Efficacy of octreotide in the control of acute upper gastrointestinal bleeding.

To evaluate the efficacy and safety of octreotide in the control of acute upper gastrointestinal (GI) bleeding and prevention of rebleeding, the Gastroenterology Unit, Chulalongkorn University Hospital, conducted a prospective open study in patients with acute upper GI bleeding. All patients with acute upper GI bleeding were given octreotide by intravenous infusion. The patients then had endoscopic confirmation within 24 hours, were divided into variceal and nonvariceal groups, and then randomly allocated to receive either 48 hours of octreotide infusion or 48 hours of octreotide infusion plus 72 hours subcutaneous injection. Efficacy and safety of octreotide were evaluated during the 5 days observation period. Forty-three patients with acute upper GI bleeding were treated with octreotide infusion. After endoscopy, 16 patients in the variceal group and 22 patients in the non-variceal group were randomized to receive 48 hours infusion or 48 hours infusion plus 72 hours subcutaneous infusion. Failure to control active bleeding occurred in 11 patients (28.9%) and failure to prevent rebleeding was found in 5 patients (13.2%). The results showed that the effect of octreotide infusion in controlling acute upper GI bleeding appeared to be not different between the variceal and non-variceal causes. Subcutaneous injection of octreotide for another 72 hours showed no apparent benefit for the prevention of rebleeding.

Long-term effect of interferon therapy on incidence of cirrhosis and hepatocellular carcinoma in Thai patients with chronic hepatitis B.

The aim of this study was to assess the long-term effects of interferon (IFN) therapy on the incidence of disease progression to cirrhosis and hepatocellular carcinoma (HCC) in Thai patients with chronic hepatitis B. Sixty-seven patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B who received IFN therapy were retrospectively analyzed. The average duration of follow-up was 59.4+/-30.9 months (ranging from 20 to 119 months). Seventy-two untreated patients with comparable clinical data and mean duration of follow-up served as a control group. During follow-up, 24 (35.8%) treated and 7 (9.7%) untreated patients had a sustained loss of HBeAg. However, none of the treated patients or controls became negative for hepatitis B s antigen (HBsAg). Among treated patients, the response was independent of type and dose of IFN, as well as the presence of steroid priming. In addition, 1 of 24 (4.2%) sustained responders and 6 of 43 (14%) non-responders progressed to cirrhosis whereas 16 of 72 (22.2%) in the control group progressed to such sequelae. The overall incidence of new cirrhosis in sustained responders was significantly lower than in the control group (p=0.04). HCC appeared in 11 cirrhotic patients: 9 (12.5%) in the control group and 2 (4.7%) of the non-responders, whereas none of the sustained responders developed HCC. The average period to detection of HCC was 70.5+/-12.4 months for non-responders and 65.3+/-27.6 months for the control group, with no significant differences between these groups. In conclusion, our data suggest that IFN therapy might prevent the progression of cirrhosis and the development of HCC in patients with chronic hepatitis B. These beneficial effects were particularly observed in those who achieved a sustained virological response to treatment.

Malignant duodenal stromal tumor: the first case report in Thailand and review of the literature.

The authors presented a middle aged Thai patient with malignant duodenal stromal tumor identified at a tertially care centre in Thailand. The patient presented with obscure gastrointestinal bleeding and the small bowel endoscopy revealed a bleeding tumor mass at the fouth part of the duodenum. The patient underwent segmental duodenectomy with end to end anstosomis. The histopathology of the tumor composed of interlacing bundles of spindle cells with oval to elongated pleomorphic nuclei and eosinophilic cytoplasm. The immunohistochemistrical study confirmed the diagnosis of malignant stromal tumor with smooth muscle differentiation. The computer tomography scan (CT scan) of the abdomen showed no evidence of metastasis. Postoperatively, the patient's clinical condition showed continuous improvement without further gastrointestinal bleeding. The patient has remained healthy up to present (six months of follow-up). A high level of suspicion to detect this malignant tumor especially in a patient presenting with obscure gastrointestinal bleeding and effective surgical treatment allow better clinical outcome in this rare and fatal malignancy.

Necrotizing ileitis caused by cytomegalovirus in patient with systemic lupus erythematosus: case report.

