Huan Song

Incidence of gastric cancer among patients with gastric precancerous lesions: observational cohort study in a low risk Western population

Objective To accurately measure the incidence of gastric cancer among patients with gastric precancerous lesions, and to quantify the excess incidence in comparison with people with normal mucosa on endoscopy and a general population. Design Population based cohort study. Setting Population of Sweden using data from its national disease registers. Participants 405u2009172 patients who had gastric biopsy samples taken for non-malignant indications between 1979 and 2011. Main outcome measures Incidence of gastric cancer, reported separately for patients with different mucosal changes in biopsy samples. Standardised incidence ratios provided estimation of the relative risk, using the general Swedish population as reference; and hazard ratios were derived from Cox regression modelling for internal comparisons with patients with normal gastric mucosa. Results After excluding the first two years of follow-up, 1599 cases of gastric cancer were identified. The annual crude incidence of gastric cancer was 20×10−5 for those in the normal mucosa group (standardised incidence ratio 1.0), 42×10−5 for those with minor changes (1.5), 59×10−5 for the gastritis group (1.8), 100×10−5 for the atrophic gastritis group (2.8), 129×10−5 for the intestinal metaplasia group (3.4), and 263×10−5 for the dysplasia group (6.5). Cox regression modelling confirmed that excess risks increased monotonically with progressive severity of gastric lesions, with the highest hazard ratio of 10.9 (dysplasia versus normal mucosa, 95% confidence interval 7.7 to 15.4). The increased incidence was stable throughout the follow-up period, and the gaps between cumulative incidence curves grew continuously. Conclusions Among patients who undergo gastroscopy with biopsy for clinical indications, approximately 1 in 256 with normal mucosa, 1 in 85 with gastritis, 1 in 50 with atrophic gastritis, 1 in 39 with intestinal metaplasia, and 1 in 19 with dysplasia will develop gastric cancer within 20 years. These numbers, along with cost-benefit analyses, should guide future surveillance policies for these particular patient groups.

A CagA‐independent cluster of antigens related to the risk of noncardia gastric cancer: Associations between Helicobacter pylori antibodies and gastric adenocarcinoma explored by multiplex serology

Because of the differences in bacterial epitopes and host characteristics, infections with Helicobacter pylori (H. pylori) induce different immune responses. We explored the possibility that certain antibody response patterns are more closely linked to gastric adenocarcinoma (GAC) than others. In a Swedish population‐based case‐control study, serum samples were obtained from 268 cases and 222 controls, aged 40–79 years and frequency‐matched according to age and sex. We measured antibodies against 17 H. pylori proteins using multiplex serology. Associations were estimated with multivariably adjusted logistic regression models, using odds ratio (OR) with 95% confidence interval (CI) as measures of relative risk. Associations were essentially confined to non‐cardia GAC but did not differ significantly between intestinal and diffuse subtypes. Point estimates for all antibodies were above unity, 15 significant with top three being CagA (ORu2009=u20099.2), GroEL (6.6), HyuA (3.6). ORs were substantially attenuated in individuals with chronic atrophic gastritis. Principal component analysis identified two significant factors: a CagA‐dominant factor (antibodies against CagA, VacA and Omp as prominent markers), and a non‐CagA factor (antibodies against NapA and Catalase as prominent markers). Both factors showed dose‐dependent associations with non‐cardia GAC risk (CagA‐dominant factor, highest vs. lowest quartiles, ORu2009=u200916.2 [95% CI 4.8–54.9]; non‐CagA factor ORu2009=u20095.3 [95% CI 2.1–13.3]). Overall, our results confirm that serum antibodies against different H. pylori proteins are associated with the presence of non‐cardia GAC. Although strongest association is detected by antibodies against CagA and covarying proteins, a pattern of antibodies unrelated to CagA is also significantly linked to the risk of non‐cardia GAC.

