Randomized comparative multicenter study of hydroxyethyl starch versus albumin as a plasma expander in cirrhotic patients with tense ascites treated with paracentesis.
Altman C. Bernard B. Roulot D. Vitte RL. Ink O.
Department of Hepatology, Hopital Bicetre, Le Kremlin Bicetre, France.
OBJECTIVE: Large-volume paracentesis associated with plasma volume expansion with albumin is an effective, safe, but costly therapy for ascites in patients with cirrhosis. The aim of this study was to compare the use of a synthetic plasma expander, hydroxyethyl starch (HES), with that of albumin. DESIGN: Sixty cirrhotic patients with ascites were studied. Patients were randomly assigned to be infused with either albumin (8 g/l of ascites removed, n = 33) or HES (200 ml/l of ascites removed, n = 27). None of the patients was treated with diuretics or had renal impairment or hyponatremia at entry. Clinical and laboratory data were obtained before and 1, 3 and 15 days after treatment. RESULTS: There were no significant differences in clinical and laboratory parameters between the two groups at entry into the study. None of the patients developed renal impairment during the trial. One patient (HES group) presented with hyponatremia. Plasma atrial natriuretic factor and aldosterone levels did not differ between the two groups at baseline or at 1 and 3 days after paracentesis. The volume of ascites removed did not differ between the albumin (7.9 +/- 4.4 l) and HES (6.9 +/- 5.3 l) groups. However, there was a significant difference in weight loss between the albumin and HES groups (7.9 +/- 5.2 kg vs 4.7 +/- 3.4 kg; p = 0.01). Clinical and laboratory parameters indicated that HES was well tolerated except for hypoalbuminemia. CONCLUSION: HES is well tolerated in patients with cirrhosis. There is no difference between HES and albumin in the prevention of complications related to large-volume paracentesis. The lesser degree of weight loss observed with HES needs further study.
Effect of dopamine on portal blood flow in cirrhotic patients.
Kaya N. Yesildag O. Kahraman H. Boyunaga H. Demircan C. Yalcintas U. Kapicioglu S.
Section of Gastroenterology, Faculty of Medicine, Ondokuz Mayis University, Samsun, Turkey.
OBJECTIVE: The effects of dopamine infusion on portal blood flow were examined in 12 cirrhotic patients (seven men, five women) in a Child-B group. METHODS: Dopamine was administered as an intravenous infusion (2 micrograms kg-1 min-1). RESULTS: At 0, 30 and 60 min, portal blood flow, left ventricular systolic and diastolic functions were evaluated using the pulsed doppler method. No significant difference was found between heart rate, blood pressure and parameters demonstrating left ventricular systolic and diastolic functions before and after dopamine infusions. Portal blood flow decreased significantly at 30 and 60 min. Portal blood flow fell from 1802 +/- 88 to 1339 +/- 50 ml min-1 (P < 0.001) at 30 min and to 1121 +/- 60 ml min-1 (P < 0.001) at 60 min. CONCLUSION: The reducing effects of dopamine on portal blood flow in cirrhotic patients were demonstrated by the pulsed doppler method, which is a noninvasive test.
Influence of the transmission route and disease duration in the histopathology of chronic hepatitis C: a study of 101 patients.
Lopez-Morante A. Saez-Royuela F. Echevarria C. Llanos C. Martin-Lorente JL. Yuguero L. Ojeda C.
Department of Gastroenterology, General Yague Hospital, Burgos, Spain.
OBJECTIVE: Different studies have demonstrated that factors such as transmission route, disease duration and age at the time of infection can influence the histological evolution of chronic hepatitis by the hepatitis C virus (HCV). The aim of this study was to determine if epidemiological factors such as disease duration and transmission route influence the severity of the histological lesions of patients with chronic hepatitis by HCV. DESIGN: A prospective study. METHODS: The hepatic biopsies of 101 patients diagnosed with chronic hepatitis by HCV were studied. The patients were divided into three groups according to transmission mode: (1) post-transfusional (n = 28), (2) associated with the use of drugs by parenteral route or intravenous drug use (n = 28), and (3) sporadic hepatitis (n = 45). RESULTS: We found more severe forms of hepatopathy in post-transfusional hepatitis and sporadic groups than in the intravenous drug user group of patients. The disease evolution time was significantly higher in patients diagnosed as having chronic active hepatitis with or without cirrhosis (13.8 +/- 9 years) than in patients with chronic persistent hepatitis (8 +/- 4 years), P < 0.01. We found a significant correlation between the evolution time of the infection by HCV and the Histology Activity Index (P < 0.01). The multivariate analysis showed that only the transmission route and the disease evolution time are predictive variables of Histology Activity Index in chronic hepatitis C. CONCLUSION: These results suggest that the post-transfusional and sporadic transmission routes and a greater evolution time of the disease are epidemiological variables that are associated with the presence of more severe histological lesions in chronic hepatitis C.
Prognostic factors in cirrhotic patients receiving long-term sclerotherapy for the first bleeding from oesophageal varices.
Sakaki M. Iwao T. Oho K. Toyonaga A. Tanikawa K.
Department of Medicine II, Kurume University School of Medicine, Japan.
OBJECTIVE AND DESIGN: The aim of this study was to identify prognostic factors in cirrhotic patients receiving long-term sclerotherapy for their first bleeding from oesophageal varices. METHODS: Ninety-eight patients with acute bleeding from oesophageal varices receiving long-term endoscopic injection sclerotherapy were retrospectively investigated. Thirteen variables (five qualitative and eight quantitative) related to clinical, biological, and radiographic features were collected at admission. The qualitative variables were: gender, hepatocellular carcinoma, cause of cirrhosis, ascites and degree of encephalopathy. The quantitative variables were age, bilirubin, albumin, prothrombin index, number of sessions of sclerotherapy, volume of ethanolamine oleate, time taken to reach the hospital and shock index. These variables were examined with a multivariate analysis using stepwise logistic regression procedures and a prognostic index was calculated from the Cox equation. The predictive power of the final Cox model was prospectively tested in 43 patients with cirrhosis receiving long-term sclerotherapy for their first variceal bleeding. RESULTS: Of the 13 variables studied in a multivariate analysis using a logistic regression model, four had an independent prognostic value: the presence of hepatocellular carcinoma, bilirubin, albumin and time taken to reach the hospital. When the Cox model was examined in an independent set of 43 patients, there were no statistically significant differences between the observed and expected survival. CONCLUSION: Prognosis of patients with bleeding from oesophageal varices is related to residual liver function and time taken to reach the hospital. Furthermore, the presence of hepatocellular carcinoma is an additional risk factor.
CagA protein seropositivity in a random sample of adult population and gastric cancer patients in Estonia.
Vorobjova T. Nilsson I. Kull K. Maaroos HI. Covacci A. Wadstrom T. Uibo R.
Department of Immunology, University of Tartu, Hospital of Oncology, Estonia.
OBJECTIVE: The prevalence of antibodies to CagA protein, associated with the risk of developing gastric cancer (GC), was studied in an Estonian adult population with a high prevalence of Helicobacter pylori (HP) infection and in a group of GC patients. DESIGN: In a representative sample of a random adult population from the South Estonian town of Karksi-Nuia, containing 199 subjects (86 M, 113 F, mean age 42.4) and in 45 (22 M, 23 F, mean age 64.5) consecutive patients with gastric adenocarcinoma, recruited during the periods 1986-87 and 1995-96 in the Hospital of Oncology, University of Tartu, anti-CagA IgG antibodies were determined by enzyme-linked immunosorbent assay (ELISA) using a recombinant fragment of CagA protein. The occurrence of anti-CagA IgG in ELISA was compared with immunoblot results for 141 subjects. RESULTS: Seropositivity to acid glycine extracted cell surface proteins of HP was 85% in the population and 91% in GC patients (p = 0.39). Anti-CagA IgG antibodies were present in 63% of the population and in 87% of GC patients (p = 0.004). The highest prevalence of anti-CagA IgG in the population sample occurred in the age group 20-29 (76%). A comparison of anti-CagA positivity evaluated by using ELISA and immunoblot showed an agreement of results in 80% of cases. CONCLUSION: HP seropositivity was similarly high in the Estonian random adult population sample and in GC patients, however, the prevalence of anti-CagA IgG was significantly higher in GC patients. Moreover, persons aged 20-29 years in the population possess the highest prevalence of anti-CagA IgG and should be given further attention with respect to the development of GC later in life.
Antibiotic use, childhood affluence and irritable bowel syndrome (IBS).
Mendall MA. Kumar D.
Mayday Hospital, Thornton Health, Surrey, UK.
BACKGROUND: Antibiotics cause well defined short-lived disturbances in bowel habit. There is evidence to suggest that antibiotics may play a role in the pathogenesis of IBS. Atopy has been associated with small household size in childhood and could also play a role in IBS. We conducted a survey examining the relation of drug use and other epidemiological correlates of IBS. SETTING: General practice health screening clinic. SUBJECTS AND METHODS: 421 subjects (46% male, mean age 47 years (range 18-80 years) attending a general practice health screening clinic were interviewed by a research nurse and completed a previously validated questionnaire. Symptoms of IBS were said to be present if abdominal pain with 2 or more Manning criteria symptoms occurred more than once per month over the previous 6 months. RESULTS: 48 subjects had symptoms of IBS. The following were strongly related to its presence: antibiotic use [adjusted OR 3.70 (1.80-7.60)], female sex and childhood living density < 1 person per room [OR 3.47 (1.57-7.64)], manual father's occupation [OR 0.35 (0.16-0.76)]. The use of NSAIDS, H2 antagonists or other types of medication was not greater in this group. CONCLUSION: Antibiotic use is associated with IBS. The association with antibiotic use requires testing in prospective studies. Privileged childhood living conditions were also an important risk factor which is consistent with an allergic aetiology for IBS.
