Showing papers in "Journal of Gastroenterology and Hepatology in 2005"

Stress and the gastrointestinal tract.

Abstract: Stress, defined as an acute threat to homeostasis, evokes an adaptive or allostatic response and can have both a short- and long-term influence on the function of the gastrointestinal tract. The enteric nervous system is connected bidirectionally to the brain by parasympathetic and sympathetic pathways forming the brain-gut axis. The neural network of the brain, which generates the stress response, is called the central stress circuitry and includes the paraventricular nucleus of the hypothalamus, amygdala and periaqueductal gray. It receives input from the somatic and visceral afferent pathways and also from the visceral motor cortex including the medial prefrontal, anterior cingulate and insular cortex. The output of this central stress circuit is called the emotional motor system and includes automatic efferents, the hypothalamus-pituitary-adrenal axis and pain modulatory systems. Severe or long-term stress can induce long-term alteration in the stress response (plasticity). Corticotropin releasing factor (CRF) is a key mediator of the central stress response. Two CRF receptor subtypes, R1 and R2, have been described. They mediate increased colonic motor activity and slowed gastric emptying, respectively, in response to stress. Specific CRF receptor antagonists injected into the 0 block these visceral manifestations of stress. Circulating glucocorticoids exert an inhibitory effect on the stress response by receptors located in the medial prefrontal cortex and hippocampus. Many other neurotransmitters and neuroimmunomodulators are being evaluated. Stress increases the intestinal permeability to large antigenic molecules. It can lead to mast cell activation, degranulation and colonic mucin depletion. A reversal of small bowel water and electrolyte absorption occurs in response to stress and is mediated cholinergically. Stress also leads to increased susceptibility to colonic inflammation, which can be adaptively transferred among rats by sensitized CD4(+) lymphocytes. The association between stress and various gastrointestinal diseases, including functional bowel disorders, inflammatory bowel disease, peptic ulcer disease and gastroesophageal reflux disease, is being actively investigated. Attention to the close relation between the brain and gut has opened many therapeutic avenues for the future.

Clinical features of hepatocellular carcinoma with extrahepatic metastases

Abstract: Background: There are few detailed clinical reports about extrahepatic metastases of hepatocellular carcinoma (HCC). The purpose of the present study was to elucidate the clinical features of extrahepatic metastases of HCC. Methods: The clinical records of 482 patients who had been diagnosed as having HCC during the period from January 1995 to March 2001 were retrospectively reviewed. Extrahepatic metastases had been detected in 65 patients. Clinical features of those 65 patients were analyzed. Results: Patients with extrahepatic metastases had more advanced intrahepatic tumors at the first diagnosis of HCC: 73.8% of the patients with extrahepatic metastases had tumors of intrahepatic tumor stage T3 or T4 according to the TNM classification, while only 28.5% of the patients without extrahepatic metastases had tumors of T3 or T4 (P < 0.001). Vessel invasion was also detected at the first diagnosis of HCC more frequently in the patients with extrahepatic metastasis (P < 0.001). The frequent metastatic sites were lung (53.8%), bone (38.5%), and lymph node (33.8%). Other metastatic sites were the adrenal gland, peritoneum, skin, brain and muscle. The median survival time and 1-year survival rate were 7 months (range: 1–59 months) and 24.9%, respectively. Patients with Child–Pugh grade B and C (P = 0.0018) and patients with positive serum α-fetoprotein (P = 0.011) had significantly poor prognosis. Conclusions: Extrahepatic metastases of HCC are not rare. The possibility of extrahepatic metastases and the clinical features of extrahepatic metastases should be considered when examining patients with HCC, particularly those with advanced intrahepatic tumors, to enable precise evaluation of the spread of HCC and determination of the appropriate treatment method. © 2005 Blackwell Publishing Asia Pty Ltd

Azathioprine and 6-mercaptopurine pharmacogenetics and metabolite monitoring in inflammatory bowel disease

Abstract: The thiopurine drugs azathioprine and 6-mercaptopurine (6-MP) are well-established in the treatment of inflammatory bowel disease (IBD). However, there is a wide inter- and intra-patient variation in the concentrations of active and toxic metabolites due to their complex metabolism and genetic polymorphisms in metabolizing enzymes. Serious drug toxicity leads to cessation of therapy in 9-25% of patients, and there is failure to achieve efficacy in approximately 15% of cases. Advances in the understanding of thiopurine drug metabolism have led to new genetic and metabolite tests to help clinicians optimize thiopurine use. Thiopurine methyltransferase (TPMT) enzyme activity can predict life-threatening myelotoxicity in the one in 300 patients who are TPMT-deficient. However, myelotoxicity can also occur in the presence of normal TPMT activity so blood count monitoring should remain standard practice. TPMT testing may also aid in dose individualization. 6-Thioguanine nucleotides (6-TGN) are thought to be the predominant active metabolites of the thiopurines. 6-thioguanine nucleotide concentration is correlated with bone marrow toxicity and may also correlate with efficacy in IBD. Measurement of 6-TGN and 6-methylmercaptopurine (6-MMP) concentration is most useful in determining why a patient is not responding to a standard dose of a thiopurine drug and may help in avoiding myelosuppression. The ratio of these metabolites can help distinguish non-compliance, under-dosing, thiopurine-resistant and thiopurine-refractory disease. Some of these investigations are entering routine clinical practice but more research is required to determine their optimal use in patients with IBD.

Fatty liver and the metabolic syndrome among Shanghai adults.