Increase in the Prevalence of Atrophic Gastritis Among Adults Age 35 to 44 Years Old in Northern Sweden Between 1990 and 2009

BACKGROUND & AIMSnAtrophic corpus gastritis (ACG) is believed to be an early precursor of gastric adenocarcinoma. We aimed to investigate trends of ACG in Northern Sweden, from 1990 through 2009, and to identify possible risk factors.nnnMETHODSnWe randomly selected serum samples collected from 5284 participants in 1990, 1994, 1999, 2004, and 2009, as part of the population-based, cross-sectional Northern Sweden Multinational Monitoring of Trends and Determinants in Cardiovascular Disease study (ages, 35-64 y). Information was collected on sociodemographic, anthropometric, lifestyle, and medical factors using questionnaires. Serum samples were analyzed for levels of pepsinogen I to identify participants with functional ACG; data from participants with ACG were compared with those from frequency-matched individuals without ACG (controls). Blood samples were analyzed for antibodies against Helicobacter pylori and Cag pathogenicity island protein A. Associations were estimated with unconditional logistic regression models.nnnRESULTSnOverall, 305 subjects tested positive for functional ACG, based on their level of pepsinogen I. The prevalence of ACG in participants age 55 to 64 years old decreased from 124 per 1000 to 49 per 1000 individuals between 1990 and 2009. However, the prevalence of ACG increased from 22 per 1000 to 64 per 1000 individuals among participants age 35 to 44 years old during this time period. Cag pathogenicity island protein A seropositivity was associated with risk for ACG (odds ratio, 2.29; 95% confidence interval, 1.69-3.12). Other risk factors included diabetes, low level of education, and high body mass index. The association between body mass index and ACG was confined to individuals age 35 to 44 years old; in this group, overweight and obesity were associated with a 2.8-fold and a 4.7-fold increased risk of ACG, respectively.nnnCONCLUSIONSnAmong residents of Northern Sweden, the prevalence of ACG increased from 1990 through 2009, specifically among adults age 35 to 44 years old. The stabilizing seroprevalence of H pylori and the increasing prevalence of overweight and obesity might contribute to this unexpected trend. Studies are needed to determine whether these changes have affected the incidence of gastric cancer.

Cigarette smoking and gastric cancer in the Stomach Cancer Pooling (StoP) Project.

Tobacco smoking is a known cause of gastric cancer, but several aspects of the association remain imprecisely quantified. We examined the relation between cigarette smoking and the risk of gastric cancer using a uniquely large dataset of 23 epidemiological studies within the ‘Stomach cancer Pooling (StoP) Project’, including 10u2009290 cases and 26u2009145 controls. We estimated summary odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) by pooling study-specific ORs using random-effects models. Compared with never smokers, the ORs were 1.20 (95% CI: 1.09–1.32) for ever, 1.12 (95% CI: 0.99–1.27) for former, and 1.25 (95% CI: 1.11–1.40) for current cigarette smokers. Among current smokers, the risk increased with number of cigarettes per day to reach an OR of 1.32 (95% CI: 1.10–1.58) for smokers of more than 20 cigarettes per day. The risk increased with duration of smoking, to reach an OR of 1.33 (95% CI: 1.14–1.54) for more than 40 years of smoking and decreased with increasing time since stopping cigarette smoking (P for trend<0.01) and became similar to that of never smokers 10 years after stopping. Risks were somewhat higher for cardia than noncardia gastric cancer. Risks were similar when considering only studies with information on Helicobacter pylori infection and comparing all cases to H. pylori+ controls only. This study provides the most precise estimate of the detrimental effect of cigarette smoking on the risk of gastric cancer on the basis of individual data, including the relationship with dose and duration, and the decrease in risk following stopping smoking.

