Cost-effectiveness of albumin in the treatment of decompensated cirrhosis in resource-limited healthcare settings.

Background: Human albumin (HA) is an effective adjuvant treatment for patients with cirrhosis developing spontaneous bacterial peritonitis (SBP), hepatorenal syndrome (HRS) and ascites requiring large-volume paracentesis (LVP). However, cost remains a barrier to use, particularly in resource-limited settings. This study aims to assess the cost-effectiveness of HA in patients with cirrhosis with SBP, HRS or ascites requiring LVP in the Indonesian healthcare system as a representative of a resource-limited setting. Methods: Three decision-tree models were developed to assess the cost-effectiveness of (1) antibiotics and HA versus antibiotics alone in patients with SBP, (2) terlipressin and HA versus terlipressin alone in patients with HRS, and (3) LVP and HA versus LVP and gelatine for patients with ascites. Clinical utility and economic inputs were pooled from the available literature. Time horizon was 3 months. Outcomes were expressed as incremental cost-effectiveness ratios (ICER) reported as 2021 IDR per quality-adjusted life year (QALY) (exchange rate June 30, 2021: 1 EUR = 17,245 IDR). Willingness-to-pay thresholds considered were: three times the GDP per capita (199,355,561 IDR/QALY; 11,560 EUR/QALY) and one time the GDP per capita (66,451,854 IDR/QALY; 3853 EUR/QALY). Results: The ICER for antibiotics and HA (versus antibiotics alone) for SBP was 80,562,652 IDR per QALY gained (4672 EUR/QALY). The ICER for terlipressin and HA (versus terlipressin) for HRS was 23,085,004 IDR per QALY gained (1339 EUR/QALY). The ICER for LVP and HA versus LVP and gelatine was 24,569,827 IDR per QALY gained (1425 EUR/QALY). Conclusion: Adjunctive HA may be a cost-effective treatment for SBP, HRS and LVP in resource-limited settings.

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.

A survey of colonoscopists with and without in-depth knowledge of water-aided colonoscopy.

BACKGROUND AND AIM: Endoscopy featured water-aided colonoscopy (WAC) as novel in the Innovation Forum in 2011. Gastrointestinal Endoscopy published a modified Delphi consensus review (MDCR) that supports WAC for clinical practice in 2021. We tested the hypothesis that experience was an important predictor of WAC use, either as water immersion (WI), water exchange (WE), or a combination of WI and WE. METHODS: A questionnaire was sent by email to the MDCR authors with an in-depth knowledge of WAC. They responded and also invited colleagues and trainees without in-depth knowledge to respond. Logistic regression analysis was used with the reasons for WAC use treated as the primary outcome. Reports related to WAC post MDCR were identified. RESULTS: Of 100 respondents, > 80% indicated willingness to adopt and modify practice to accommodate WAC. Higher adenoma detection rate (ADR) incentivized WE use. Procedure time slots ≤ 30 and > 30 min significantly predicted WI and WE use, respectively. Co-authors of the MDCR were significantly more likely to perform WAC (odds ratio [OR] = 7.5, P = 0.037). Unfamiliarity with (OR = 0.11, P = 0.02) and absence of good experience (OR = 0.019, P = 0.002) were associated with colonoscopists less likely to perform WAC. Reports related to WAC post MDCR revealed overall and right colon WE outcomes continued to improve. Network meta-analyses showed that WE was superior to Cap and Endocuff. On-demand sedation with WE shortened nursing recovery time. CONCLUSIONS: An important predictor of WAC use was experience. Superior outcomes continued to be reported with WE.

Potential plasma biomarkers: miRNA-29c, miRNA-21, and miRNA-155 in clinical progression of Hepatocellular Carcinoma patients.