Abstract: Background and Aim: To explore the relationship between fatty liver and the metabolic syndrome in the adults of Shanghai and evaluate the value of fatty liver as a marker for risk factor clustering. Methods: Questionnaires, physical examinations, laboratory tests (blood lipid and glucose) and real-time liver ultrasonographies were performed in Shanghai adults and analyzed using randomized, multistage, stratified cluster sampling. Prevalence of the metabolic syndrome was defined by the National Cholesterol Education Program–Adult Treatment Panel III (NCEP-ATPIII) criteria with the exception of abdominal obesity (waist circumference > 90 cm in men and > 80 cm in women); fatty liver was diagnosed in accordance with the presence of an ultrasonographic pattern consistent with ‘bright’ liver (brightness and posterior attenuation of liver). Results: The study population consisted of 3175 subjects (1218 men) with a mean (± SD) age of 52.4 ± 15.1 years. Metabolic syndrome and fatty liver were found in 726 (22.87%) and 661 (20.82%) of sampled cases, respectively. After adjustment by age and sex, the prevalence of the metabolic syndrome and fatty liver in the general population of Shanghai were 15.30 and 17.29%, respectively. The risk for fatty liver in subjects with abdominal obesity, diabetes, dyslipidemia and hypertension increased 32.78-fold (95% confidence interval (CI) 14.85–72.35), 31.58-fold (95% CI 14.18–70.35), 22.64-fold (95% CI 10.26–49.99) and 23.25-fold (95% CI 10.54–51.30), respectively, compared with controls, whereas the risk for fatty liver in subjects with metabolic syndrome was increased by 39.33-fold (95% CI 17.77–87.05). After the 661 patients with fatty liver had been stratified by body mass index (BMI), the prevalence of abdominal obesity, hypertension and the metabolic syndrome were increased from 25.0, 47.2 and 36.1%, respectively, in people with normal BMI to 81.0, 73.8 and 55.4%, respectively, in obese persons. However, the prevalence of hypertriglyceridemia, high fasting glucose and low high-density lipoprotein–cholesterol showed no significant changes with increased BMI. Moreover, among fatty liver patients with normal BMI, the detection rate for one or more features of metabolic disorders was as high as 83.3% and that for five features was 2.8%. Compared with obesity (BMI ≥ 25 kg/m2) and abdominal obesity, fatty liver had the highest clustering rate, specificity, positive predictive value and attributable risk percentage in detecting risk factor clustering in both sexes. Conclusions: There is a high prevalence of metabolic syndrome and fatty liver among Shanghai adults. Metabolic disorders are closely related to fatty liver; moreover, fatty liver appears to be a good predictor for the clustering of risk factors for metabolic syndrome.

Gastrointestinal stromal tumors: clinical profile, pathogenesis, treatment strategies and prognosis.

Abstract: Gastrointestinal stromal tumors (GIST), although the most common mesenchymal neoplasms of the gastrointestinal (GI) tract, account for <1% of all GI malignancies. Up to 94% of these tumors express the CD117 antigen. Most patients present in the fifth to seventh decade, the commonest symptom being that of an abdominal mass. Surgery is the main modality of therapy, but even after adequate resection the vast majority of GIST reoccur, and in approximately 50% the liver is the main site of the metastasis. Long-term, maybe even lifelong follow up of these patients after initial resection cannot be over-emphasized. Initial tumor size and mitotic rate are the most useful parameters to predict malignant potential. In view of high postoperative recurrence, adjuvant forms of therapy are being explored, and the tyrosine kinase inhibitor imatinib holds the most promise. © 2005 Blackwell Publishing Asia Pty Ltd

Post-infectious irritable bowel syndrome in patients with Shigella infection.

Abstract: Background and Aims: Bacterial gastroenteritis has been known as a risk factor of irritable bowel syndrome (IBS). Several risk factors of post-infectious IBS (PI-IBS) have been documented. The aims of this study were to verify the role of bacterial gastroenteritis in the development of IBS and the risk factors for the development of PI-IBS. The clinical course of PI-IBS was also investigated. Methods: We recruited 143 patients with shigellosis during its outbreak and 113 controls. Both groups were followed up for 12 months. Bowel symptoms were evaluated by use of questionnaires at 3, 6 and 12 months after the initial recruitment. Results: Complete data were obtained from 101 patients (70.6%) and 102 healthy controls (90.3%). At 12 months, 15 patients and six controls had IBS (adjusted OR; 2.9, 95% CI; 1.1–7.9). Of the 15 patients, five had IBS symptoms consistently for 12 months, three did not have IBS symptoms initially and seven had fluctuating bowel symptoms. The duration of diarrhea was an independent risk factor of PI-IBS. Conclusions: Bacterial gastroenteritis is a risk factor of IBS and the duration of diarrhea as the index of severity of initial illness is an independent risk factor of PI-IBS. The clinical course of PI-IBS is variable over the 1 year of follow-up.

Inflammatory bowel disease in Iran: a review of 457 cases.

Abstract: Background and Aims: Inflammatory bowel disease (IBD) was believed to be infrequent in Iran; however, unofficial reports have confessed the continuing rise in IBD in our country. Methods: Demographic and clinical features, extraintestinal manifestations, extension of disease and complications of 401 patients with ulcerative colitis (UC), 47 with Crohn's disease (CD), and nine with indeterminatn colitis (IC) were assessed retrospectively. The exact course of physicians’ visits of 250 IBD patient was asked through face-to-face interview. Results: Mean age at diagnosis was 31.9 years in UC and 30.5 years in CD patients. The male to female ratio was 0.8 for UC and 1.3 for CD. The percentage of CD and UC patients who were non-smokers was 82.9 and 84.5%, respectively. Patients with UC presented with rectal bleeding (41.9%), whereas those with CD complained of abdominal pain (46.9%). Among UC patients, proctosigmoid was affected in 51.9%. Colorectal cancer was diagnosed in two patients. The mean lag time between the onset of symptoms and definite diagnosis was 13.9 and 17.7 months for UC and CD patients, respectively. A total of 32.4% of patients with IBD had at least one of the five major extra-intestinal diseases. Conclusion: The demographic and clinical picture of IBD is more or less the same as that of other developing countries; however, the rarity of CD in Iran is noted. Although the true epidemiologic profile of IBD in Iran is still unknown, it is not as rare as previously thought, and it seems as if gradual adoption of a Western lifestyle may be associated with the continuing rise in IBD. © 2005 Blackwell Publishing Asia Pty Ltd

A review of juvenile polyposis syndrome.

Abstract: Juvenile Polyposis Syndrome is an uncommon hamartomatous disorder with significant gastrointestinal malignant potential. Mutations in SMAD4 and BMPR1A, implicated in the Transforming Growth Factor beta pathway, have recently been characterized, and hold significance in the management of patients and at risk family members. This article reviews our knowledge to date of the genetics and clinicopathological features of the Juvenile Polyposis Syndrome, and discusses the current expert recommendations for genetic testing, disease screening and management.

