Dadang Makmun

International consensus recommendations for difficult biliary access

ERCP is the standard procedure for endoscopic biliary therapy. The endoscopic approach to the ampulla followed by selective deep biliary cannulation is the first step before further therapy. Difficult biliary access can occur during endoscope intubation or when attempting selective biliary cannulation in normal or surgically altered anatomy. Difficult cannulation increases the risk of post-ERCP adverse events, particularly post-ERCP pancreatitis (PEP) and perforation. In normal anatomy, about 11% of therapeutic ERCPs may be considered difficult biliary cannulation. Biliary access in patients with surgically altered anatomy, such as Billroth II or Roux-en-Y anastomosis, is considered difficult because special instruments and maneuvers are often needed. Various methods are used to overcome difficult biliary access, including advanced ERCP-based techniques using precut papillotomy or double guidewires (DGWs), specialized instruments like echoendoscopes or device-assisted enteroscopy, or percutaneous approach. These techniques and procedures are more complex and carry significant risks, requiring specific training. This consensus aims to develop an evidence-based framework for biliary endoscopists to tackle difficult biliary access.

Per oral cholangiopancreatoscopy in pancreatico biliary diseases - Expert consensus statements

AIM To provide consensus statements on the use of per-oral cholangiopancreatoscopy (POCPS). METHODS A workgroup of experts in endoscopic retrograde cholangiopancreatography (ERCP), endosonography, and POCPS generated consensus statements summarizing the utility of POCPS in pancreaticobiliary disease. Recommendation grades used validated evidence ratings of publications from an extensive literature review. RESULTS Six consensus statements were generated: (1) POCPS is now an important additional tool during ERCP; (2) in patients with indeterminate biliary strictures, POCS and POCS-guided targeted biopsy are useful for establishing a definitive diagnosis; (3) POCS and POCS-guided lithotripsy are recommended for treatment of difficult common bile duct stones when standard techniques fail; (4) in patients with main duct intraductal papillary mucinous neoplasms (IPMN) POPS may be used to assess extent of tumor to assist surgical resection; (5) in difficult pancreatic ductal stones, POPS-guided lithotripsy may be useful in fragmentation and extraction of stones; and (6) additional indications for POCPS include selective guidewire placement, unexplained hemobilia, assessing intraductal biliary ablation therapy, and extracting migrated stents. CONCLUSION POCPS is important in association with ERCP, particularly for diagnosis of indeterminate biliary strictures and for intra-ductal lithotripsy when other techniques failed, and may be useful for pre-operative assessment of extent of main duct IPMN, for extraction of difficult pancreatic stones, and for unusual indications involving selective guidewire placement, assessing unexplained hemobilia or intraductal biliary ablation therapy, and extracting migrated stents.

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.

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.

The Causes of Upper Gastrointestinal Bleeding in the National Referral Hospital: Evaluation on Upper Gastrointestinal Tract Endoscopic Result in Five Years Period

Backgrounds: Gastrointestinal bleeding such as hematemesis or melena are common conditions in clinical practice and endoscopic service. The mortality rate due to gastrointestinal bleeding is relatively high. In this study, we evaluate the causes of hematemesis melena for the last 5 years and the factors associated with the bleeding. Methods: The study was done retrospectively. We obtained data from medical record of patients that performed endoscopy of upper gastrointestinal tract in Division of Gastroenterology, Department of Internal medicine, Cipto Mangunkusumo hospital (Jakarta, Indonesia) during the period of 2001 to 2005. Results: Of 4.154 patients who underwent upper gastrointestinal tract endoscopy from 2001 to 2005, we found that 837 patients (20.1%) were due to upper gastrointestinal bleeding. They were 552 male (65.9%) and 285 female patients (34.1%). Mean age of male patients was 52.7 ± 15.82 years, while for female patients was 54.46 ± 17.6 years. Of 837 patients who came due to hematemesis were 150 patients (17.9%), melena were 310 patients (37.8%), both melena and hematemesis were 371 patients (44.3%), 557 cases (66.5 %) due to non varices. Endoscopic results showed that 280 cases (33.4%) were due to esophageal varices. In general, this study had demonstrated that esophageal varices was the most frequent cause of upper gastrointestinal bleeding. We found 229 cases of esophageal varices were coincidence with portal hypertensive gastropathy. While ulcer was found in 225 cases (26.9%) and most of them were gastric ulcer (51.1%). Of gastrointestinal bleeding caused by esophageal varices, most were grade III in 138 cases (49.3%). The incidence of bleeding of bleeding were found more frequently in patients age group of 40 - 60 years (389 cases; 46.5%), > 60 years (305 cases; 36.2%), 60 years, most were caused by ulcer (37.4%). In this study, we also found that cancer as the cause of gastrointestinal bleeding in 26 cases (3.1%). Gastrointestinal cancer comprised of gastric cancer in 15 cases (57.7%), duodenal cancer in 7 cases (26.9%), and esophageal cancer in 4 patients (15.4%). Conclusion: The most frequent cause of upper gastrointestinal bleeding was esophageal varices and usually had reached stage III. The non variceal cause of bleeding was gastric cancer. Upper gastrointestinal malignancy was also found to be the etiology of bleeding in this study. Keywords : upper gastrointestinal bleeding, endoscopy

