Genomic profiles of Indonesian colorectal cancer patients.

Background: Colorectal cancer (CRC) is one of the most commonly diagnosed cancers worldwide and genetic mutation plays a vital role in CRC development. A previous study has suggested that genetic alterations among Indonesian patients with CRC might differ from those known in developed countries. This study aimed to describe the genomic profiles of Indonesian patients with CRC. Methods: A total of 13 patients were recruited for this study from May to July 2019. Tissue samples were collected, and genomic DNA was extracted from the samples. AmpliSeq for Illumina Cancer HotSpot Panel v2 Next-generation sequencing was used for DNA sequencing and a genome analysis toolkit was used for local realignment around the discovered variants. Results: A total of 45 genes comprising 391 single nucleotide variants (SNVs) with a depth >10 were observed. The genes with the most variants were STK11, SMAD4, EGFR, and ERBB4 and the genes with the most non-synonymous variants were SMAD4, TP53, FGFR3, CDKN2A, and STK11. Genes and SNVs in at least 90% of all samples consisted of 43 genes comprising 286 variants. Genes with the most non-synonymous SNVs were EGFR, SMO, FGFR3, TP53, STK11, CDKN2A. Genes related to the chromosomal instability pathway, such as TP53, SMAD4, KRAS, and APC, are also found in the analysis. Conclusions: Our findings showed that all patients with CRC in this study had genetic mutations in the chromosomal instability pathway. Analysis of genetic mutation of Indonesian patients with CRC might be crucial for advanced targeted therapy and for better clinical outcomes.

Colorectal cancer patients in a tertiary hospital in Indonesia: Prevalence of the younger population and associated factors.

BACKGROUND: An increasing trend in colorectal cancer (CRC) occurring at younger ages has been observed worldwide, even though incidence is declining in the general population. Most currently available guidelines still recommend CRC screening for older populations, despite an alarming rise in early-onset CRC incidence. Risk stratification is necessary to further determine the population most at risk for early-onset CRC. However, epidemiological data on related clinical characteristics and potential risk factors, especially in developing countries, have not been widely reported. AIM: To investigate the prevalence, demographics, clinicopathologic features, and associated factors of young-onset CRC patients in a tertiary hospital in Indonesia. METHODS: Patients undergoing colonoscopy examination between 2008 and 2019, yielding a diagnosis of CRC were identified from medical records. The subjects were classified into two groups according to their age at diagnosis, namely early-onset (18-49 years old) and late-onset (≥ 50-years-old). Demographic data, characteristics, and risk factors of both onset age groups were evaluated using the chi-square and Fisher's exact test. RESULTS: Among 495 CRC patients confirmed by histopathology, 205 (41.4%) were classified as early-onset and 290 (58.6%) as late-onset. Most subjects in the early-onset CRC group were male (53.7%), with 89.8% displaying adenocarcinoma histopathology. A majority (78%) of the early-onset CRC patients had left-sided tumors, with the rectum (41%) and rectosigmoid (17.6%) being the most common sites. Abdominal pain was the most frequent symptom in the early-onset CRC patients (55.6%), which was significantly higher than that in the late-onset CRC patients (43.8%, P < 0.05). Early-onset CRC cases were more likely to be underweight (34.6% vs 20.0%, P < 0.001) compared to late-onset CRC cases. The proportion of subjects with suspected hereditary nonpolyposis colorectal cancer (HNPCC) was also higher in the early-onset CRC group than in the late-onset age group (9.3% vs 4.1%, P < 0.05). However, no difference was observed in the parental or family histories of CRC cases. CONCLUSION: Early-onset CRC patients were more likely to have abdominal pain, underweight status, and HNPCC suspicion than late-onset CRC patients.

Survival, stent patency, and cost-effectiveness of plastic biliary stent versus metal biliary stent for palliation in malignant biliary obstruction in a developing country tertiary hospital.

BACKGROUND AND AIM: Patients with advanced malignant obstructive jaundice often require biliary drainage. Resources restraint makes clinicians need to outweigh effectiveness of each biliary stents and their costs. Hence, a cost-effectiveness analysis is necessary. METHODS: A retrospective cohort study was done on malignant biliary obstruction patients undergoing palliative biliary stenting between January 2015 and December 2018. We evaluated 180-day survival rate using log-rank test and stent patency duration using Mann-Whitney U test. Effectiveness was defined as stent patency, while cost was calculated using hospital perspective using decision tree model and reported as incremental cost-effectiveness ratio. RESULTS: A total of 81 men and 83 women were enrolled in this study. One hundred and eighty days survival rate was 35.9% (median 76 days, 95% confidence interval [CI] 50-102 days) and 33.3% (median 55 days, 95% CI 32-78 days), while average stent patency was 123 (8) days versus 149 (13) days for plastic and metal stent groups, respectively (P > 0.05). Metal stent could save Indonesian Rupiah (IDR) 1 217 750 to get additional 26 days of patency. CONCLUSION: There were no differences in survival and stent patency between the two groups. Metal biliary stent is more cost-effective than plastic stent for palliation in malignant biliary obstruction.