We report a systemic lupus erythematosus (SLE) patient with necrotizing ileitis diagnosed at a tertially care centre in Thailand. The patient was surgically explored because peritonitis was suspected and segmental gangrenous and perforation of the terminal iliem were found. The pathological finding was necrotizing ileitis with appearance of cytomegalic intranuclear inclusion body. The presence of cytomegalovirus (CMV) infection in tissue was confirmed by CMV-DNA detection using polymerase chain reaction and ELISA probe hybridization method. The hemoculture and peritoneal fluid culture results revealed no pathogenic organisms. Postoperatively, the clinical course of the patient deteriorated and she developed hypotension. Vasopressive drugs were administered without clinical improvement. She expired on day 5 postoperation. Regarding CMV infection, the organism involves the small bowel in only 4.3 per cent of all CMV infections of the gastrointestinal tract. Isolated cases of ileal perforation due to CMV infection have never been reported in a SLE patient. Thus, chronic right lower abdominal pain, fever with or without diarrhea in immunocompromised patients should cause clinicians to consider CMV ileitis in the differential diagnosis. Immediate surgical resection and prompt antiviral therapy lead to successful treatment.

Eradication rates of Helicobacter pylori between metronidazole-sensitive and metronidazole-resistant strains with metronidazole containing regimen in Thai patients with peptic ulcer disease.

The results of the in vitro metronidazole resistance on Helicobacter pylori (H. pylori) eradication have been inconclusive. Metronidazole resistance varies among different geographical locations and a previous study from Thailand reported an in vitro metronidazole resistance of H. pylori of 51 per cent. This study was designed to investigate further the effect of the in vitro metronidazole resistance on the outcome of eradication of H. pylori in the Thai population. Fifty two patients with active gastric ulcer (GU) and duodenal ulcer (DU) who had positive culture for H. pylori were studied. All of these patients had positive rapid urease test (CLO test, Delta West, Australia) using gastric biopsy specimens from the antrum and body taken at the time of initial upper endoscopy. In vitro antimicrobial susceptibility test was performed using Epsilometer test (AB Biodisk, Solna, Sweden). All patients received a one-week triple regimen consisting of omeprazole 20 mg twice daily, clarithromycin 500 mg twice daily, metronidazole 500 mg twice daily. Patients with GU continued with another five weeks of omeprazole 20 mg twice daily and patients with DU received another three weeks of omeprazole 20 mg twice daily. Upper endoscopy was repeated at four weeks after the end of the treatment. Three antral and two body biopsy specimens were obtained for identification of H. pylori using CLO test, histology (modified Giemsa stain) and culture. All of these tests had to be negative to confirm a successful eradication. Metronidazole-resistant (MR) strains with MIC > or = 32 mg/l were identified in 27 of the 52 patients (51.92%), whereas, metronidazole-susceptible (MS) strains were isolated from 25 patients (48.08%). Five patients were lost to follow-up and one patient had drug allergy. Successful eradication as defined by negative CLO test, histology and culture was attained in 17/23 (73.91%) patients (GU = 6, DU = 16, GU and DU = 1) with MR strains. 20 out of 23 (86.96%) patients (GU = 9, DU = 12 GU and DU = 2) who had MS strains. The difference was not statistically significant in both groups (P > 0.05). The ulcer healing was, however, highly achieved in both groups (MS = 95.65%, MR = 91.30%, P > 0.05). In vitro metronidazole resistance was high in this population group although this does not predict the outcome of eradication in patients with GU and DU.

Current management of Helicobacter pylori infection.

Helicobacter pylori is commonly found throughout the world. It is associated with a wide range of gastroduodenal diseases. Knowledge regarding the characteristic organism, behaviour, and related clinical conditions is extensive. Indeed, the bacteria is not the only factor which can cause the diseases, the host as well as environmental factors are also important. Largely, H. pylori is disappearing worldwide due to eradication of this organism allowing frequency of an H. pylori negative ulcer to relatively increase and may be more difficult to treat. The PPI triple therapy remains the first line of treatment with quadruple therapy as the second rescue line. The rising of bacterial resistant strains is a new problem which requires new drugs to improve the efficacy of the current regimens.