Are we telling patients enough? A pilot study to assess patient information needs in a gastroenterology outpatient department.
Eaden JA. Ward B. Smith H. Mayberry JF.
Leicester General Hospital, UK.
OBJECTIVE: To define whether gastroenterology patients wish to receive more information concerning many aspects of their illness and to elicit their attitude after receiving written communication from their hospital practitioner. METHODS: In stage 1, 73 gastroenterology patients were interviewed and completed a structured questionnaire after their hospital outpatient visit, to assess whether they would like to receive more information about their condition. Stage 2 involved posting a copy of the general practitioner's letter, dictated in the clinic, to the patient and assessing their opinion of its value, by using a second questionnaire. In stage 3 a group of outpatients received a letter specifically prepared for them which summarized the outcome of their clinic visit (with avoidance of medical terms) and they again completed a questionnaire. RESULTS: More than 75% of patients wished to receive written communication from their hospital practitioner. Ninety percent wanted to know more about diagnostic tests and 92% requested more information about their medication. Ninety percent of patients who received a copy of their GP's letter claimed to understand its contents and felt it was beneficial. Ninety four percent wanted the service to continue. However, there was no advantage in preparing a special letter for patients compared with a simple copy of that sent to their GP. CONCLUSION: There is considerable interest amongst gastroenterology patients concerning their diagnosis and the management of their disease. The provision of simplified letters about their outpatient management does not seem to have any advantage over simply providing copies of all relevant correspondence sent to GPs.
Changes in liver histopathology in women infected with hepatitis C through contaminated anti-D immunoglobulin injections in Ireland.
Albloushi SS. Murray FE. Callagy G. Courtney MG. O'Keane JC. Kay E.
Hepatology Unit, Beaumont Hospital, Dublin, Ireland.
OBJECTIVE: To evaluate histological findings in untreated chronic hepatitis C patients at diagnosis 17 years after infection and to assess histological progression on repeat liver biopsy 2 years later. PATIENTS: Thirty patients infected with hepatitis C virus (HCV), genotype 1b, by contaminated anti-D immunoglobulin in Ireland in 1977 were studied. These patients were diagnosed in 1994 for the first time. All patients were positive for HCV-RNA by polymerase chain reaction (PCR). METHODS: Each patient underwent two liver biopsies approximately 2 years apart 17 and 19 years after initial infection. The liver biopsies were scored by two pathologists by the modified histological activity index using a numerical score. At first liver biopsy at time of presentation, eight patients had normal alanine aminotransferase (ALT), four had an ALT of more than 100 IU/I and 18 had an ALT level between 40 and 100 IU/I. RESULTS: In the initial (1994) biopsies, the median grade (inflammation) was 5/18, range 1-9 and the median stage (fibrosis) was 2/6, range 0-6. One patient showed cirrhosis (stage 6/6) and six patients (20%) had developed moderate fibrosis (stage 3-4/6). On the repeat biopsy, 2 years later, median grade (inflammation) was 5/18, range 2-9 and stage (fibrosis) was 1/6, range 0-6. CONCLUSION: This group of patients, infected with HCV genotype 1b and untreated for 19 years, allows evaluation of the natural history of this virus. The majority of patients showed mild chronic hepatitis. Only one patient had developed cirrhosis. There was no significant histological disease progression between the two biopsy specimens over a 2 year period. The results suggest that the prognosis in such cases could at least be guardedly optimistic and that sequential liver biopsy may be performed less frequently.
Genotype distribution of hepatitis C virus infection in Greece: correlation with different risk factors and response to interferon therapy.
Diamantis I. Vafiadis I. Voskaridou E. Dellatetsima J. Jaggi N. Gyr K. Battegay M.
Outpatient Department of Medicine, University Hospital Basle, Switzerland.
The aim of this study was to investigate the prevalence of HCV genotypes among Greek patients with chronic hepatitis C and to assess the influence of genotypes and quasi-species populations on efficacy of interferon therapy. Genotypes were determined in 65 patients (18 patients after kidney transplantation, 16 with thalassemia and 31 with no known risk factor) with elevated ALT for more than 6 months and histologically proven chronic hepatitis, using the Inno-Lipa strip assay. The quasi-species were determined using the fluorescence single-strand conformational polymorphism method. Most patients were infected with genotype 3a, namely 61% of patients with kidney transplants (n = 18), 50% of patients with thalassemia (n = 16) and 48% of patients without known risk factors (n = 31). Other genotypes were found including coinfection with different genotypes. In all patients with mixed infection, genotype 3a was present. Thirty-six patients from the last two groups received interferon (3Mio U 3x week) for 1 year. Biochemical and/or virological and histological responses were found in 11/19 patients with genotype 3a (58%), 3/5 with mixed infection, 2/4 with genotype 1b, 2/5 with genotype 2a, 1/4 with genotype 1a and 1/1 with genotype 4. The virus found in non-responders with genotype 3a was genetically more heterogeneous than in responders. These data indicate that (1) the genotype 3a is prevalent in Greek patients (68% of all patients), (2) there is no significant difference regarding genotypes among patients with different risk factors and (3) although based on a small number of patients, the genotype 3a seems to respond better to interferon therapy. Finally, the number of quasi-species may be a factor predictive of response.
Endoscopic sclerotherapy for bleeding oesophagogastric varices secondary to extrahepatic portal vein obstruction in an adult Caucasian population.
Vleggaar FP. van Buuren HR. Schalm SW.
Department of Hepatogastroenterology, University Hospital Rotterdam, The Netherlands.
BACKGROUND: The efficacy of endoscopic sclerotherapy for bleeding oesophagogastric varices secondary to extrahepatic portal vein obstruction in adult Caucasian patients is poorly documented. OBJECTIVE: To assess the results of endoscopic sclerotherapy for all patients with this condition who have been treated and followed in our hospital since 1982. DESIGN: Prospective cohort study. RESULTS: Twenty-one consecutive patients were included and followed during a mean period of 79 months (range 6-162 months). Active bleeding, encountered in five patients, was controlled by sclerotherapy in all cases. Two patients received a porto-systemic shunt after initial sclerotherapy. In all but one of the remaining 19 cases sclerotherapy resulted in eradication of the varices. The mean bleeding risk after initiation of sclerotherapy was 0.02 bleed/month/patient, which was lower than the estimated 0.13 bleed/month/patient prior to sclerotherapy. The actuarial rate of rebleeding at 5 years due to all causes and due to oesophagogastric varices was 35 and 28%, respectively. Two patients died, both from a haematological (pre-) malignancy. Actuarial 5 year survival was 95%. CONCLUSION: The results of this study are in agreement with findings for paediatric and Asian patient populations and support sclerotherapy as the primary treatment modality for oesophagogastric variceal bleeding in adult Western patients with portal vein thrombosis. Life expectancy for patients with this condition is determined by the underlying cause of the portal venous obstruction.
Sclerosing peritonitis complicated by sepsis: a potential cause of portal hypertension.
Jones EA. Bronkhorst CM. de Jonge E. ten Kate FJ.
Department of Gastrointestinal and Liver Diseases, Academic Medical Center, Amsterdam, The Netherlands.
A 27-year-old woman with chronic renal failure, who had been treated with chronic ambulatory peritoneal dialysis and had developed sclerosing peritonitis, was admitted to the hospital with intra-abdominal sepsis. In spite of antibiotic therapy, sepsis recurred and was associated with intrahepatic cholestasis. In addition, over a period of about 4.5 weeks she developed hepatomegaly and portal hypertension unassociated with occlusion of the portal vein or one of its main extrahepatic branches. A wedge biopsy of the liver revealed extensive thick fibrosis of the liver capsule, intrahepatic cholestasis, diffuse swelling of hepatocytes, central veins that were difficult to visualize and small portal tracts. It is suggested that the sepsis was responsible for the intrahepatic cholestasis, swelling of hepatocytes and hepatomegaly. It is also suggested that the rigidity of the fibrotic liver capsule provided resistance to the development of hepatomegaly, with the result that intrahepatic pressure increased (compressing intrahepatic branches of the portal vein as well as portal tracts and central veins) and portal hypertension developed.
Treatment options for cirrhotic ascites.
Derriford Hospital, Plymouth, UK.
Ascites due to cirrhosis can usually be managed successfully by dietary sodium restriction and carefully monitored diuretic therapy. However, paracentesis with an albumin infusion is a relatively safe alternative that has gained widespread acceptance. Other plasma expanders offer a cheaper alternative to albumin. Other recently developed techniques include peritoneovenous shunt and transjugular intrahepatic portosystemic stent shunt. Each of these is associated with an operative mortality and substantial complications, but for diuretic-resistant ascites a peritoneovenous shunt has comparable results to paracentesis/albumin. For patients with spontaneously occurring renal failure the prognosis is poor. None of the above treatments improves renal function. Management should therefore be symptomatic with paracentesis as necessary.