Carcinoid of the ampulla of Vater

Abstract: Endocrine neoplasms only rarely occur at the ampulla of Vater, comprising mostly carcinoids and malignant carcinoids, as well as few cases of poorly differentiated endocrine carcinomas (small cell carcinomas). Only 105 cases are reported in the literature, most as single case reports. For many years, the neoplasms of the disseminated neuroendocrine cell system of the gastrointestinal tract have been subsumed as 'carcinoids'. Instead, in the latest World Health Organization (WHO) classification published in 2000, it is recommended to distinguish between (i) well-differentiated endocrine tumors (carcinoids); (ii) well-differentiated endocrine carcinomas (malignant carcinoids); and (iii) poorly differentiated endocrine carcinomas (small cell carcinomas). Patients with carcinoid tumors of the ampulla of Vater are very often free of clinical and laboratory findings that belong to the carcinoid syndrome. Approximately 26% of all patients with carcinoid tumor reported in the literature had neurofibromatosis. Besides endoscopic retrograde cholangiopancreatography, endosonography, computed tomography or magnetic resonance imaging may complete the staging approach of this tumor. The Kausch-Whipple procedure or pylorus-preserving pancreaticoduodenectomy is considered the treatment of choice for ampullary, well-differentiated carcinoids >2.0 cm and for ampullary neuroendocrine carcinomas. However, it should be considered that long-term survival of patients with ampullary carcinoids is also reported after local tumor excision (5-year survival rate of 90%). The dilemma is that the differentiation of neuroendocrine tumors cannot be assessed intraoperatively in most cases. Therefore, considering that the 5-year survival rate in patients with neuroendocrine carcinomas of the ampulla of Vater is very low without radical resection, neuroendocrine tumors of the ampulla of Vater without definite histological differentiation should undergo extended surgery.

Immunological alterations in pregnant women with acute hepatitis E

Abstract: Background: Infection with hepatitis E virus (HEV) is a major cause of acute viral hepatitis in several developing countries. Although usually self-limiting and benign, the disease is particularly severe among pregnant women, with mortality rates reaching 15–20%. Methods: Immune parameters among pregnant women with acute hepatitis E (P-HEV) were investigated and compared with those in non-pregnant patients with hepatitis E (N-HEV), and healthy pregnant (PC) and non-pregnant (NPC) women. Results: Peripheral blood mononuclear cells (PBMC) from P-HEV patients had lower lymphocyte proliferation response to phytohemagglutinin (PHA) than those in the PC and NPC groups. A positive lymphocyte proliferation response to HEV antigen (HEVAg), a mixture of eight peptides derived from HEV proteins, was observed in 7/19 (37%) P-HEV patients, 3/9 (33%) N-HEV patients and only 2/21 (10%) PC and 2/14 (14%) NPC subjects; the stimulation indices in the P-HEV group were similar to the N-HEV group and higher than the PC group. Measurement of cytokine production by PBMC in response to PHA and HEVAg showed a reduction in production of T-helper 1 (Th1) cytokines and an increase in that of Th2 cytokines in the P-HEV group. Cytokine mRNA levels showed similar changes. Conclusion: These results show the existence of a Th2 bias in pregnant women with acute hepatitis E. The role of this Th2 bias in the greater severity of hepatitis E among pregnant women needs further investigation.

Genetic association of vitamin D receptor polymorphisms with autoimmune hepatitis and primary biliary cirrhosis in the Chinese.

Abstract: Background: Autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) are two autoimmune diseases of unknown etiology. Genetic factors appear to be involved in the pathogenesis of both diseases. Vitamin D has been shown to exert multiple immunomodulatory effects, which acts through its own receptor (VDR). Polymorphisms of VDR had been implicated in several autoimmune diseases. In the present study, the association between Chinese patients with AIH, PBC and the polymorphisms in exon 2, intron 8 and exon 9 of vitamin D receptor genes was studied. Methods: Four candidate gene loci were investigated in 49 patients with AIH, 58 patients with PBC, and 160 healthy controls. The VDR polymorphisms were assessed by FokI, BsmI, ApaI, and TaqI endonuclease digestion after specific polymerase chain reaction (PCR) amplification. Results: The result show a significant difference in FokI polymorphism between AIH patients and controls (χ2 = 5.47, P = 0.019), and a significant association in BsmI polymorphisms between PBC patients and controls (χ2 = 6.52, P = 0.01). Furthermore the distribution of FokI, BsmI, ApaI, and TaqI gene types differered between Chinese healthy controls and Caucasian healthy controls. Conclusion: It is suggested that there is a genetic link of VDR polymorphisms to autoimmune liver dieseses such as AIH and PBC in Chinese patients. Further studies are needed to elucidate the mechanisms by which VDR polymorphisms contribute to the lose of immune tolerance in autoimmune diseases. © 2004 Blackwell Publishing Asia Pty Ltd

Segmental colonoscopic biopsies in the differentiation of ileocolic tuberculosis from Crohn's disease.

Abstract: Background and Aim: The differentiation between Crohn's disease (CD) and tuberculosis (TB) of the intestine can be difficult in areas where both diseases occur. The present study examined histological criteria that would enable the diagnosis in mucosal biopsies. Methods: Colonoscopic biopsies from 33 patients with TB and 31 patients with CD were examined for several specific histological features and their distribution. Results: The salient distinguishing features of TB were granulomas larger than 400 µm in maximum dimension, more than four sites of granulomatous inflammation per site, caseation, a band of epithelioid histiocytes in ulcer bases and location of granulomas in the caecum. The salient features of CD were granulomas not showing any of the above features, focally enhanced colitis, pericryptal granulomatous inflammation, and the presence of architectural alteration/activity/chronic inflammation/deep ulceration at sites that did not show granulomatous response in the same or adjacent segments. Although granulomas in CD were distributed throughout the colon, they were more frequent in the rectosigmoid than in TB. All biopsies from endoscopically abnormal sites did not show distinguishing features of TB or CD, emphasizing the need for multiple biopsies. There was an accrual in the number of diagnoses made with increasing numbers of biopsies from rectum to ileum. Conclusions: Histology of mucosal biopsies can aid in the differentiation of TB from CD, but multiple biopsies from different colonic segments are important for complete evaluation.

