Decline of gastric cancer mortality in common variable immunodeficiency in the years 2018-2022

Introduction: In patients with Common Variable Immunodeficiency, malignancy has been reported as the leading cause of death in adults, with a high risk of B-cell lymphomas and gastric cancer.Methods: We conducted a five-year prospective study aiming to update the incidence and mortality of gastric cancer and the incidence of gastric precancerous lesions in 512 CVID patients who underwent a total of 400 upper gastrointestinal endoscopies.Results: In the pre-pandemic period, 0.58 endoscopies were performed per patient/year and in the COVID-19 period, 0.39 endoscopies were performed per patient/year. Histology revealed areas with precancerous lesions in about a third of patients. Patients who had more than one gastroscopy during the study period were more likely to have precancerous lesions. Two patients received a diagnosis of gastric cancer in the absence of Helicobacter pylori infection. The overall prevalence of Helicobacter pylori infection in biopsy specimens was 19.8% and related only to active gastritis. Among patients who had repeated gastroscopies, about 20% progressed to precancerous lesions, mostly independent of Helicobacter pylori.Discussion: While gastric cancer accounted for one in five deaths from CVID in our previous survey, no gastric cancer deaths were recorded in the past five years, likely consistent with the decline in stomach cancer mortality observed in the general population. However, during the COVID-19 pandemic, cancer screening has been delayed. Whether such a delay or true decline could be the reason for the lack of gastric cancer detection seen in CVID may become clear in the coming years. Due to the high incidence of precancerous lesions, we cannot rely on observed and predicted trends in gastric cancer mortality and strongly recommend tailored surveillance programs

Application of magnifying narrow-band imaging endoscopy for diagnosis of early gastric cancer and precancerous lesion

<p>Abstract</p> <p>Background</p> <p>Gastric carcinoma is the second commonest cause of cancer deaths worldwide. Early detection and diagnosis of gastric cancer in the stomach is important for improving the prognosis of gastric cancer. This retrospective study was designed to investigate the value of magnifying narrow-band imaging (NBI) in the diagnosis of precancerous lesions and early gastric cancer.</p> <p>Methods</p> <p>This study included 122 patients who were diagnosed with early gastric cancer or precancerous gastric lesions by endoscopy. The patients underwent an examination with conventional endoscopy, magnifying NBI, and magnifying chromoendoscopy. Images resolution was evaluated, and the morphology, pit patterns and blood capillary forms of lesions were analyzed. The presence of gastric carcinoma and high grade intraepithelial neoplasia in the biopsy samples was considered as a positive pathological result, which is used to assess accuracy of endoscopic diagnosis.</p> <p>Results</p> <p>For image resolution, magnifying NBI and magnifying chromoendoscopy were significantly superior to magnifying conventional endoscopy in morphology, pit pattern and blood capillary form (P < 0.01), and magnifying NBI was significantly superior to magnifying chromoendoscopy in blood capillary form (P < 0.01). IV, V₁, and VI type of gastric pit pattern were detected in 14 cases, 43 cases, and 17 cases in patients with high grade intraepithelial neoplasia, respectively. V₁and VI type of gastric pit pattern were detected in 9 cases and 39 cases in patients with early gastric cancer, respectively. The presence of irregular minute vessels and variation in the caliber of vessels was found in 109 cases. The accuracy, sensitivity, specificity, false positive rate and false negative rate for diagnosis of early gastric cancer and precancerous gastric lesions were 68.9%, 95.1%, 63.1%, 24.5%, and 32.4% for conventional endoscopy, 93.6%, 92.7%, 94.5%, 5.7%, and 6.9% for magnifying NBI, and 91.3%, 88.6%, 93.2%, 13.2%, and 21.48% for magnifying chromoendoscopy, respectively.</p> <p>Conclusions</p> <p>This study demonstrates that magnifying NBI is superior to conventional endoscopy in the diagnosis of early gastric cancer and precancerous gastric lesions, and can be used for screening early malignancies of the stomach.</p

Gastric Cancer Mortality in a High Incidence Area: Long-term follow-up of Helicobacter pylori-related Precancerous Lesions in the General Population

