The comparison of anastomosis strength and leakage between double-layer full-thickness and single-layer extramucosal intestine anastomosis.

Various intestine anastomosis techniques have been studied and used, but which is best is still debated. In our center, double-layer full-thickness intestine anastomosis was still considered as standard. However, a single-layer extramucosal intestine anastomosis has shown favorable results. This study created an anastomotic model to compare the anastomosis strength and leakage between double-layer full-thickness and single-layer extramucosal intestine anastomosis. Methods: This experimental study was performed in 20 randomized healthy male pigs, to be included either in Group A (Single-layer extramucosal intestine anastomosis) or Group B (Double-layer full-thickness intestine anastomosis). Enterotomy followed by an end-to-end anastomosis suture was performed in the jejunum. Fourteen days after the operation, any anastomosis leakage and its location was documented. The anastomosis strength was evaluated using manometry. Data were compared between groups using the Mann-Whitney U and Fischer Exact test, considering a significance level of P<0.05. Results: The overall mean intraluminal anastomotic bursting pressure was 4,257±1,185. Group A had a higher intraluminal anastomotic bursting pressure but was not statistically significant compared to group B (4.726±0.952 vs. 3.787±1.252 kilopascals, P=0.063). One leakage (5%, antimesenteric area) occurred in Group A and three leakages (15%, antimesenteric and mesenteric area) occurred in Group B. However, statistical analysis with Fischer exact showed no significant difference of leakage rate between those groups (P=0.291). Conclusions: The anastomosis strength and leakage did not differ significantly between the single-layer extramucosal intestine anastomosis group and the double-layer full-thickness anastomosis group. However, the location of leakage was most common in the antimesenteric area in the double-layer full-thickness anastomosis group.

Management of dyspepsia and Helicobacter pylori infection: the 2022 Indonesian Consensus Report.

Dyspepsia still becomes a major challenge in upper gastrointestinal disease in Indonesia. This disease often correlated with Helicobacter pylori infection. However, the prevalence of this bacterium is generally low in Indonesia. Therefore, several considerations should be taken into consideration during the management of dyspepsia and H. pylori infection. "Management of dyspepsia and H. pylori infection in Indonesia: The Indonesian consensus report" comprises information gathered from 22 gastroenterology centers across Indonesia. The experts gathered to evolve a consensus, that consists of the statements, grades of recommendations, evidence levels, and rationales for the dyspepsia and H. pylori infection management for daily clinical practice. The report explains several aspects from the updated epidemiology information to comprehensive management therapy. After the experts worked together on all statements in the recommendations, the results are presented with the final agreement as a consensus to help clinicians in understanding, diagnosing, and treating dyspepsia and H. pylori infection patients in daily clinical practice in Indonesia.

National Consensus on Portal Hypertension Management in Indonesia.

Portal hypertension is a clinical syndrome that consists of hypersplenism, ascites, gastroesophageal varices, and encephalopathy. This condition is marked by increased portal pressure gradient and may occur with or without liver cirrhosis. To date, portal hypertension remains as the leading cause of severe complications and death of a patient with chronic liver disease, especially liver cirrhosis. Therefore, thorough understanding about management of portal hypertension is strongly required, especially considering that many complications of portal hypertension require early diagnosis and treatment to improve the prognosis of the patients. Additionally, although hepatic venous pressure gradient (HVPG) measurement has become a gold standard procedure for measuring portal pressure in the last twenty years, utilization of this method in Indonesia has been hindered by reluctance of the patients due to its invasiveness, high cost, and limited availability. This consensus is developed with evidence-based medicine principles to provide a guideline for portal hypertension management for general practitioners, specialists, and consultants, to achieve better clinical outcomes of portal hypertension in Indonesia.  Keywords: portal hypertension, liver cirrhosis, chronic liver disease.

Family with Peutz-Jeghers syndrome in Indonesia.

Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant disorder characterised by mucocutaneous pigmentation, gastrointestinal polyps and an increased risk of gastrointestinal and other cancers. We report an Indonesian woman, aged 28, with black spots on her lips who had multiple polyps extending from the stomach to the rectum. Her father and a son also had mucocutaneous lesions but they did not undergo gastrointestinal investigations. All three had mutations in the serine/threonine kinase 11 gene (STK11).

