Showing papers in "Gut in 2002"

Guidelines for the management of oesophageal and gastric cancer

Abstract: Over the past decade the Improving Outcomes Guidance (IOG) document has led to service re-configuration in the NHS and there are now 41 specialist centres providing oesophageal and gastric cancer care in England and Wales. The National Oesophago-Gastric Cancer Audit, which was supported by the British Society of Gastroenterology, the Association of Upper Gastrointestinal Surgeons (AUGIS) and the Royal College of Surgeons of England Clinical Effectiveness Unit, and sponsored by the Department of Health, has been completed and has established benchmarks for the service as well as identifying areas for future improvements.1–3 The past decade has also seen changes in the epidemiology of oesophageal and gastric cancer. The incidence of lower third and oesophago-gastric junctional adenocarcinomas has increased further, and these tumours form the most common oesophago-gastric tumour, probably reflecting the effect of chronic gastro-oesophageal reflux disease (GORD) and the epidemic of obesity. The increase in the elderly population with significant co-morbidities is presenting significant clinical management challenges. Advances in understanding of the natural history of the disease have increased interest in primary and secondary prevention strategies. Technology has improved the options for diagnostic and therapeutic endoscopy and staging with cross-sectional imaging. Results from medical and clinical oncology trials have established new standards of practice for both curative and palliative interventions. The quality of patient experience has become a significant component of patient care, and the role of the specialist nurse is fully intergrated. These many changes in practice and patient management are now routinely controlled by established multidisciplinary teams (MDTs) which are based in all hospitals managing these patients. The original guidelines described the management of oesophageal and gastric cancer within existing practice. This paper updates the guidance to include new evidence and to embed it within the framework of the current UK National Health Service (NHS) Cancer …

Guidelines for the diagnosis and treatment of cholangiocarcinoma: consensus document

Abstract: ### 1.1 Development of guidelines There is currently no clear national consensus for the optimal diagnosis and treatment of cholangiocarcinoma. The need for these guidelines was highlighted following the annual meeting of the British Association for the Study of the Liver (BASL) in September 2000. During their development these guidelines were presented at a BASL Liver Cancer Workshop in January 2001. They were also circulated to BASL members and the Liver Section of the British Society of Gastroenterology (BSG) Committee members, including gastroenterologists, hepatologists, gastroenterological surgeons, pathologists, radiologists, and epidemiologists for comments before the final consensus document was drawn up. ### 1.2 Strategy The guidelines are based on comprehensive literature surveys including results from randomised controlled trials, systematic reviews and meta-analyses, and cohort, prospective, and retrospective studies. On issues where no significant study data were available, evidence was obtained from expert committee reports or opinions. Where possible, specific recommendations have been graded, based on the quality of evidence available (section 2.4). ### 1.3 Context and intent These guidelines are intended to bring consistency and improvement in the patient’s management from first suspicion of cholangiocarcinoma through to confirmation of the diagnosis and subsequent management. As stated in previous BSG guidelines, patient preferences must be sought and decisions made jointly by the patient and health carer, based on the risks and benefits of any intervention. Furthermore, the guidelines should not necessarily be regarded as the standard of care for all patients. Individual cases must be managed on the basis of all clinical data available for that case. The guidelines are subject to change in light of future advances in scientific knowledge. Mortality rates from intrahepatic cholangiocarcinoma have risen steeply and steadily over the past 30 years and since the mid 1990s more deaths have been coded annually in England and Wales as being due to this tumour than to hepatocellular carcinoma.1 In 1997 and …

The efficacy of azathioprine for the treatment of inflammatory bowel disease: a 30 year review

Abstract: Background: There are limited data on factors predicting response to azathioprine and uncertainty regarding the optimal duration of treatment. Patients and methods: The notes of patients attending the Oxford IBD clinic from 1968 to 1999 were reviewed. Remission was defined as no need for oral steroids for at least three months and relapse was defined as active disease requiring steroids. Results: A total of 622 of 2205 patients were treated with azathioprine (272 Crohn's disease, 346 ulcerative colitis, and four indeterminate colitis). Mean duration of the initial course of treatment was 634 days. The overall remission rates were 45% for Crohn's disease and 58% for ulcerative colitis. For the 424 patients who received more than six months of treatment, remission rates were 64% and 87%, respectively. Factors favouring remission were ulcerative colitis (p=0.0001), lower white blood cell (WBC) or neutrophil count (p=0.0001), higher mean cell volume (p=0.0001), and older age (p=0.05). For Crohn's disease, colonic disease favoured remission (p=0.03). Factors that were not significant were age, sex, lymphocyte count, and dose (mg/kg). The proportion of patients remaining in remission at one, three, and five years was 0.95, 0.69, and 0.55, respectively. The chance of remaining in remission was higher if WBC was less than 5×109 (p=0.03) and in male patients (p=0.01; Crohn's disease only). There was no difference in relapse rates between Crohn's disease and ulcerative colitis. After stopping azathioprine, the proportion of patients remaining in remission at one, three, and five years was 0.63, 0.44, and 0.35 (222 patients). Duration of azathioprine treatment did not affect the relapse rate after stopping treatment (p=0.68). Conclusions: Azathioprine is effective treatment for ulcerative colitis and Crohn's disease. The efficacy of azathioprine is reasonably well sustained over five years.

