pure chronic pancreatitis

We previously demonstrated the increased expression of angiogenin (ANG) in pancreatic cancer and its relation to cancer aggressiveness; however, the expression patterns and the roles of angiogenin in chronic pancreatitis are still unknown. We investigated the expression of ANG both in the tissues and in the sera of chronic pancreatitis patients (pure chronic pancreatitis) by using in situ hybridization, Western blot analysis, and enzyme-linked immunosorbent assay. In situ hybridization revealed no detectable ANG messenger RNA (mRNA) signals in all tissues of pure chronic pancreatitis and normal pancreas. Only a small amount of protein band expression was obtained in all of the protein lysates of pure chronic pancreatitis and normal pancreas. Accordingly, there was no significant difference between the mean serum ANG concentration of chronic pancreatitis patients (352.1+/-72.5 ng/ml) and that of healthy volunteers (357.6+/-45.2 ng/ml). By contrast, acinar cells and interstitial fibroblasts in the tissues surrounding pancreatic cancer showed increased ANG mRNA expression. Strong protein band expression was obtained in the protein lysates of pancreatic cancer surrounding tissue, and mean serum ANG concentration was increased in pancreatic cancer patients. These findings suggest that ANG expression is increased in pancreatic cancer surrounding tissue but is not increased in pure chronic pancreatitis, and that ANG is potentially involved in the pancreatic cancer microenvironment rather than the establishment of pure chronic pancreatitis.     

Cigarette smoking increases the mean platelet volume in elderly patients with risk factors for atherosclerosis

Summary To study the effects of cigarette smoking and atherosclerosis on platelet size, we measured the mean platelet volume (MPV) and other platelet parameters in 142 elderly smokers and nonsmokers with or without atherosclerotic risk factors. The MPV and the platelet count were highest and their inverse correlation was strongest in the atherosclerotic smokers (r= 0.54, P < 0.05) when compared with the nonsmoking and non-atherosclerotic groups. A 10% decrease of MPV was found in 8 smoking subjects in the atherosclerotic group, who successfully discontinued smoking (P < 0.05). These results suggest that smoking may increase platelet consumption in atherosclerotic vessels and that subsequently megakaryocytes are activated to produce larger platelets, which are more active. Thus, an increase in MPV due to smoking may also contribute to the acceleration of atherosclerosis and should be considered as a risk factor for atherosclerotic disease.     

Cigarette smoking increases the mean platelet volume in elderly patients with risk factors for atherosclerosis.

To study the effects of cigarette smoking and atherosclerosis on platelet size, we measured the mean platelet volume (MPV) and other platelet parameters in 142 elderly smokers and nonsmokers with or without atherosclerotic risk factors. The MPV and the platelet count were highest and their inverse correlation was strongest in the atherosclerotic smokers (r = 0.54, P < 0.05) when compared with the nonsmoking and non-atherosclerotic groups. A 10% decrease of MPV was found in 8 smoking subjects in the atherosclerotic group, who successfully discontinued smoking (P < 0.05). These results suggest that smoking may increase platelet consumption in atherosclerotic vessels and that subsequently megakaryocytes are activated to produce larger platelets, which are more active. Thus, an increase in MPV due to smoking may also contribute to the acceleration of atherosclerosis and should be considered as a risk factor for atherosclerotic disease.     

Increased expression of glutathione S-transferase-pi in the islets of patients with primary chronic pancreatitis but not secondary chronic pancreatitis

The mechanism of tissue alteration in chronic pancreatitis (CP) is still unclear. Different hypotheses have been discussed, including increasing oxidant stress in the acinar cells, often as a result of exposure to xenobiotics. To evaluate the role of oxidative stress in CP, the authors investigated the expression of the drug-metabolizing phase II enzyme, glutathione S-transferase-pi (GST-pi), in the pancreatic tissue of patients with CP and compared it with the healthy pancreatic tissue from age-matched donors. Pancreatic tissue from patients with secondary CP resulting from ductal obstruction by pancreatic cancer (PC) was also examined. The percentage of cells immunoreacting with anti-GST-pi was counted within 15 randomly selected islets in each slide of the three groups. In all specimens, ductal and ductular cells, and in PC, cancer cells, expressed GST-pi in a moderate intensity. Acinar cells did not stain. Various numbers of islet cells in each of the three groups were stained strongly. More islet cells expressed GST-pi in CP (42%) than in healthy pancreatic tissue (16%, p < 0.001) or PC (17%, p < 0.001). Our results imply an important role of islet cells in the metabolism of substances, which are the substrate for GST-pi, and lend support to the hypothesis of oxidative stress as the cause of CP.     

