Calcium and vitamin D supplementation and increased risk of serrated polyps: results from a randomised clinical trial.
Crockett Seth D,Barry Elizabeth L,Mott Leila A,Ahnen Dennis J,Robertson Douglas J,Anderson Joseph C,Wallace Kristen,Burke Carol A,Bresalier Robert S,Figueiredo Jane C,Snover Dale C,Baron John A
OBJECTIVE:Serrated lesions such as sessile serrated adenomas or polyps (SSA/Ps) are important colorectal cancer precursors, but aetiological factors for these lesions are largely unknown. We aimed to determine the effects of calcium and vitamin D supplementation on the incidence of serrated polyps (SPs) in general and hyperplastic polyps and SSA/Ps specifically. DESIGN:Participants with one or more adenoma at baseline were randomised to receive 1200 mg/day of elemental calcium, 1000 IU/day of vitamin D, both or neither agent. Treatment continued for 3 or 5 years, when risk of polyps was determined from surveillance colonoscopy (treatment phase). Outcomes after treatment ceased were also assessed (observational phase). Adjusted risk ratios (aRRs) of SPs were determined via multivariable generalised linear models. RESULTS:SPs were diagnosed in 565 of 2058 (27.5%) participants during the treatment phase and 329/1108 (29.7%) during the observational phase. In total, 211 SSA/Ps were identified during follow-up. In the treatment phase, there was no effect of either calcium or vitamin D on incidence of SSA/Ps. However, during the later observational phase, we observed elevated risks of SSA/Ps associated with calcium alone and calcium+vitamin D treatment (aRR (95% CI): 2.65 (1.43 to 4.91) and 3.81 (1.25 to 11.64), respectively). CONCLUSION:In a large multicentre chemoprevention study, we found evidence that calcium and vitamin D supplementation increased the risk of SSA/Ps. This appeared to be a late effect: 6-10 years after supplementation began. These possible risks must be weighed against the benefits of calcium and vitamin D supplementation. : NUMBER: NCT00153816; Results.
Severity of gastric intestinal metaplasia predicts the risk of gastric cancer: a prospective multicentre cohort study (GCEP).
OBJECTIVE:To investigate the incidence of gastric cancer (GC) attributed to gastric intestinal metaplasia (IM), and validate the Operative Link on Gastric Intestinal Metaplasia (OLGIM) for targeted endoscopic surveillance in regions with low-intermediate incidence of GC. METHODS:A prospective, longitudinal and multicentre study was carried out in Singapore. The study participants comprised 2980 patients undergoing screening gastroscopy with standardised gastric mucosal sampling, from January 2004 and December 2010, with scheduled surveillance endoscopies at year 3 and 5. Participants were also matched against the National Registry of Diseases Office for missed diagnoses of early gastric neoplasia (EGN). RESULTS:There were 21 participants diagnosed with EGN. IM was a significant risk factor for EGN (adjusted-HR 5.36; 95% CI 1.51 to 19.0; p<0.01). The age-adjusted EGN incidence rates for patients with and without IM were 133.9 and 12.5 per 100 000 person-years. Participants with OLGIM stages III-IV were at greatest risk (adjusted-HR 20.7; 95% CI 5.04 to 85.6; p<0.01). More than half of the EGNs (n=4/7) attributed to baseline OLGIM III-IV developed within 2 years (range: 12.7-44.8 months). Serum trefoil factor 3 distinguishes (Area Under the Receiver Operating Characteristics 0.749) patients with OLGIM III-IV if they are negative for . Participants with OLGIM II were also at significant risk of EGN (adjusted-HR 7.34; 95% CI 1.60 to 33.7; p=0.02). A significant smoking history further increases the risk of EGN among patients with OLGIM stages II-IV. CONCLUSIONS:We suggest a risk-stratified approach and recommend that high-risk patients (OLGIM III-IV) have endoscopic surveillance in 2 years, intermediate-risk patients (OLGIM II) in 5 years.
The Colombian Chemoprevention Trial: 20-Year Follow-Up of a Cohort of Patients With Gastric Precancerous Lesions.