BACKGROUND: Due to a lack of clear criteria for recognizing subjects at risk of progression to gastric cancer (GC), this cohort study seeks to identify predictors of GC death in a high-risk population. METHODS: During 2000-2001, 1011 randomly selected residents of Ardabil, Iran without a history of gastrointestinal diseases, underwent upper endoscopy with targeted biopsy sampling. Until 2013, cancer mortality data were obtained using cancer and death registry data and verbal autopsy reports. Cox regression was used to estimate hazard ratios (HR). RESULTS: A total of 3.95% of the participants [mean age: 53.1 ± 9.9 years, 49.8% males, and 88.2% Helicobacter pylori (H. pylori-positive)] died of GC. In the multivariate model, precancerous lesions at the beginning of follow-up were associated with increased GC mortality. The HR [95% confidence interval (CI)] was 7.4 (1.6-33.8) for atrophic gastritis (AG) and 23.6 (5.5-102.3) for intestinal metaplasia (IM). Age over 50 (HR = 4.4; 1.3-14.2), family history of GC (HR = 6.8; 3.3-13.8), smoking (HR = 7.4; 3.2-17.3), and endoscopically confirmed gastric ulcer (GU, HR = 6.5; 2.5-16.4) were independently associated with GC mortality. The concomitant presence of a precancerous lesion increased the HR to 46.5 (10.8-198.6) for a family history of GC, 27.6 (6.5-116.4) for smoking, and 25.1 (6.3-105.3) for age >50 years. CONCLUSIONS: In this population with a high rate of H. pylori infection, age over 50 years, smoking, family history of GC, IM, AG, and in particular, an undiagnosed GU were significant independent risk factors for mortality due to GC. The assessment of a combination of these risk factors might identify individuals at risk of GC who could possibly benefit from regular surveillan

Differentially localized survivin and STAT3 as markers of gastric cancer progression: Association with Helicobacter pylori

BackgroundLocalization and differential expression of STAT3 and survivin in cancer cells are often related to distinct cellular functions. The involvement of survivin and STAT3 in gastric cancer has been reported in separate studies but without clear understanding of their kinetics in cancer progression.MethodsWe examined intracellular distribution of STAT3 and survivin in gastric adenocarcinoma and compared it with normal and precancer tissues using immunoblotting and immunohistochemistry.ResultsAnalysis of a total of 156 gastric samples comprising 61 histologically normal, 30 precancerous tissues (comprising intestinal metaplasia and dysplasia), and 65 adenocarcinomas, collected as endoscopic biopsies from treatment naïve study participants, revealed a significant (P < .001) increase in overall protein levels. Survivin expression was detectable in both cytoplasmic (90.8%) and nuclear (87.7%) compartments in gastric adenocarcinomas lesions. Precancerous dysplastic gastric lesions exhibited a moderate survivin expression (56.7%) localized in cytoplasmic compartment. Similarly, STAT3 and pSTAT3 expression was detected at high level in gastric cancer lesions. The levels of compartmentalized expression of survivin and STAT3/pSTAT3 correlated in precancerous and adenocarcinoma lesions. Although overexpression of these proteins was found associated with the tobacco use and alcohol consumption, their expression invariably and strongly correlated with concurrent Helicobacter pylori infection. Receiver operating characteristic analysis of nuclear survivin, STAT3, and pSTAT3 in different study groups showed acceptable positive and negative predictive values with area under the curve above 0.8 (P < .001).ConclusionOverall, our results suggest that overall increase in survivin and STAT3 and their subcellular localization are key determinants of gastric cancer progression, which can be collectively used as potential disease biomarkers and therapeutic targets for gastric cancer.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/144680/1/cnr21004-Supplementary_Methods_20180313.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/144680/2/cnr21004-sup-0001-F1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/144680/3/cnr21004_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/144680/4/cnr21004.pd

Decline of gastric cancer mortality in common variable immunodeficiency in the years 2018-2022

IntroductionIn patients with Common Variable Immunodeficiency, malignancy has been reported as the leading cause of death in adults, with a high risk of B-cell lymphomas and gastric cancer.MethodsWe conducted a five-year prospective study aiming to update the incidence and mortality of gastric cancer and the incidence of gastric precancerous lesions in 512 CVID patients who underwent a total of 400 upper gastrointestinal endoscopies.ResultsIn the pre-pandemic period, 0.58 endoscopies were performed per patient/year and in the COVID-19 period, 0.39 endoscopies were performed per patient/year. Histology revealed areas with precancerous lesions in about a third of patients. Patients who had more than one gastroscopy during the study period were more likely to have precancerous lesions. Two patients received a diagnosis of gastric cancer in the absence of Helicobacter pylori infection. The overall prevalence of Helicobacter pylori infection in biopsy specimens was 19.8% and related only to active gastritis. Among patients who had repeated gastroscopies, about 20% progressed to precancerous lesions, mostly independent of Helicobacter pylori.DiscussionWhile gastric cancer accounted for one in five deaths from CVID in our previous survey, no gastric cancer deaths were recorded in the past five years, likely consistent with the decline in stomach cancer mortality observed in the general population. However, during the COVID-19 pandemic, cancer screening has been delayed. Whether such a delay or true decline could be the reason for the lack of gastric cancer detection seen in CVID may become clear in the coming years. Due to the high incidence of precancerous lesions, we cannot rely on observed and predicted trends in gastric cancer mortality and strongly recommend tailored surveillance programs