The role of per oral cholangiopancreatoscopy (POCPS) in complicated pancreaticobiliary disease.

A fifty-five year old female patient presented with jaundice, subfebrile fever and dark yellow urine since one month before admission. She lost weight 10 kilograms during one month. One day before admission to Ciptomangunkusumo General Hospital, she complained of worsened abdominal pain at right upper quadrant urging her to come to the emergency room. An abdominal examination revealed Murphy sign, mild hepatomegaly and deeply icteric sclera. Serum bilirubin was 21.8 mg/dl, alkaline phosphatase and gamma-glutamyltransferase levels were significantly elevated (1090 IU/L and 560 IU/L consecutively) while the transaminases were moderately high (ALT 80 U/L). The C-reactive protein was 555 mg/L. An abdominal ultrasound examination revealed dilatation of right and left intrahepatic bile duct and presence of common hepatic duct stone. Subsequent magnetic resonance imaging/magnetic cholangiopancreatography (MRI/MRCP) revealed intrahepatic bile duct dilatation, multiple CBD stone and benign stricture at common hepatic duct causing right and left intrahepatic bile duct obstruction.We assessed the patient as acute cholangitis and obstructive jaundice suspected to be caused by biliary duct stone then we performed endoscopic retrograde cholangiopancreatography (ERCP), we revealing stenosis at distal CBD, multiple CBD stone, giant stone in CHD and dilatation of bilateral IHBD. We performed CBD stone extraction then inserted biliary stent for drainage. Then we planned to do second ERCP with SpyGlassTM for giant stone extraction. After the first ERCP, the clinical condition of the patient improved and the bilirubin decreased to 10 mg/dL. In the next two weeks we performed a second ERCP to extract the giant stone with SpyGlass TM. However, after we inserted SpyGlassTM into the biliary duct, what we found were not as we expected before. We revealed that there was a mass in biliary duct and there was no CBD stone. We did the biopsy and inserted a new plastic stent (after removed the older one) to the common biliary duct. Surprisingly, the result of histopathology also supports our findings, which was the adenocarcinoma at common bile duct.

Survey of clinical practice for irritable bowel syndrome in East asian countries.

AIM: Sociocultural factors are important because their different effects on the features of irritable bowel syndrome (IBS) between countries will provide clues towards solving this problem. The aims of this study were to depict the clinical realities of IBS in East Asian countries and test the hypothesis that the diagnosis and treatment of IBS differ between countries. SUBJECTS AND METHODS: Study participants were 251 physicians involved in the clinical practice of IBS at major institutions in Japan, South Korea, China, the Philippines, Indonesia and Singapore. The questionnaire contained 45 questions focused on the clinical practice of IBS. RESULTS: Subjects in Japan, South Korea, China, Indonesia, the Philippines and Singapore accounted for 55.4, 17.9, 8.8, 8.0, 6.4 and 3.6% of the study cohort, respectively. Amongst East Asian physicians, the most important symptom was considered to be abdominal pain by 33.4%, whilst 24.3% regarded alternating diarrhea and constipation to be the most important symptoms. Total colonoscopy and histopathology use showed no difference among countries. Prescriptions given for mild (p < 0.0001), moderate (p < 0.0001), severe (p < 0.0001), intractable (p = 0.002), diarrheal (p < 0.0001) and constipating (p < 0.0001) patients with IBS significantly differed between the countries. Except for several minor points, IBS specialists showed no significant difference in their diagnosis and treatment of IBS when compared to nonspecialists. CONCLUSION: This survey provided data on the clinical treatment of IBS among East Asian countries. The results supported the hypothesis that the diagnosis and treatment of IBS differs between countries.

The value of fecal tumor M2 pyruvate kinase as a diagnostic tool for colorectal cancer screening.