Piazuelo M Blanca,Bravo Luis E,Mera Robertino M,Camargo M Constanza,Bravo Juan C,Delgado Alberto G,Washington M Kay,Rosero Alicia,Garcia Luz S,Realpe Jose L,Cifuentes Sandra P,Morgan Douglas R,Peek Richard M,Correa Pelayo,Wilson Keith T
BACKGROUND & AIMS:Helicobacter pylori eradication and endoscopic surveillance of gastric precancerous lesions are strategies to reduce gastric cancer (GC) risk. To our knowledge, this study is the longest prospective cohort of an H pylori eradication trial in a Hispanic population. METHODS:A total of 800 adults with precancerous lesions were randomized to anti-H pylori treatment or placebo. Gastric biopsy samples taken at baseline and 3, 6, 12, 16, and 20 years were assessed by our Correa histopathology score. A generalized linear mixed model with a participant-level random intercept was used to estimate the effect of H pylori status on the score over time. Logistic regression models were used to estimate progression by baseline diagnosis and to estimate GC risk by intestinal metaplasia (IM) subtype and anatomic location. RESULTS:Overall, 356 individuals completed 20 years of follow-up. Anti-H pylori therapy (intention-to-treat) reduced progression of the Correa score (odds ratio [OR], 0.59; 95% confidence interval [CI], 0.38-0.93). H pylori-negative status had a beneficial effect on the score over time (P = .036). Among individuals with IM (including indefinite for dysplasia) at baseline, incidence rates per 100 person-years were 1.09 (95% CI, 0.85-1.33) for low-grade/high-grade dysplasia and 0.14 (95% CI, 0.06-0.22) for GC. Incomplete-type (vs complete-type) IM at baseline presented higher GC risk (OR, 13.4; 95% CI, 1.8-103.8). Individuals with corpus (vs antrum-restricted) IM showed an OR of 2.1 (95% CI, 0.7-6.6) for GC. CONCLUSIONS:In a high-GC-risk Hispanic population, anti-H pylori therapy had a long-term beneficial effect against histologic progression. Incomplete IM is a strong predictor of GC risk.
Dynamics of infection as a determinant of progression of gastric precancerous lesions: 16-year follow-up of an eradication trial.
Mera Robertino M,Bravo Luis E,Camargo M Constanza,Bravo Juan C,Delgado Alberto G,Romero-Gallo Judith,Yepez Maria C,Realpe José L,Schneider Barbara G,Morgan Douglas R,Peek Richard M,Correa Pelayo,Wilson Keith T,Piazuelo M Blanca
OBJECTIVE:To evaluate the long-term effect of cumulative time exposed to infection on the progression of gastric lesions. DESIGN:795 adults with precancerous gastric lesions were randomised to receive anti- treatment at baseline. Gastric biopsies were obtained at baseline and at 3, 6, 12 and 16 years. A total of 456 individuals attended the 16-year visit. Cumulative time of exposure was calculated as the number of years infected during follow-up. Multivariable logistic regression models were used to estimate the risk of progression to a more advanced diagnosis (versus no change/regression) as well as gastric cancer risk by intestinal metaplasia (IM) subtype. For a more detailed analysis of progression, we also used a histopathology score assessing both severity and extension of the gastric lesions (range 1-6). The score difference between baseline and 16 years was modelled by generalised linear models. RESULTS:Individuals who were continuously infected with for 16 years had a higher probability of progression to a more advanced diagnosis than those who cleared the infection and remained negative after baseline (p=0.001). Incomplete-type IM was associated with higher risk of progression to cancer than complete-type (OR, 11.3; 95% CI 1.4 to 91.4). The average histopathology score increased by 0.20 units/year (95% CI 0.12 to 0.28) among individuals continuously infected with . The effect of cumulative time of infection on progression in the histopathology score was significantly higher for individuals with atrophy (without IM) than for individuals with IM (p<0.001). CONCLUSIONS:Long-term exposure to infection was associated with progression of precancerous lesions. Individuals infected with with these lesions may benefit from eradication, particularly those with atrophic gastritis without IM. Incomplete-type IM may be a useful marker for the identification of individuals at higher risk for cancer.