Prevalence of gastroesophageal reflux disease and gastroesophageal reflux disease symptoms in Japan

Abstract: Background and Aim: Epidemiological studies have shown that 10–48% of people in developed countries have gastroesophageal reflux disease (GERD) symptoms such as heartburn and acid regurgitation The present study aimed to examine the prevalence of GERD symptoms and GERD in Japanese subjects Methods: A cross-sectional study of Japanese subjects who visited a clinic for a routine health check up was carried out Subjects were asked to fill out a self-report questionnaire GERD was defined as the presence of heartburn and/or acid regurgitation at least twice per week Results: Of the 6035 eligible subjects, 2662 (441%) reported having had heartburn and/or acid regurgitation during the past year: 124 (21%) daily, 275 (46%) twice per week, 773 (128%) twice per month and 1490 (247%) less than twice per month Three hundred and ninety-nine (66%) subjects were diagnosed as having GERD and there was no relationship between the prevalence of GERD and either sex or age The prevalence of bothersome GERD symptoms was significantly higher in subjects with GERD than in those without GERD Conclusion: Approximately 66% of Japanese have GERD and most persons with GERD described heartburn or acid regurgitation as bothersome

Elevated plasma homocysteine concentrations as a predictor of steatohepatitis in patients with non-alcoholic fatty liver disease.

Abstract: Background: Although steatosis is common in patients with severe hyperhomocysteinemia due to deficiency of cystathionine β-synthase, there are no satisfactory data on homocysteine concentrations in patients with non-alcoholic fatty liver disease. The main aim of the present study was to evaluate the clinical significance of plasma homocysteine concentrations in patients with non-alcoholic fatty liver disease. Methods: Seventy-one non-alcoholic fatty liver disease patients, 36 patients with chronic viral hepatitis and 30 healthy persons were enrolled in the study. Homocysteine levels were measured by high-performance liquid chromatography. Insulin, folate, vitamin B12 and lipoprotein levels were also determined in all groups. Results: Homocysteine in the non-alcoholic fatty liver disease group was found to be significantly higher than other groups. Homocysteine was found to be significantly higher in the non-alcoholic steatohepatitis group when compared with simple steatosis group. A positive correlation was found between homocysteine and triglyceride, very-low-density-lipoprotein (VLDL) cholesterol, insulin, and index of insulin resistance in the non-alcoholic fatty liver disease group, and a negative correlation was found between homocysteine and folate, or vitamin B12 in all groups. The homocysteine threshold for the prediction of steatohepatitis was 11.935 ng/mL. Furthermore; plasma homocysteine was a statistically significant predictor for severity of necroinflammatory activity in non-alcoholic steatohepatitis. Conclusions: The plasma homocysteine concentrations were significiantly higher in patients with non-alcoholic fatty liver disease, while the concentrations were not affected by chronic viral hepatitis. Plasma homocysteine is a parameter for discriminating steatohepatitis from simple steatosis. Determining the plasma homocysteine concentrations may facilitate selection of steatosis patients in whom a liver biopsy should be performed. © 2005 Blackwell Publishing Asia Pty Ltd

Jaundice in malaria

Abstract: Jaundice is not an unusual accompaniment of malaria. It can occur due to intravascular hemolysis, disseminated intravascular coagulation, and, rarely, 'malarial hepatitis'. Although the primary schizogony of the malarial parasite always leads to the rupture of the infected hepatocyte, alteration of the hepatic functions is uncommonly recorded due to this event. Histologically, the hepatitis or the actual inflammation in the liver has never been demonstrated. Nonetheless, the term 'malarial hepatitis' (MH) has been used in the literature to describe the occurrence of hepatocellular jaundice in patients with Plasmodium falciparum infection. The authors' own data and review of the literature indicate that it is not an uncommon entity. In endemic areas, jaundice is seen in approximately 2.5% of patients with falciparum malaria. It also appears to be a heterogeneous syndrome and one can recognize two clinical subsets. In one group there was an acute, virulent presentation with coma, renal failure and in some cases even hemorrhagic manifestations. It is only in this setting that jaundice signified a 'severe' disease as noted by the World Health Organization action program. This presentation is often confused with acute viral hepatitis and acute hepatic failure in non-endemic areas, but can be clinically differentiated.

Electrogastrography: Basic knowledge, recording, processing and its clinical applications

Abstract: The slow wave (SW) of the gastrointestinal (GI) tract mainly functions to trigger the onset of spike to elicit smooth muscle contraction, which provides the essential power of motility. Smooth muscle myogenic control activity or SW is believed to originate in the interstitial cells of Cajal (ICC). The electrical coupling promotes interaction between muscle cells, and ICC additionally contribute to SW rhythmicity. Stomach SW originates in the proximal body showing the continuous rhythmic change in the membrane potential and propagates normally to the distal antrum with a regular rhythm of approximately 3 c.p.m. A technique using electrodes positioned on the abdominal skin to pick up stomach rhythmic SW refers to electrogastrography (EGG). The stomach SW amplitude is very weak, while many visceral organs also produce rhythmic electricities, for example heartbeat, respiration, other organs of the GI tract and even body movements. Thus noise other than SW should be filtered out during the recording, while motion artifacts are visually examined and deleted. Finally, the best signal among all recordings is selected to compute EGG parameters based on spectral analysis. The latter is done not only to tranform frequency domain to time domain but also to provide information of time variability in frequency. Obtained EGG parameters include dominant frequency/power, % normal rhythm, % bradygastria, % tachygastria, instability coefficient and power ratio. Clinical experience in EGG has been markedly accumulated since its rapid evolution. In contrast, lack of standardized methodology in terms of electrode positions, recording periods, test meals, analytic software and normal reference values makes the significance of EGG recording controversial. Unlike imaging or manometrical studies, stomach motility disorders are not diagnosed based only on abnormal EGG parameters. Limitations of EGG recording, processing, computation, acceptable normal parameters, technique and reading should be known to conduct subjective assessments when EGG is used to resolve stomach dysfunction. Understanding basic SW physiology, recording methodology and indications may open EGG as a new domain to approach the stomach motor dysfunction.

