The very high incidence of oesophageal squamous cell carcinoma (ESCC) in Golestan Province in northeastern Iran was suggested by studies in the 1970s as partly due to opium use, which is not uncommon in this area, but based on limited numbers. From December 2003 to June 2007, we administered a validated structured questionnaire to 300 ESCC cases and 571 controls, matched on neighbourhood of residence, age (±2 years), and sex. We used conditional logistic regression models to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs) adjusted for potential confounders. Compared with those who used neither tobacco nor opium, risk of ESCC was increased in those who used tobacco only (OR, 95% CI: 1.70, 1.05 -2.73), in those who used opium only (2.12, 1.21 -3.74), and in those who used both tobacco and opium (2.35, 1.50 -3.67). All forms of tobacco use (cigarettes, hookah, and nass) were associated with higher ESCC risk. Similarly, use of both crude opium and other forms of opium were associated with higher risk. Alcohol consumption was seen in only 2% of the cases and 2% of the controls, and was not associated with ESCC risk.

Background Worldwide, both the incidence and death rates of pancreatic cancer are increasing. Evaluation of pancreatic cancer burden and its global, regional, and national patterns is crucial to policy making and better resource allocation for controlling pancreatic cancer risk factors, developing early detection methods, and providing faster and more effective treatments. Methods Vital registration, vital registration sample, and cancer registry data were used to generate mortality, incidence, and disability-adjusted life-years (DALYs) estimates. We used the comparative risk assessment framework to estimate the proportion of deaths attributable to risk factors for pancreatic cancer: smoking, high fasting plasma glucose, and high body-mass index. All of the estimates were reported as counts and age-standardised rates per 100 000 person-years. 95% uncertainty intervals (UIs) were reported for all estimates. Findings In 2017, there were 448 000 (95% UI 439 000-456 000) incident cases of pancreatic cancer globally, of which 232 000 (210 000-221 000; 51•9%) were in males. The age-standardised incidence rate was 5•0 (4•9-5•1) per 100 000 person-years in 1990 and increased to 5•7 (5•6-5•8) per 100 000 person-years in 2017. There was a 2•3 times increase in number of deaths for both sexes from 196 000 (193 000-200 000) in 1990 to 441 000 (433 000-449 000) in 2017. There was a 2•1 times increase in DALYs due to pancreatic cancer, increasing from 4•4 million (4•3-4•5) in 1990 to 9•1 million (8•9-9•3) in 2017. The age-standardised death rate of pancreatic cancer was highest in the highincome super-region across all years from 1990 to 2017. In 2017, the highest age-standardised death rates were observed in Greenland (17•4 [15•8-19•0] per 100 000 person-years) and Uruguay (12•1 [10•9-13•5] per 100 000 personyears). These countries also had the highest age-standardised death rates in 1990. Bangladesh (1•9 [1•5-2•3] per 100 000 person-years) had the lowest rate in 2017, and São Tomé and Príncipe (1•3 [1•1-1•5] per 100 000 personyears) had the lowest rate in 1990. The numbers of incident cases and deaths peaked at the ages of 65-69 years for males and at 75-79 years for females. Age-standardised pancreatic cancer deaths worldwide were primarily attributable to smoking (21•1% [18•8-23•7]), high fasting plasma glucose (8•9% [2•1-19•4]), and high body-mass index (6•2% [2•5-11•4]) in 2017. Interpretation Globally, the number of deaths, incident cases, and DALYs caused by pancreatic cancer has more than doubled from 1990 to 2017. The increase in incidence of pancreatic cancer is likely to continue as the population ages. Prevention strategies should focus on modifiable risk factors. Development of screening programmes for early detection and more effective treatment strategies for pancreatic cancer are needed. Funding Bill & Melinda Gates Foundation.

This trial shows that rectal indomethacin given immediately before ERCP can reduce the incidence and severity of post-ERCP pancreatitis.