Self-expanding metal oesophageal endoprostheses: which is best?
University Department of Surgery, Royal Free Hospital School of Medicine, London, UK.
Palliation is necessary in over 50% of patients with oesophageal cancer, and the most effective means of achieving this is still debated. Plastic or stainless steel reinforced endoprostheses have been available for some 20 years, but have the disadvantages of bulky introducing systems, a significant incidence of perforation and, frequently, sub-optimal palliation. The introduction of self-expanding metallic stents (SEMS) in 1990 was received enthusiastically on account of their relative ease of insertion, with low perforation risk and greater internal diameter of 20-25 cm, resulting in better relief of dysphagia. However, disadvantages of SEMS include the high cost of the stents and disposable delivery systems, the difficulty in removing or repositioning these stents, and the high rate of re-intervention because of tumour ingrowth with uncovered stents, stent displacement with their covered counterparts, and obstruction owing to stent compression or tumour overgrowth at either end of the stent. Published studies include a randomized study between conventional plastic prostheses and uncovered Wallstents, a non-randomized study comparing uncovered Wallstents and Ultraflex stents, and the study published in this issue comparing uncovered Ultraflex stents with covered Wallstents. Somewhat surprisingly, 30 day mortality and relief of dysphagia were similar between conventional prostheses and uncovered Wallstents, and despite a 10-fold increase in cost of the SEMS over plastic prostheses, the overall cost of palliation was less because of a mean hospital stay of 5.4 days compared with 12.5 days for plastic prostheses, which is higher than many reported series and may relate to their insertion under general anaesthesia in this study. From the comparative studies of different SEMS, uncovered stents are associated with a higher incidence of tumour ingrowth and covered stents with a higher incidence of stent migration, particularly when they traverse the cardia. Thirty day mortality is relatively high (16-27%), although one study found no procedure-related mortality using the uncovered Ultraflex stent, but the reintervention rate was uniformly higher with those stents as compared with covered or uncovered Wallstents. Improvements in SEMS design are likely to overcome many of the technical problems, at which point it would be necessary to conduct prospective randomized studies against conventional prostheses inserted under sedation, with quality of life and economic assessment and sufficient numbers to enable sub-group analysis for variables such as tumour site and morphology. In the meantime, specialized centres should have facilities for each of the current palliative modalities so as to be able to deploy those most suited to individual circumstances.
Self-expanding metal oesophageal endoprostheses, covered and uncovered: a review of 30 cases.
Hills KS. Chopra KB. Pal A. Westaby D.
Department of Gastroenterology, Chelsea and Westminster Hospital, London, UK.
OBJECTIVE: Oesophageal self-expanding metal endoprostheses (SEMS, or stents) are recognized as a safe means of palliating dysphagia caused by malignancy. Stent designs that have covered or uncovered walls are now available. The purpose of this study was to compare the outcome of use of these two designs. DESIGN: Thirty consecutive cases were reviewed. All the patients had been referred over a period of 25 months for palliation of dysphagia caused by malignant obstruction. Either a covered or an uncovered stent was placed in each patient. Palliation of dysphagia, 30 day mortality, mean survival time, and the number of endoscopic re-interventions required, were assessed. RESULTS: Uncovered Ultraflex stents were used in 14 patients, and Schneider Wallstents were used in 16 patients. Dysphagia improved by one grade or more in 69% of patients. The 30 day mortality was 27%, with an overall mean survival time of 99 days. There was no significant difference between the two groups for these three parameters. Ten patients needed a total of 28 repeat endoscopic procedures to maintain stent patency, with overall rates for each group of 1.64 procedures per patient, for uncovered stents, compared with 0.31 for covered stents (significant at the P < 0.05 level). The number of repeat procedures increased with survival time. CONCLUSION: The use of covered self-expanding metal oesophageal endoprostheses is associated with a significant reduction in the need for endoscopic reintervention after stent placement.
A community-based study of the epidemiology of Helicobacter pylori infection and associated asymptomatic gastroduodenal pathology.
Buckley MJ. O'Shea J. Grace A. English L. Keane C. Hourihan D. O'Morain CA.
Dept of Gastroenterology, Meath/Adelaide Hospitals, Trinity College, Dublin, Ireland.
OBJECTIVES: To document the epidemiology of Helicobacter pylori infection in a normal population, to assess asymptomatic H. pylori positive individuals for the presence of gastroduodenal disease, and to compare the macroscopic and microscopic findings at endoscopy in this group with those of patients presenting with dyspepsia. DESIGN/METHODS: Serum was collected from blood donors and assessed for the presence of anti-H. pylori IgG antibodies. A randomly selected group of asymptomatic blood donors and dyspeptic patients underwent endoscopy. RESULTS: The seroprevalence of H. pylori in 1000 subjects was 43.0%. The prevalence of infection increased from 29% in 18-30 year olds to 62% in 46-60 year olds (P < 0.01). The infection was more prevalent in individuals from social classes IV and V (50.0%) than social classes I and II (36.9%) (P < 0.01). There was no difference between the H. pylori positive asymptomatic individuals (n = 37) and matched dyspeptic patients (n = 29) at endoscopy with regard to duodenal ulcer (13.5% vs. 17.2%) or gastroduodenal erosions (24.3% vs. 20.7%) while 5.4% of the former had gastro-oesophageal reflux compared to 27.6% of the latter. Overall, 56.8% of the H. pylori positive asymptomatic group had a normal macroscopic endoscopy compared with 31% of the dyspeptic group. Histology of the gastric mucosa did not reveal any significant differences between the two groups. In H.pylori negative asymptomatic individuals (n = 13) 92.3% had a normal endoscopy (7.7% had grade I gastro-oesophageal reflux) compared with 61.5% of a matched dyspeptic group (n = 13). CONCLUSION: H.pylori infection, symptomatic and asymptomatic, is associated with significant pathology, and screening for the infection may be indicated for the prevention of gastroduodenal diseases.
Helicobacter pylori cagA status, vacA genotypes and ulcer disease.
Stephens JC. Stewart JA. Folwell AM. Rathbone BJ.
Department of Medicine and Therapeutics, University of Leicester, UK.
OBJECTIVE: Helicobacter pylori is the causative organism of peptic ulcer disease and has two putative virulence determinants: the cagA gene which encodes a protein of unknown function in 60% of strains, and the vacA gene, which is present in all strains, although active cytotoxin is produced in only about 50% of these. The relationship between genotypes of both cagA and vacA and resultant gastroduodenal pathology is unclear. The objective of this study was to correlate vacA genotype and cagA status with gastroduodenal pathology. METHODS: One hundred and six dyspeptic patients were studied (average age 56 years, range 19-86 years, 56 men) referred for routine endoscopy. Macroscopic evidence of gastroduodenal disease was noted and antral biopsies taken for culture and genotyping of H. pylori. The polymerase chain reaction (PCR) was used to detect the cagA and vacA genes of H. pylori using specific primers. RESULTS: Seventy eight of the 106 (73.6%) patients were cagA positive. Of those who had peptic ulcer disease 29/32 (90.6%) were cagA positive. The presence of the cagA gene was significantly associated with peptic ulcer disease (P = 0.006). The presence of the vacA s1 genotype was also significantly associated with peptic ulcer disease (P = 0.01). The presence of the cagA gene was significantly associated with the vacA s1 genotype (P < 0.001). There was no significant difference in the distribution of the s1/m1 and s1/m2 strains between ulcer and non-ulcer patients. CONCLUSION: There is a significant association of the cagA gene and vacA s1 signal sequence with gastroduodenal ulcer disease. The relationship of the various other vacA genotypes to gastroduodenal ulcer disease is less clear.
The temporal relationship between oesophageal bile reflux and pH in gastro-oesophageal reflux disease.
Marshall RE. Anggiansah A. Owen WA. Owen WJ.
Department of Surgery, Guy's Hospital, London SE1 9RT, UK.
OBJECTIVE: Damage caused to oesophageal mucosa by bile constituents is pH dependent. The aim of this study was to evaluate the relationship between pH and duodeno-gastro-oesophageal reflux in gastro-oesophageal reflux disease at night in the supine position. DESIGN: A prospective study of 113 patients with reflux symptoms [63 without erosive oesophagitis (group 1), 23 with erosive oesophagitis (group 2), 27 Barrett's oesophagus (group 3)] and 15 controls. METHODS: All subjects underwent 24 h ambulatory oesophageal pH and bilirubin and gastric pH monitoring. For the supine period, oesophageal pH during episodes of bile reflux was calculated, and the temporal relationship between individual oesophageal and gastric alkaline shift and oesophageal bile reflux episodes was established. The supine period was divided into four equal segments and the temporal patterns of acid and bile reflux and alkaline shift in each of the four supine time segments were investigated. RESULTS: Both acid and bile reflux are severe in Barrett's oesophagus, particularly at night. Nocturnal oesophageal bile reflux occurs mostly between pH 4 and 7 in all groups: 67.6%, 76.5% and 41.4% of the supine period for groups 1, 2 and 3 respectively (P < 0.001 vs. pH < 4 or > 7). Individual oesophageal bile reflux and oesophageal or gastric alkaline shift episodes rarely coincide. Acid reflux predominates in the first half of the night (P < 0.001), oesophageal bile reflux and alkaline shift continue throughout the night, gastric alkaline shift increases towards the end of the night (P < 0.001). CONCLUSION: Duodenal contents in the oesophagus exist at a wide pH range, and may have passed through an acid or an alkaline stomach. This has implications for the damage which individual constituents are able to cause.