Gallbladder cancer in India: A dismal picture

Abstract: Background: Gallbladder cancer (GBC) is one of the most common gastrointestinal malignancies. The data regarding GBC are, however, limited. Methods: Records of 634 patients with GBC over a 10-year period were examined with regard to the clinical presentation, investigative findings, treatment, operative findings and outcome. Results: The mean age of patients was 51 ± 11 years and men : women ratio was 0.36:1.00. Pain, jaundice and hepatomegaly were seen in 81.0%, 76.0% and 61.5% patients, respectively. On imaging, a mass replacing the gallbladder was seen in 73% patients. Gallstones were present in 54% patients. Surgery was carried out in 291 (46%) patients and endoscopic treatment in 72 (19%) patients but no intervention was carried out in the remaining patients because of disseminated disease. Among the patients who were operated on, 2.0% had stage I GBC, 3.4% stage II, 17.5% stage III, 47.0% stage IVa and 29.8% stage IVb. Radical resection was possible in 133 (46%) patients. The 30-day mortality was 10% with most (90%) deaths in patients with stage IV disease. The median survival after simple cholecystectomy and radical surgery was 33.5 and 12.0 months, respectively. However, among those who underwent debulking, palliative bypass or exploratory laparotomy alone, the survival ranged between 1 and 3 months. Logistic regression analysis showed that only radical resection improved the long-term survival (P < 0.05). Conclusions: The majority of patients with GBC in India have advanced unresectable disease. Detection of GBC at an early stage is incidental and rare but is associated with long-term survival. Radical surgery, when feasible, is the only option for achieving long-term survival. © 2005 Blackwell Publishing Asia Pty Ltd

Pilot study using transcutaneous electrical stimulation (interferential current) to treat chronic treatment-resistant constipation and soiling in children.

Abstract: Background: Chronic constipation in children may have organic or behavioral causes. The purpose of the present study was to investigate the effect of treatment with transcutaneous electrical stimulation (using interferential current) in children with chronic treatment-resistant constipation with proven organic disorders. Methods: Eight children (7–16 years) with at least 4 years of chronic treatment-resistant constipation and soiling, who had failed diet, laxative treatment and behavioral therapy were given 1 month of transcutaneous electrical stimulation. The three most severe cases had appendicostomies with antegrade washouts every 2–3 days to prevent impaction and reduce their soiling. Children and carers kept a daily diary of bowel habits, recording number of spontaneous defecations, episodes of soiling, use of bowel washouts and medications. Transcutaneous stimulation using interferential current was applied three times per week for 3–4 weeks using four surface electrodes, two to the paraspinal area of T9–10 to L2 and one to either side of the anterior abdominal wall beneath the costal margin. Diaries were recorded for 1 month before, during, and after stimulation and for 2 weeks 3 months later. Results: Transcutaneous electrical stimulation using interferential current stopped soiling in 7/8 children and increased the frequency of spontaneous defecations in 5/8. Defecations remained high and soiling low for 3 months in 3/6 children (with data). Conclusions: These results suggest that transcutaneous electrical stimulation using interferential current has a beneficial effect for children with chronic treatment-resistant constipation. Further trials using larger series of patients are needed to confirm this benefit, to determine the ideal stimulation parameters and to investigate why electrical stimulation might be effective. © 2005 Blackwell Publishing Asia Pty Ltd

No correlation between clinical symptoms and Blastocystis hominis in immunocompetent individuals

Abstract: UNLABELLED Abstract Background and Aim: Previous reports regarding the clinical significance and pathogenicity of Blastocystis hominis have been contradictory. The aim of this study was to examine the association between Blastocystis and gastrointestinal symptoms in immunocompetent individuals. METHODS We monitored over 2800 healthy people for a period of 15 months, and took stool specimens during both asymptomatic periods and during periods of gastrointestinal symptoms. RESULTS After exclusion of individuals who had simultaneous identification of other fecal pathogens, we compared the proportions of asymptomatic versus symptomatic individuals positive for Blastocystis and found no significant difference (P = 0.5). Symptom status did not correlate with parasite abundance. We found that some individuals were likely to have Blastocystis detected during both asymptomatic and symptomatic periods, possibly suggesting carriage of the organism. CONCLUSION In conclusion, we found no correlation between clinical symptoms and the presence or absence of Blastocystis among this healthy cohort.

Treatment with proton pump inhibitors in acute non-variceal upper gastrointestinal bleeding: A meta-analysis