Caffeine clearance in patients with chronic viral hepatitis: before and after interferon therapy.

The purpose of this study was to evaluate caffeine clearance, a quantitative measurement of metabolizing capacity of the liver, in chronic hepatitis B and C before and after interferon treatment. Biochemical test using AST and ALT, virological test, and caffeine clearance were measured in eighteen patients with chronic hepatitis B and five patients with chronic hepatitis C at pre and post treatment with interferon. Caffeine clearance was determined in each patient using two point analysis following a 3.5 mg/kg oral administration of caffeine solution. Blood samples were subsequently collected at 12 and 16 hours after caffeine administration and assayed for serum caffeine level by HPLC technique. Clearance was calculated using the equation of Cl = Kel x Vd. It was found that caffeine clearances determined before and after interferon treatment were not significantly different in both chronic hepatitis B and C inspite of biochemical and virological responses after therapy. Caffeine clearance change in two diffferent groups of chronic hepatitis B defined as biochemical response and nonresponse were compared. Although caffeine clearance change between responders and nonresponders to interferon treatment was not significantly different, it tended to increase in those patients who had biochemical response to interferon. It appeared that metabolic capacity of the liver does not change with interferon therapy inspite of biochemical and virological responses.

Adenocarcinoma of the pancreas: the clinical experience of 45 histopathologically proven patients, a 6 year study.

A retrospective study of 45 cases of adenocarcinoma of the pancreas at Chulalongkorn University Hospital from 1993 to 1998 was reviewed by clinical and histopathological criteria. Male and female ratio was 25:20. The mean age of the patients was 59.5 +/- 10.0 years. The common presenting symptoms and signs were epigastric discomfort (80.0%), weight loss (60.0%) and jaundice (51.1%). Twenty four patients (53.3%) were screened for a tumor marker (CA 19-9) and 87.5 per cent of these had high level of CA 19-9 (> 37 IU/ml). Thirty five patients (77.8%) had tumors located in the head of the pancreas. Most of the cases were investigated by using radiological imaging (ultrasonography or computerized tomography of the abdomen). Thirty five histopathological data (77.8%) were made by the operation, and the rest (22.2%) were performed by a fine needle aspiration from the pancreatic mass or liver metastasis. Whipple operation and the bypass procedure were the most common surgical procedures in our studies. Twenty five patients (55.6%) had post treatment complications from all modalities consisting of gastrointestinal bleeding, respiratory failure and infection. However, the mortality rate within 30 days postoperatively was 8.11 per cent which was due to blood loss during the operation and infections. The post treatment mortality rate from all modalities was 33.3 per cent. The average duration from the diagnosis until death was 82.3 days.

Current status of gastric cancer in Thai patients.

To determine the current status in various aspects of gastric cancer in Thai patients, we retrospectively reviewed the records of 119 patients with histologically proven gastric cancer in King Chulalongkorn Memorial Hospital during the five-year period from 1994 to 1998. There were 72 males (60.5%) and 47 females (39.5%) with ages ranging from 22 to 91 years (mean age 60.2+/-15.1 years). Among these, 20 patients (16.8%) were younger than 40 years. The duration of symptoms prior to first presentation averaged 20 weeks and dyspepsia and weight loss were the most common complaints. Lesion location was lower third in 40.3 per cent, middle third in 31.9 per cent, upper third in 15.1 per cent and entire stomach in 3.4 per cent of patients. Adenocarcinoma was the most common histological finding (91.6%), followed by lymphoma and leiomyosarcoma (3.4% each). Helicobacter pylori infection was detected in 17 of 25 (68%). The TMN staging was as follows: stage II, 5.9 per cent; stage III, 9.2 per cent; and stage IV, 68.9 per cent. (the stage was unknown in 16%). The overall 1-year, 2-year and 5-year survival rates were 51.6 per cent, 17.5 per cent and 4.4 per cent, respectively. Management was surgical treatment in 58.9 per cent (total gastrectomy 14.5%, subtotal gastrectomy 33.3% and palliative bypass surgery in 11.1%). Systemic chemotherapy was the primary modality of therapy in 16.8 per cent and was adjuvant therapy in 18.5 per cent. The median survival time of resectable cases was 1.00+/-0.53 years, significantly longer than that of unresectable cases (0.11+/-0.03 years) (p=0.0025). However, the administration of chemotherapy did not improve the survival rate. It is concluded that, in Thailand, gastric cancer continues to be an important health problem and is generally associated with a poor prognosis.

