Changing trends and characteristics of peptic ulcer disease:A multicenter study from 2010 to 2019 in Korea

BACKGROUND The clinical trend and characteristics of peptic ulcer disease(PUD)have not fully been investigated in the past decade.AIM To evaluate the changing trends and characteristics of PUD according to age and METHODS We analyzed seven hospital databases converted into the Observational Medical Outcomes Partnership-Common Data Model between 2010 and 2019.We classified patients with PUD who underwent rapid urease tests or Helicobacter pylori(H.pylori)serology into three groups:H.pylori-related,drug[nonsteroidal anti-inflammatory drugs(NSAIDs)or aspirin]-related,and idiopathic(H.pylori/NSAID/aspirin-negative)PUD and compared the yearly trends and characteristics among the three groups.RESULTS We included 26785 patients in 7 databases,and the proportion of old age(≥65 years)was 38.8%.The overall number of PUD exhibited no decrease,whereas PUD in old age revealed an increasing trend(P=0.01 for trend).Of the 19601 patients,41.8%had H.pylori-related,36.1%had drug-related,and 22.1%had idiopathic PUD.H.pylorirelated PUD exhibited a decreasing trend after 2014(P=0.01),drug-related PUD demonstrated an increasing trend(P=0.04),and idiopathic PUD showed an increasing trend in the old-age group(P=0.01)during 10 years.Patients with drug-related PUD had significantly more comorbidities and concomitant ulcerogenic drugs.The idiopathic PUD group had a significantly higher number of patients with chronic liver disease.CONCLUSION With the aging population increase,the effects of concomitant ulcerogenic drugs and preventive strategies should be investigated in drug-induced PUD.Further studies are required to clarify the relationship between idiopathic PUD and chronic liver disease.

Peptic ulcer disease in non-alcoholic fatty liver disease hospitalizations:A new challenge on the horizon in the United States

BACKGROUND Peptic ulcer disease(PUD)is frequently seen in patients with liver cirrhosis.However,current literature lacks data on PUD in non-alcoholic fatty liver disease(NAFLD)hospitalizations.AIM To identify trends and clinical outcomes of PUD in NAFLD hospitalizations in the United States.METHODS The National Inpatient Sample was utilized to identify all adult(≥18 years old)NAFLD hospitalizations with PUD in the United States from 2009-2019.Hospitalization trends and outcomes were highlighted.Furthermore,a control group of adult PUD hospitalizations without NAFLD was also identified for a comparative analysis to assess the influence of NAFLD on PUD.RESULTS The total number of NAFLD hospitalizations with PUD increased from 3745 in 2009 to 3805 in 2019.We noted an increase in the mean age for the study population from 56 years in 2009 to 63 years in 2019(P<0.001).Racial differences were also prevalent as NAFLD hospitalizations with PUD increased for Whites and Hispanics,while a decline was observed for Blacks and Asians.The all-cause inpatient mortality for NAFLD hospitalizations with PUD increased from 2%in 2009 to 5%in 2019(P<0.001).However,rates of Helicobacter pylori(H.pylori)infection and upper endoscopy decreased from 5%in 2009 to 1%in 2019(P<0.001)and from 60%in 2009 to 19%in 2019(P<0.001),respectively.Interestingly,despite a significantly higher comorbidity burden,we observed lower inpatient mortality(2%vs 3%,P=0.0004),mean length of stay(LOS)(11.6 vs 12.1 d,P<0.001),and mean total healthcare cost(THC)($178598 vs$184727,P<0.001)for NAFLD hospitalizations with PUD compared to non-NAFLD PUD hospitalizations.Perforation of the gastrointestinal tract,coagulopathy,alcohol abuse,malnutrition,and fluid and electrolyte disorders were identified to be independent predictors of inpatient mortality for NAFLD hospitalizations with PUD.CONCLUSION Inpatient mortality for NAFLD hospitalizations with PUD increased for the study period.However,there was a significant decline in the rates of H.pylori infection and upper endoscopy for NAFLD hospitalizations with PUD.After a comparative analysis,NAFLD hospitalizations with PUD had lower inpatient mortality,mean LOS,and mean THC compared to the non-NAFLD cohort.