Gastrointestinal epithelial neoplasia: Vienna revisited

Abstract: International consensus meetings in Padova and Vienna have attempted to rationalise the grading and classification of gastrointestinal epithelial neoplasia (GEN). With its minor adjustments, the Vienna classification of GEN seeks to be more closely in tune with patient management and it is hoped that it is not seen as fiddling around with terms but as a genuine contribution to patient care.

Ineffectiveness of probiotics in preventing recurrence after curative resection for Crohn's disease: a randomised controlled trial with Lactobacillus GG

Abstract: Background and aims: Experimental studies have shown that luminal bacteria may be involved in Crohn's disease. Probiotics are a possible alternative to antibiotics. The aim of this randomised placebo controlled study was to determine if Lactobacillus GG, given by mouth for one year, could prevent Crohn's recurrent lesions after surgery or to reduce their severity. Methods: Patients operated on for Crohn's disease in whom all of the diseased gut had been removed were randomly allocated to receive 12 billion colony forming units of Lactobacillus or identical placebo for one year. Ileocolonoscopy was performed at the end of the trial or at the onset of symptoms. Endoscopic recurrence was defined as grade 2 or higher of Rutgeerts scoring system. Results: Eight of 45 patients were excluded from the trial (three for non-compliance and five for protocol violations). Clinical recurrence was ascertained in three (16.6%) patients who received Lactobacillus and in two (10.5%) who received placebo. Nine of 15 patients in clinical remission on Lactobacillus (60%) had endoscopic recurrence compared with six of 17 (35.3%) on placebo (p=0.297). There were no significant differences in the severity of the lesions between the two groups. Conclusions: Lactobacillus GG seems neither to prevent endoscopic recurrence at one year nor reduce the severity of recurrent lesions.

Infliximab treatment induces apoptosis of lamina propria T lymphocytes in Crohn's disease.

Abstract: Background and aims: Treatment with infliximab induces remission in about 70% of patients with steroid refractory Crohn9s disease. Because Crohn9s disease is considered to be mediated by uncontrolled activation of mucosal T lymphocytes, we hypothesised that infliximab could induce apoptosis of T lymphocytes. Methods: Induction of apoptosis in vivo was studied in 10 patients with therapy refractory Crohn9s disease. In vitro, resting or stimulated Jurkat T cells were incubated with infliximab. Results: Infusion of infliximab (5 mg/kg) in steroid refractory patients with Crohn9s disease induced a clinical response in 9/10 patients but did not influence expression of activation markers, homing receptors, memory cells, Fas expression, or Bax/Bcl-2 expression on peripheral blood T lymphocytes. In contrast, a significant increase in CD3 and TUNEL positive cells within colonic biopsies was detected 24 hours after infusion of infliximab, suggesting that infliximab stimulates apoptosis of activated T lymphocytes but not of resting T cells. To test this hypothesis, the effects of infliximab on Jurkat T cells were investigated. We observed that infliximab induced apoptosis and an increase in the Bax/Bcl-2 ratio of CD3/CD28 stimulated Jurkat T cells but not of unstimulated Jurkat cells. Conclusions: Our data indicate that infliximab treatment causes a rapid and specific increase in apoptosis of T lymphocytes in the gut mucosa. These findings may explain the rapid and sustained therapeutic effects of infliximab in Crohn9s disease.