Treatment of esophageal anastomotic leakage with self-expanding metal stents: analysis of risk factors for treatment failure

Background and study aim: The endoscopic placement of self-expandable metallic esophageal stents (SEMS) has become the preferred primary treatment for esophageal anastomotic leakage in many institutions. The aim of this study was to investigate possible risk factors for failure of SEMS-based therapy in patients with esophageal anastomotic leakage. Patients and methods: Beginning in 2003, all patients with an esophageal leak were initially approached and assessed for temporary closure with a SEMS.u200aUntil 2014, all patients at the Karolinska University Hospital with a leak from an esophagogastric or esophagojejunal anastomosis were identified. Data regarding the characteristics of the patients and leaks and the treatment outcomes were compiled. Failure of the SEMS treatment strategy was defined as death due to the leak or a major change in management strategy. The risk factors for treatment failure were analyzed with simple and multivariable logistic regression statistics. Results: A total of 447 patients with an esophagogastric or esophagojejunal anastomosis were identified. Of these patients, 80 (18u200a%) had an anastomotic leak, of whom 46 (58u200a%) received a stent as first-line treatment. In 29 of these 46 patients, the leak healed without any major change in treatment strategy. Continuous leakage after the application of a stent, decreased physical performance preoperatively, and concomitant esophagotracheal fistula were identified as independent risk factors for failure with multivariable logistic regression analysis. Conclusion: Stent treatment for esophageal anastomotic leakage is successful in the majority of cases. Continuous leakage after initial stent insertion, decreased physical performance preoperatively, and the development of an esophagotracheal fistula decrease the probability of successful treatment.

Tonsillectomy and Incidence of Oropharyngeal Cancers

Background: Rising incidence of oropharyngeal cancers in numerous countries since the 1970s has been attributed to increased oral human papillomavirus (HPV) exposure. However, the contribution of coincidental declines in the surgical removal of the tonsils (tonsillectomy) is unknown. We quantified the association of tonsillectomy with risk of tonsillar, other oropharyngeal, and other head and neck cancers and the contribution of declines in tonsillectomies to cancer incidence trends. Methods: We conducted a nation-wide cohort study in Sweden (1970–2009). Tonsillectomies (N = 225,718) were identified through national patient registers, which were linked with the cancer register. Cancer incidence in the tonsillectomy cohort was compared with Swedens general population through standardized incidence ratios (SIR). Results: Tonsillectomies were associated with reduced risk of tonsil cancers [SIRs 1+ years post-tonsillectomy = 0.31; 95% confidence interval (CI), 0.08–0.79 and 5+ years post-tonsillectomy = 0.17; 95% CI, 0.02–0.62], but unrelated to other oropharyngeal or other head and neck cancers (SIRs 1+ years post-tonsillectomy = 1.61; 95% CI, 0.77–2.95 and 0.92; 95% CI, 0.64–1.27, respectively). The cumulative incidence of tonsillectomy declined significantly (40%–50%) during 1970–2009. However, tonsil cancer incidence significantly increased during 1970–2009 both without and with corrections for declines in tonsillectomies (relative risks per 5-year periods = 1.23, P < 0.001 and 1.20, P < 0.001, respectively). Conclusions: The reduced tonsil cancer risk with tonsillectomy reflects the removal of most of the relevant tissue. The absence of associations with other head and neck cancers indicates that tonsillectomy may not impact carcinogenesis at other sites. Impact: The significant increases in oropharyngeal cancer incidence since the 1970s in Sweden appear independent of declines in tonsillectomies, reinforcing increased oral HPV exposure as the likely cause. Cancer Epidemiol Biomarkers Prev; 25(6); 944–50. ©2016 AACR.

Alcohol consumption and gastric cancer risk—A pooled analysis within the StoP project consortium