Abstract: Medical therapy is an attractive adjuvant to endoscopic treatment in upper gastrointestinal (UGI) bleeding. This review aims to assess the treatment effects of proton pump inhibitor (PPI) therapy in acute non-variceal UGI bleeding. Outcome measures evaluated were further bleeding, surgery, all-cause deaths, ulcer deaths and non-ulcer deaths. We searched MEDLINE (1966-2002) and EMBASE (1974-2002) using the terms 'gastrointestinal hemorrhage', 'peptic ulcer hemorrhage', 'proton pump inhibitor', 'omeprazole', 'pantoprazole', 'lansoprazole', 'rabeprazole' and 'esomeprazole'. The search was extended to the Cochrane controlled trials registry database, published abstracts from five international gastroenterology conferences, manufacturers of PPI, known contacts and bibliographies from each full-length published report. We included trials published in English and non-English languages. Eligible studies were randomized controlled trials that compared the treatment effects of PPI therapy with placebo or H2 receptor antagonists in patients with acute non-variceal UGI bleeding. Of the 175 articles screened, 26 controlled trials including 4670 subjects (2317 in treatment arm and 2353 in control arm) were analyzed. The methodology, population, intervention, and outcomes of each selected trial were evaluated using duplicate independent review. Disagreements were resolved by consensus. PPI therapy significantly reduced rates of further bleeding (odds ratio [OR], 0.48; 95% confidence interval [CI], 0.40-0.57) and surgery (OR, 0.61; 95% CI, 0.48-0.76). All-cause deaths were unaffected (OR, 1.02; 95% CI, 0.76-1.37). Ulcer deaths showed a significant reduction (OR, 0.58; 95% CI, 0.35-0.96), while non-ulcer deaths showed a significant increase (OR, 1.60; 95% CI, 1.06-2.41) in the PPI therapy group. Sensitivity analysis of 22 trials published in peer-reviewed journals, 10 trials with double-blind design and 19 trials with high quality score and 22 trials using omeprazole in the treatment group showed results similar to those seen in the analysis of all 26 trials, confirming the stability of the conclusions. Subgroup analysis revealed that summary outcome measures were not influenced by control group therapy (placebo vs H2 receptor antagonists) or the use of prior endoscopic treatment to achieve hemostasis (given vs not given). However, the summary treatment effects for further bleeding and need for surgery were significant in only those trials enrolling patients with peptic ulcers having high risk for rebleeding and not in those trials enrolling patients with all causes of UGI bleeding. The summary treatment effects for further bleeding and need for surgery were significant in trials using intravenous as well as oral PPI. However, summary OR for all-cause deaths and non-ulcer deaths in trials using intravenous PPI were higher in the treatment group and not in trials using oral PPI. This raised the possibility of intravenous PPI-therapy-associated non-ulcer deaths in high-risk patients. PPI therapy in acute non-variceal UGI bleeding reduced rates of further bleeding, surgery and deaths caused by ulcer complications. However, non-ulcer deaths were increased. The overall mortality was unaffected. PPI therapy is useful only in a selected group of patients with acute non-variceal UGI bleeding, namely those with peptic ulcers having endoscopic high-risk stigmata for rebleeding.

Chronic hepatitis B virus infection in the Asia–Pacific region and Africa: Review of disease progression

Abstract: Countries in the the Asia-Pacific region and Africa tend to have the highest prevalence of hepatitis B infection worldwide. Hepatitis B infection progresses from an asymptomatic persistently infected status to chronic hepatitis B, cirrhosis, decompensated liver disease and/or hepatocellular carcinoma. The aim of this review was to summarize rates and risk factors for progression between disease states in the Asia-Pacific region and Africa. A literature search was conducted employing MEDLINE and EMBASE (1975-2003) using the following key words: hepatitis B, natural history, disease progression, cirrhosis, hepatocellular carcinoma, mortality, Africa and the Asia-Pacific region. Bibliographies of articles reviewed were also searched. Ranges for annual progression rates were: (i) asymptomatic persistent infection to chronic hepatitis B, 0.84-2.7%; (ii) chronic hepatitis B to cirrhosis, 1.0-2.4%; and (iii) cirrhosis to hepatocellular carcinoma, 3.0-6.6%. Patients with asymptomatic persistent infection and chronic hepatitis B had relatively low 5-year mortality rates ( 50%) were much higher in patients with decompensated liver disease and hepatocellular carcinoma. No data were found for progression rates in African populations. Hepatitis B e antigen was a risk factor for chronic hepatitis B, and bridging hepatic necrosis in chronic hepatitis B increased the risk of cirrhosis. Risk factors for hepatocellular carcinoma included cirrhosis, co-infection with hepatitis C virus, and genetic and environmental factors. In this review, wide ranges of disease progression estimates are documented, emphasizing the need for further studies, particularly in Africa, where progression rates are largely not available. Summarizing information on factors associated with disease progression should assist in focusing efforts to arrest the disease process in those at most risk.

Gallstone disease in non-alcoholic fatty liver: prevalence and associated factors.

Abstract: Background: Insulin resistance is a risk factors for non-alcoholic fatty liver disease (NAFLD) and for gallstone disease (GD). Aims of the present study were to assess the prevalence of and factors associated with GD in unselected patients with NAFLD. Methods: A total of 161 consecutive patients with NAFLD diagnosed through compatible ultrasonography in the absence of known etiologies of liver disease (in all patients) and/or confirmed histologically (in 61 patients), was studied. Gallstone disease was diagnosed through ultrasound scanning or on the basis of previous cholecystectomy. Anthropometric and biochemical variables and concurrent diseases were compared in 32 NAFLD-GD patients and in 129 NAFLD patients without GD (controls) according to gender. Results: The overall prevalence of GD was 19.88%, higher in female patients (P < 0.05), who were older (P < 001). The overall percentage of GD increased with age (P < 0.05). The GD patients had higher uric acid (men), total cholesterol and apolipoprotein B (apo-B) serum concentrations (women; P < 0.05); women also had a higher prevalence of hypertriglyceridemia (P < 0.05). The age-corrected odds ratio of having GD by tertiles increased significantly with increasing uric acid (men) and with increasing total cholesterol, triglycerides and apo-B (women). At univariate continuous analysis GD was associated with insulin 120 min and uric acid in male patients; and with body mass index, insulin 120 min, apo-B, total cholesterol and triglycerides in female patients. On multivariate analysis it was found that among these factors only uric acid in men and apo-B in women were independently associated with GD in NAFLD. Conclusions: The prevalence of GD in NAFLD is more elevated than reported in the general population. The factors independently associated with GD in NAFLD are different from those reported in the general population and vary according to the gender. © 2005 Blackwell Publishing Asia Pty Ltd

Association between adenomas of rectosigmoid colon and metabolic syndrome features in a Chinese population