This study evaluated differences in the clinical appearance of patients with hepatocellular carcinoma (HCC) based on plasma level and regulation of microRNAs (miRNA-29c, miRNA-21, and miRNA-155). The observational-analytical study with a cross-sectional design was conducted on 36 HCC patients and 36 healthy controls. The blood samples were collected from 2 Province Hospitals (Dr. Sardjito Hospital and Prof. Dr. Margono Soekarjo Hospital) for HCC and the Blood Bank Donor of the Indonesian Red Cross for 36 healthy controls. These blood samples were treated as follows: plasma isolation, RNA isolation, cDNA synthesis, quantification by qRT-PCR using a sequence-specific forward primer, and normalization of miRNA using housekeeping-stably miRNA-16. There were only 27 HCC patients with complete clinical variables (neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), platelet count, albumin, C-reactive protein (CRP), and cholinesterase (ChE)) that were able to analyses for regulation miRNAs based on its fold change expression miRNA target. All 27 HCC subjects were follow-up until 3-years of monitoring for their overall survival. The miRNA plasma expression was analyzed by Bio-Rad CFX 96 Manager software to determine the cycle of quantification, followed by the calculation of expression levels using Livak's methods. Data were analyzed using STATA 11.0, with a significant value of p<0.05. The miRNAs expression of HCC subjects were lower than that healthy control subjects in miRNA-29c (down-regulation 1.83-fold), higher than that healthy control subjects in miRNA 21 and miRNA-155 (up-regulation, 1.74-fold; 1.55-fold) respectively. NLR, CRP, ChE, and platelet count showed a significant difference in miRNA-29c regulation, though neutrophil count showed a significant difference in miRNA-21 and miRNA-155 regulation (p<0.05). Conclusion: Plasma biomarkers: miRNA-21 and miRNA-155 might be potential biomarkers as onco-miR in HCC subjects, while miRNA-29c might act as a tumor suppressor. Significant evidence was identified with clinical progression based on the regulation of miRNAs, which was consistent with miRNA -29c.

Clinical Application of Stem Cell Therapy for Liver Cirrhosis: Progress, Pitfalls, and Prospects.

Liver cirrhosis is the advanced stage of liver disease accounting for high morbidity and mortality rates worldwide. Liver transplantation for liver cirrhosis has several limitations, rendering stem cell transplantation as a potential therapy. Clinical trials of stem cell applications for liver cirrhosis are being established using various types of stem cells. This review will provide a current report of the achievements, limitations, and future directions of stem cell transplantation. Current progress of clinical trials is valuable in defining the best type of stem cells, mode of delivery, the number and frequency of cells to be injected, and determining potential candidates for cell therapy. Some of the encountered pitfalls are the limited homing and differentiation potential of stem cells, the use of non-xenofree culture system, and the risk for tumorigenesis in certain types of stem cells. The prospective developments of liver stem cell transplantation are the generation of genetically modified stem cells and the formation of liver organoids for treating liver cirrhosis.

Water-assisted colonoscopy: an international modified Delphi review on definitions and practice recommendations.

BACKGROUND AND AIMS: Since 2008, a plethora of research studies has compared the efficacy of water-assisted (aided) colonoscopy (WAC) and underwater resection (UWR) of colorectal lesions with standard colonoscopy. We reviewed and graded the research evidence with potential clinical application. We conducted a modified Delphi consensus among experienced colonoscopists on definitions and practice of water immersion (WI), water exchange (WE), and UWR. METHODS: Major databases were searched to obtain research reports that could potentially shape clinical practice related to WAC and UWR. Pertinent references were graded (Grading of Recommendations, Assessment, Development and Evaluation). Extracted data supporting evidence-based statements were tabulated and provided to respondents. We received responses from 55 (85% surveyed) experienced colonoscopists (37 experts and 18 nonexperts in WAC) from 16 countries in 3 rounds. Voting was conducted anonymously in the second and third round, with ≥80% agreement defined as consensus. We aimed to obtain consensus in all statements. RESULTS: In the first and the second modified Delphi rounds, 20 proposed statements were decreased to 14 and then 11 statements. After the third round, the combined responses from all respondents depicted the consensus in 11 statements (S): definitions of WI (S1) and WE (S2), procedural features (S3-S5), impact on bowel cleanliness (S6), adenoma detection (S7), pain score (S8), and UWR (S9-S11). CONCLUSIONS: The most important consensus statements are that WI and WE are not the same in implementation and outcomes. Because studies that could potentially shape clinical practice of WAC and UWR were chosen for review, this modified Delphi consensus supports recommendations for the use of WAC in clinical practice.