Polymorphism of -765G > C COX-2 is a risk factor for gastric adenocarcinoma and peptic ulcer disease in addition to H pylori infection:A study from northern India

AIM: To investigate -765G > C COX-2 polymorphism and H pylori infection in patients with gastric adenocarcinoma, peptic ulcer disease (PUD) and non- ulcer dyspepsia (NUD). METHODS: We enrolled 348 adult patients (62 gastric adenocarcinoma, 45 PUD and 241 NUD) undergoing upper gastrointestinal endoscopy at two referral centers between September, 2002 and May, 2007. H pylori infection was diagnosed when any of the four tests (RUT, culture, histopathology and PCR) were positive. Genotyping for -765G > C polymorphism of COX-2 was performed by PCR-RFLP analysis. RESULTS: Frequency of C carrier had significantassociation with gastric adenocarcinoma as compared to NUD [77.4% vs 29%, P < 0.001, odds ratio (OR) 8.20; 95% confidence interval (95% CI), 4.08-16.47] and PUD (77.4% vs 31.1%, P < 0.001; OR 8.04; 95% CI, 3.25-19.90). Risk of gastric adenocarcinoma was significantly higher in patients having C carrier with (OR 7.83; 95% CI 3.09-19.85) and without H pylori infection (OR 7.06; 95% CI, 2.61-19.09). Patients with C carrier and H pylori infection had significant risk for the development of PUD (P < 0.001; OR 5.65; 95% CI, 2.07-15.34). CONCLUSION: -765G > C COX-2 polymorphism with or without H pylori could be a marker for genetic susceptibility to gastric adenocarcinoma. COX-2 polymorphism in presence of H pylori infection might be useful in predicting the risk of PUD.

Risk factors and therapeutic response in Chinese patients with peptic ulcer disease

AIM:To assess the risk factors and the eff icacy of medications of patients with gastric and duodenal ulcers among Chinese patients in Taiwan.METHODS:Patients with peptic ulcers,diagnosed by upper endoscopy,were retrospectively collected between January 2008 and December 2008.The differences were compared.RESULTS:Among all 448 cases,254(56.6%) and 194(43.4%) patients had gastric ulcers and duodenal ulcers respectively.Patients with gastric ulcers were younger than those with duodenal ulcers.Although more men existed,there was a female predominance in middle-aged cases.Patients with duodenal ulcers had a higher rate of Helicobacter pylori(H.pylori) infection(62.4% vs 43.3%,P = 0.001),and those with gastric ulcers owned a significantly higher amount of aspirin and nonsteroidal anti-inflammatory drug(NSAID) use(7.5% vs 1.5%,6.7% vs 2.1%,P = 0.001).Tobacco smoking and alcohol drinking had no different impact between these two groups.Proton-pump inhibitors and H2-receptor antagonists(H2RA) were effective,but significantly less so in cases with duodenal ulcers receiving H2RAs,or in those with H.pylori infection and a history of NSAID use.CONCLUSION:Patients with gastric ulcers had lower H.pylori infection but more aspirin or NSAID use.Antisecretory therapy was ineffective in gastric ulcers underwent H2RA treatment,and cases combined H.pylori infection and NSAID use.

Association between acute pancreatitis and peptic ulcer disease

AIM:To evaluate the relationship between peptic ulcer disease(PUD) and acute pancreatitis.METHODS:A cohort of 78 patients with acute pancreatitis were included in this study.The presence of PUD and the Helicobacter pylori(H.pylori) status were assessed by an endoscopic method.The severity of acute pancreatitis was assessed using Ranson's score,the Acute Physiology and Chronic Health Evaluation(APACHE) □ score,computed tomography severity indexand the clinical data during hospitalization,all of which were compared between the patients with and without PUD.The risk factors for PUD were also evaluated.RESULTS:Among 78 patients,41 patients(52.6%) with acute pancreatitis suffered from PUD,but only 13(31.7%) patients with PUD were infected by H.pylori.On univariate analysis,male gender,an etiology of alcohol-induced pancreatitis,a history of smoking or alcohol consumption,elevated triglyceride and C-reactive protein levels,and high APACHE □ score were signif icantly associated with PUD.However,on multivariate logistic regressionanalysis,the APACHE □ score(odds ratio:7.69;95% conf idence interval:1.78-33.33;P < 0.01) was found to be the only independent risk factor for PUD.CONCLUSION:Patients with acute pancreatitis are liable to suffer from PUD.PUD is associated with severeacute pancreatitis according to the APACHE □ score,and treatment for PUD should be considered for patients with severe acute pancreatitis.