Direct measurement of post-prandial portal haemodynamics in cirrhotic patients with a transjugular intrahepatic portosystemic stent-shunt.
Stanley AJ. Forrest EH. Redhead DN. Bouchier IA. Hayes PC.
Department of Medicine, Royal Infirmary of Edinburgh, UK.
OBJECTIVE: Portal haemodynamics vary in response to eating and other stimuli, but any increase in portal venous pressure (PVP) in cirrhotic patients may be a risk factor for variceal bleeding. We directly assessed post-prandial splanchnic haemodynamics in cirrhotic patients with a transjugular intrahepatic portosystemic stent-shunt (TIPSS) in situ. METHODS: A thermodilution catheter was inserted via the patent TIPSS into the portal vein in 12 cirrhotic patients. PVP,portal venous flow (PVF) (thermodilution method), portal vascular resistance (PVR), porto-atrial pressure gradient (PPG), heart rate, mean arterial pressure (MAP) and right atrial pressure (RAP) were measured. A 505 kcal meal was given and all haemodynamic measurements were repeated at 15 min intervals for 60 min. RESULTS: Following the meal, there was a significant rise in PVP from 11.2 +/- 1.5 to 14.0 +/- 1.9 mmHg at 15 min, and 14.0 +/- 1.8 mmHg at 30 min (P < 0.001); in PPG from 9.5 +/- 1.4 to 12.7 +/- 2.2 mmHg at 15 min and 12.7 +/- 2.1 mmHg at 30 min (P < 0.005); and in PVF from 1110.2 +/- 141.1 to 1543.2 +/- 227.6 ml/min at 30 min (P < 0.01). PVR feil from 0.08 +/- 0.01 to 0.05 +/- 0.01 RU at 30 min (P < 0.05). Heart rate increased from 77 +/- 4.1 to 80.5 +/- 5.4 bpm at 15 min (p < 0.05), but MAP and RAP remained unchanged. CONCLUSION: In cirrhotic patients with TIPSS, significant changes in portal haemodynamics occur at 15-30 min following a meal, with minimal effect on systemic haemodynamics. This model offers a new technique to directly assess the causes for and possible treatments of post-prandial splanchnic hyperaemia in cirrhosis.
Chronic hepatitis C long-term responders to human leukocyte interferon-alpha therapy: persistence of a sustained biochemical and virological response during 5 years of surveillance.
Morisco F. Tuccillo C. Iasevoli P. Sessa G. Brunasso G. Caporaso N.
Department of Internal Medicine F. Magrassi, Second University of Naples, Italy.
OBJECTIVES: To define the biochemical and virological course and IgM response to HCV-core protein in long-term responders (LTRs) during a long surveillance (5 years). DESIGN: From 1989 to 1991, 98 patients (pts) with biopsy-proven chronic hepatitis C were enrolled into this study. These pts underwent human leukocyte interferon-alpha (LE-IFN alpha) therapy at the prolonged schedule (3 MU thrice weekly for 1 year). METHODS: Serum alanine-aminotransferases (ALTs) were assessed monthly during and until 1 year after treatment, then every 3 months during the observation period. Qualitative and quantitative HCV RNA and HCV IgM were measured in all pts on baseline samples and in LTRs also after treatment and every following year. RESULTS: Based on serum ALT course, the pts were defined as: LTRs (14 pts), if their serum ALT levels returned to the normal range during therapy and remained so for at least 1 year afterwards; responders with relapse (RRs, 20 pts), if their serum ALT levels returned to the normal range during therapy but increased after ending treatment; and non-responders (NRs, 64 pts), if their serum ALT levels remained abnormal throughout therapy. No significant differences were seen regarding IgM anti-HCV positivity and serum ALT levels among the three groups. LTRs (12 HCV-RNA negative and two HCV-RNA positive at the end of treatment) maintained their virological status and not one of them experienced an elevation of serum ALT levels throughout the surveillance. CONCLUSION: Patients affected by chronic hepatitis C and treated with interferon, but who did not experience a biochemical or virological relapse within the first year of follow-up would not relapse later on; thus, we are able to conclude that these subjects made a complete recovery.
Prognostic and therapeutic score for colorectal adenomas and the role of serum and tissue carcinoembryonic antigen.
Rosandic M. Paar V.
Department of Internal Medicine, University Hospital, Rebro, Zagreb, Croatia.
OBJECTIVE: To study the tissue carcinoembryonic antigen (TCEA) concentrations with regard to multiplicity, diameter, pathohistological finding, degree of dysplasia and serum CEA (SCEA) concentrations. METHODS: Our study included 46 patients with single or multiple adenomas. For 56 adenomas TCEA concentrations were measured in addition to standard determinations of multiplicity, diameter, pathohistology, degree of dysplasia and SCEA. The measurements of TCEA concentrations were performed using the CEA-EIA method (Abbott) modified for wet tissue obtained from the head of the adenoma (TCEA-A), margin of resection at the neck or base of the adenoma (TCEA-B), mucosa near the adenoma (TCEA-C) and rectal mucosa (TCEA-D). The Mann-Whitney test and M estimates were used to differentiate CEA distribution between various classes of adenomas within each characterization. RESULTS: TCEA concentrations from the head of the adenoma (TCEA-A) demonstrated highly significant difference between mild and severe dysplasia (P = 0.0003), between mild dysplasia and invasive adenocarcinoma (P = 0.001) and significant difference between mild and moderate dysplasia (P = 0.04). There was a statistically significant difference in TCEA-A also between tubular and villous adenomas (P = 0.04). On the other hand, no significant correlations with regard to multiplicity, diameter and pathohistological features were found. CONCLUSION: These results suggest that there is a highly significant difference between the tissue CEA concentration from the head of the adenoma (TCEA-A) in the presence or absence of severe dysplasia. Furthermore, combining a number of pathological variables together with TCEA and routine SCEA, a new score was proposed to be used as a guide to the frequency of follow-up colonoscopy following polypectomy.
Intravenous cyclosporin as rescue therapy in severe ulcerative colitis: time for a reappraisal?
Hyde GM. Thillainayagam AV. Jewell DP.
Gastroenterology Unit, Radcliffe Infirmary, Oxford, UK.
BACKGROUND: Intravenous cyclosporin is the only new therapy in recent years to have made a significant impact on the management of acute severe ulcerative colitis (UC). It is increasingly recommended for use in patients who prove refractory to the standard regimen of intravenous (i.v.) and rectal hydrocortisone but do not warrant immediate surgery. This practice is based on uncontrolled and controlled studies which suggest a short-term efficacy of 80% and long-term efficacy of 60% in avoiding colectomy. AIM: The aim of this study was to assess the short- and long-term efficacy of i.v. cyclosporin in patients admitted to our hospital with acute severe ulcerative colitis refractory to i.v. steroids, over a 6-year period. METHOD: A retrospective survey of patients admitted to the John Radcliffe Hospital, Oxford, with acute severe UC over a 6-year period (1991-97) was performed. Truelove and Witts criteria for acute severe UC were satisfied by 216 patients. RESULTS: The standard regimen achieved remission in 132 patients (61%). Of the 84 patients who failed to respond, 34 (40%) proceeded directly to colectomy whilst 50 received cyclosporin (4 mg/kg by continuous slow infusion). Remission was achieved by i.v. cyclosporin in 28/50 (56%) patients who were subsequently transferred to oral cyclosporin (5 mg/kg). However, 8/28 (29%) who initially responded later relapsed after discharge from hospital and underwent colectomy. The short-term efficacy of 56% therefore falls to 40% in the longer term (mean follow-up of 19 months). CONCLUSION: This is the largest survey to date of patients with refractory severe UC treated with i.v. cyclosporin. The findings confirm the potential value of i.v. cyclosporin in severe UC but its effectiveness in clinical practice is less dramatic than previously reported.
Pain is temporally related to eating but not to defaecation in the irritable bowel syndrome (IBS). Patients description of diarrhea, constipation and symptom variation during a prospective 6-week study.
Ragnarsson G. Bodemar G.
Department of Health and Environment, Faculty of Health Services, Linkoping University, Sweden.