The Effectiveness of Right- vs Left-lateral Starting Position in Unsedated Diagnostic Colonoscopy with Modified-water Immersion Method: A Randomized Controlled Trial Study.

OBJECTIVE: A colonoscopy study in sedated patients with air insufflation showed that right-lateral starting position (RLP) improved abdominal discomfort and reduced cecal intubation time. The aim of this study was to determine if RLP vs left-lateral starting position (LLP) may produce similar results in unsedated patients examined with a modified-water immersion (m-WI) method. METHODS: Consecutive patients for diagnostic colonoscopy meeting the inclusion criteria were randomized. Patients and colonoscopist were unblinded. The m-WI method entailed suction during insertion not only for fecal debris evacuation but also to facilitate passage through difficult or angulated colonic flexures. Water was infused as needed when any difficulty was encountered during insertion. A bowel visualization scale (BVS) (0=totally blurred visualization; 1=blurred lumen visualization; 2=small fecal debris with clear mucosa visualization; 3= clear visualization) was used to evaluate the interference of fecal debris with cecal intubation rate and time. RESULTS: A total of 142 patients (72 in RLP and 70 in LLP) were enrolled. The respective pain score, visual analog scale, (VAS) and cecal intubation rate were not significantly different. The cecal intubation time was nearly significantly different (13.4±4.5 min vs 11.7±5.4 min; p=0.054) and was significantly different in the constipation subgroup (16.0±3.5 min vs 8.6±3.8 min; p=0.001). The cecal intubation time based on BVS showed significant difference between RLP and LLP in Scale 2 (13.9±4.6 min vs 10.3±4.2 min; p=0.003) and Scale 2 and 3 combined (13.2±4.3 min vs 10.6±4.8 min; p=0.01), respectively. CONCLUSION: RLP did not improve the pain score, and LLP showed better performance in unsedated m-WI colonoscopy patients (ClinicalTrial.gov, NCT03489824).

Impressive Response to Capecitabine in a Patient with Obstructive Jaundice due to Metastatic Triple-Negative Breast Cancer.

BACKGROUND: Metastatic breast cancer with obstructive jaundice due to para-aortic lymph node enlargement is an unusual case that poses a therapeutic challenge in determining a chemotherapy regimen. CASE REPORT: A 61-year-old woman presented with triple-negative left invasive ductal breast carcinoma with liver and pulmonary metastases. After receiving gemcitabine and carboplatin as the 4th-line treatment, chemotherapy was postponed due to an increased bilirubin level. Abdominal imaging revealed para-aortic lymph node metastases compressing the distal common hepatic duct. The patient then received capecitabine along with ursodeoxycholic acid. This relieved her jaundice after 8 cycles of chemotherapy, and radiologic evaluation revealed a complete resolution of the obstructive jaundice. CONCLUSION: This finding emphasizes the success of capecitabine regimen as a salvage therapy in a metastatic breast cancer patient with hyperbilirubinemia and opens up the possibility of optimizing systemic chemotherapy for metastatic obstructive jaundice in the setting of limited facility resources.

Endoscope-connected water pump with high flow rates improves the unsedated colonoscopy performance by water immersion method.