Trends in indigenous foodborne disease and deaths, England and Wales: 1992 to 2000

Abstract: Background: Commitment to food safety is evidenced by high profile governmental initiatives around the globe. To measure progress towards targets, policy makers need to know the baseline from which they started. Aim: To describe the burden (mortality, morbidity, new presentations to general practice, hospital admissions, and hospital occupancy) and trends of indigenous foodborne disease (IFD) in England and Wales between 1992 and 2000. Methods: Routinely available surveillance data, special survey data, and hospital episode statistics were collated and arithmetic employed to estimate the burden and trends of IFD in England and Wales. Adjustments were made for underascertainment of disease through national surveillance and for foreign travel. The final estimates were compared with those from the USA. Results: In 1995 there were an estimated 2 365 909 cases, 21 138 hospital admissions, and 718 deaths in England and Wales due to IFD. By 2000 this had fallen to 1 338 772 cases, 20 759 hospital admissions, and 480 deaths. In terms of disease burden the most important pathogens were campylobacters, salmonellas, Clostridium perfringens , verocytotoxin producing Escherichia coli (VTEC) O157, and Listeria monocytogenes . The ratio of food related illness in the USA to IFD in England and Wales in 2000 was 57:1. Taking into account population rates, this ratio fell to 11:1 and converged when aetiology and disease severity were considered. Conclusion: Reducing IFD in England and Wales means tackling campylobacter. Lowering mortality rates however also requires better control and prevention of salmonellas, Cl perfringens , L monocytogenes , and VTEC O157.

Prevalence of faecal incontinence in adults aged 40 years or more living in the community

Abstract: Background: Prevalence studies of faecal incontinence in the general population are rare and the impact of faecal incontinence on quality of life has not been previously addressed. Aims: To establish the prevalence of faecal incontinence in adults in terms of frequency of leakage, degree of soiling, and level of impact on quality of life. Methods: In a cross sectional postal survey, 15 904 adults aged 40 years or more (excluding residents of nursing and residential homes) were selected randomly by household from the Leicestershire Health Authority patient register. Participants were asked to complete a confidential health questionnaire. Major faecal incontinence was defined as soiling of underwear or worse with a frequency of several times a month or more. Respondents were also asked if bowel symptoms had an impact on their quality of life. Results: From a total sample of 10 116 respondents, 1.4% reported major faecal incontinence and 0.7% major faecal incontinence with bowel symptoms that had an impact on quality of life. Major faecal incontinence was significantly associated with a lot of impact on quality of life (odds ratio 12.4, 95% confidence interval 7.5–20.6). Incontinence was more prevalent and more severe in older people but there was no significant difference between men and women. Conclusions: This study has confirmed that faecal incontinence is a fairly common symptom, particularly in older people. Faecal incontinence in men has received little attention in the past and the results from this study indicate that it is as much of a problem in men as it is in women while the level of unmet need in this group is high. Estimates of need for health care for this symptom should be multidimensional and assess both the severity of symptoms and the impact it has on quality of life.

Risk of pancreatic adenocarcinoma in chronic pancreatitis

Abstract: Background: The risk of pancreatic cancer in patients with chronic pancreatitis (CP) is difficult to assess. Previous studies, mostly case control studies or studies relying on data case registers, reported relative risks varying from 2.3 to 18.5. Methods: We studied a prospective, single centre, medical-surgical cohort of 373 consecutive patients (322 (86%) men, median age 40 years) with proven CP (alcoholic origin 85%) and a follow up of at least two years (median follow up 9.2 years; range 2.0–34.8) in order to exclude pancreatitis revealing pancreatic cancer. We calculated the age and sex standardised incidence ratio (SIR) as the ratio of the number of observed cases of pancreatic cancer in this cohort to the number of expected cases, as provided by the French National Cancer Register. Results: Four cases of pancreatic adenocarcinoma (1.1% of patients) were observed in 3437 patient years (expected number of cases 0.15; SIR 26.7, 95% confidence interval (CI) 7.3–68.3; p=0.00002). In a second analysis in which patients lost to follow up were considered to be followed up until the end point without having developed pancreatic adenocarcinoma (4762 patient years), SIR was 19.0 (CI 5.2–48.8; p=0.00007). Conclusion: Patients with CP have a markedly increased risk of pancreatic cancer compared with the general population.