OBJECTIVES: To study the intensity and variation of pain and its temporal relation to eating and defaecation. Furthermore, what irritable bowel (IBS) patients mean by constipation and diarrhea and how bowel symptoms vary. DESIGN: Prospective daily symptom recording over 6 weeks. SETTING: The primary catchment area of University Hospital of Linkoping. PARTICIPANTS: Eighty consecutive patients fulfilling the Rome criteria; 63 finished the study. RESULTS: Fifty-nine of 63 patients recorded an average of 29 pain periods and 24 days with pain during the 6 weeks. Over-all pain burden decreased slightly over the study period. At inclusion 38 (64%) patients claimed that pain was relieved by defaecation. However, on average, only 10% of each patient's recorded pain periods were relieved by defaecation. At inclusion 29 (49%) patients claimed postprandial worsening of pain. On average, 50% of each patient's recorded pain periods worsened postprandially. The patients defined constipation as hard stools and diarrhea as loose stools and urgency. Stool frequency did not differ. Bowel symptoms varied within, but not between, fortnightly periods. CONCLUSIONS: Postprandial worsening of pain should be included as a criterion in the clinical definition of IBS while the criterion 'pain relieved by defaecation' should be re-evaluated. IBS patients can probably be divided into subgroups based on stool consistency, not frequency. Daily records are superior to structured clinical interviews or questionnaires for a detailed study of symptoms in IBS.
Post-ERCP pancreatitis and hyperamylasaemia: the role of operative and patient factors.
Dickinson RJ. Davies S.
Department of Medicine, Hinchingbrooke Hospital, Huntingdon, Cambs., UK.
BACKGROUND AND AIM: Pancreatitis and hyperamylasaemia are common complications of ERCP and this study was designed to explain which operative and patient factors predispose to them. PATIENTS AND METHODS: A 1 year prospective study of consecutive patients in a single operator centre with detailed attention to technical factors and the findings. RESULTS: Four hundred and thirty ERCPs were performed. Pancreatitis occurred in 12 cases (2.8%). Amylase results were available in 407 cases; 17 were excluded because of pre-operative hyperamylasaemia (n = 5) and because of pancreatitis (n = 12). Of the remaining 390, 30 (7.7%) had hyperamylasaemia. Pancreatitis and hyperamylasaemia usually occurred after difficult procedures in which pancreatography was achieved. Smaller common bile-ducts, pre-cut papillotomy and some preoperative indications also significantly increased the risk of pancreatitis, while prior papillotomy was protective. Pancreatitis occurred in patients with a younger median age (52.5 vs 68.0; P < 0.05) and was more common in women (F:M = 11:1 vs 241:177; P < 0.05). CONCLUSION: Operative factors are, in part, responsible for the development of pancreatitis and hyperamylasaemia but the age and sex of the patient also appear to be important.
Kappa light chain deposition disease of the liver.
Girelli CM. Lodi G. Rocca F.
Servizio di Gastroenterologia ed Endoscopia Digestiva, Ospedale di Circolo di Busto Arsizio, VA, Italy.
We report the case of a middle-aged woman presenting epigastric discomfort, hepatomegaly, biochemical signs of cholestasis, bone marrow plasmocytosis and Bence Jones proteinuria. Percutaneous liver biopsy disclosed kappa light chain deposition disease of the liver and fine needle aspiration of abdominal fat showed amyloid substance. Renal blood chemistries and urinalysis were repeatedly normal. To our knowledge, this is the first reported case of kappa light chain deposition disease of the liver and concomitant amyloidosis without renal involvement as the first manifestation of plasma cell dyscrasia. This condition should be considered in the differential diagnosis of intrahepatic cholestatic liver disease.
Crohns disease presenting as adenocarcinoma of the small bowel.
Mohan IV. Kurian KM. Howd A.
Department of Surgery, Queen Margaret Hospital, Dunfermline, Fife, UK.
Crohn's adenocarcinoma of the small bowel is extremely rare. We report a patient with a 10-year history of nonspecific abdominal symptoms who was found on his first presentation to have Crohn's adenocarcinoma of the small bowel. Despite adequate surgical resection, prognosis for this condition is poor with 2-year cancer free survival of around 9%. Crohn's carcinoma should be suspected in patients with long-standing disease and those with and without excluded segments of bowel.
Association between ulcerative colitis and systemic lupus erythematosus: report of two cases.
Koutroubakis IE. Kritikos H. Mouzas IA. Spanoudakis SM. Kapsoritakis AN. Petinaki E. Kouroumalis EA. Manousos ON.
Dept of Gastroenterology, University Hospital of Heraklion, Crete, Greece.
BACKGROUND: Common aetiopathogenic factors may explain the association of ulcerative colitis with autoimmune disorders such as systemic lupus erythematosus. PATIENTS: We report two cases of ulcerative colitis associated with idiopathic systemic lupus erythematosus: one patient who developed ulcerative colitis 11 years after having been diagnosed as a case of systemic lupus erythematosus and one case of simultaneous appearance of the two diseases. The lupus clinical manifestations were in neither case correlated with the treatment of ulcerative colitis. CONCLUSION: The association between ulcerative colitis and systemic lupus erythematosus is rare. Although a chance occurrence cannot be excluded it is possible that both conditions share some genetic or immunological defects.
Multivariate analysis of prognostic factors in resected colorectal cancer: a new prognostic index.
Guerra A. Borda F. Javier Jimenez F. Martinez-Penuela JM. Larrinaga B.
Department of Gastroenterology, Hospital of Navarra, Pamplona, Spain.
OBJECTIVE: We analysed different clinicopathological variables in colorectal cancer and their independent prognostic significance in order to elaborate a prognostic index, which may be used to categorize patients into homogeneous groups and indicate adjuvant therapy. DESIGN: Retrospective study. METHODS: Patients (n = 108) undergoing surgery for colorectal cancer were studied (5-year-survival was controlled). Different clinicopathological variables and biological parameters (tumoural ploidy, proliferating cell nuclear antigen PCNA and nucleolar organizing regions NORs) were analysed. The Kaplan-Meier method and log-rank test were used for univariate analysis and the Cox regression method was used for multivariate analysis. RESULTS: Some variables with prognostic effect in univariate analysis (e.g. rectal bleeding, altered bowel habit, intestinal obstruction, type of surgery, histological type, venous and neural invasion and invasive margin) did not have independent prognostic significance after Cox analysis. Final multivariate analysis model was defined by five parameters: postoperative carcinoembryonic antigen, Astler-Coller-Turnbull staging, histological grade, lymphatic invasion and tumour ploidy. A new prognostic index was elaborated that provided information to group patients in three prognostic categories of different risk: high, medium and low. CONCLUSION: The prognostic index allowed categorization of patients into different risk groups with identical tumoural stage and histological grade. Therefore, this index provides better prognostic information that may be helpful when selecting patients for adjuvant therapy.
Taylor AC. Palmer KR.
Gastroenterology Department, Western General Hospital, Edinburgh, UK.
Caroli's disease is characterized by multifocal segmental dilatation of the intrahepatic bile ducts. It is a rare congenital condition, which appears to be autosomal recessively inherited in most cases. There are two forms of disease, one associated with congenital hepatic fibrosis and a simple form occurring alone. Recent reports suggest that the simple form may be as common as that with congenital hepatic fibrosis. Other conditions, including choledochal cyst and renal cystic disease, are frequently associated. The major clinical feature is recurrent cholangitis, which may be complicated by intrahepatic calculi and hepatic abscess formation. There is good evidence that malignancy complicates Caroli's disease in approximately 7% of cases. The diagnosis rests on demonstrating that the cystic liver lesions are in continuity with the biliary tree. Modern imaging techniques allow the diagnosis to be made more easily and without invasive imaging of the biliary tree. The treatment depends on the clinical features and the location of the biliary abnormality. When the disease is localized to one hepatic lobe, hepatectomy relieves symptoms and appears to remove the risk of malignancy. In diffuse Caroli's disease, treatment options include conservative or endoscopic therapy, internal biliary bypass procedures and liver transplantation in carefully selected cases.
Carolis disease: 1977-1995 experiences.
Dagli U. Atalay F. Sasmaz N. Bostanoglu S. Temucin G. Sahin B.
Department of Gastroenterology, Yuksek Ihtisas Hospital, Ankara, Turkey.
OBJECTIVE: Until recently, congenital cystic dilatation of the intrahepatic biliary ducts (Caroli's disease) has been recognized infrequently. This report aimed to analyse and discuss our observations on 21 adult patients with the disease. PATIENTS: From 1977 to 1995, 21 patients (eight women and 13 men), aged 17 to 68 years, were diagnosed and treated for Caroli's disease at Yuksek Ihtisas Hospital. The mean duration of the disease was 6.5 years. RESULTS: The commonest presenting symptom was abdominal pain, a feature in 18 cases. The distribution of the biliary lesions was bilobar in 12 patients and monolobar in nine. Two of them were congenital hepatic fibrosis. Twenty-one patients had coexisting hepatobiliary disease, associated with Caroli's disease. Approximately 95% of our patients had cystolithiasis, cholelithiasis or both. Surgical treatment was used in 18 patients, a partial hepatectomy being carried out in seven of them, an internal biliary drainage by choledocystojejunostomy in five cases, and by choledochotomy in four cases. Three cases with Caroli's disease were treated with endoscopic sphincterotomy and stone extraction. In the follow-up period, four of our patients died. CONCLUSION: Caroli's disease is being diagnosed more frequently as a result of improved diagnostic capabilities. The aim of the treatment is to obtain sufficient biliary drainage and to relieve the symptoms.
Gastro-oesophageal reflux disease in primary care: an international study of different treatment strategies with omeprazole. International GORD Study Group.
Carlsson R. Dent J. Watts R. Riley S. Sheikh R. Hatlebakk J. Haug K. de Groot G. van Oudvorst A. Dalvag A. Junghard O. Wiklund I.