An association between heavy alcohol drinking and gastric cancer risk has been recently reported, but the issue is still open to discussion and quantification. We investigated the role of alcohol drinking on gastric cancer risk in the “Stomach cancer Pooling (StoP) Project,” a consortium of epidemiological studies. A total of 9,669 cases and 25,336 controls from 20 studies from Europe, Asia and North America were included. We estimated summary odds‐ratios (ORs) and the corresponding 95% confidence intervals (CIs) by pooling study‐specific ORs using random‐effects meta‐regression models. Compared with abstainers, drinkers of up to 4 drinks/day of alcohol had no increase in gastric cancer risk, while the ORs were 1.26 (95% CI, 1.08–1.48) for heavy (>4 to 6 drinks/day) and 1.48 (95% CI 1.29–1.70) for very heavy (>6 drinks/day) drinkers. The risk for drinkers of >4 drinks/day was higher in never smokers (OR 1.87, 95% CI 1.35–2.58) as compared with current smokers (OR 1.14, 95% CI 0.93–1.40). Somewhat stronger associations emerged with heavy drinking in cardia (OR 1.61, 95% CI 1.11–2.34) than in non‐cardia (OR 1.28, 95% CI 1.13–1.45) gastric cancers, and in intestinal‐type (OR 1.54, 95% CI 1.20–1.97) than in diffuse‐type (OR 1.29, 95% CI 1.05–1.58) cancers. The association was similar in strata of H. pylori infected (ORu2009=u20091.52, 95% CI 1.16–2.00) and noninfected subjects (ORu2009=u20091.69, 95% CI 0.95–3.01). Our collaborative pooled‐analysis provides definite, more precise quantitative evidence than previously available of an association between heavy alcohol drinking and gastric cancer risk.

Risk of Gastrointestinal Cancers among Patients with Appendectomy: A Large-Scale Swedish Register-Based Cohort Study during 1970-2009.

Background Removal of the appendix might induce physiological changes in the gastrointestinal tract, and subsequently play a role in carcinogenesis. Therefore, we conducted a nationwide register-based cohort study in Sweden to investigate whether appendectomy is associated with altered risks of gastrointestinal cancers. Methods A population-based cohort study was conducted using the Swedish national registries, including 480,382 eligible patients followed during the period of 1970–2009 for the occurrence of site-specific gastrointestinal cancer (esophageal/gastric/colon/rectal cancer). Outcome and censoring information was collected by linkage to health and demography registers. We examined the incidence of appendectomy in Sweden using data from 1987–2009. We also calculated standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) to estimate the relative gastrointestinal cancer risk through comparison to the general population. Results We noted an overall decrease in the age-standardized incidence of appendectomy among the entire Swedish population from 189.3 to 105.6 per 100,000 individuals between 1987 and 2009. Grouped by different discharge diagnosis, acute appendicitis, incidental appendectomy, and entirely negative appendectomy continuously decreased over the study period, while the perforation ratio (18%–23%) stayed relatively constant. Compared to the general population, no excess cancer risk was observed for gastrointestinal cancers under study with the exception of a marginally elevated risk for esophageal adenocarcinoma (SIR 1.32, 95% CI 1.09–1.58). Conclusions In Sweden, the incidence of appendectomy and acute appendicitis has decreased during 1987–2009. No excess gastrointestinal cancer risks were observed among these appendectomized patients, with the possible exception of esophageal adenocarcinoma.