Do patients with non-ulcer dyspepsia respond differently to Helicobacter pylorieradication treatments from those with peptic ulcer disease? A systematic review

AIM: It is controversial whether patients with non-ulcer dyspepsia (NUD) respond differently to Helicobacter pylori (H pylori) eradication treatment than those with peptic ulcer disease (PUD). To review the evidence for any difference in H pylorieradication rates between PUD and NUD patients. METHODS: A literature search for full articles and meeting abstracts to July 2004 was conducted. We included studies evaluating the efficacy of a proton pump inhibitor (P) or ranitidine bismuth citrate (RBC) plus two antibiotics of clarithromycin (C), amoxicillin (A), metronidazole (M), or P-based quadruple therapies for eradicating the infection. RESULTS: Twenty-two studies met the criteria. No significant difference in eradication rates was found between PUD and NUD patients when treated with 7-d RBCCA, 10-d PCA or P-based quadruple therapies. When the 7-d PCA was used, the pooled H pylori eradication rate was 82.1% (431/525) and 72.6% (448/617) for PUD and NUD patients, respectively, yielding a RR of 1.15 (95%CI 1.01-1.29). However, the statistically significant difference was seen only in meeting abstracts, but not in full publications. CONCLUSION: There is no convincing evidence to suggest that NUD patients respond to H pylori eradication treatments differently from those with PUD, although a trend exists with the 7-d PCA therapy.

GC/MS-based differential metabolic profiling of human peptic ulcer disease to study Helicobacter pylori-induced metabolic perturbations

Helicobacter pylori infection has been significantly linked to Peptic Ulcer Disease and Gastric Cancer.Metabolomic fingerprinting may offer a principal way of early diagnosis and to understand the molecular mechanism of H.pylori-induced pathogenicity.The rationale of the study is to explore the underlying distinct metabolic mechanisms of H.pylori-induced PUD and to identify potential biomarkers for disease diagnosis and associated risks using Gas chromatography/mass spectrometry.GC/MS-based analytical method was used to compare metabolic profiles of healthy controls(N=20)and peptic ulcer patients(N=45).Acquired metabolomic data were analyzed by constructing a diagnostic model using principal component analysis and a non-parametric two-tailed paired Wilcoxon analysis to identify disease-specific metabolic biomarkers.A total of 75 low-molecular-weight endogenous metabolites were detected during comparative metabolomic analysis of PUD vs.healthy gut tissues,among which 16 metabolites are being proposed to be diagnostic markers of Human PUD.Perturbations related to amino acids,carbohydrates,fatty acids,organic acids,and sterol metabolism were significantly revealed during this differential metabolomic profiling.Results convincingly suggest that metabolic profiles can contribute immensely in early diagnosis of the disease and understanding molecular mechanisms of disease progression for predicting novel drug targets for prophylactic and anaphylactic measures.