Department of Surgery, Sahlgren's University Hospital, Gothenburg, Sweden.
OBJECTIVE: To assess the efficacy of omeprazole in patients presenting with troublesome reflux symptoms. DESIGN: Randomized, double-blind, parallel-group, placebo-controlled comparison. SETTING: Primary care. SUBJECTS: Patients were recruited using a symptom-based questionnaire for diagnosis of gastro-oesophageal reflux disease. INTERVENTIONS: After endoscopy, patients without endoscopic oesophagitis were randomized to omeprazole 20 mg (Ome20), omeprazole 10 mg (Ome10) or placebo once daily for 4 weeks (n = 261) and those with oesophagitis (except circumferential/ulcerative) were randomized to receive either Ome20 or Ome10 once daily for 4 weeks (n = 277). Patients not symptom-free at 4 weeks received open treatment with Ome20 once daily for a further 4 weeks. Those symptom-free at 4-8 weeks were followed up for 6 months off treatment, to see whether their symptoms recurred. MAIN OUTCOME MEASURE: Complete upper GI symptom relief during week 4 on Ome20 or Ome10 in patients with or without endoscopic oesophagitis. RESULTS: Forty one percent of all patients on Ome20 and 35% on Ome10 reported complete relief from upper GI symptoms during week 4, whilst 73% of the patients on Ome20 and 62% on Ome10 obtained sufficient control. Complete relief during week 4 was reported by 19% of endoscopy-negative patients on placebo, and sufficient control by 35%. Endoscopic healing at 4 weeks occurred in 76% of oesophagitis patients on Ome20 and in 56% on Ome10. After 6 months off treatment, 90% of patients with oesophagitis and 75% of endoscopy-negative patients reported symptomatic relapse. CONCLUSION: Both 10 mg and 20 mg of omeprazole gave effective relief of symptoms, although 20 mg gave superior healing in patients with oesophagitis. After cessation of treatment, symptomatic relapse was rapid and frequent in both endoscopy-positive and endoscopy-negative patients.
Effects of interferon therapy on fibrosis serum markers in HCV-positive chronic liver disease.
Mazzoran L. Tamaro G. Mangiarotti MA. Marchi P. Baracetti S. Gerini U. Fanni-Cannelles M. Zorat F. Pozzato G.
Istituto di Medicina Clinica, University School of Medicine, Trieste, Italy.
OBJECTIVE: To evaluate serum levels of prolyl-hydroxylase and helical domain of Type IV collagen, markers of hepatic fibrogenesis, in patients with HCV-positive chronic liver disease and the effects of interferon therapy on these markers. DESIGN: Prolyl-hydroxylase and Type IV collagen were determined before therapy and each month during the treatment and follow-up. METHODS: Fifty-seven HCV-positive patients were studied. All the subjects received alpha2a recombinant interferon, 6 MU subcutaneously three times a week for 4 weeks, followed by 3 MU thrice weekly for 5 months. After cessation of treatment, each patient was followed for 12 months. Prolyl-hydroxylase and helical domain of Type IV collagen were measured by using immunoenzymatic methods. HCV-RNA and HCV genotype were determined according to the method of Okamoto. RESULTS: In the patients prolyl-hydroxylase (39.8+/-8.9 ng/ml) was not different from controls (39.1+/-5.9 ng/ml). On the contrary, the patients showed a mean Type IV collagen (133.6+/-93.3 ng/ml) significantly (P < 0.01) higher than controls (100.2+/-10.5 ng/ml). A good relationship between the degree of liver fibrosis and the Type IV collagen serum level was found (r = 0.68; P < 0.005). In both responders and non-responders the Type IV collagen levels decreased during interferon therapy. During the follow-up, in responders the Type IV collagen did not show modifications, while in non-responders/relapsers it returned rapidly to the pretreatment levels (139.1+/-100.7 ng/ml). CONCLUSION: In HCV-positive chronic liver disease, prolylhydroxylase is not a good marker of hepatic fibrosis, while Type IV collagen is a useful tool for evaluating fibrogenic activity. Interferon seems to be able to reduce the liver fibrosis even without the inhibition of viral replication and independently from liver necrosis.
Screening for osteoporosis in Crohns disease. A detailed evaluation of calcaneal ultrasound.
Robinson RJ. Carr I. Iqbal SJ. al-Azzawi F. Abrams K. Mayberry JF.
Gastrointestinal Research Unit, Leicester General Hospital, UK.
OBJECTIVES: To compare calcaneal broadband ultrasonic attenuation (BUA) and velocity of sound (VOS) in patients with Crohn's disease with an age-matched control population. The validity of BUA as a screening tool for osteoporosis was evaluated and the relationship between BUA and previous fracture studied. DESIGN: Cross-sectional study. BACKGROUND: Since patients with Crohn's disease are at risk of osteoporosis and premature fracture, routine assessment of bone mineral density (BMD) is recommended. Quantitative ultrasound of the calcaneum is an inexpensive and radiation-free means of assessing bone density which also provides information on bone microstructure. METHODS: BUA (dB/MHz) and VOS (m/s) were measured at the calcaneum (CUBAclinical, McCue Ultrasonics, Winchester, UK) and compared with bone mineral density at the hip and lumbar spine measured by dual-energy X-ray absorptiometry (DEXA); 100 patients (42 men) with Crohn's disease and 52 age-matched healthy controls (23 men) were studied. RESULTS: BUA was significantly reduced in patients with Crohn's disease compared with age-matched controls [76.53 dB/MHz (+/-17.3) vs 87.29 dB/MHz (+/-17.9), difference in means = 10.76, 95% CI -16.67, -4.85, P = 0.0004] and was significantly associated with BMD at the spine (r = 0.49, 95% CI 0.32, 0.63, P< 0.0001) and femoral neck (r = 0.54, 95% CI 0.38, 0.67, P < 0.0001). In the diagnosis of osteoporosis (t score
A 5-year follow-up of self-expanding metal stents in the endoscopic management of patients with benign bile duct strictures.
O'Brien SM. Hatfield AR. Craig PI. Williams SP.
Department of Gastroenterology, The Middlesex Hospital, London, UK.
BACKGROUND: Metal stents offer superior biliary drainage in patients with malignant bile duct obstruction, with fewer episodes of stent occlusion compared with polyethylene stents. Metal stent patency has only been studied over limited time periods in such patients with malignant disease. OBJECTIVE: To assess the long-term patency of metal stents in a group of patients with benign bile duct strictures who are suitable for extended follow-up. METHODS: Between May 1989 and May 1992, eight patients (median age 59.0 years; range 26-88 years) with benign biliary strictures were selected at a tertiary referral centre for insertion of a metal stent. Strictures were secondary to bile duct trauma (n = 5), chronic pancreatitis (n = 2) or idiopathic (n = 1). A long metal stent was inserted in three patients and a short metal stent in five patients. RESULTS: After a median follow-up of 64.5 months (range 26-81 months, seven of the eight patients are alive. Baby scope examination at 1 year showed complete epithelialization of the metal stent in all subjects examined. Median stent patency was 35 months (range 7-72 months). Symptomatic episodes of metal stent occlusion have occurred on nine occasions in five patients (62.5%) secondary to mucosal hypertrophy (n = 3) or biliary calculi (n = 2). CONCLUSION: The long-term management of selected patients with benign bile duct strictures may be significantly improved by the use of metal stents avoiding the need for frequent polyethylene stent changes.
Idiopathic megacolon associated with oesophageal achalasia.
Martin E. Perez San Jose C. Emparan C. Aguinagalde M. Sabas J.
Department of General and Digestive Surgery, Hospital de Basurto, Bilbao, Spain.
We report a rare case of achalasia coexistent with megacolon. The patient, a 25-year-old woman, presented at our hospital with a history of abdominal pain with distension, and was finally operated on for a megacolon. Five months later she presented symptoms of progressive dysphagia and heartburn. Oesophageal manometry of the upper and lower oesophageal sphincter and X-ray studies showed images compatible with achalasia. Oesophagomyotomy of the oesophagogastric junction (Heller procedure with Dor haemifundoplication technique) was performed. In the specimens taken for biopsy, neither pathology of the myenteric plexuses, nor atrophy of the muscle fibres was evident. Chagas' disease serological diagnosis for Trypanosoma cruzii, neurological disease, diabetes and all the pathological events related with neuromuscular disorders of the gastrointestinal tract proved negative. We believe that the pathological findings are related to a dysfunction of the physiological mediators of the upper and lower digestive tract motility. The present case is extraordinary and, to our knowledge, extremely rare. The association of the two pathological diseases is questionable, and the literature is reviewed.
Prophylactic endoscopic ligation of high-risk oesophageal varices in a cirrhotic patient with severe haemophilia A.
Yamada M. Fukuda Y. Koyama Y. Nakano I. Urano F. Katano Y. Imada K. Toyoda H. Takamatsu J. Imoto M. Hayakawa T.
Second Department of Internal Medicine, Nagoya University School of Medicine, Showa, Japan.
