Smoking cessation at the clinical onset of chronic pancreatitis and risk of pancreatic calcifications.

OBJECTIVE: Cigarette smoking is associated with a higher risk of developing chronic pancreatitis (CP) and increases the likelihood of developing pancreatic calcifications. The aim of this study was to know whether smoking cessation modifies the course of the disease. METHODS: Patients with CP who had been followed up for more than 6 years from clinical onset and who had not developed calcifications after 5 years were analyzed. We studied smokers, never-smokers, and patients who had given up smoking within 5 years. For actuarial analysis, the sixth year was considered as time 0. RESULTS: Of the 360 patients, there were 43 women and 317 men (88.1%) with a mean age of 38.7 years. The median follow-up was 19.0 years. Chronic pancreatitis was alcohol-associated in 255 patients, hereditary in 10, obstructive in 54, and idiopathic in 41. There were 317 smokers (88.1%) and 259 alcohol drinkers (71.9%). At the end of the follow-up, 212 patients (59.8%) developed calcifications. Concerning the risk of calcifications, never-smokers and ex-smokers had similar actuarial curves, and these were significantly different from the curve for smokers (P < 0.003). Considering never-smokers as the reference class, ex-smokers had an odds ratio (OR) of 0.56 (95.0% confidence interval [CI], 0.2-1.4; P = not significant), patients smoking 1 to 10 cigarettes per day had an OR of 1.95 (95.0% CI, 1.1-3.4; P < 0.019), patients smoking 11 to 20 cigarettes per day had an OR of 1.76 (95.0% CI, 1.1-2.8; P < 0.0018), and those smoking more than 20 cigarettes per day had an OR of 1.79 (95.0% CI, 1.1-2.9; P < 0.019). Alcohol cessation seems to have no influence. CONCLUSIONS: Smoking cessation in the first years from the clinical onset of CP reduces the risk of developing pancreatic calcifications.

Intraductal papillary mucinous neoplasms and chronic pancreatitis.

BACKGROUND: Intraductal papillary mucinous neoplasms (IPMNs) may present with clinical and radiological pictures resembling those of chronic pancreatitis (CP). AIMS: To compare the clinical and epidemiological characteristics of patients suffering from CP with those of patients suffering from IPMN. To assess whether CP is associated with an increased risk of developing IPMN. METHODS: In our departments, from 1981 to 1998, we prospectively followed 473 patients suffering from CP, including 93 cases of chronic obstructive pancreatitis (COP), and 45 patients with a histologically confirmed diagnosis of IPMN. Another 6 patients had an initial diagnosis of CP and a subsequent diagnosis of IPMN. RESULTS: Patients with IPMN were more often female (females 53 vs. 15%; p < 0.001), were older (mean age 63.1 vs. 42.8 years; p < 0.001), drank less alcohol (19 vs. 107 g/day; p < 0.001) and smoked fewer cigarettes (mean 8 vs. 21 cigarettes/day) than CP patients. These results were also confirmed when considering only patients with COP. The 6 patients with a subsequent diagnosis of IPMN were males (p n.s.) with a mean age of 51.4 years (p < 0.05). Only 1 patient was a drinker (p < 0.05) and 4 were smokers (p n.s.). Comparing CP and IPMN, logistic regression analysis selected sex, age, alcohol and smoking, whereas only sex and age were selected when comparing COP vs. IPMN. CONCLUSIONS: In general patients with IPMN present different epidemiological characteristics than those with CP and the subgroup with COP. The clinical and pathological features suggest that in most cases IPMN is the cause of CP and not vice versa.

Obesity and gastro-esophageal acid reflux: physiopathological mechanisms and role of gastric bariatric surgery.