Effects of treatment and vitamin and garlic supplementation on gastric cancer incidence and mortality: follow-up of a randomized intervention trial.
Li Wen-Qing,Zhang Jing-Yu,Ma Jun-Ling,Li Zhe-Xuan,Zhang Lian,Zhang Yang,Guo Yang,Zhou Tong,Li Ji-You,Shen Lin,Liu Wei-Dong,Han Zhong-Xiang,Blot William J,Gail Mitchell H,Pan Kai-Feng,You Wei-Cheng
BMJ (Clinical research ed.)
OBJECTIVE:To assess the effects of treatment, vitamin supplementation, and garlic supplementation in the prevention of gastric cancer. DESIGN:Blinded randomized placebo controlled trial. SETTING:Linqu County, Shandong province, China. PARTICIPANTS:3365 residents of a high risk region for gastric cancer. 2258 participants seropositive for antibodies to were randomly assigned to treatment, vitamin supplementation, garlic supplementation, or their placebos in a 2×2×2 factorial design, and 1107 seronegative participants were randomly assigned to vitamin supplementation, garlic supplementation, or their placebos in a 2×2 factorial design. INTERVENTIONS: treatment with amoxicillin and omeprazole for two weeks; vitamin (C, E, and selenium) and garlic (extract and oil) supplementation for 7.3 years (1995-2003). MAIN OUTCOME MEASURES:Primary outcomes were cumulative incidence of gastric cancer identified through scheduled gastroscopies and active clinical follow-up through 2017, and deaths due to gastric cancer ascertained from death certificates and hospital records. Secondary outcomes were associations with other cause specific deaths, including cancers or cardiovascular disease. RESULTS:151 incident cases of gastric cancer and 94 deaths from gastric cancer were identified during 1995-2017. A protective effect of treatment on gastric cancer incidence persisted 22 years post-intervention (odds ratio 0.48, 95% confidence interval 0.32 to 0.71). Incidence decreased significantly with vitamin supplementation but not with garlic supplementation (0.64, 0.46 to 0.91 and 0.81, 0.57 to 1.13, respectively). All three interventions showed significant reductions in gastric cancer mortality: fully adjusted hazard ratio for treatment was 0.62 (95% confidence interval 0.39 to 0.99), for vitamin supplementation was 0.48 (0.31 to 0.75), and for garlic supplementation was 0.66 (0.43 to 1.00). Effects of treatment on both gastric cancer incidence and mortality and of vitamin supplementation on gastric cancer mortality appeared early, but the effects of vitamin supplementation on gastric cancer incidence and of garlic supplementation only appeared later. No statistically significant associations were found between interventions and other cancers or cardiovascular disease. CONCLUSIONS: treatment for two weeks and vitamin or garlic supplementation for seven years were associated with a statistically significant reduced risk of death due to gastric cancer for more than 22 years. treatment and vitamin supplementation were also associated with a statistically significantly reduced incidence of gastric cancer. TRIAL REGISTRATION:ClinicalTrials.gov NCT00339768.
Fecal Signatures of Streptococcus anginosus and Streptococcus constellatus for Noninvasive Screening and Early Warning of Gastric Cancer.