Serum pepsinogen level as a biomarker for atrophy, reflux esophagitis, and gastric cancer screening in Indonesia.

Background: Chronic dyspepsia's symptoms are frequently seen in primary to tertiary healthcare in Indonesia. This study aimed to describe the potential usability of pepsinogen (PG) values in determining gastric mucosal conditions, including superficial gastritis and atrophic gastritis. Materials and Methods: We recruited 646 adult dyspeptic patients and then analyzed PG values (including PGI, PGII, and PGI/II ratio) with endoscopic findings, gastric mucosal damages, and Helicobacter pylori infection. The gastric mucosal damage and H. pylori infection were evaluated using histological examination based on the updated Sydney system. Results: Among 646 enrolled patients, 308 (47.2%), 212 (32.8%), 91 (14.1%), 34 (5.2%), and 1 (0.2%) patient were diagnosed with normal mucosa, gastritis, reflux esophagitis, peptic ulcer disease, and gastric cancer, respectively. Significant differences in PGI, PGII, and PGI/II ratio values were observed among ethnic groups (all P < 0.01). The PGI and PGII levels were significantly higher and PGI/II was significantly lower in H. pylori-infected patients than in uninfected ones (all P < 0.001). The optimal cutoff value for PGII and PGI/II was 12.45 ng/mL with an area under the curve (AUC) value of 0.755 (0.702-0.811), sensitivity 59.3%, and specificity 77.1%; and 4.75 with AUC value of 0.821 (0.763-0.855), sensitivity 81.5%, and specificity 78.7%, respectively, to determine moderate-severe atrophy. Conclusion: Serum PG levels, a useful biomarker, represent the endoscopic findings, especially for reflux esophagitis. In addition, the benefits of PG values detecting atrophic gastritis were limited to moderate-severe atrophic gastritis. This usefulness requires careful attention for several ethnic groups in Indonesia.

CYP2C19 Polymorphisms in Indonesia: Comparison among Ethnicities and the Association with Clinical Outcomes.

CYP2C19 polymorphisms are important factors for proton pump inhibitor-based therapy. We examined the CYP2C19 genotypes and analyzed the distribution among ethnicities and clinical outcomes in Indonesia. We employed the polymerase chain reaction-restriction fragment length polymorphism method to determine the CYP2C19 genotypes and evaluated inflammation severity with the updated Sydney system. For CYP2C19*2, 46.4% were the homozygous wild-type allele, 14.5% were the homozygous mutated allele, and 39.2% were the heterozygous allele. For CYP2C19*3, 88.6% were the homozygous wild-type allele, 2.4% were the homozygous mutated allele, and 9.0% were the heterozygous allele. Overall, the prevalence of rapid, intermediate, and poor metabolizers in Indonesia was 38.5, 41.6, and 19.9%, respectively. In the poor metabolizer group, the frequency of allele *2 (78.8%) was higher than the frequency of allele *3 (21.2%). The Papuan had a significantly higher likelihood of possessing poor metabolizers than the Balinese (OR 11.0; P = 0.002). The prevalence of poor metabolizers was lower compared with the rapid and intermediate metabolizers among patients with gastritis and gastroesophageal reflux disease. Intermediate metabolizers had the highest prevalence, followed by rapid metabolizers and poor metabolizers. Dosage adjustment should therefore be considered when administering proton pump inhibitor-based therapy in Indonesia.

Analysis of risks of gastric cancer by gastric mucosa among Indonesian ethnic groups.