Environmental risk factors for chronic pancreatitis and pancreatic cancer

Chronic pancreatitis has long been thought to be mainly associated with immoderate alcohol consumption. The observation that only ～10% of heavy drinkers develop chronic pancreatitis not only suggests that other environmental factors, such as tobacco smoke, are potent additional risk factors, but also that the genetic component of pancreatitis is more common than previously presumed. Either disease-causing or protective traits have been indentified for mutations in different trypsinogen genes, the gene for the trypsin inhibitor SPINK1, chymotrypsinogen C, and the cystic fibrosis transmembane conductance regulator (CFTR). Other factors that have been proposed to contribute to pancreatitis are obesity, diets high in animal protein and fat, as well as antioxidant deficiencies. For the development of pancreatic cancer, preexisting chronic pancreatitis, more prominently hereditary pancreatitis, is a risk factor. The data on environmental risk factors for pancreatic cancer are, with the notable exception of tobacco smoke, either sparse, unconfirmed or controversial. Obesity appears to increase the risk of pancreatic cancer in the West but not in Japan. Diets high in processed or red meat, diets low in fruits and vegetables, phytochemicals such as lycopene and flavonols, have been proposed and refuted as risk or protective factors in different trials. The best established and single most important risk factor for cancer as well as pancreatitis and the one to clearly avoid is tobacco smoke.     

Computer tomogram of changes in pancreatic calcification during pancreatitis

In 3 patients an increase of pancreatic calcification was observed in the course of 2 months. The increase of the calcification was combined with an improvement of the patient and a decrease of pseudocysts. Therefore the increase of pancreatic calcification was considered as a good sign. After surgical drainage of a pseudocyst one patient showed a decrease of pancreatic calcification in the course of 1 year. In this patient the clinical picture indicated a favourable development. This observation demonstrates that a recovering pancreas may show diminishing calcifications.     

胰腺癌和慢性胰腺炎的相关因素

目的:对比胰腺癌(pancreatic carcinoma,PC)和慢性胰腺炎(chronic pancreatitis,CP)的相关因素,为临床早期发现PC提供一定帮助.方法:对比分析新疆医科大学第一附属医院2005-01/2010-06住院胰腺癌(pancreaticcarcinoma,PC)患者265例及同期住院期间慢性胰腺炎(chronic pancreatitis,CP)患者294例,并进行单因素分析及多因素的非条件Logistic回归分析胰腺癌相关因素.结果:单因素分析显示:年龄、民族、吸烟、吸烟>20支/d、饮酒、饮酒>40g/d且>10年、糖尿病、胆石症、血、尿淀粉酶、空腹血糖水平、门冬氨酸氨基转移酶、丙氨酸氨基转移酶、CA19-9水平在2组间差异有统计学意义(P<0.05).多因素非条件Logistic回归分析显示:年龄(OR=1.607,P<0.05),CA19-9>35KU/L(OR=1.004,P<0.05),空腹血糖>6.4mmol/L(OR=1.453,P<0.05)是胰腺癌发生的独立危险因素.对265例胰腺癌患者用Logistic回归方程预测发现251例胰腺癌,正确率为94.7%;对294例慢性胰腺炎患者中用Logistic回归方程预测有282例非胰腺癌,正确率为95.9%;总正确率为95.3%.结论:对具备年龄、CA19-9、空腹血糖水平等高危因素的CP患者应定期监测空腹血糖及CA19-9,以期早期发现PC,对临床工作具有指导意义.     

Cigarette smoking as a risk factor for chronic pancreatitis: a case-control study in Japan. Research Committee on Intractable Pancreatic Diseases

We conducted a hospital-based, case-control study to examine the association of cigarette smoking with chronic pancreatitis. Ninety-one male patients with chronic pancreatitis newly diagnosed from July 1997 to December 1998 were recruited as cases, and 175 controls were individually matched to each case for gender, age (+/- 5 years), hospital, and time of the first visit to a hospital (+/- 1 year). A self-administered questionnaire was used to collect information on tobacco and alcohol use, diet, and other factors. The odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated by multiple conditional logistic models, adjusting for body mass index, education level, and alcohol consumption. Compared with nonsmokers, the ORs (95% CIs) were 7.8 (2.2-27.3) for all current smokers, and 14.7 (3.1-69.9), 5.5 (1.5-20.1), 12.2 (2.4-71.0) for those consuming < 20, 20-39, and > or = 40 cigarettes per day, respectively. Much greater risk was observed for those who had smoked for > or = 25 years. Risk of chronic pancreatitis significantly increased with increasing cumulative amount of smoking (p < 0.05). Analysis for the effect of combined use of tobacco and alcohol showed that cigarette smoking was associated with the higher risk in both of the two alcohol consumption levels. Our findings indicated that cigarette smoking may be an independent and significant risk factor for chronic pancreatitis.     

HLA antigens in chronic idiopathic pancreatitis compared with chronic alcoholic pancreatitis

HLA A and B antigens in 46 patients with chronic pancreatitis were studied in Japan. Patients were divided into the two groups according to the etiology of the disease: one was chronic idiopathic pancreatitis (18 cases) and the other was chronic alcoholic pancreatitis (28 cases). One hundred twenty unrelated subjects were also examined as control. HLA B5 was detected in 14 of 18 cases of chronic idiopathic pancreatitis, which was significantly higher statistically than in control (P<0.001, correctedP<0.05). In contrast, no HLA antigens of locus A and B were found which had a relationship to chronic alcoholic pancreatitis. These results suggest that some genetic factors may be implicated in the development of chronic idiopathic pancreatitis and differing from that of alcoholic pancreatitis.