OBJECTIVES: The aim of this study was to determine if different water pump flow rates influence the insertion time of water immersion method in unsedated patients. We tested the hypothesis that high flow rate (HFR) is more effective than low flow rate (LFR) in facilitating insertion. Clinical registration number: NCT01869296. METHODS: Consecutive symptomatic patients without prior abdominal surgery were consented and enrolled. They were randomized to an HFR (10.4 mL/s) or LFR (1.7 mL/s) group. The patients were not informed about the flow rate of the water pump (single blinded). Patients underwent unsedated colonoscopy examination with standard colonoscope. Demographic and procedural parameters were recorded. Data were analyzed with Student's t-test or Chi-square test as appropriate. RESULTS: A total of 132 patients (66 in HFR and 66 in LFR group) were recruited. The HFR group showed significantly shorter cecal intubation time (12.5±6.2 min in HFR vs 16.3±7.3 min in LFR, p=0.004), shorter time to pass rectosigmoid (3.6±2.2 min in HFR vs 6.2±4.6 min in LFR, p<0.001), and lower pain score (4.2±2.8 in HFR vs 5.3±2.6 in LFR, p=0.024). The cecal intubation rate was not significantly different (87.9% in HFR vs 80.3% in LFR, p=0.34), and 29 (14 in HFR and 15 in LFR) patients with signs of colon redundancy were successfully intubated to the cecum after repeated loop reduction and position changes. CONCLUSION: Compared to LFR, HFR of the water infusion pump significantly reduced colonoscopy insertion time and pain score in unsedated patients. Significantly shorter time to pass the rectosigmoid appeared to play a contributory role.

Are Mucosa CD4+/CD8+ T-Cells Expressions Correlated with the Endoscopic Appearance of Chronic Gastritis Related with Helicobacter pylori Infection?

Local inflammatory processes in the gastric mucosa are followed by extensive immune cell infiltration, resulting in chronic active gastritis characterized by a marked infiltration of T(h)1 cytokine-producing CD4+ and CD8+T-cells Objective. To investigate the correlation between CD4+/CD8+ T-cells in gastric mucosa with endoscopic appearance in chronic gastritis with or without H.pylori infection. Prospective, cross sectional study is performed in a chronic dyspepsia population in July-November 2009 at Dr. Sardjito General Hospital Yogyakarta, Indonesia. The update Sydney system was used to analyze the gastroscopy appearance. Biopsy specimens were stained with HE-stain and IHC-stain. Data were analyzed by t-test, Mann-Whitney and Spearman correlation test. Number of 88 consecutive subjects are enrolled the study (50% male; 50% female), age 46±15 years; 25% H.pylori positive. The expression of CD4+ and CD8+ were higher in H.pylori negative subjects, but only the CD4+ was significant (P=0.011). A significant correlation was found between CD4+ and CD8+ in both subjects (r(Hp+)=0.62 and r(Hp-)=0.68; P<0.05). The expression of CD4+ and CD8+ in H.pylori positive showed a significant correlation with gastric lesions (r(CD4+)=-0.60; r(CD8+)=-0.42 ; P<0.05), only erosion showed a significant difference in both subjects. A positive correlation was found between CD4+ and CD8+ infiltration in both subjects with or without H.pylori infection, and a negative correlation was only found between gastric lesion with CD4+ and CD8+ infiltration in H.pylori subject.

Abdominal malignant fibrous histiocytoma infiltrating stomach with Chilaiditi's sign manifestation (a rare case report).

The incidence and mortality rate of gastric cancer are decreasing within last 60 years. Approximately 85% of gastric cancer is carcinoma where as the rest 15% is lymphoma and sarcoma. Leiomyosarcoma is the most frequently encountered sarcoma in stomach and represents 1-3% gastric cancer. This tumor is frequently located in the anterior and posterior wall of gastric fundus accompanied by ulceration and bleeding. Malignant fibrous histiocytoma (MFH) is a soft tissue tumor with poor prognosis, rarely found in stomach. This tumor is most frequently originated from inner fascia or skeletal muscle (58-75%) and most frequently happen in the peritoneal cavity and abdomen (9-16 %). We reported a 45-year-old woman with abdominal MFH which infiltrated to the lesser curvature of stomach with Chilaiditi sign. Chilaiditi sign is a condition of intestine disposition (usually at the hepatic flexure of colon) which lies between liver and diagfragma, found in 0.1 ? 0.25% cases which is diagnosed by chest X Ray. This case is a very rare case.