Prevalence and risk factors of asymptomatic peptic ulcer disease in Taiwan

AIM:To investigate the prevalence and risk factors of asymptomatic peptic ulcer disease(PUD)in a general Taiwan Residents population. METHODS:From January to August 2008,consecutive asymptomatic subjects undergoing a routine health check-up were evaluated by upper gastrointestinal endoscopy.Gastroduodenal mucosal breaks were carefully assessed,and a complete medical history and demographic data were obtained from each patient.Logistic regression analysis was conducted to identify indepen-dent risk factors for asymptomatic PUD. RESULTS:Of the 572 asymptomatic subjects,54(9.4%) were diagnosed as having PUD.The prevalence of gastric ulcer,duodenal ulcer and both gastric and duodenal ulcers were 4.7%,3.9%,and 0.9%,respectively. Multivariate analysis revealed that prior history of PUD [odds ratio(OR),2.0,95%CI:1.3-2.9],high body mass index[body mass index(BMI)25-30:OR,1.5,95%CI: 1.0-2.2;BMI>30 kg/m 2 :OR,3.6,95%CI:1.5-8.7] and current smoker(OR,2.6,95%CI:1.6-4.4)were independent predictors of asymptomatic PUD.In contrast, high education level was a negative predictor of PUD (years of education 10-12:OR,0.5,95%CI:0.3-0.8; years of education>12:OR,0.6,95%CI:0.3-0.9). CONCLUSION:The prevalence of PUD in asymptomatic subjects is 9.4%in Taiwan.Prior history of PUD, low education level,a high BMI and current smoker are independent risk factors for developing asymptomatic PUD.

Surgical perspectives in peptic ulcer disease and gastritis

For much of the twentieth century, surgery was frequently the solution for peptic ulcer disease. Our understanding of the pathophysiology of ulcers paralleled the development of potent pharmaceutical therapy. As the surgical world developed parietal cell vagotomy which would minimize the complications of surgery, patients failing medical therapy became rare. Emergent surgery for complicated peptic ulcers has not declined however. The development of proton pump inhibitors and the full understanding of the impact of H pylori has led to a trend towards minimalism in surgical therapy for complicated peptic ulcer disease. In addition to the changes in patient care, these developments have had an impact on the training of surgeons. This article outlines these trends and developments.

Impact of epinephrine volume on further bleeding due to high-risk peptic ulcer disease in the combination therapy era

BACKGROUND In monotherapy studies for bleeding peptic ulcers,large volumes of epinephrine were associated with a reduction in rebleeding.However,the impact of epinephrine volume in patients treated with combination endoscopic therapy remains unclear.AIM To assess whether epinephrine volume was associated with bleeding outcomes in individuals who also received endoscopic thermal therapy and/or clipping.METHODS Data from 132 patients with Forrest class Ia,Ib,and IIa peptic ulcers were reviewed.The primary outcome was further bleeding at 7 d;secondary outcomes included further bleeding at 30 d,need for additional therapeutic interventions,post-endoscopy blood transfusions,and 30-day mortality.Logistic and linear regression and Cox proportional hazards analyses were performed.RESULTS There was no association between epinephrine volume and all primary and secondary outcomes in multivariable analyses.Increased odds for further bleeding at 7 d occurred in patients with elevated creatinine values(aOR 1.96,95%CI 1.30-3.20;P<0.01)or hypotension requiring vasopressors(aOR 6.34,95%CI 1.87-25.52;P<0.01).Both factors were also associated with all secondary outcomes.CONCLUSION Epinephrine maintains an important role in the management of bleeding ulcers,but large volumes up to a range of 10-20 mL are not associated with improved bleeding outcomes among individuals receiving combination endoscopic therapy.Further bleeding is primarily associated with patient factors that likely cannot be overcome by increased volumes of epinephrine.However,in carefully-selected cases where ulcer location or size pose therapeutic challenges or when additional modalities are unavailable,it is conceivable that increased volumes of epinephrine may still be beneficial.

Peptic Ulcer Disease in CHUYO

Background: Prevalence of Peptic Ulcer Disease (PUD) is decreasing in developed countries since the use of the treatments for eradication of Helicobacter pylori. Objectives: To revalue the sociodemographic, clinical and evolutionary aspects of the PUD among hospitalized patients in CHUYO. Methodology: This prospective study is related to 65 files of patients hospitalized in hepato-gastroenterology and general surgical services of the CHUYO between March 1st and August 31st, 2015. Results: Hospital utilization rate was 6.59%. The average age of patients was 40.6 years with extremes of 17 and 80 years. The sex ratio was 9.8. The location of the ulcer was 69.23% in stomach. A notion of taking aggressive gastrointestinal products was found in 62 patients (95.4%). The clinical picture was represented by diffuse abdominal pain (76.92%), peritoneal irritation syndrome (64.61%) and epigastric pain (56.92%), anemia (23.07%). Gastric perforations (64.61%) and gastrointestinal bleeding (12.30%) were the main complications. Consumption of non-steroidal anti-inflammatory drugs (NSAIDs) was found in 81.5% of cases. The management was medical and/or surgical with an overall mortality rate of 7.7%. Conclusion: The PUD rate decreased from 10.12% to 6.59% in 5 years. The complications are dominated by stomach perforations. They are relative increase and seem related to NSAIDs. Better management of this disease requires awareness of the population to self-medication.