The first large population based twin study of coeliac disease

Abstract: Background and aims: The genetic load in coeliac disease has hitherto been inferred from case series or anecdotally referred twin pairs. We have evaluated the genetic component in coeliac disease by estimating the concordance rate for the disease among twin pairs in a large population based study. Methods: The Italian Twin Registry was matched with the membership lists of a patient support group. Forty seven twin pairs were recruited and screened for antiendomysial (EMA) and antihuman-tissue transglutaminase (anti-tTG) antibodies; zygosity was verified by DNA fingerprinting and twins were typed for HLA class II DRB1 and DQB1 molecules. Results: Concordance rates for coeliac disease differ significantly between monozygotic (MZ) (0.86 probandwise and 0.75 pairwise) and dizygotic (DZ) (0.20 probandwise and 0.11 pairwise) twins. This is the highest concordance so far reported for a multifactorial disease. A logistic regression model, adjusted for age, sex, number of shared HLA haplotypes, and zygosity, showed that genotypes DQA1*0501/DQB1*0201 and DQA1*0301/DQB1*0302 (encoding for heterodimers DQ2 and DQ8, respectively) conferred to the non-index twin a risk of contracting the disease of 3.3 and 1.4, respectively. The risk of being concordant for coeliac disease estimated for the non-index twin of MZ pairs was 17 (95% confidence interval 2.1–134), independent of the DQ at risk genotype. Conclusion: This study provides substantial evidence for a very strong genetic component in coeliac disease, which is only partially due to the HLA region.

A randomised, double blind, placebo controlled study of celecoxib, a selective cyclooxygenase 2 inhibitor, on duodenal polyposis in familial adenomatous polyposis.

Abstract: Background: Non-selective cyclooxygenase (COX) inhibitors (non-steroidal anti-inflammatory drugs) inhibit large bowel carcinogenesis in patients with familial adenomatous polyposis (FAP). Their role in the duodenum of these patients is less certain. The disease modifying activity of specific COX-2 inhibitors has not been explored in humans. Patients and methods: This was a randomised, double blind, placebo controlled study of celecoxib (100 mg twice daily (n=34) or 400 mg twice daily (n=32)) versus placebo (n=17), given orally twice daily for six months to patients with FAP. Efficacy was assessed qualitatively by blinded review of shuffled endoscopy videotapes comparing the extent of duodenal polyposis at entry and at six months and quantitatively by measurement of the percentage change in duodenal area covered by discrete and plaque-like adenomas from photographs of high and low density polyposis. Results: Shuffled and blinded video review showed a statistically significant effect of 400 mg twice daily celecoxib compared with placebo treatment (p=0.033) with all five independent observers scoring a beneficial effect. Overall, patients taking celecoxib 400 mg twice daily showed a 14.5% reduction in involved areas compared with a 1.4% for placebo (p=0.436). However, patients with clinically significant disease at baseline (greater than 5% covered by polyps) showed a 31% reduction in involved areas with celecoxib 400 mg twice daily compared with 8% on placebo (p=0.049). Conclusions: A panel of five endoscopists found a significant reduction in duodenal polyposis after six months of treatment with celecoxib 400 mg twice daily. COX-2 inhibition may help this otherwise untreatable condition.

A randomised study of screening for colorectal cancer using faecal occult blood testing: results after 13 years and seven biennial screening rounds.

Abstract: Background: Three randomised trials have demonstrated reduction in mortality from colorectal cancer (CRC) by repeated screening with faecal occult blood tests, including the trial presented here, which is the only one still in progress. Aims: To evaluate reduction in mortality after seven screening rounds and the possible influence of compliance on mortality from CRC. Methods: At Funen in Denmark, random allocation to biennial screening with Hemoccult-II in 30 967 subjects aged 45–75 years and 30 966 controls was performed in 1985 from a population of 137 485 of the same age. Only participants who completed the first screening round were invited for further screening. Colonoscopy was offered if the test was positive. The primary end point was death from CRC, and the 10 year results were published in 1996. Results: From the beginning of the first screening to the seventh round, mean age increased from 59.8 to 70.0 years in the screening and control groups, and the male/female ratio decreased from 0.92 to 0.81. Those who accepted screening were younger than non-responders. Positivity rates varied from 0.8% to 3.8%, the cumulative ratio of a positive test was 5.1% after seven rounds, and 4.8% of patients had at least one colonoscopy. Mortality from CRC was significantly less in the screening group (relative risk (RR) 0.82 (0.69–0.97)), and the reduction in mortality was most pronounced above the sigmoid colon. After seven rounds, RR was reduced to less than 0.70 compared with controls. Mortality rates from causes other than CRC did not differ. Non-responders had a significantly increased risk of death from CRC compared with those who accepted the full programme. Subjects who accepted the first screening, but not subsequent ones, demonstrated a tendency towards increased risk. Conclusions: The persistent reduction in mortality from CRC in a biennial screening program with Hemoccult-II, and a reduction in RR to less than 0.70 in those adhering to the programme, support attempts to introduce larger scale population screening programmes. The smaller effect on mortality from CRC in the rectum and sigmoid colon suggests evaluation by additional flexible sigmoidoscopy with longer intervals.