Abstract: Background and Aims: Metabolic syndrome (MS) consists of a cluster of diseases, including obesity, dyslipidemia, hyperglycemia and high blood pressure. The purpose of the present study was to assess the association of MS with adenomas of the rectosigmoid colon, a well-established precancerous lesion. Methods: A total of 4938 Taiwanese patients (2891 men and 2047 women with a mean age of 50.1 years), who had a physical examination at our hospital between January 2001 and October 2002, were enrolled in this study. All patients underwent a sigmoidoscopic examination to 60 cm from the anus. A modified National Cholesterol Education Program (NCEP) definition of MS was used in this study, in which body mass index (BMI) was substituted for the waist circumference measurement. Results: Overall, 14% of patients had an elevated fasting glucose, 27% had high blood pressure, 14% had an increased triglyceride (TG) level, 8% had low high density lipoprotein (HDL) cholesterol, and 18% were obese. Rectosigmoid polyps were present in 17% of patients, among whom 568 received polypectomy. Pathological findings were hyperplastic in 138 subjects, adenomas in 341, carcinomas in 10, and other benign lesions in 79. In patients without polyps, the adjusted mean TG level and calculated BMI level were lower than those in patients with adenomas. No such difference existed, however, between patients without polyps and those with hyperplastic polyps. The odds ratio of adenomas in situ as compared to either a polyp-free state or the presence of hyperplastic polyps increased significantly with the number of MS diagnostic criteria the patient exhibited. Conclusion: Our study shows that MS is associated with rectosigmoid adenomas in a Chinese population. In patients with rectosigmoid polyps, the coexistence of MS may portend an increased risk of adenomas. © 2005 Blackwell Publishing Asia Pty Ltd

Risk factors for the development of hepatocellular carcinoma among patients with chronic hepatitis C who achieved a sustained virological response to interferon therapy.

Abstract: Background and Aim: Hepatitis C virus (HCV)-infected patients who responded to interferon (IFN) treatment with clearance of serum HCV RNA may rarely develop hepatocellular carcinoma (HCC). The aim of the present study was to elucidate the risk factors for liver carcinogenesis among such patients. Methods: In total, 126 patients with chronic hepatitis C (CHC) who achieved a sustained virological response (SVR) to IFN monotherapy, which was defined as the absence of detectable HCV RNA in the serum at 6 months after completion of treatment, were enrolled and possible risk factors for HCC were analyzed. Results: During the observation period of 66 ± 36 months after cessation of IFN treatment, five (4.0%) of the 126 patients developed HCC. The cumulative incidence of HCC at 3, 5 and 10 years was estimated to be 0.9, 4.7 and 7.5%, respectively. The cumulative incidence of HCC was significantly higher among patients with severe fibrosis (F3 or F4) than among patients with no or mild fibrosis (F0 to F2) in the liver before treatment (P = 0.007); among patients with alcohol intake of ≥ 27 g/day than among patients with that of < 27 g/day (P = 0.015); and among patients who were ≥ 65 years old than among patients who were < 65 years old at the start of treatment (P = 0.026). Conclusions: Patients with CHC who had severe fibrosis, who had regularly taken moderate amounts of alcohol, or who were ≥ 65 years at the start of IFN treatment should be carefully followed to detect small and controllable HCC, even after eradication of HCV.

Epidemiology and clinical pattern of hepatitis delta virus infection in Pakistan.

Abstract: Background and Aims: The global epidemiology of hepatitis delta virus (HDV) infection is changing. This study was performed to determine the epidemiology and clinical impact of hepatitis delta in Pakistan. Methods: Countrywide data was collected from 1994 to 2001. A total of 8721 patients were tested for hepatitis delta antibody. A subset of 97 hepatitis delta antibody reactive inpatients with chronic liver disease were compared to 97 patients admitted with liver disease due to hepatitis B alone. Results: Of the 8721 patients tested, 1444 (16.6%) were reactive for hepatitis delta antibody. Most were males (87.4%, P < 0.001) and younger (mean age 31 years, P < 0.001) compared to HDV non-reactive patients. Prevalence of delta infection was highest in the rural (range 25–60%) compared to the urban population (range 6.5–11%). Analysis of the inpatient data showed that delta infected patients had significantly less severe clinical liver disease and a trend towards lesser development of hepatocellular carcinoma compared to delta negative patients. Conclusions: (i) HDV infection is present in 16.6% of hepatitis B infected patients in Pakistan, most commonly in younger males living in rural areas; and (ii) delta virus infected patients have less severe clinical liver disease compared to delta negative, hepatitis B patients.

Decreased density of interstitial cells of Cajal and neuronal cells in patients with slow-transit constipation and acquired megacolon.

Abstract: Background: The pathophysiology of constipation is not clearly identified as yet, and the interstital cells of Cajal (ICC), known to generate the slow wave activity and to be involved in intestinal neurotransmission and the enteric nervous system (ENS), are suspected to play an important role. The aims of the present study were to assess the distribution of ICC and neuronal cells of ENS in patients with slow-transit constipation and acquired megacolon. Methods: Sigmoid colon specimens were obtained from patients who underwent colectomy due to slow-transit constipation (n = 10), acquired megacolon (n = 9) and non-obstructive colon cancer (n = 10) as a control group. The ICC were visualized by c-Kit immunohistochemistry and neuronal cells of the ENS were demonstrated by protein gene product (PGP) 9.5. Density of cells stained by c-Kit and PGP 9.5 was calculated as percent area (area stained/area of X–Y plane) × 100, when images were collected at a magnification of ×40 objective, with maximum area examined in the horizontal X–Y plane of 400 µm × 400 µm using an image analyzer. Results: The densities of ICC and PGP 9.5 reactive neuronal structures were significantly decreased in all layers of sigmoid colon specimens in patients with slow-transit constipation and acquired megacolon, compared with that of the control group. However, there was no statistically significant difference in either the density of ICC or that of neuronal structures between the patients with slow-transit constipation and acquired megacolon. Conclusions: Slow-transit constipation and acquired megacolon were associated with alteration of ICC and neuronal cells of ENS in the sigmoid colon. © 2005 Blackwell Publishing Asia Pty Ltd

Comparative study of diagnostic value of cytologic sampling by endoscopic ultrasonography-guided fine-needle aspiration and that by endoscopic retrograde pancreatography for the management of pancreatic mass without biliary stricture.