Previous studies have shown that oesophageal and gastric cancers are the most common causes of cancer death in the Golestan Province, Iran. In 2001, we established Atrak Clinic, a referral clinic for gastrointestinal (GI) diseases in Gonbad, the major city of eastern Golestan, which has permitted, for the first time in this region, endoscopic localisation and histologic examination of upper GI cancers. Among the initial 682 patients seen at Atrak Clinic, 370 were confirmed histologically to have cancer, including 223 (60%) oesophageal squamous cell cancers (ESCC), 22 (6%) oesophageal adenocarcinomas (EAC), 58 (16%) gastric cardia adenocarcinomas (GCA), and 58 (16%) gastric noncardia adenocarcinomas. The proportional occurrence of these four main site-cell type subdivisions of upper GI cancers in Golestan is similar to that seen in Linxian, China, another area of high ESCC incidence, and is markedly different from the current proportions in many Western countries. Questioning of patients about exposure to some known and suspected risk factors for squamous cell oesophageal cancer confirmed a negligible history of consumption of alcohol, little use of cigarettes or nass (tobacco, lime and ash), and a low intake of opium, suggesting that the high rates of ESCC seen in northeastern Iran must have other important risk factors that remain speculative or unknown. Further studies are needed to define more precisely the patterns of upper GI cancer incidence, to test other previously suspected risk factors, and to find new significant risk factors in this high-risk area.

Background: The eradication of Helicobacter pylori plays a pivotal role in the treatment of peptic ulcer disease. Metronidazole resistance, common in Iran, is claimed to be a major reason for the failure of metronidazole‐containing regimens. Both clarithromycin and furazolidone are potential alternatives for metronidazole. Aim: To assess and compare the effectiveness of clarithromycin‐ and furazolidone‐based regimens in eradicating H. pylori in a population with a high metronidazole resistance rate. Methods: Patients with proven duodenal ulcer and H. pylori infection were randomly assigned to one of two groups. The patients received 2 weeks of omeprazole 20 mg b.d., amoxicillin 1000 mg b.d, bismuth subcitrate 240 mg b.d. and either clarithromycin 500 mg b.d. (the OABC group) or furazolidone 200 mg b.d. (the OABF group). Results: A total of 118 patients were randomized, 55 in the OABC group and 63 in the OABF group. The intention‐to‐treat eradication rate was 84% and 85% for the OABF and OABC groups, respectively. The per protocol eradication rates were 90% for both groups. Conclusions: OABC and OABF are both effective in eradicating H. pylori in areas where metronidazole resistance is a problem. OABF is a good alternative in the face of growing resistance to clarithromycin in developed countries, and is attractive for developing countries where clarithromycin is not readily available.

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Background Acute pancreatitis is a serious complication of endoscopic retrograde cholangiopancreatography (ERCP). The aim of this noninferiority study was to evaluate the effectiveness of pancreatic duct (PD) stenting plus pharmacological prophylaxis vs. pharmacological prophylaxis alone in the prevention of post-ERCP pancreatitis (PEP) in high risk patients. Methods In this randomized, controlled, double-blind, noninferiority trial, patients at high risk of developing PEP were randomly allocated to pharmacological prophylaxis (rectal indomethacin, sublingual isosorbide dinitrate, and intravenous hydration with Ringer’s lactate) plus PD stenting (group A) or pharmacological prophylaxis alone (group B). The rate and severity of PEP, serum amylase levels, and length of hospital stay after ERCP were assessed. Results During 21 months, a total of 414 patients (mean age 55.5 ± 17.0 years; 60.2 % female) were enrolled (207 in each group). PEP occurred in 59 patients (14.3 %, 95 % confidence interval [CI] 11.1 % – 17.9 %: 26 patients [12.6 %, 95 %CI 8.6 % – 17.6 %] in group A and 33 [15.9 %, 95 %CI 11.4 % – 21.4 %] in group B). There was no significant difference between the two groups in PEP severity (P = 0.59), amylase levels after 2 hours (P = 0.31) or 24 hours (P = 0.08), and length of hospital stay (P = 0.07). Conclusions The study failed to demonstrate noninferiority or inferiority of pharmacological prophylaxis alone compared with PD stenting plus pharmacological prophylaxis in the prevention of PEP in high risk patients.

Combination of rectal indomethacin and sublingual nitrate given before ERCP was significantly more likely to reduce the incidence of PEP than indomethacin suppository alone. Multicenter trials to confirm these promising findings are needed.