Indonesia is a big country with multiethnic populations whose gastric cancer risks have not been elucidated. We performed a nationwide survey and obtained histological specimens from 1053 individuals in 19 cities across the country. We examined the gastric mucosa, the topography, the atrophic gastritis risk factors, and the gastric cancer risk scores. Almost half (46.1%) of the patients with dyspeptic symptoms had histological abnormalities; chronic (36.3%) and atrophic gastritis (28.9%) being the most frequent. Individuals of the Timor ethnicity had the highest prevalence of acute (52.6%) and chronic gastritis (68.4%), even those negative for H. pylori. Our topographic analysis showed the majority of patients had predominantly antral acute and chronic gastritis. A multivariate logistic regression model showed age (Odds ratio [OR], 1.107), Timor ethnicity (OR, 8.531), and H. pylori infection (OR, 22.643) as independent risk factors for presence of atrophic gastritis. In addition, the gastric cancer risk score was highest in those from Timor, Papuan, and Bugis ethnic populations. Overall, Indonesia is a low-risk gastric cancer country. However, several ethnic groups displayed severe gastric mucosa symptoms suggesting policy makers should focus on those ethnic groups to perform gastric cancer screenings and to eradicate H. pylori.

Gastric mucosal status in populations with a low prevalence of Helicobacter pylori in Indonesia.

In Indonesia, endoscopy services are limited and studies about gastric mucosal status by using pepsinogens (PGs) are rare. We measured PG levels, and calculated the best cutoff and predictive values for discriminating gastric mucosal status among ethnic groups in Indonesia. We collected gastric biopsy specimens and sera from 233 patients with dyspepsia living in three Indonesian islands. When ≥5.5 U/mL was used as the best cutoff value of Helicobacter pylori antibody titer, 8.6% (20 of 233) were positive for H. pylori infection. PG I and II levels were higher among smokers, and PG I was higher in alcohol drinkers than in their counterparts. PG II level was significantly higher, whereas PG I/II ratios were lower in H. pylori-positive than in H. pylori-negative patients. PG I/II ratios showed a significant inverse correlation with the inflammation and atrophy scores of the antrum. The best cutoff values of PG I/II were 4.05 and 3.55 for discriminating chronic and atrophic gastritis, respectively. PG I, PG II, and PG I/II ratios were significantly lower in subjects from Bangli than in those from Makassar and Surabaya, and concordant with the ABC group distribution; however, group D (H. pylori negative/PG positive) was the lowest in subjects from Bangli. In conclusion, validation of indirect methods is necessary before their application. We confirmed that serum PG level is a useful biomarker determining chronic gastritis, but a modest sensitivity for atrophic gastritis in Indonesia. The ABC method should be used with caution in areas with a low prevalence of H. pylori.

Surveillance of Helicobacter pylori Antibiotic Susceptibility in Indonesia: Different Resistance Types among Regions and with Novel Genetic Mutations.

Information regarding Helicobacter pylori antibiotic resistance in Indonesia was previously inadequate. We assessed antibiotic susceptibility for H. pylori in Indonesia, and determined the association between virulence genes or genetic mutations and antibiotic resistance. We recruited 849 dyspeptic patients who underwent endoscopy in 11 cities in Indonesia. E-test was used to determine the minimum inhibitory concentration of five antibiotics. PCR-based sequencing assessed mutations in 23S rRNA, rdxA, gyrA, gyrB, and virulence genes. Next generation sequencing was used to obtain full-length sequences of 23S rRNA, infB, and rpl22. We cultured 77 strains and identified 9.1% with clarithromycin resistance. Low prevalence was also found for amoxicillin and tetracycline resistance (5.2% and 2.6%, respectively). In contrast, high resistance rates to metronidazole (46.7%) and levofloxacin (31.2%) were demonstrated. Strains isolated from Sumatera Island had significantly higher metronidazole resistance than those from other locations. Metronidazole resistant strains had highly distributed rdxA amino acid substitutions and the 23S rRNA A2143G mutation was associated with clarithromycin resistance (42.9%). However, one strain with the highest MIC value had a novel mutation in rpl22 without an A2143G mutation. Mutation at Asn-87 and/or Asp-91 of gyrA was associated with levofloxacin-resistance and was related to gyrB mutations. In conclusions, although this is a pilot study for a larger survey, our current data show that Indonesian strains had the high prevalence of metronidazole and levofloxacin resistance with low prevalence of clarithromycin, amoxicillin, and tetracycline resistance. Nevertheless, clarithromycin- or metronidazole-based triple therapy should be administered with caution in some regions of Indonesia.

Risk Factors and Prevalence of Helicobacter pylori in Five Largest Islands of Indonesia: A Preliminary Study.