UPPER GASTROINTESTINAL CANCER IN ARDABIL,NORTH-WEST OF IRAN: A REVIEW

Introduction: Cancer is a serious health problem worldwide, imposing a large economical and psychological burden as well as loss of life and productivity.1 Lots of effort and money have been put in the fields of clinical, epidemiological, pharmacological, and biological research on cancer in the recent decades. Although we have witnessed dramatic progress in the field, but still there is a long way to go. Cancer is the third most common cause of death in Iran, accounting for 14% of the total death toll.2 It stands just after cardiovascular events and accidents (46% and 17% of the total death toll respectively, Table 1) according to the latest census of the Iranian Ministry of Health and Medical Education (IMHME). Overall, gastrointestinal (GI) cancers cause about half of all cancer deaths in Iran. Of the 17,450 GI cancers recorded in the IMHME report, 7,560 (43.3%) were gastric cancers.2 In other words, of every 100 people dying of cancer in Iran, 22 die of gastric cancer, and six from esophageal cancer. Unfortunately, both of these cancers come to medical attention when they are rather advanced and limited or no effective therapies are available for them. Theoretically, these cancers may be treatable in their early stage; therefore, finding them at the earliest possible stage may subject them to effective therapy. Other nations, such as the Japanese, have managed to decrease the toll of gastric cancer by effective screening programs and timely intervention.3 Therefore, if we are to plan meaningfully to combat this still deadly disease we should have accurate information about the epidemiology and clinical characteristics of various cancers, especially the upper GI cancers in Iran. Earlier reports indicated that Ardabil, in North-West of Iran, had a rather high incidence of upper GI cancers. 4 – 8 In their 1973 report, Mahboubi et al reported that about 64% of all cancer deaths in Ardabil are due to esophageal and gastric cancers (56% esophagus and 8% stomach).4 This background and the availability of facilities of a collaborating local medical university and easy means of air travel to the area made Ardabil an appropriate place for epidemiological and clinical cancer studies in the past few years. This review focuses on the background and recent studies done in the region as a model of cancer research in Ira

Diagnostic values of serum levels of pepsinogens and gastrin-17 for screening gastritis and gastric cancer in a high risk area in Northern Iran

Background: Gastric cancer (GC) is the second cause of cancer related death in the world. It may develop by progression from its precancerous condition, called gastric atrophy (GA) due to gastritis. The aim of this study was to evaluate the accuracy of serum levels of pepsinogens (Pg) and gastrin-17 (G17) as non-invasive methods to discriminate GA or GC (GA/GC) patients. Materials and Methods: Subjects referred to gastrointestinal clinics of Golestan province of Iran during 2010 and 2011 were invited to participate. Serum levels of PgI, PgII and G17 were measured using a GastroPanel kit. Based on the pathological examination of endoscopic biopsy samples, subjects were classified into four groups: normal, non-atrophic gastritis, GA, and GC. Receiver operating curve (ROC) analysis was used to determine cut-off values. Indices of validity were calculated for serum markers. Results: Study groups were normal individuals (n=74), non-atrophic gastritis (n=90), GA (n=31) and GC patients (n=30). The best cut-off points for PgI, PgI/II ratio, G17 and HP were 80 μg/L, 10, 6 pmol/L, and 20 EIU, respectively. PgI could differentiate GA/GC with high accuracy (AUC=0.83; 95%CI: 0.76-0.89). The accuracy of a combination of PgI and PgI/II ratio for detecting GA/GC was also relatively high (AUC=0.78; 95%CI: 0.70-0.86). Conclusions: Our findings suggested PgI alone as well as a combination of PgI and PgI/II ratio are valid markers to differentiate GA/GC. Therefore, Pgs may be considered in conducting GC screening programs in high-risk areas

Proteomics and Metabolomics Unveil Codonopsis pilosula (Franch.) Nannf. Ameliorates Gastric Precancerous Lesions via Regulating Energy Metabolism

