Long-term proton pump inhibitor usage and the association with pancreatic cancer in Sweden

Background The long-term safety of proton pump inhibitors (PPIs) is increasingly questioned. The aim of our study was to assess the risk of pancreatic cancer among long-term PPI users in Sweden. Methods This population-based nationwide Swedish cohort study including 796,492 adult long-term PPI users has been used to calculate the standardized incidence rate ratios (SIRs) and 95% confidence intervals (CI) for pancreatic cancer, stratifying by indications of use, age, sex, and duration of use. The risk among all 20,210 long-term H2-receptor antagonist users was assessed as comparison. Results Pancreatic cancer was found in 1733 long-term PPI users, and 25 H2-receptor antagonist users. For PPI users, the risk of pancreatic cancer was increased overall (SIRs = 2.22; 95% CI 2.12-2.32) and in all subgroup analyses, with the highest risk among PPI-users younger than 40 years (SIR = 8.90, 95% CI 4.26-16.37), and among individuals with a history of Helicobacter pylori (SIR = 2.99, 95% CI 2.54-3.49). After the first year after enrolment (during which PPI use may be because of early symptoms of pancreatic cancer), the risk remained increased over time, with SIR = 1.57 (95% CI 1.38-1.76) after 5 years. No associations were found for H2-receptor antagonists (SIR = 1.02, 95% CI 0.66-1.51). Conclusions This large study showed an increased risk of pancreatic cancer in long-term users of PPIs in Sweden, in particular among the youngest users

Patients With Celiac Disease Have an Increased Risk for Pancreatitis

Background & Aims Patients with celiac disease have been reported to be at increased risk for pancreatitis and pancreatic insufficiency, but the risk might have been overestimated because of patient selection and limited numbers of patients for analysis. Furthermore, no distinction has been made between patients with gallstone-related and non–gallstone-related pancreatitis. We performed a nationwide study to determine the risk for any pancreatitis or subtype of pancreatitis among patients with biopsy-verified celiac disease. Methods We analyzed data from patients in Sweden with celiac disease (n = 28,908) who were identified on the basis of small intestinal biopsy records from 28 pathology departments (those with villous atrophy, Marsh 3). Biopsies were performed from 1969 to 2008, and biopsy report data were collected from 2006 to 2008. Patients with pancreatitis were identified on the basis of diagnostic codes in the Swedish Patient Register and records of pancreatic enzyme use in the Swedish Prescribed Drug Register. Data were matched with those from 143,746 individuals in the general population; Cox regression was used to estimate hazard ratios (HRs) for pancreatitis. Results We identified 406 patients with celiac disease who were later diagnosed with pancreatitis (and 143 with expected pancreatitis) (HR, 2.85; 95% confidence interval [CI], 2.53–3.21). The absolute risk of any pancreatitis among patients with celiac disease was 126/100,000 person-years, with an excess risk of 81/100,000 person-years. The HR for gallstone-related acute pancreatitis was 1.59 (95% CI, 1.06–2.40), for non–gallstone-related acute pancreatitis HR was 1.86 (95% CI, 1.52–2.26), for chronic pancreatitis HR was 3.33 (95% CI, 2.33–4.76), and for supplementation with pancreatic enzymes HR was 5.34 (95% CI, 2.99–9.53). The risk of any pancreatitis within 5 years of diagnosis was 2.76 (95% CI, 2.36–3.22). Conclusions Based on an analysis of medical records from Sweden, patients with celiac disease have an almost 3-fold increase in risk of developing pancreatitis, compared with the general population

Tobacco smoking, high body mass index and the outcome after surgery : The role of intervention