BACKGROUND & AIMS:Most patients with gastric cancer (GCa) are diagnosed at an advanced stage. We aimed to investigate novel fecal signatures for clinical application in early diagnosis of GCa. METHODS:This was an observational study that included 1043 patients from 10 hospitals in China. In the discovery cohort, 16S ribosomal RNA gene analysis was performed in paired samples (tissues and feces) from patients with GCa and chronic gastritis (ChG) to determine differential abundant microbes. Their relative abundances were detected using quantitative real-time polymerase chain reaction to test them as bacterial candidates in the training cohort. Their diagnostic efficacy was validated in the validation cohort. RESULTS:Significant enrichments of Streptococcus anginosus (Sa) and Streptococcus constellatus (Sc) in GCa tumor tissues (P < .05) and feces (P < .0001) were observed in patients with intraepithelial neoplasia, early and advanced GCa. Either the signature parallel test Sa∪Sc or single signature Sa/Sc demonstrated superior sensitivity (Sa: 75.6% vs 72.1%, P < .05; Sc: 84.4% vs 64.0%, P < .001; and Sa∪Sc: 91.1% vs 81.4%, P < .01) in detecting early GCa compared with advanced GCa (specificity: Sa: 84.0% vs 83.9%, Sc: 70.4% vs 82.3%, and Sa∪Sc: 64.0% vs 73.4%). Fecal signature Sa∪Sc outperformed Sa∪CEA/Sc∪CEA in the discrimination of advanced GCa (sensitivity: 81.4% vs 74.2% and 81.4% vs 72.3%, P < .01; specificity: 73.4% vs 81.0 % and 73.4% vs 81.0%). The performance of Sa∪Sc in the diagnosis of both early and advanced GCa was verified in the validation cohort. CONCLUSION:Fecal Sa and Sc are noninvasive, accurate, and sensitive signatures for early warning in GCa. (ClinicalTrials.gov, Number: NCT04638959).
Prediction model of bleeding after endoscopic submucosal dissection for early gastric cancer: BEST-J score.
Hatta Waku,Tsuji Yosuke,Yoshio Toshiyuki,Kakushima Naomi,Hoteya Shu,Doyama Hisashi,Nagami Yasuaki,Hikichi Takuto,Kobayashi Masakuni,Morita Yoshinori,Sumiyoshi Tetsuya,Iguchi Mikitaka,Tomida Hideomi,Inoue Takuya,Koike Tomoyuki,Mikami Tatsuya,Hasatani Kenkei,Nishikawa Jun,Matsumura Tomoaki,Nebiki Hiroko,Nakamatsu Dai,Ohnita Ken,Suzuki Haruhisa,Ueyama Hiroya,Hayashi Yoshito,Sugimoto Mitsushige,Yamaguchi Shinjiro,Michida Tomoki,Yada Tomoyuki,Asahina Yoshiro,Narasaka Toshiaki,Kuribasyashi Shiko,Kiyotoki Shu,Mabe Katsuhiro,Nakamura Tomohiro,Nakaya Naoki,Fujishiro Mitsuhiro,Masamune Atsushi
OBJECTIVE:Bleeding after endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) is a frequent adverse event after ESD. We aimed to develop and externally validate a clinically useful prediction model (BEST-J score: Bleeding after ESD Trend from Japan) for bleeding after ESD for EGC. DESIGN:This retrospective study enrolled patients who underwent ESD for EGC. Patients in the derivation cohort (n=8291) were recruited from 25 institutions, and patients in the external validation cohort (n=2029) were recruited from eight institutions in other areas. In the derivation cohort, weighted points were assigned to predictors of bleeding determined in the multivariate logistic regression analysis and a prediction model was established. External validation of the model was conducted to analyse discrimination and calibration. RESULTS:A prediction model comprised 10 variables (warfarin, direct oral anticoagulant, chronic kidney disease with haemodialysis, P2Y12 receptor antagonist, aspirin, cilostazol, tumour size >30 mm, lower-third in tumour location, presence of multiple tumours and interruption of each kind of antithrombotic agents). The rates of bleeding after ESD at low-risk (0 to 1 points), intermediate-risk (2 points), high-risk (3 to 4 points) and very high-risk (≥5 points) were 2.8%, 6.1%, 11.4% and 29.7%, respectively. In the external validation cohort, the model showed moderately good discrimination, with a -statistic of 0.70 (95% CI, 0.64 to 0.76), and good calibration (calibration-in-the-large, 0.05; calibration slope, 1.01). CONCLUSIONS:In this nationwide multicentre study, we derived and externally validated a prediction model for bleeding after ESD. This model may be a good clinical decision-making support tool for ESD in patients with EGC.