Ramadan Fasting Decreases Body Fat but Not Protein Mass.

Background: Many studies have shown various results regarding the effects of Ramadan fasting on weight and body composition in healthy individuals. Objectives: This study aimed to evaluate the effect of Ramadan fasting on body composition in healthy Indonesian medical staff. Objectives: In this study, we examined the influence of Ramadan fasting on body composition in healthy medical staff. Patients and Methods: The longitudinal study was performed during and after Ramadan fasting in 2013 (August to October). Fourty-three medical staff members (physicians, nurses and nutritionists) at the Internal Medicine Ward of the Dr. Cipto Mangunkusumo General Hospital were measured to compare their calorie intake, weight, body mass index, waist-to-hip ratio (WHR), and body composition, including body fat, protein, minerals and water, on the first and 28th days of Ramadan and also 4-5 weeks after Ramadan fasting. Measurements were obtained for all 43 subjects on the 28th day of Ramadan, but they were obtained for only 25 subjects 4 - 5 weeks after Ramadan. Results: By the 28th day of Ramadan, it was found that the body weight, BMI, body fat, water and mineral measures had decreased significantly (-0.874 ± 0.859 kg, P < 0.001; -0.36 ± 0.371 kg/m2, P < 0.001; -0.484 ± 0.597 kg, P < 0.001; -0.293 ± 0.486 kg, P = 0.001; -0.054 ± 0.059 kg, P < 0.001, respectively). Protein body mass and calorie intake did not significantly change (-0.049 ± 0.170 kg, P = 0.561; 12.94 ± 760.608 Kcal, P = 0.082 respectively). By 4 - 5 weeks after Ramadan, body weight and composition had returned to the same levels as on the first day of Ramadan. Conclusions: Ramadan fasting resulted in weight loss even it was only a temporary effect, as the weight was quickly regained within one month after fasting. The catabolism catabolic state, which is related to protein loss, was not triggered during Ramadan fasting. Further research is needed to evaluate the effects of weight loss during Ramadan fasting in healthy individuals.

Present status of endoscopy, therapeutic endoscopy and the endoscopy training system in Indonesia

Recently, Indonesia was ranked as the fourth most populous country in the world. Based on 2012 data, 85 000 general practitioners and 25 000 specialists are in service around the country. Gastrointestinal (GI) disease remains the most common finding in daily practise, in both outpatient and inpatient settings, and ranks fifth in causing mortality in Indonesia. Management of patients with GI disease involves all health‐care levels with the main portion in primary health care. Some are managed by specialists in secondary health care or are referred to tertiary health care. GI endoscopy is one of the main diagnostic and therapeutic modalities in the management of GI disease. Development of GI endoscopy in Indonesia started before World War II and, today, many GI endoscopy procedures are conducted in Indonesia, both diagnostic and therapeutic. Based on August 2013 data, there are 515 GI endoscopists in Indonesia. Most GI endoscopists are competent in carrying out basic endoscopy procedures, whereas only a few carry out advanced endoscopy procedures, including therapeutic endoscopy. Recently, the GI endoscopy training system in Indonesia consists of basic GI endoscopy training of 3–6 months held at 10 GI endoscopy training centers. GI endoscopy training is also eligible as part of a fellowship program of consultant gastroenterologists held at six accredited fellowship centers in Indonesia. Indonesian Society for Digestive Endoscopy in collaboration with GI endoscopy training centers in Indonesia and overseas has been working to increase quality and number of GI endoscopists, covering both basic and advanced GI endoscopy procedures.