The negative effects of smoking and obesity on public health are well-known. Despite this knowledge, the smoking-attributable morbidity and mortality is estimated to rise rapidly in the forthcoming years, and obesity has become an emerging worldwide epidemic. In the field of surgery, smokers and the obese constitute important risk groups, prone to develop postoperative complications, ranging from impaired wound healing to deadly cardiovascular and pulmonary events. Abstinence is known to halt the negative effects of smoking. However, the effect of preoperative smoking cessation on postoperative outcomes has only been investigated in a few randomised clinical trials, with differing results. Therefore, the efficacy remains uncertain. Similarly, interventions to reduce weight exist, but the effect of weight reduction on the outcome after planned surgery has not been investigated. The main focus of this thesis was to study the effect of preoperative smoking cessation on the risk of postoperative complications. A secondary aim was to shed light on the magnitude of impact that obesity has on the development of postoperative complications in elective surgery. Using the large nation-wide Swedish Construction Workers Cohort, the effect of smoking on the risk of postoperative complications in patients undergoing elective total hip replacement (THR) or open appendectomy (OA) was evaluated. By record linkage, 3,309 male construction workers, who underwent THR between 1971 and 2002, were identified. After controlling for confounders, heavy smoking (>40 pack-years) increased the risk of systemic complications by 121% (Odds ratio (OR) =2.21, 95% Confidence Interval [CI]: 1.28 - 3.82) compared to never-smoking. Being obese (≥30 kg/m2) increased this risk by 58% (OR=1.58, 95% CI: 1.06 - 2.35) compared to those of normal weight (18.0-24.9 kg/m2) and also prolonged hospital stay. Neither smoking nor obesity was significantly associated with increased risk of local complications. There was no effect of smoking on the risk of implant dislocation up to eight years after THR. However, high weight increased the risk of implant dislocation within three years after surgery. Overweight (BMI ≥25 kg/m2) increased this risk by 150% (Hazard ratio (HR) = 2.5, 95% CI: 1.1 - 5.5) and obesity increased this risk by 270% (HR = 3.7, 95% CI: 1.5 - 9.3) compared to those of normal weight. By record linkage, 6,676 male construction workers who underwent OA for acute appendicitis between 1971 and 2004 were identified. Current smokers with more than 10 pack-years of smoking had 29% (RR= 1.29; 95 % CI: 1.11 - 1.50) increased risk of perforated appendicitis (PA) compared to never-smokers. Moreover, in patients with non-perforated appendicitis, current smoking with more than 10 pack-years (RR= 1.51; 95% CI: 1.03 - 2.22) and obesity (RR=2.60; 95% CI: 1.71 - 3.95) were significantly associated with increased risk of overall complications compared to never-smokers and those of normal weight, respectively. There was no significant association between obesity, smoking and overall complications in patients with PA. This was probably due to the high baseline complication frequency, which reduced the risk difference between the subgroups. In a smoking cessation intervention, 117 patients undergoing elective orthopaedic and general surgery were randomised to intervention (N=55) or control (N=62). Between March 2004 and December 2006, 102 patients, 48 in the intervention group and 52 in control group completed the trial. The intervention group underwent an intensive smoking cessation programme, on average 4 (2 - 7) weeks before surgery, with weekly meetings or phone calls, and was provided with free nicotine replacement therapy. The control group received standard care. According to intention to treat analysis, the risk of postoperative complications was reduced from 30/62 (48%) in the control group to 17/55 (31%) in the intervention group, resulting in a 37% (RR=0.63, 95% CI: 0.40 - 1.02) relative risk reduction. Based on this clinical effect, it was concluded that preoperative smoking cessation, initiated as late as four weeks before surgery, could efficiently be used to reduce the risk of postoperative complications after elective orthopaedic and general surgery

Acute Pancreatitis – Beyond Gallstones and Alcohol

Acute pancreatitis is the most common disorder of the pancreas. The incidence of the disease has increased markedly during the past decades. Whilst alcohol abuse and gallstone disease might explain a large proportion of the disease etiology, in one quarter of the patients, the cause remains unknown. Life-style and pharmaceutical drug use are potential risk factors for the disease. This brief review highlights the recent research on the role of these factors in the etiology of acute pancreatitis.</jats:p

Acute Pancreatitis – Beyond Gallstones and Alcohol

Acute pancreatitis is the most common disorder of the pancreas. The incidence of the disease has increased markedly during the past decades. Whilst alcohol abuse and gallstone disease might explain a large proportion of the disease etiology, in one quarter of the patients, the cause remains unknown. Life-style and pharmaceutical drug use are potential risk factors for the disease. This brief review highlights the recent research on the role of these factors in the etiology of acute pancreatitis

Pattern of increasing HbA 1c

Background. Diabetes mellitus is a risk factor for pancreatic cancer. Impaired insulin resistance might precede the clinical detection of this cancer by several years. Methods. This was a nested case-control population-based study assessing the pattern of glycated hemoglobin (HbA(1c)) change before clinical detection of pancreatic cancer in a population of individuals with diabetes mellitus. All patients registered in the Swedish National Diabetes Register with a prescription of an anti-diabetic drug between 2005 and 2011 were identified. For each case of pancreatic cancer, 10 controls were randomly selected, matched for age, sex, and factors related to diabetes mellitus. Multivariable conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between HbA(1c) and pancreatic cancer. Results. In total, 391 cases and 3910 matched controls were identified. The risk of pancreatic cancer was increased more than two-fold in individuals with the highest HbA(1c) quartile compared with the lowest (OR 1.96, 95% CI 1.40-2.75). The risk of pancreatic cancer remained elevated when comparing the highest HbA(1c) quartile measured within five years from the clinical detection of pancreatic cancer to the lowest HbA(1c) quartile (p-value for trend &lt; 0.05). No association was found between HbA(1c) and pancreatic cancer if HbA(1c) was measured &gt; 5 years before the clinical detection of pancreatic cancer. Conclusions. The pattern of increasing HbA(1c) in patients with diabetes mellitus preceded the clinical detection of pancreatic cancer by up to five years. These findings indicate that there is a lead time of several years during which the development of pancreatic cancer might be detectable through screening in patients with diabetes mellitus.</p