AIM: to evaluate the performance of fecal tumor M2 pyruvate kinase (M2PK) as a diagnostic biomarker for colorectal cancer (CRC) screening in high-risk or symptomatic populations. METHODS: consecutive patients (N=328) who were referred for elective colonoscopy were prospectively enrolled. One walnut-sized stool sample was collected from each patient for analysis of tumor M2PK content using an ELISA kit. No dietary restrictions were applied. The clinical pathologists who conducted the M2PK analyses were blinded to the patients' confirmed diagnoses. Levels of fecal tumor M2PK were compared with histopathological results from colorectal biopsies. RESULTS: of the 328 patients who underwent colonoscopy examinations, 197 (60.1%) were men and 131 (39.9%) were women. Based on histopathological examination, 83 (25.3%) patients had normal bowel histology, 42 (12.8%) patients had CRC, 67 (20.4%) patients had adenoma, 19 (5.8%) patients had inflammatory bowel disease, three (0.9%) patients had amoebic colitis, and 114 (34.8%) patients had infective colitis. The cutoff level for tumor M2PK concentration was defined as 4.00 U/mL. The sensitivity, specificity, positive predictive value, and negative predictive value of the M2PK test were 71.4%, 71.0%, 73.5%, and 94.4%, respectively. There was a significant association between CRC and fecal tumor M2PK level (P<0.001). The M2PK test detected 16 tumors among 67 (23.9%) cases of adenoma, eight tumors among 19 (42.1%) cases of inflammatory bowel disease, 35 tumors among 114 (30.7%) cases of infective colitis, and two tumors among three (66.7%) cases of amoebic colitis. CONCLUSION: the fecal tumor M2PK test has good sensitivity and specificity for CRC detection, especially in high-risk or symptomatic populations.

The effectiveness of endoscopic retrograde cholangiopancreatography in the management of patients with jaundice at Cipto Mangunkusumo Hospital, Jakarta.

AIM: to evaluate endoscopic retrograde cholangiopancreatography (ERCP) benefits in treating patients with clinical appearance of yellowish discoloration. METHODS: a descriptive retrospective cross-sectional study was performed on 122 patients at Cipto Mangunkusumo Hospital from January 2008 to December 2010. The main complained was yellowish discoloration of the skin. ERCPs were performed as appropriate, and then the distribution of disease entity, results of procedure and complications were noted. RESULTS: subjects of this study consist of 63 males (52%) and 59 females (48%), 7 patients have undergone ERCP 2 times. Data showed 63 cases (51%) were indicated by stone and 52 cases (43%) by tumor/mass and 7 cases by infection (6%). Ten out of 122 cases (7%) showed normal results. Difficult canulation was encountered in 23 cases (18%) as access to the CBD could not be obtained. From 53 cases with stone, the extraction was successful in 43 (81%) including while 12 procedures with high grade of difficult ERCP left stone remnants (23%), and the remaining 10 procedures entailed stones retention (19%). Radioopaque stones found in 2 cases (4%) and radioluscent in 51 cases (96%). Stent placement was done in CBD (30 cases, 83%), pancreatic duct (4 cases, 11%), and extraneous CBD (2 cases, 5%). Complications found 3 cases (2%) migration stent outside CBD in 2 cases, 1 case with crand radioluscentin 51 acked basket. CONCLUSION: ERCP procedure is really helpful in assisting clinicians to diagnose and manage therapeutic measures, especially in pancreaticobilliar tract disorder, while performing stone extraction and stent placement.

Gastric ulcers induced by systemic hypoxia.

AIM: to assess the effect of systemic hypoxia on gastric mucosa and the activation of stress-responsive transcription factors induced by hypoxia. METHODS: in this experimental study, rats were allocated to control and experimental groups. The experimental group was divided into subgroups and subjected to hypoxia conditions for 1, 7, 14 or 21 days. Afterwards, histopathological evaluation and study of the protein expression of the gastric mucosa were performed. RESULTS: the results showed that longer exposure to hypoxic conditions leads to more severe gastric ulceration. Twenty-four hours after induction, 60% of rats had developed gastric ulcers. Seven days after induction, 80% of rats developed gastric ulcers. In the 14-day and 21-day hypoxia conditions, epithelialization (a sign of gastric ulcer healing) was observed. Evaluation of the average ulcer depth on the day of treatment showed that the greatest depth was on day 7, and the shallowest was on day 21 of treatment. Western blot analyses demonstrated that systemic hypoxia resulted in the expression of heat shock factor (HSF) and heat shock protein 70 (HSP-70), which were highest on day 7 and then regressed gradually. In control, HSF-1 and HSP-70 were not detected by Western blot analysis in the control group (normoxia). CONCLUSION: in this study, systemic hypoxia caused gastric ulcers, and during the time of exposure to hypoxia, an adaptation process in the form of gastric epithelialization occurred in the rats. This development of gastric lesions was in line with the expression pattern of HSF-1 HIF-1 and HSP-70.