The Value of Caspase-3 after the Application of Annona muricata Leaf Extract in COLO-205 Colorectal Cancer Cell Line

Annona muricata, commonly known as soursop, contains annonacin, acetogenin, and polyphenol which are known to have chemopreventive effects on cancer. In this study, we tend to evaluate the apoptosis-inducing effect of soursop (Annona muricata) leaf extract on the colorectal cancer cell line COLO-205 through the activities of caspase-3 which is a marker of cell apoptosis. Cell cultures were incubated with soursop leaf with a concentration of 10 μg/ml and then compared with those of the incubated positive control leucovorin 10 μg/ml and placebo as a negative control. The apoptotic activity of caspase-3 was measured with ELISA. After the administration of each treatment in the colorectal cancer cell line COLO-205, the expression of caspase-3 activity was 1422 ng/ml after incubation with the extract of Annona muricata leaves, 1373 ng/ml after the administration of leucovorin, and 1297 ng/ml in the one with placebo. Annona muricata leaf extract elevated caspase-3 by 1.09 times compared to that of the pure cell line. Annona muricata leaf extract had a higher value of caspase-3 activity than leucovorin and placebo in the COLO-205 colorectal cancer cell line. These results may suggest that Annona muricata leaf extract had anticancer properties by enhancing caspase-3 activity which is a proapoptotic marker.

New insights on the pathomechanisms of inflammatory bowel disease

Pathogenesis of inflammatory bowel disease (IBD) remains an enigma on whether germs, genes or a combination of these two with excessive immune responses to gut‐associated bacteria explicates its pathomechanisms. The incidence of IBD is 0.76747 per 100 000 in Central Indonesia, as shown in the Project Indonesian IBD ACCESS 2012 progress report. This result, together with other epidemiological studies in Asia, may conclusively reflect increased rates of the disease, while its pathogenesis still undoubtedly obscured. However, knowledge of the pathophysiology of IBD is rapidly growing, abreast with new developments. A series of recent updates in core pathomechanisms such as bacterial, endoplasmic reticulum stress, new immune cell populations, T‐cell differentiation and function, mucosal immune defenses and oxidative stress are relevant pathomechanism keypoints in IBD.

Upper Gastrointestinal Malignancy among Dyspepsia Patients in Cipto Mangunkusumo Hospital Jakarta

Background : Upper gastrointestinal (GI) malignancy was still a health problem in all over the world. The prevalence of the upper GI malignancy vary among Asian countries. Data from Indonesia was scarcely reported. The aim of this study is to determine the frequency of upper GI malignancy among dyspepsia patients who underwent esophagoduodenoscopy (EGD) procedure. Method : This is a retrospectives study from subject with dyspepsia that had underwent upper GI endoscopy at the Department of Internal Medicine Cipto Mangunkusumo hospital from January 2005 to December 2007. All complete data from medical report and histopathology appearance will be recorded. Results : Out of 2,116 subjects underwent endoscopy due to dyspepsia, 110 (5.19%) subjects was diagnosed as cancer. This upper GI malignancy consisted of gastric cancer in 63 (2.97%) cases, esophageal cancer 32 (1.51%) and duodenal cancer 15 (0.71%). The mean ages of the subjects was 53.36 ± 10.97 years, age less than 45 years was 20 (18.20%) subjects, more than 45 years was 90 (81.18%), male 71 (64.50%) subjects, female 39 (35.50%). Most of them had alarm signs 96 (87.30%). Histopathology finding showed adeno-carcinoma in 75 (68.20%) cases, signet ring cell carcinoma in 14 (12.70%), squamous cell carcinoma in 8 (7.30%), others in 13 (11.80%). Out of 59 gastric cancer, 48 (76.20%) cases was located at distal part while the rest 11 (17.50%) cases was located at the proximal gaster, and 4 (6.30%) in diffuse. By the ethnics founded Javanese 37 (33.60%) subjects, Betawinese 22 (20.00%), Sundanese 12 (10.90%) and Batak 13 (11.80%) . Conclusions : Upper GI malignancy was found in five percent of subjects with dyspepsia who undergo colonoscopy. The three most frequent malignancies were gastric carcinoma, esophageal carcinoma, and duodenal carcinoma respectively. Most of gastric adenocarcinoma was located at distal stomach. Keywords : upper gastrointestinal malignancy, dyspepsia, endoscopy, alarm sign, histopathology