The prevalence of Helicobacter pylori infection in Indonesia is still controversial and mainly investigated in the largest ethnic group, Javanese. We examined the prevalence of H. pylori infection using four different tests including culture, histology confirmed by immunohistochemistry and rapid urease test. We also analyzed risk factors associated with H. pylori infection in five largest islands in Indonesia. From January 2014-February 2015 we consecutively recruited a total of 267 patients with dyspeptic symptoms in Java, Papua, Sulawesi, Borneo and Sumatera Island. Overall, the prevalence of H. pylori infection was 22.1% (59/267). Papuan, Batak and Buginese ethnics had higher risk for H. pylori infection than Javanese, Dayak and Chinese ethnics (OR = 30.57, 6.31, 4.95; OR = 28.39, 5.81, 4.61 and OR = 23.23, 4.76, 3.77, respectively, P <0.05). The sensitivity and specificity for RUT and culture were 90.2%, 92.9% and 80.5%, 98.2%, respectively. The patients aged 50-59 years group had significantly higher H. pylori infection than 30-39 years group (OR 2.98, P = 0.05). Protestant had significantly higher H. pylori infection rate than that among Catholic (OR 4.42, P = 0.008). It was also significantly lower among peoples who used tap water as source of drinking water than from Wells/river (OR 9.67, P = 0.03). However only ethnics as become independent risk factors for H. pylori infection. Although we confirmed low prevalence of H. pylori in Javanese; predominant ethnic in Indonesia, several ethnic groups had higher risk of H. pylori infection. The age, religion and water source may implicate as a risk factor for H. pylori infection in Indonesia.

Helicobacter pylori virulence genes in the five largest islands of Indonesia.

BACKGROUND: It remains unclear whether the low incidence of gastric cancer in Indonesia is due to low infection rates only or is also related to low Helicobacter pylori pathogenicity. We collected H. pylori strains from the five largest islands in Indonesia and evaluated genetic virulence factors. METHODS: The genotypes of H. pylori virulence factors were determined by polymerase chain reaction (PCR)-based sequencing. Histological severity of the gastric mucosa was classified into 4 grades, according to the updated Sydney system. RESULTS: A total of 44 strains were analyzed. Forty-three (97.7 %) were cagA-positive: 26 (60.5 %) were East-Asian-type-cagA, 9 (20.9 %) were Western-type-cagA, and 8 (18.6 %) were novel ABB-type, most of which were obtained from Papuan. EPIYT sequences were more prevalent than EPIYA sequences (P = 0.01) in the EPIYA-B motif of all types of cagA. The majority of cagA-positive strains (48.8 %, 21/43) had a 6-bp deletion in the first pre-EPIYA region. Subjects infected with East-Asian-type-cagA strains with a 6-bp deletion had significantly lower inflammation and atrophy scores in the corpus than those infected with Western-type-cagA strains (both P = 0.02). In total, 70.4 % of strains possessed the vacA s1m1 genotype and 29.5 % were m2. All strains from peptic ulcer patients were of the iceA1 genotype, which occurred at a significantly higher proportion in peptic ulcer patients than that in gastritis patients (55.3 %, P = 0.04). The double positive genotype of jhp0562/ß-(1,3)galT was predominant (28/44, 63.6 %), and subjects infected with this type had significantly higher inflammation scores in the corpus than those with the jhp0562 negative/ß-(1,3)galT positive genotype (mean [median]; 1.43 [1] vs. 0.83 [1], P = 0.04). There were significant differences in cagA and pre-EPIYA cagA type, oipA status, and jhp0562/ß-(1,3)galT type among different ethnic groups (P < 0.05). CONCLUSIONS: In addition to a low H. pylori infection rate, the low incidence of gastric cancer in Indonesia might be attributed to less virulent genotypes in predominant strains, which are characterized by the East-Asian-type-cagA with a 6-bp deletion and EPIYT motif, a high proportion of m2, dupA negative or short type dupA, and the jhp0562/ß-(1,3)galT double positive genotype.

The role of xenobotic metabolism MGST1 gene polymorphism in colorectal cancer patients.