One of the main complications in cirrhosis is haemorrhage from oesophageal varices. It is serious and often fatal, especially in cirrhotic patients with haemophilia. We describe the use of endoscopic variceal ligation (EVL) for prophylaxis of oesophageal variceal bleeding in a high-risk patient, a 40-year-old Japanese man, with severe haemophilia A and liver cirrhosis caused by hepatitis C virus. He had large, coil-shaped varices with a red colour sign, predicting the likelihood of haemorrhage. Administration of omeprazole and factor VIII concentrate achieved rapid healing of the post-EVL ulcers and prevented bleeding from them. Four EVL sessions eradicated oesophageal varices completely, and he has had no recurrence of varices for 2 years, indicating that the procedure was of considerable benefit.
Autoimmune chronic active hepatitis associated with the presence of antiphospholipid antibodies.
Pathmakanthan S. Kay EW. Murray FE.
Department of Hepatology, Beaumont Hospital, Dublin, Ireland.
We report a patient with clinical, biochemical and immunological indices suggestive of autoimmune hepatitis with marked transaminasaemia, raised immunoglobulins and positive anti-nuclear and anti-smooth muscle antibodies. A coagulation screen revealed a transient, markedly increased, activated, partial thromboplastin time and a normal prothrombin time, with elevated levels of anticardiolipin antibodies and the presence of lupus anticoagulant, indicating the presence of antiphospholipid antibodies. Subsequent histology confirmed moderate hepatitis with piecemeal necrosis and fibrosis. Appropriate autoimmune therapy was commenced. This presentation illustrates the rare association of anti-phospholipid antibodies with autoimmune chronic active hepatitis presenting with a temporarily abnormal coagulation screen.
Upper gastrointestinal bleeding due to a malignant Schwannoma of the stomach.
Loffeld RJ. Balk TG. Oomen JL. van der Putten AB.
Department of Internal Medicine, Ziekenhuis De Heel, Zaandam, The Netherlands.
A case history of a patient showing signs of upper gastrointestinal bleeding is described. Extensive analysis showed that the bleeding was due to a malignant Schwannoma of the stomach with several lymph node metastases. The patient was operated on and is doing well 5 years after surgery. The literature on this rare malignant tumour is reviewed.
Late-onset idiopathic hypoparathyroidism as a cause of diarrhoea.
Peracchi M. Bardella MT. Conte D.
Cattedra di Malattie del Metabolismo, Universita degli Studi di Milano, IRCCS-Ospedale Maggiore, Italy.
A 62-year-old man presented with a 20-month history of intermittent watery diarrhoea and hypocalcaemia. At age 43 he had undergone partial gastrectomy with Billroth II anastomosis for perforated peptic ulcer and at age 57 developed megaloblastic anaemia with low serum cobalamin and folate levels. Exhaustive gastrointestinal studies performed to ascertain the cause of the diarrhoea were all negative. Plasma parathyroid hormone levels were undetectable and late-onset idiopathic hypoparathyroidism was diagnosed. Normalization of hypocalcaemia promptly corrected the bowel habit. Idiopathic hypoparathyroidism is an unusual cause of diarrhoea that should, however, be considered in patients with hypocalcaemia and associated diarrhoea without evidence of primary intestinal disease.
Metastatic transitional cell carcinoma presenting as diffuse liver disease.
Ansari NA. Keen CE.
Department of Histopathology, University Hospital Lewisham, London, UK.
Three cases of transitional cell carcinoma (TCC) metastatic to the liver are reported. Each case presented as diffuse liver disease. This is a rare presentation, most liver metastases occurring as an isolated mass or multiple discrete masses.
What can we conclude from the randomized controlled trials of fecal occult blood test screening?
Lang CA. Ransohoff DF.
The results of three published randomized controlled trials of fecal occult blood testing (FOBT) provide unequivocal proof of the principle that screening reduces mortality from colorectal cancer (CRC). However, several interesting questions remain in interpreting and applying the results of the clinical trials, including: how well does FOBT screening work (i.e. how much can CRC mortality be reduced), how does it work, when is it worthwhile and worthwhile doing, and how can technique be optimized? The answers to these questions have important practical and clinical implications.
Screening for colorectal cancer: alternative faecal occult blood tests.
Flinders University of South Australia, Flinders Medical Centre, Bedford Park (Adelaide), Australia.
Hemoccult-based colorectal cancer (CRC) screening, while shown to be effective in randomized controlled trials, is suboptimal; alternative faecal occult blood tests which are either modifications of current guaiac-peroxidase tests or newer technologies (immunochemical), are available and show real promise. The goals of the alternative tests are improved sensitivity with acceptable specificity and improved compliance by screenees. The process of demonstrating superiority to Hemoccult need not include mortality as an endpoint, but must involve a direct comparison in large numbers of screenees (say 20,000) with cancer yields, apparent specificity and compliance determined for each test. Only the more sensitive and more readable guaiac test, HemoccultSENSA, and the immunochemical test Immudia-HemSp (the international version is HemeSelect) have undergone such extensive testing and could be considered as acceptable alternatives to Hemoccult for population-based screening. Even then, the test positivity rate of HemoccultSENSA warrants checking in a pilot study in the target population because it may pose a problem of specificity in some populations.
Molecular approaches for colorectal cancer screening.
Jen J. Johnson C. Levin B.
Department of Otolaryngology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. firstname.lastname@example.org
Molecular genetic approaches for colorectal cancer screening using stool samples have the potential to be very specific, sensitive and cost effective. K-ras oncogene mutation, observed in about 50% of the colorectal tumours, serves as an ideal target for such an approach. Several studies have shown that K-ras gene mutations present in the tumours can be detected from the stool of patients with colorectal cancer. The challenge for clinical application, however, is to develop a simple method for robust PCR amplification and a reliable assay for K-ras gene mutation detection in the stool samples.
Flexible sigmoidoscopy as a mass screening tool.
ICRF Colorectal Cancer Unit, St Mark's Hospital, Northwick Park, Harrow, Middlesex, UK.
Endoscopic removal of premalignant adenomas from the distal bowels of the entire population, 3 to 5-yearly from age 50, is advocated in the US as a feasible method of reducing colorectal cancer mortality rates. In the UK, a single flexible sigmoidoscopy (FS) is regarded as a more cost-effective option. Although more acceptable than colonoscopy, FS and polypectomy are expensive and invasive procedures carrying a small risk of serious harm. We believe that, before implementing mass screening, precise estimates are required of the magnitude of the reduction in mortality and costs (financial, physical and emotional). Several randomized trials, including a large British study, are currently evaluating these aspects.
Colonoscopy as a mass screening tool.
Division of Gastroenterology, Oregon Health Sciences University, Portland VA Medical Center, 97207, USA.
There is strong evidence that population screening can reduce mortality from colorectal cancer. Screening tests such as faecal occult blood test and flexible sigmoidoscopy are used to identify patients with an increased risk of cancer who would benefit from a full colon examination. There is indirect evidence that colonoscopy may be effective as a mass screening tool. Potential benefits of colonoscopy include the ability to visualize the entire colon and to detect and remove polyps, which could prevent cancers, and identify cancers if present anywhere in the colon. Issues related to the implementation of a colonoscopy screening programme are discussed.
The case for surveillance of high-risk families.
Department of Surgery, University of Edinburgh and MRC Human Genetics Unit, Western General Hospital, UK.
Patients who have an elevated colorectal cancer risk on the basis of heritable susceptibility can be identified in two ways. First, family history information may indicate empirical risks approaching 50%, while assignment of relative risks of 2.0-4.0 to groups of patients fulfilling certain family history criteria is commonplace. Second, assessment of blood samples by mutation analysis of DNA mismatch repair genes that are known to be responsible for hereditary nonpolyposis colorectal cancer (HNPCC) now affords diagnostic assessment in increasing numbers of families. This review explores the issues involved in identifying families with genetic susceptibility to colorectal cancer and discusses the rationale for clinical screening in at-risk relatives.
Nutritional factors in inflammatory bowel disease.
Addenbrooke's Hospital, Gastroenterology Research Unit, Cambridge, UK.
During the past 20 years there has been growing interest in the importance of nutritional factors in the pathogenesis of inflammatory bowel disease. There are so far no definite links between ulcerative colitis and diet, but links with Crohn's disease have been studied by both epidemiologists and clinicians. Epidemiological studies, although retrospective, have suggested that patients with Crohn's disease eat more sugar and sweets that control individuals; however, when dietary sugar is restricted, there is little clinical benefit. The clinical approach to nutrition in Crohn's disease has been by the use of elemental diets, which will produce symptomatic and objective remission in up to 90% of compliant patients. Those who return to normal eating soon relapse but, in some studies, have enjoyed prolonged remission on exclusion diets. The foods excluded have been not sugar, but predominantly cereals, dairy products and yeast. Attention has now switched to the possible harmful role of fat in Crohn's disease. The efficacy of elemental feeds appears to depend not on the presentation of nitrogen but on the amount of long chain triglyceride present. Increases in recent years in the frequency of Crohn's disease in Japan have been correlated with increased dietary fat intake, and a recent study suggested that W-3 fatty acids, which are metabolized by immunomodulatory leukotrienes and prostaglandins, may have a beneficial role to play. The links between nutrition and Crohn's disease have now become strong and the role of fat may be the most exciting of all.
Modern life in the epidemiology of inflammatory bowel disease: a case-control study with special emphasis on nutritional factors.