Abstract: Background: Endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) can now provide a cytopathological diagnosis of underlying pancreatic malignancy with higher success rates than endoscopic retrograde pancreatography (ERP). To determine the significance of EUS-FNA for the diagnosis of pancreatic mass without biliary stricture, the value of cytopathological diagnosis obtained by EUS-FNA was retrospectively compared with that by ERP, and the complications associated with these procedures evaluated. Methods: Eighty-three patients who were suspected to have a pancreatic mass (excluding a cystic mass), without biliary stricture on conventional ultrasound and/or computed tomography were enrolled. The EUS-FNA biopsy was performed in 53 patients and cytology utilizing ERP was performed in 30 patients. Results: The sampling rate of adequate specimen was 100% in both groups. In the EUS-FNA group, the overall results for the available samples were sensitivity 92.9% and accuracy 94.3%. In contrast, in the ERCP group, the overall results were sensitivity 33.3% and accuracy 46.7%. There was a significant difference between the two groups (P < 0.01). With regard to complications, there was a significant difference (P < 0.01) in the frequency of post-procedure pancreatitis between the EUS-FNA group and ERP group (0%, 0/53 vs 33.3%, 10/30, respectively). Conclusion: Endoscopic ultrasonography-guided fine-needle aspiration is safer and more accurate for the cytopathological diagnosis of suspected pancreatic masses without a biliary stricture as compared with cytology during ERP. Endoscopic ultrasonography with FNA should be considered a preferred test (prior to attempting endoscopic retrograde cholangiopancreatography) when a cytological diagnosis of a pancreatic mass is required, especially when there is no biliary obstruction, or when emergent decompression of an obstructed biliary tree is not considered clinically necessary due to lack of signs and symptoms of cholangitis. © 2005 Blackwell Publishing Asia Pty Ltd

Monitoring and management of antituberculosis drug induced hepatotoxicity

Abstract: Background: Hepatotoxicity to antituberculosis therapy (ATT) poses a major challenge. This often results in inadequate therapy. The risk of fulminant hepatic failure and mortality is high once icteric hepatitis develops. There is no consensus on monitoring protocols and for the reintroduction of ATT. Methods: All patients (from the Department of Internal Medicine and Gastroenterology, Jagjivanram Hospital and the Department of Gastroenterology, Bombay Hospital, Mumbai, India) with a diagnosis of tuberculosis, who were to receive ATT during the study period, were included in the present study for prospective periodic laboratory monitoring for the development of hepatotoxicity. Those patients who developed hepatotoxicity formed Group A (n = 21), whereas those who did not develop hepatotoxicity were included in Group C (n = 179). For the purpose of comparison with Group A, all the patients who presented directly with ATT induced hepatotoxicity during the study period were categorized as Group B (n = 24). Group A and B were further studied after normalization of liver functions for sequential reintroduction with therapeutic doses at a weekly interval. Results: In Group A, 66.6% (14 patients) of the patients were diagnosed in the asymptomatic period. Seven patients had symptomatic hepatitis, but none had icteric illness. There were no mortalities in Group A. In contrast, all the patients in Group B had symptomatic hepatitis (75% icteric hepatitis). There was a mortality rate of 16.6% (four patients). Of the 41 patients from Groups A and B who survived, reintroduction was successful in 38/39 (97.4%). In the remaining two patients who were in Group B, reintroduction was not attempted because of decompensated liver disease. Conclusions: Periodic laboratory monitoring is important in detecting hepatotoxicity at an early stage, thereby preventing mortality. Sequential reintroduction is often successful.

Effect of liver cirrhosis on body composition: Evidence of significant depletion even in mild disease

Abstract: Background and Aims: Malnutrition is common in liver cirrhosis patients. However, it is under-diagnosed because liver disease affects the traditional nutritional assessment. An understanding of changes in body composition and the establishment of the tissue-loss pattern in liver cirrhosis patients could help practitioners to better manage malnutrition in this setting. The aims of this study were: to quantify body composition changes, to determine tissue loss pattern, and to assess the relation of these to the severity of hepatic dysfunction. Methods: Seventy-nine patients and 17 controls were studied. Total body water and extracellular water were measured using dilution techniques. Intracellular water and body cell mass were calculated from these parameters. Total body fat was obtained using absorptiometry. Results: Extracellular water was increased and intracellular water was decreased in patients. The two major compartments (body cell mass and body fat) were significantly reduced, mainly in patients with moderate and severe disease. However, significant losses occurred even in Child–Pugh class A patients. We established a tissue-loss pattern. In Child–Pugh class A patients body fat loss predominated. Child–Pugh class B patients had losses in at least one of the two compartments. Most Child–Pugh class C patients had simultaneous depletion in both compartments. Conclusions: Liver cirrhosis was characterized by a significant reduction in body cell mass and body fat and by a redistribution of body water. Significant losses occurred even in patients with mild disease. There was a more pronounced loss of fat in the initial stages, followed by an accelerated loss of body cell mass in the advanced stages of liver cirrhosis. © 2004 Blackwell Publishing Asia Pty Ltd

Community-based epidemiology of hepatitis B virus infection in West Bengal, India: prevalence of hepatitis B e antigen-negative infection and associated viral variants.

Abstract: Background and Aims: There is a paucity of population-based epidemiological information regarding hepatitis B virus (HBV) infection in India. The present study was planned to outline the magnitude and pattern of HBV infection, hepatitis B e antigen (HBeAg)-negative infection and the associated viral mutants in India. Methods: A community-based epidemiological study of HBV infection was carried out in West Bengal, India. Serological markers of infection and potential risk factors for HBV transmission were determined. Among the infected individuals, HBV-DNA, genotypes and mutations in the precore (PC) stop codon and basal core promoter (BCP) regions were determined by DNA sequencing and polymerase chain reaction (PCR) restriction fragment length polymorphism methods. Results: Of the 7653 people included in the study, 227 (2.97%) tested positive for hepatitis B surface antigen (HBsAg), of whom 204 (90%) were HBeAg-negative and hepatitis B e antibody (anti-HBe)-positive, and 78% had normal alanine aminotransferase (ALT) levels. HBV-DNA could be detected by PCR in only 32% of people. G1896A PC stop codon mutants were present in 12% of people, BCP mutants in 18% and the remainder (70%) of the HBeAg-negative infections were associated with wild type sequences in these regions. Conclusions: This first general population-based epidemiological study of HBV infection from India suggests that HBV acquisition starts in early childhood and peaks in adulthood. Most infections in the community are e-negative and inactive. The point prevalence of PC stop codon and BCP mutants is low in this primarily inactive and asymptomatic HBV-infected population sample in eastern India.