Association of Stress-Related Disorders With Subsequent Autoimmune Disease

Importance Psychiatric reactions to life stressors are common in the general population and may result in immune dysfunction. Whether such reactions contribute to the risk of autoimmune disease remains unclear. Objective To determine whether there is an association between stress-related disorders and subsequent autoimmune disease. Design, Setting, and Participants Population- and sibling-matched retrospective cohort study conducted in Sweden from January 1, 1981, to December 31, 2013. The cohort included 106 464 exposed patients with stress-related disorders, with 1 064 640 matched unexposed persons and 126 652 full siblings of these patients. Exposures Diagnosis of stress-related disorders, ie, posttraumatic stress disorder, acute stress reaction, adjustment disorder, and other stress reactions. Main Outcomes and Measures Stress-related disorder and autoimmune diseases were identified through the National Patient Register. The Cox model was used to estimate hazard ratios (HRs) with 95% CIs of 41 autoimmune diseases beyond 1 year after the diagnosis of stress-related disorders, controlling for multiple risk factors. Results The median age at diagnosis of stress-related disorders was 41 years (interquartile range, 33-50 years) and 40% of the exposed patients were male. During a mean follow-up of 10 years, the incidence rate of autoimmune diseases was 9.1, 6.0, and 6.5 per 1000 person-years among the exposed, matched unexposed, and sibling cohorts, respectively (absolute rate difference, 3.12 [95% CI, 2.99-3.25] and 2.49 [95% CI, 2.23-2.76] per 1000 person-years compared with the population- and sibling-based reference groups, respectively). Compared with the unexposed population, patients with stress-related disorders were at increased risk of autoimmune disease (HR, 1.36 [95% CI, 1.33-1.40]). The HRs for patients with posttraumatic stress disorder were 1.46 (95% CI, 1.32-1.61) for any and 2.29 (95% CI, 1.72-3.04) for multiple (≥3) autoimmune diseases. These associations were consistent in the sibling-based comparison. Relative risk elevations were more pronounced among younger patients (HR, 1.48 [95% CI, 1.42-1.55]; 1.41 [95% CI, 1.33-1.48]; 1.31 [95% CI, 1.24-1.37]; and 1.23 [95% CI, 1.17-1.30] for age at ⩽33, 34-41, 42-50, and ≥51 years, respectively; P for interactionu2009<u2009.001). Persistent use of selective serotonin reuptake inhibitors during the first year of posttraumatic stress disorder diagnosis was associated with attenuated relative risk of autoimmune disease (HR, 3.64 [95% CI, 2.00-6.62]; 2.65 [95% CI, 1.57-4.45]; and 1.82 [95% CI, 1.09-3.02] for duration ⩽179, 180-319, and ≥320 days, respectively; P for trendu2009=u2009.03). Conclusions and Relevance In this Swedish cohort, exposure to a stress-related disorder was significantly associated with increased risk of subsequent autoimmune disease, compared with matched unexposed individuals and with full siblings. Further studies are needed to better understand the underlying mechanisms.

Waiting time for cancer treatment and mental health among patients with newly diagnosed esophageal or gastric cancer: a nationwide cohort study

BackgroundExcept for overall survival, whether or not waiting time for treatment could influences other domains of cancer patients’ overall well-being is to a large extent unknown. Therefore, we performed this study to determine the effect of waiting time for cancer treatment on the mental health of patients with esophageal or gastric cancer.MethodsBased on the Swedish National Quality Register for Esophageal and Gastric Cancers (NREV), we followed 7,080 patients diagnosed 2006–2012 from the time of treatment decision. Waiting time for treatment was defined as the interval between diagnosis and treatment decision, and was classified into quartiles. Mental disorders were identified by either clinical diagnosis through hospital visit or prescription of psychiatric medications. For patients without any mental disorder before treatment, the association between waiting time and subsequent onset of mental disorders was assessed by hazard ratios (HRs) with 95% confidence interval (CI), derived from multivariable-adjusted Cox model. For patients with a preexisting mental disorder, we compared the rate of psychiatric care by different waiting times, allowing for repeated events.ResultsAmong 4,120 patients without any preexisting mental disorder, lower risk of new onset mental disorders was noted for patients with longer waiting times, i.e. 18–29 days (HR 0.86; 95% CI 0.74-1.00) and 30–60 days (HR 0.79; 95% CI 0.67-0.93) as compared with 9–17 days. Among 2,312 patients with preexisting mental disorders, longer waiting time was associated with more frequent psychiatric hospital care during the first year after treatment (37.5% higher rate per quartile increase in waiting time; p for trendu2009=u20090.0002). However, no such association was observed beyond one year nor for the prescription of psychiatric medications.ConclusionsThese data suggest that waiting time to treatment for esophageal or gastric cancer may have different mental health consequences for patients depending on their past psychiatric vulnerabilities. Our study sheds further light on the complexity of waiting time management, and calls for a comprehensive strategy that takes into account different domains of patient well-being in addition to the overall survival.