Russel MG. Engels LG. Muris JW. Limonard CB. Volovics A. Brummer RJ. Stockbrugger RW.
Department of Gastroenterology, University Hospital Maastricht, The Netherlands. email@example.com
OBJECTIVE: The rising incidence of inflammatory bowel disease (IBD) since the Second World War coincides with profound changes of the dietary pattern. The aim of the study was to investigate the possible pathogenic role of some characteristic 'modern life' dietary factors in IBD. DESIGN: Case-control, studying risk factors in recently diagnosed cases, 290 with Crohn's disease and 398 with ulcerative colitis, compared with 616 population controls. Smoking, age, gender and education were taken into account by using logistic regression analysis. SETTING: Hospital cases and population controls. INTERVENTIONS: Questionnaires. MAIN OUTCOME MEASURES: Logistic regression-derived odds ratios. RESULTS: A positive association with cola drinks [OR: 2.2 (95% CI 1.5-3.1)], chewing gum [OR: 1.5 (95% CI: 1.1-2.1)] and chocolate consumption [OR: 2.5 (95% CI: 1.8-3.5)] and a negative association with citrus fruit consumption [OR: 0.5 (95% CI 0.3-0.7)] and the development of Crohn's disease were found. Consumption of cola drinks [OR: 1.6 (95% CI 1.1-2.3)] and chocolate consumption [OR: 2.5 (95% CI 1.8-3.5)] were positively associated with developing ulcerative colitis. There was a negative association between the intake of citrus fruits [OR: 0.5 (95% CI 0.4-0.8)] and 'having a stuffed pet' for a period longer than 5 years [OR: 0.6 (95% CI 0.4-0.9)] and developing the disorder. No association with the frequency of tooth brushing and developing IBD was found. CONCLUSION: All the nutritional items mentioned may be true risk factors or they just might be the expression of a modern life-style also involving other risk factors for the development of IBD which at the present are still unknown.
Gastric ulcers and Helicobacter heilmannii.
Debongnie JC. Donnay M. Mairesse J. Lamy V. Dekoninck X. Ramdani B.
Department of Medicine and Laboratory Medicine, Clinique St Pierre, Ottignies, Belgium.
OBJECTIVE: To compare 14 patients with gastric ulcer and Helicobacter heilmannii with other patients with gastric ulcer: age and sex matched patients, patients colonized by Helicobacter pylori and patients on nonsteroidal anti-inflammatory drugs (NSAIDs). SETTING: The endoscopy unit of a university-affiliated hospital. PATIENTS AND METHODS: All patients underwent endoscopy with two antral biopsies and smears from biopsies (touch cytology) in addition to biopsies of ulcers. Most patients had fundic biopsies (n = 10), antral biopsies for culture (n = 7) and/or a urease test (n = 9). Serologic determination of antibodies against H. pylori was obtained in nine patients. RESULTS: Patients with H. heilmannii diagnosed on smears from biopsies (touch cytology) had multiple and antral ulcers in 11 samples, and nodular or irregular lesions in five samples. No patient had a history of peptic ulcer disease. Biopsy revealed mild chronic gastritis in all patients, with features of reactive gastritis in nine. No patient had coexistent infection with H. pylori. Only two of ten patients with follow-up endoscopies had persistent H. heilmannii infection on smear or biopsy. No patient had symptomatic recurrence. Patients with H. pylori infection were older and often had recurrent ulceration. The majority of ulcers associated with NSAIDs occurred in elderly women. CONCLUSIONS: Newly diagnosed gastric ulcers are associated with H. heilmannii infection. Healing is associated with the disappearance of H. heilmannii and the regression of reactive gastritis. Ulcers differ from those associated with H. pylori infection or with the use of NSAIDs, suggesting that H. heilmannii is a possible cause of gastric ulcers.
Liver biopsy pathology in human immunodeficiency virus infection.
Kennedy M. O'Reilly M. Bergin CJ. McDonald GS.
Department of Histopathology, St James's Hospital and Trinity College, Dublin, Ireland.
OBJECTIVES: To determine the hepatic changes in patients with human immunodeficiency virus (HIV) infection in Dublin and to assess the usefulness of liver biopsy in this condition. DESIGN: A consecutive series of liver biopsies was examined retrospectively and correlated with clinical findings. METHODS: A histological review was conducted of specimens from all patients who had undergone liver biopsy in a tertiary referral centre for HIV-infected patients in Dublin. RESULTS: Thirty-nine liver biopsies were studied from 36 patients. Thirty-one (86%) showed pathological changes. Non-specific changes were most frequent, followed by viral-induced chronic hepatitis (15 cases). Acute hepatitis was documented in five and cirrhosis in four cases. Five biopsies performed for pyrexia of unknown origin (PUO) or suspected tuberculosis showed granulomas. Organisms were rarely identified (2) and bile duct changes were uncommon. CONCLUSIONS: Liver biopsy was useful in detecting primary hepatic pathology and, in some cases, the cause of PUO, but not useful in detecting opportunistic infections despite their known presence in other organs.
Serological markers for coeliac disease: changes with time and relationship to enteropathy.
Johnston SD. Watson RG. McMillan SA. Evans AE. Love AH.
Department of Medicine, Queen's University of Belfast, Northern Ireland, UK.
Antigliadin antibodies (AGA) may be present in healthy adults. One previous study has reported that IgA-AGA detected by population screening may become negative after a 6-year follow-up period. OBJECTIVES: To determine the variability of coeliac disease-associated antibodies with time and to ascertain which antibodies are predictive of the presence of enteropathy. DESIGN: A clinical follow-up study of subjects with positive serological markers detected by screening at the time of the Belfast MONICA Project. METHODS: Jejunal biopsies were carried out endoscopically by means of a Crosby capsule. IgA-antigliadin was detected by a commercial ELISA; IgA-antiendomysial and antireticulin antibodies were determined by indirect immunofluorescence. RESULTS: Of 48 subjects followed up after 4 years, 28 (58%) had developed negative serology and 20 (42%) had persistently positive serology. Thirteen of 20 subjects with persistent serology had villous atrophy. Of 68 subjects followed up after 13 years, 32 (47%) had developed negative serology and 36 (53%) had persistent serology. Of 10 subjects with persistent serology who were biopsied, four had villous atrophy. None of the subjects who developed negative serology were found to have coeliac disease. CONCLUSIONS: Persistence of serological markers as a follow-up to a population screening programme may predict enteropathy in some subjects, whereas subjects who develop negative serology may be reassured. Subjects with persistent serology and normal histology require follow-up to determine if these markers are indicative of latent coeliac disease.
Which Helicobacter pylori-positive dyspeptics are likely to respond symptomatically to empirical H. pylori eradication?
Asante MA. Mendall MA. Northfield TC.
Department of Gastroenterology, Endocrinology and Metabolism, St George's Hospital Medical School, London, UK.
OBJECTIVE: To identify which Helicobacter pylori-positive dyspeptic patients have an increased likelihood of having peptic ulcer and may thus be more likely to benefit from empirical H. pylori eradication therapy. METHODS: 622 out of 740 consecutive dyspeptic subjects (median age 45 years, range 14-91, 51% male) attending for rapid access endoscopy were eligible for the study. Demographic data and endoscopic findings were recorded. H. pylori status was determined by urease and histology. RESULTS: In all age groups, peptic ulcers were commoner in males than females [44% (85/195) vs 23% (32/139), P < 0.001] and in smokers than non-smokers [47% (46/97) vs 32% (50/159), P < 0.05]. Males, heavy smokers and those with a family history of peptic ulcer had increased adjusted odds of having a peptic ulcer (2.59, 1.96 and 1.90, respectively). Corresponding odds ratios for those aged under 45 were 2.59, 0.94 and 2.52. In H. pylori-positive dyspepsia, being a male who either smoked heavily or had a family history of peptic ulcer gave a sensitivity and positive predictive value for peptic ulcer of 86 and 45% for all age groups and 85 and 49% for those aged under 45. CONCLUSION: Male H. pylori dyspeptics who smoke >10 cigarettes per day and/or have a family history of peptic ulcer are likely to have peptic ulcer and are thus likely to benefit from empirical eradication therapy.
Graves hyperthyroidism in a patient with primary sclerosing cholangitis. Coincidence or combined pathogenesis?
Janssen HL. Smelt AH. van Hoek B.
Department of Internal Medicine, Leiden University Medical Center, The Netherlands.
Several autoimmune disorders have been associated with the diagnosis of primary sclerosing cholangitis (PSC). We report on a 19-year-old male PSC patient with a history of ulcerative colitis who developed hyperthyroidism consistent with Graves' disease. In contrast to primary biliary cirrhosis, hyperthyroidism appears to be very uncommon in PSC patients. Nevertheless, the rarity of Graves' disease in young males, the presence of a human leucocyte antigen (HLA) phenotype often encountered in both Graves' disease and PSC and the presence of several autoantibodies suggest a common immunogenetic predisposition, rather than mere coincidence, of both diseases in this patient. Since many patients with thyroid disease exhibit mild cholestatic liver function abnormalities but few of them undergo cholangiographic examination, PSC may be underdiagnosed. Physicians should therefore be aware of the potential association between thyroid disease and PSC.