H pylori infection and other risk factors associated with peptic ulcers in Turkish patients: A retrospective study

AIM: To identify and evaluate the relative impact of H pylori infection and other risk factors on the occurrence of gastric ulcer (GU), duodenal ulcer (DU) and gastritis in Turkish patients. METHODS: A total of 4471 patients (48.3% female) out of 4863 attended the Samatya hospital in Istanbul (June 1999 - October 2003) were included. The records of H pylori status (CLO-test), endoscopic f indings of GU, DU and gastritis, personal habits (smoking, alcohol intake) and medication [non-steroidal anti-inflammatory drugs (NSAIDs), aspirin intake] were analyzed using multi-way frequency analysis. RESULTS: We have found that GU in the presence of H pylori had significant association with aspirin (P = 0.0001), alcohol (P = 0.0090) and NSAIDs (P = 0.0372). DU on the other hand had significant association with aspirin/ smoking/NSAIDs (P = 0.0259), aspirin/alcohol (P = 0.0002) and aspirin/smoking (P = 0.0233), also in the presence of H pylori. In the absence of H pylori GU had significant association with alcohol/NSAIDs (P = 0.0431), and NSAIDs (P = 0.0436). While DU in the absence of H pylori had significant association with smoking/alcohol/ NSAIDs (P = 0.0013), aspirin/NSAIDs (P = 0.0334), aspirin/alcohol (P = 0.0360). CONCLUSION: In the presence of H pylori, aspirin, alcohol and NSAIDs intake act as an independent risk factors that had an augmenting impact on the occurrence of GU and only together on the occurrence of DU in Turkish patients.

Membrane-bound mucins and mucin terminal glycans expression in idiopathic or Helicobacter pylori, NSAID associated peptic ulcers

AIM: To determine the expression of membrane-bound mucins and glycan side chain sialic acids in Helicobacter pylori (H. pylori)-associated, non-steroidal inflammatory drug (NSAID)-associated and idiopathic-gastric ulcers.

Low serum albumin may predict poor efficacy in patients with perforated peptic ulcer treated nonoperatively

BACKGROUND Nonoperative management(NOM)is a promising therapeutic modality for patients with perforated peptic ulcer(PPU).However,the risk factors for poor efficacy and adverse events of NOM are a concern.AIM To investigate the factors predictive of poor efficacy and adverse events in patients with PPU treated by NOM.METHODS This retrospective case-control study enrolled 272 patients who were diagnosed with PPU and initially managed nonoperatively from January 2014 to December 2018.Of these 272 patients,50 converted to emergency surgery due to a lack of improvement(surgical group)and 222 patients were included in the NOM group.The clinical data of these patients were collected.Baseline patient characteristics and adverse outcomes were compared between the two groups.Logistic regression analysis and receiver operating characteristic curve analyses were conducted to investigate the factors predictive of poor efficacy of NOM and adverse outcomes in patients with PPU.RESULTS Adverse outcomes were observed in 71 patients(32.0%).Multivariate analyses revealed that low serum albumin level was an independent predictor for poor efficacy of NOM and adverse outcomes in patients with PPU.CONCLUSION Low serum albumin level may be used as an indicator to help predict the poor efficacy of NOM and adverse outcomes,and can be used for risk stratification in patients with PPU.

Helicobacter pylori and upper gastrointestinal diseases: A review

Since its first isolation by Marshall and Warren, Helicobacter pylori (H. pylori) has been recognized to have a causal role in the upper gastrointestinal diseases development, especially in chronic gastritis, peptic ulcer disease, mucosa-associated lymphoid tissue (MALT lymphoma) and gastric adenocarcinoma. H. pylori is a spiral-shaped gram-negative flagellate bacterium that has a high genetic diversity, which is an important factor in its adaptation to the host stomach and also for the clinical outcome of the infection, an aspect that remains unclear. However, it is thought to involve a interplay among the virulence of the infecting strain, host genetics and environmental factors. This review chapter brings the principal characteristics of the diseases associated with H. pylori infection and summarizes some important characteristics concerning the virulence of bacterium strain, host genetics and external environment.