BACKGROUND: Controversial findings about the relationships between obesity and gastro-esophageal reflux have been reported, as well as about the effects of weight loss and bariatric surgery on reflux. The aims of this study were to evaluate esophageal motility and gastro-esophageal acid circadian patterns in obese patients and to test the effects of vertical banded gastroplasty (VBG) on these parameters. METHODS: 14 obese subjects (BMI 36-53 kg/m2), 4 men, 10 women, 27-61 years old, admitted for elective bariatric surgery, underwent clinical evaluation, upper endoscopy, esophageal manometry and gastroesophageal pH monitoring. Evaluations were repeated 6 to 12 months after gastric surgery that consisted of a VBG (7 patients), accompanied in the other 7 patients with an anti-reflux procedure (fundoplication). Manometric and pH-metric findings in the obese patients were compared with a normal-weight control group before and after the two different surgical treatments. RESULTS: Gastro-esophageal reflux was significantly more frequent in obese (57.1%) than in control group (7.1%). Esophageal motility in obese subjects was not different from controls. After VBG alone, we found a reduction in basal lower esophageal sphincter (LES) pressure and an increase of acid reflux. When VBG was accompanied by fundoplication, basal LES pressure increased and acid reflux frequency decreased. CONCLUSIONS: Obesity is associated with gastroesophageal reflux. VBG reduced weight, but not gastro-esophageal acid reflux. Therefore, in our population, this operation cannot be considered as an antireflux procedure.

Exocrine pancreatic cancer, cigarette smoking, and diabetes mellitus: a case-control study in northern Italy.

The role of cigarette smoking and diabetes mellitus as risk factors for exocrine pancreatic cancer (PC) was investigated in a hospital based case-control study. Current smokers were at increased risk for PC (OR = 2.36, 95% CI 1.53-3.63): the magnitude of the risk was related to the lifetime amount of smoking (chi2(trend) = 17.00; P < 0.0001). Among former smokers, after 15 years from ceasing smoking, the risk for PC dropped to the level of a lifetime non-smoker, whichever the lifetime smoking amount. Diabetes was associated with a 2.89-fold increased risk for PC (95% CI 1.71-4.86): the risk was 4.76 (95% CI 1.99-11.53) for diabetes diagnosed up to 2 years before the diagnosis of PC and dropped to 2.07 (95% CI 1.02-4.20) for diabetes diagnosed more than 5 years before PC. The risk for PC was estimated according to the treatment used to control diabetes: it was 6.49 (95% CI 2.28-18.48) for insulin treated diabetes and 2.12 (95% CI 1.16-3.87) for diabetes treated with oral hypoglycemic drugs. The risk of PC for diabetes treated for more than 5 years before the diagnosis of PC was 6.21 (95% CI 1.61-23.96) for patients treated with insulin and 1.21 (95% CI 0.50-2.92) for those treated with oral hypoglycemic drugs: the type of treatment needed to control the disease may discriminate between the diabetes that represents a consequence of cancer from the diabetes that could represent an etiological co-factor. More studies are needed to clarify whether long-lasting insulin-treated diabetes is an etiological co-factor in PC.

Association of HLA-DRB1*0401 allele with chronic pancreatitis.

INTRODUCTION: Chronic pancreatitis (CP) is characterized by irreversible morphologic and functional alterations of the pancreas, clinically presenting with upper abdominal pain as well as exocrine and endocrine insufficiencies. According to a more recent hypothesis, the pathogenesis may involve genetic and immunologic factors. AIM: To investigate the major histocompatibility complex (MHC) genes as a genetic background of chronic pancreatitis. METHODOLOGY: Allelic polymorphisms were investigated in the genes of the MHC region (HLA B, DRB, DQB) with PCR-based methodologies (PCR-SSP) in 56 patients with CP (44 males and 12 females) and 183 normal controls (78 males and 105 females) of the same ethnic group. All patients and controls gave their informed consent. RESULTS: Among HLA-DRB1 genes, DRB1*04 was significantly higher in CP patients than in controls (26.78% versus 8.1%; pc < 0.003; OR = 4.1; CI = 1.85-9.06). DRB1*04 allele specificities in the DRB1*04-positive patients demonstrated significantly higher frequencies of DRB1*0401 allele (14.3% versus 1.1%; p = 0.00017; OR = 15.08; CI = 3.1-73.36). Neither HLA-B nor HLA-DQB1 associations with the disease were found. CONCLUSIONS: This study supports a role of HLA-DRB1*0401 as a susceptibility factor for patients with CP. HLA DRB1*0401 contains the 70QKRAA74 amino acid sequence, which is also expressed by several human pathogens, including Epstein-Barr virus. T cells may be triggered in the pancreatic tissue upon exposure to foreign peptides similar enough to cross-react and to break immunologic tolerance.