Objective: This study aimed to systematically evaluate the efficacy of Codonopsis pilosula (Franch.) Nannf. (Codonopsis Radix, CR) and reveal the mechanism of its effects on suppressing Gastric Precancerous Lesions.Methods: First, we established the GPL rat model which was induced by N-methyl-N′-nitro-N-nitrosoguanidine, a disordered diet, and 40% ethanol. The CR’s anti-Gastric Precancerous Lesions effect was comprehensively evaluated by body weight, pathological section, and serum biochemical indexes. Then, quantitative proteomics and metabolomics were conducted to unveil the disturbed protein-network and pharmacodynamic mechanism. Furthermore, serum pharmacology was employed to confirm that CR’s anti-gastritis and anti-cancer phenotype in cell models.Results: In animal models, CR had been shown to control inflammation and ameliorate Gastric Precancerous Lesions. Considering the combination of proteomics and metabolomics, we found that CR could significantly reverse the biological pathways related to energy metabolism which were disturbed by the Gastric Precancerous Lesions model. Furthermore, the results of serum pharmacology indicated that the Codonopsis Radix containing serum could ameliorate gastritis injury and selectively inhibit the proliferation of gastric cancer cells rather than normal cells, which was closely related to ATP production in the above mentioned cells.Conclusion: In summary, CR exerted anti-Gastric Precancerous Lesions effects by ameliorating gastritis injury and selectively inhibiting the proliferation of gastric cancer cells rather than normal cells. Proteomics and metabolomics unveiled that its efficacy was closely related to its regulation of the energy-metabolism pathway. This research not only provided new ideas for exploring the mechanism of complex systems such as Chinese herbals but also benefited the treatment strategy of Gastric Precancerous Lesions via regulating energy metabolism

Treatment of helicobacter pylori infection in atrophic gastritis

Helicobacter pylori (Hp) is a major human pathogen causing chronic, progressive gastric mucosal damage and is linked to gastric atrophy and cancer. Hp-positive individuals constitute the major reservoir for transmission of infection. There is no ideal treatment for Hp. Hp infection is not cured by a single antibiotic, and sometimes, a combined treatment with three or more antibiotics is ineffective. Atrophic gastritis (AG) is a chronic disease whose main features are atrophy and/or intestinal metaplasia of the gastric glands, which arise from long-standing Hp infection. AG is reportedly linked to an increased risk for gastric cancer, particularly when extensive intestinal metaplasia is present. Active or past Hp infection may be detected by conventional methods in about two-thirds of AG patients. By immunoblotting of sera against Hp whole-cell protein lysates, a previous exposure to Hp infection is detected in all AG patients. According to guidelines, AG patients with Hp positivity should receive eradication treatment. The goals of treatment are as follows: (1) Cure of infection, resolution of inflammation and normalization of gastric functions; (2) possible reversal of atrophic and metaplastic changes of the gastric mucosa; and (3) prevention of gastric cancer. An ideal antibiotic regimen for Hp should achieve eradication rates of approximately 90%, and complex multidrug regimens are required to reach this goal. Amongst the factors associated with treatment failure are high bacterial load, high gastric acidity, Hp strain, smoking, low compliance, overweight, and increasing antibiotic resistance. AG, when involving the corporal mucosa, is linked to reduced gastric acid secretion. At a non-acidic intra-gastric pH, the efficacy of the common treatment regimens combining proton pump inhibitors with one or more antibiotics may not be the same as that observed in patients with Hp gastritis in an acid-producing stomach. Although the efficacy of these therapeutic regimens has been thoroughly tested in subjects with Hp infection, there is a paucity of evidence in the subgroup of patients with AG. Bismuth-based therapy may be an attractive treatment in the specific setting of AG, and specific studies on the efficacy of bismuth-based therapies are needed in patients with AG

헬리코박터 제균치료가 후시성 위암 발생에 미치는 장기간의 영향

학위논문 (석사)-- 서울대학교 대학원 : 임상의과학과, 2017. 2. 김상균.Background: Gastric mucosal atrophy and intestinal metaplasia by Helicobacter pylori infection are the main precursor lesions of gastric cancer. This study aims to evaluate the long-term effect of Helicobacter pylori eradication on the progression of precancerous lesions to metachronous cancer development after endoscopic resection of early gastric cancer. Methods: The patients who underwent endoscopic resection of early gastric cancer were reviewed retrospectively. Changes in precancerous lesions and development of metachronous cancer were compared according to Helicobacter pylori eradication and final status of infection. Results: In total, 565 patients were followed up for over 5 years after endoscopic resection of early gastric cancer. The grade of mucosal atrophy on corpus was significantly lower in the eradicated group than the persistent group during follow-up (p=0.029). In patients less than 70 years of age, the cumulative incidence rate of metachronous cancer was significantly lower in the Helicobacter pylori-eradicated group than the Helicobacter pylori-persistent group (p = 0.018). Age was an independent risk factor for metachronous cancer development. Conclusions: Helicobacter pylori eradication might prevent the long-term development of metachronous cancer in younger patients by delaying the progression of precancerous lesions after endoscopic resection of early gastric cancer.Introduction 1 Material and Methods 3 Results 6 Discussion 21 References 24 Abstract in Korean 28Maste