AIM: to asses the role of Microsomal Glutathione S-Transferase1 (MGST1) gene as one of enzym metabolism that plays in enviromental factor. METHODS: using case-control study, subjects with age less than 50 years were collected from teaching hospital Makassar between 2008-2010. Frozen or routinely processed tumour samples biopsy and peripheral blood were obtained from 35 CRC patients undergoing surgery and endoscopic examination with 61 subject as control. CRC cases were diagnosis by clinical examination and confirm by histopathology without familial aggregation of CRC. DNA resequencing was conducted for the 3 kb genomic DNA region MGST1 using PCR-restriction fragment length polymorphism (PCR-RFLP). RESULTS: from 96 subject, two varian single nucleotide polymorphisms (SNPs) 16454T>G and 16416G>A MGST1 were identified. Significant CRC association (p= 0.047) was detected in GG genotipe SNP 16454T>G MGST1 with 3.5 fold risk (95% confidence interval (CI) 0.962-13.191). CONCLUSION: the results suggest that MGST1 gene polymorphisms as one of environment gene may contribute to CRC risk in younger age (<50 years old).

Alpha-fetoprotein gene polymorphisms and risk of HCC and cirrhosis.

BACKGROUND: Elevated level of alpha fetoprotein (AFP) is found in approximately 60% of hepatocellular carcinoma (HCC) cases. Other liver diseases including cirrhosis and chronic hepatitis are related with an increased level of AFP. The regulation of AFP gene expression has been relatively less studied although the gene has been suggested to play a role in HCC development. This study aimed at identifying genetic variations in AFP that might be associated with the presence of HCC and cirrhosis among ethnic Indonesians. METHODS: Direct DNA sequencing was carried out to sequence AFP promoter, exons, and 3' untranslated region (UTR) in DNA samples isolated from 119 HCC, 119 cirrhosis and 105 control subjects. For each sample serum AFP level was determined and association studies with single nucleotide polymorphisms (SNPs) and haplotypes were performed. RESULTS: In this study we identified 47 SNPs in the AFP gene. Statistically significant associations with HCC and cirrhosis were detected for six individual SNPs in the AFP promoter, AFP intron 1 and intron 2 (rs6834059, rs3796678, rs3796677, rs3796676, rs28532518 and rs4646038). Furthermore, we identified two SNPs in AFP intron 7 and 3'UTR, rs2298839 and rs10020432, which are associated with increased risk of cirrhosis. CONCLUSION: Genetic variants in the AFP gene may be associated with HCC and cirrhosis risk for ethnic Indonesians.

Hepatitis B virus subgenotypes and basal core promoter mutations in Indonesia.

AIM: To identify the distribution of hepatitis B virus (HBV) subgenotype and basal core promoter (BCP) mutations among patients with HBV-associated liver disease in Indonesia. METHODS: Patients with chronic hepatitis (CH, n = 61), liver cirrhosis (LC, n = 62), and hepatocellular carcinoma (HCC, n = 48) were included in this study. HBV subgenotype was identified based on S or preS gene sequence, and mutations in the HBx gene including the overlapping BCP region were examined by direct sequencing. RESULTS: HBV genotype B (subgenotypes B2, B3, B4, B5 and B7) the major genotype in the samples, accounted for 75.4%, 71.0% and 75.0% of CH, LC and HCC patients, respectively, while the genotype C (subgenotypes C1, C2 and C3) was detected in 24.6%, 29.0%, and 25.0% of CH, LC, and HCC patients, respectively. Subgenotypes B3 (84.9%) and C1 (82.2%) were the main subgenotype in HBV genotype B and C, respectively. Serotype adw2 (84.9%) and adrq+ (89.4%) were the most prevalent in HBV genotype B and C, respectively. Double mutation (A1762T/G1764A) in the BCP was significantly higher in LC (59.7%) and HCC (54.2%) than in CH (19.7%), suggesting that this mutation was associated with severity of liver disease. The T1753V was also higher in LC (46.8%), but lower in HCC (22.9%) and CH (18.0%), suggesting that this mutation may be an indicator of cirrhosis. CONCLUSION: HBV genotype B/B3 and C/C1 are the major genotypes in Indonesia. Mutations in BCP, such as A1762T/G1764A and T1753V, might have an association with manifestations of liver disease.