Interaction between Helicobacter pylori infection, nonsteroidal anti-inflammatory drugs and/or low-dose aspirin use: Old question new insights

Previous reports clearly demonstrated that Helicobacter pylori(H.pylori)infection,nonsteroidal anti-inflammatory drugs(NSAID)or low dose aspirin(ASA)use significantly and independently increased the risk for the development of peptic ulcer disease.Today,the presence of H.pylori infection associated with low dose ASA and/or NSAID use in the same patient is becoming more frequent and therefore the potential interaction between these factors and the consequences of it has important implications.Whether NSAID intake in the presence of H.pylori infection may further increase the risk of peptic ulcer carried by the presence of only one risk factor is still a matter of debate.Studies on the interaction between the two risk factors yielded conflicting data and no consensus has been reached in the last years.In addition,the interaction between H.pylori infection and low-dose ASA remains even more controversial.In real clinical practice,we can find different clinical scenarios involving these three factors associated with the presence of different gastrointestinal and cardiovascular risk factors.These huge variety of possible combinations greatly hinder the decision making process of physicians.

Clinical significance of Helicobacter pylori cagA and iceA genotype status

AIM:To study the presence of Helicobacter pylori(H.pylori) virulence factors and clinical outcome in H.pylori infected patients.METHODS:A prospective analysis of ninety nine H.pylori-positive patients who underwent endoscopy in our Endoscopy suite were included in this study.DNA was isolated from antral biopsy samples and the presence of cagA,iceA,and iceA2 genotypes were determined by polymerase chain reaction and a reverse hybridization technique.Screening for H.pylori infection was performed in all patients using the rapid urease test(CLO-Test).RESULTS:From a total of 326 patients who underwent endoscopy for upper gastrointestinal symptoms,99 patients were determined to be H.pylori-positive.Peptic ulceration was seen in 33 patients(33%).The main virulence strain observed in this cohort was the cagA gene isolated in 43 patients.cagA was associated with peptic ulcer pathology in 39.5%(17/43) and in 28%(16/56) of non-ulcer patients.IceA1 was present in 29 patients(29%) and iceA2 in 15 patients(15%).Ulcer pathology was seen in 39%(11/29) of patients with iceA1,while 31%(22/70) had normal findings.The corresponding values for iceA2 were 33%(5/15) and 33%(28/84),respectively.CONCLUSION:Virulence factors were not common in our cohort.The incidence of factors cagA,iceA1 and iceA2 were very low although variations were noted in different ethnic groups.

Helicobacter pylori neutrophil activating protein as target for new drugs against H.pylori inflammation

Helicobacter pylori(H.pylori) infection is among the most common human infections and the major risk factor for peptic ulcer disease and gastric cancer.With-in this work we present the implication of C-terminal region of H.pylori neutrophil activating protein in the stimulation of neutrophil activation as well as the evi-dence that the C-terminal region of H.pylori activating protein is indispensable for neutrophil adhesion to endothelial cells,a step necessary to H.pylori inflammation.In addition we show that arabino galactan proteins derived from chios mastic gum,the natural resin of the plant Pistacia lentiscus var.Chia inhibit neutrophil activation in vitro.

Evidence-based assessment of proton-pump inhibitors in Helicobacter pylori eradication: A systematic review

Peptic ulcer disease continues to be issue especially due to its high prevalence in the developing world.Helicobacter pylori(H.pylori)infection associated duodenal ulcers should undergo eradication therapy.There are many regimens offered for H.pylori eradication which include triple,quadruple,or sequential therapy regimens.The central aim of this systematic review is to evaluate the evidence for H.pylori therapy from a meta-analytical outlook.The consequence of the dose,type of proton-pump inhibitor,and the length of the treatment will be debated.The most important risk factor for eradication failure is resistance to clarithromycin and metronidazole.