Side effects of endoscopic variceal ligation by using Indonesian Endoscopic Ligator versus Endoscopic Variceal Sclerotherapy.

AIM: to investigate the side effects and survival of endoscopic variceal ligation by using Indonesian Endoscopic Ligator versus Endoscopic Variceal Sclerotherapy. METHODS: we studied the medical records and endoscopy reports of patients who underwent endoscopic variceal ligation (EVL) or endoscopic sclerotherapy (EST) from January 2003 until December 2006. EST was done using ethoxysclerol injection; and ligation was done using a home-made Indonesian endoscopic ligating device. Patient characteristics, side effects of EVL and EST, as well as survival and length of stay were collected. Data of side effects was analyzed by chi-square test. RESULTS: there were no statistically significant differences of patients characteristics among both groups. The side effects in EVL group (29.2%) were less frequent than the EST group (60.9%) (p = 0.009). The death side effect in the EVL group (1.0%) was less frequent than in the EST group (21.7%) (p<0.001). The four-year survival in patients who had EVL and EST were 91.7% and 16.7%, respectively (p<0.001). CONCLUSION: EVL had fewer side effects than EST in the treatment of esophageal varices bleeding. Death in the EVL group was lower than in the EST group.

Clinical evaluation of dyspepsia in patients with functional dyspepsia, with the history of Helicobacter pylori eradication therapy in Cipto Mangunkusumo Hospital, Jakarta.

AIM: to obtain the proportion of dyspepsia symptom in non-ulcerative dyspepsia patient after eradication treatment of H. pylori, and recent status of H. pylori after eradication therapy. METHODS: cross-sectional study in patients with history symptoms of dyspepsia in non ulcer dyspepsia with positive H. pylori and had been administered eradication treatment of H. pylori for 1 week in 2002-2007 period. Conditions that influence the result of urea breath test such as proton pump inhibitor, antibiotic treatment, and gastric malignancy have been excluded. Patients were invited to be interviewed about current symptoms of dyspepsia and then underwent urea breath test (UBT) examination to identify H. pylori. Global overall symptom of dyspepsia scale was used to assess the symptoms of dyspepsia. RESULTS: twenty one patients (14 male and 11 female) fulfilled the eligibility criteria for this study, 9 patients with eradication treatment history less than 1 year, and 12 patients more than 1 year. The symptoms of dyspepsia were evaluated and as many as 17 patients (81%) dyspepsia symptoms' were subsided and 4 patients had persistent symptoms after eradication. After eradication treatment, 17 patients (81%) resulted with negative Helicobacter pylori findings, and 4 patients remained positive. One patient of the positive group was reinfected by H. pylori, proved by previous negative result of UBT. In the negative group, 13 patients (76.4%) dyspepsia symptoms' were free from dyspepsia symptoms, and 4 patients had persistent symptoms. All the symptoms of the patients in the positive group were relieved. CONCLUSION: majority of patients had improvement of dyspepsia symptoms after eradication treatment, and 81% of patients had negative H. pylori findings, proved by UBT after eradication. The percentage of symptomatic improvement on H. pylori negative patients after eradication is 76.4%.

Helicobacter pylori infection and gastropathy: a comparison between Indonesian and Japanese patients.

AIM: To compare the effects of Helicobacter pylori (H. pylori) infection on gastropathy between Indonesian and Japanese patients. METHODS: Biopsy specimens were obtained during upper gastrointestinal endoscopy from 167 subjects (125 Indonesians and 42 Japanese) with uninvestigated symptoms of dyspepsia. The specimens were analyzed for the presence of H. pylori using urease analysis, histopathology, and cell culture. The grade and activity of gastritis was assessed using the updated Sydney system. RESULTS: The percentages of Indonesian and Japanese patients who were H. pylori-positive at the antrum or body of the stomach were similar (68% and 59.5%, respectively; P = 0.316). Of those who were H. pylori-positive, more Japanese patients than Indonesian patients had high levels of polymorphonuclear cells (P = 0.001), mononuclear cells (P = 0.013), glandular atrophy (P = 0.000), and intestinal metaplasia (P = 0.011) in both the antrum and body of the stomach. CONCLUSION: The grade of gastritis and prevalence of mucosal atrophy and intestinal metaplasia were higher in Japanese patients. The difference between Indonesian and Japanese patients was significant.