Core promoter and precore mutants of hepatitis B virus: prevalence and clinical relevance in chronic hepatitis patients.

The present study was conducted to determine prevalence and exact type, as well as nucleotide position of the precore/core mutations of hepatitis B virus found in Thai patients diagnosed with chronic hepatitis and/or cirrhosis in relation to the clinical parameters established with the respective patients. To that end, 24 HBeAg-positive and 56 HBeAg-negative individuals were selected at random from a cohort of altogether 256 chronic liver disease patients. DNA was extracted from their blood sera, amplified by polymerase chain reaction using semi-nested primers and subjected to direct sequencing. Clinically, the HBeAg-positive chronic hepatitis patients displayed significantly higher transaminase levels than those negative for HBeAg. Our results showed 2 of the 7 (28.6%) PCR-positive HBeAg-positive sera displaying double mutations in the core promoter region at position 1762/64. The nucleotide sequences obtained from the 24 PCR-positive HBeAg-negative sera revealed 18 (75%) mutations in the core promoter region (1762/64), and/or 7 (29.2%) mutations at position 1753, and/or 6 (25%) mutations of the start codon (1814), and/or 8 of (33.3%) nucleotide 1896 turning codon 28 into a stop codon and one sample (4.2%) displaying a deletion between nucleotides 1758-1772. It is suggested that the mutations observed have an impact on the DNA secondary structure in such a way that successful transcription of the HBeAg gene is rendered impossible. To what extent this mutation influences the severity of chronic liver disease remains to be elucidated.

Streptococcus suis peritonitis: case report.

A 45-year-old Thai man who presented with peritonitis was seen in a tertiary care centre in Thailand. An exploratory laparotomy was done because of peritonitis from abdominal trauma. Postoperatively the patient received intravenous ceftriaxone and metronidazole, but he developed rhabdomyolysis and acute renal failure. Hemodialysis was performed. After 8 days, the peritonitis had relapsed with hypotension. The patient was given vasopressives but clinicaly deteriorated and expired on day 11. The peritoniteal fluid culture grew Streptococcus suis serotype 2 and the organism was resistant to multiple antimicrobial agents including penicillin (MIC > 32 mcg/ml) but was susceptible to vancomycin.

Effect of omeprazole on gastric mucosa and serum levels of amoxicillin in patients with non-ulcer dyspepsia.

The aim of this study was to determine the interaction between omeprazole and amoxicillin, being common agents used in the eradication regimen for H. pylori infection. Amoxicillin concentrations in gastric mucosa and serum were quantitatively analysed in 12 patients with non-ulcer dyspepsia following the administration of one week duration of placebo as group I and omeprazole as group II. The study was a blind, cross-over design with a one week wash out period between the two treatment groups. Six antral gastric mucosa were biopsied 90 minutes after oral administration of amoxicillin. Blood samples were collected before and after administration at intervals up to 6 hours. All samples were analysed for amoxicillin concentration using the HPLC technique. Highly intersubject variations of amoxicillin concentrations were observed. The concentration of amoxicillin in gastric mucosa ranged from 0.00-1.74 and 0.00-1.25 micrograms/mg for group I and group II, respectively, with the mean concentration of 0.25 +/- 0.48 microgram/mg for group I and 0.28 +/- 0.40 microgram/mg for group II. The difference was not statistically significant (p = 0.89). Pharmacokinetic parameters of amoxicillin in serum following regimen I and regimen II were not significantly different (p > 0.05). The mean Cmax values were 14.62 +/- 5.39 and 12.65 +/- 4.76 micrograms/ml, the Tmax were 2.3 +/- 1.0 and 2.0 +/- 0.9 hour and the AUC0-6 were 40.79 +/- 13.26 and 38.75 +/- 15.04 micrograms/ml.h in the group I and group II, respectively. From these results, we concluded that omeprazole has no effect on gastric mucosa level nor serum levels of amoxicillin. The therapeutic efficacy of using these two agents in the eradication regimen of H. pylori may be related to other factors rather than pharmacokinetic interaction.

Eradication of Helicobacter pylori with lansoprazole based triple therapy in peptic ulcer disease.

Lansoprazole 30 mg, amoxicillin 1000 mg, and tinidazole 500 mg were given twice daily to 39 peptic ulcer patients (26 duodenal and 13 gastric ulcer, mean age 52.4 +/- 15.01) who had H. pylori infection for two weeks. Additional lansoprazole 30 mg daily was given to duodenal and gastric ulcer patients for another two and six weeks respectively. Follow-up gastroduodenoscope was performed at fourth and eighth week and eighth and twelfth week for all duodenal and gastric ulcer patients, respectively. H. pylori status was evaluated by rapid urease test (CLO test) and histology at first and last endoscope. The ulcers were healed at the last endoscopy in 11 (85%) gastric ulcer patients and 24 (92%) duodenal ulcers patients. H. pylori infection was eradicated in 31 patients (79%). Mild side effects were observed in 15 per cent. In conclusion, 2 week regimen of lansoprazole, amoxicillin, and tinidazole triple therapy resulted in a relatively high healing rate of peptic ulcer (90%) and an acceptable eradication rate of H. pylori infection (79%).

Serodiagnosis of Helicobacter pylori infection by immunoblot assay.

We compared a noninvasive serological test using a commercial immunoblot assay (Helicoblot 2.0) to tissue-based methods [rapid urease test (CLO test), histology and culture] in eighty Thai patients undergoing upper endoscopy. A true positive test was defined as at least two of the biopsy-related tests being positive. The CLO test was the most accurate test with sensitivity and specificity as high as 100%, whereas histology and culture had sensitivity of 100% and 72.2%, respectively, and the specificity of 72.7% and 96%, respectively. The serological test had a high sensitivity (97.2%) but exhibited an unsatisfactory specificity (40.9%). We concluded that the rapid urease test using multiple gastric biopsies was the most appropriate method for diagnosing H. pylori status. The role of immunoblot assay as a serological screening test in our population remains doubtful, but it may identify patients who have been infected with certain strains of H. pylori.

Short-term effects of branched-chain amino acids on liver function tests in cirrhotic patients.

A randomized study was conducted in 29 ambulatory cirrhotic patients to determine the short-term effects of branched-chain amino acids (BCAA) on nutritional status, biochemical liver function tests and caffeine clearance. Each patient received a 4-week period of isonitrogenous and isocaloric regimens, either a standardized diet contained 40 g protein with supplementation of BCAA 150 g daily (group I) or only a standardized diet contained 80 g protein daily (group II). At the end of treatment, only group I showed significant improvements in transaminase levels as well as the caffeine clearance test compared with those of the pre-treatment levels. Nonetheless, significant improvements in nutritional parameters and additional liver function tests were not yet detected. We conclude that the short-term nutritional supplementation of BCAA is well tolerated and leads to improvement in hepatic metabolic capacity assessed by the caffeine clearance test.

Caffeine clearance study in hepatocellular carcinoma.

The purpose of this study was to evaluate hepatic metabolic capacity in cirrhotic patients with hepatocellular carcinoma (HCC). We compared plasma caffeine clearance, calculated by two point analysis, between patients with cirrhosis alone and cirrhosis complicated with HCC. These two groups were comparable with regards to age, sex, and the severity of liver disease, graded by Child-Pugh score as compensated and decompensated cases. From our result, caffeine clearance in compensated cases was clearly higher than that of decompensated cases in both groups studied, particularly in the HCC group (p = 0.001). The mean value of caffeine clearance in HCC patients correlated well with the tumor staging as classified by Okuda's criteria. There was also a reversal correlation between tumor size and the clearance tested in compensated cases of HCC (p = 0.046), but this finding was not detected in decompensated cases (p > 0.05). We conclude that the determination of caffeine clearance can serve as a useful parameter for the assessment of hepatic functional reserve in cirrhotic patients complicated with HCC, and may be a useful predictor for survival outcome.