Autoimmune related pancreatitis

Abstract: Since the first documented case of a particular form of pancreatitis with hypergammaglobulinaemia, similar cases have been reported, leading to the concept of an autoimmune related pancreatitis or so-called “autoimmune pancreatitis”. Although it has not yet been widely accepted as a new clinical entity, the present article discusses the recent concept of autoimmune pancreatitis.

A global emerging disease of Klebsiella pneumoniae liver abscess: is serotype K1 an important factor for complicated endophthalmitis?

Abstract: Background and aims: Over the past two decades in Taiwan, pyogenic liver abscess has usually been caused by a single microorganism, Klebsiella pneumoniae , and is frequently associated with the serious complication of endophthalmitis, especially in diabetic patients. However, the relationship between the clinical presentation and bacterial factors remains unclear. The aim of this study was to investigate the clinical features of patients and the serotype and ribotype of K pneumoniae liver abscess. Methods: From July 1991 to June 1998, a total of 134 cases of K pneumoniae liver abscess with 248 K pneumoniae isolates from the same patients were collected from two large medical centres in northern Taiwan. Clinical data were collected from medical records. Serotyping and ribotyping were performed using the countercurrent immunoelectrophoresis method and automated Riboprinter. Results: Serotyping revealed that the most common serotypes were K1 (63.4%) and K2 (14.2%). K1 isolates occurred at a significantly higher frequency (p K pneumoniae in all patients. Among patients with septic endophthalmitis, 92.3% (13/14) were diabetic, and 85.7% (12/14) of the isolates belonged to serotype K1. For molecular typing, different degrees of genetic polymorphism among isolates with the same K1 serotype suggested no particular prevalence of any one strain in K pneumoniae liver abscess. Conclusion: K pneumoniae serotype K1 was significantly associated with liver abscess and the complication of endophthalmitis, especially in diabetic patients. Physicians should request an immediate report of serotyping and susceptibility test results simultaneously if a diagnosis of pyogenic liver abscess has been made so that early and appropriate management for possible complications will not be delayed. The use of ceftriaxone because of its higher concentration in the aqueous humor is suggested to decrease the chance of septic endophthalmitis.

Probiotics: a role in the treatment of intestinal infection and inflammation?

Abstract: Probiotic therapy is based on the concept of normal healthy microflora. The development of novel means of characterising the gut microflora, in particular those based on the different levels of conservation in the ribosomal RNA sequences of different genera, have opened up new angles on the role of the gut microflora in health and disease. Components of the human intestinal microflora or organisms entering the intestine may have harmful or beneficial effects on human health. Abundant evidence implies that specific strains selected from the healthy gut microflora exhibit powerful antipathogenic and anti-inflammatory capabilities, and are consequently involved with enhanced colonisation resistance in the intestine. Realisation of this has led to the introduction of novel modes of therapeutic and prophylactic intervention based on the consumption of mono and mixed cultures of beneficial live microorganisms as probiotics.

Control of transient lower oesophageal sphincter relaxations and reflux by the GABA(B) agonist baclofen in patients with gastro-oesophageal reflux disease.

Abstract: Background and aims: Transient lower oesophageal sphincter relaxations (TLOSRs) are the major cause of gastro-oesophageal reflux in normal subjects and in most patients with reflux disease. The gamma aminobutyric acid (GABA) receptor type B agonist, baclofen, is a potent inhibitor of TLOSRs in normal subjects. The aim of this study was to investigate the effect of baclofen on TLOSRs and postprandial gastro-oesophageal reflux in patients with reflux disease. Methods: In 20 patients with reflux disease, oesophageal motility and pH were measured, with patients in the sitting position, for three hours after a 3000 kJ mixed nutrient meal. On separate days at least one week apart, 40 mg oral baclofen or placebo was given 90 minutes before the meal. Results: Baclofen reduced the rate of TLOSRs by 40% from 15 (13.8–18.3) to 9 (5.8–13.3) per three hours (p<0.0002) and increased basal lower oesophageal sphincter pressure. Baclofen also significantly reduced the rate of reflux episodes by 43% from 7.0 (4.0–12.0) to 4.0 (1.5–9) per three hours (median (interquartile range); p<0.02). However, baclofen had no effect on oesophageal acid exposure (baclofen 4.9% (1.7–12.4) v placebo 5.0% (2.7–15.5)). Conclusions: In patients with reflux disease, the GABAB agonist baclofen significantly inhibits gastro-oesophageal reflux episodes by inhibition of TLOSRs. These findings suggest that GABAB agonists may be useful as therapeutic agents for the management of reflux disease.

Guidelines for screening and surveillance of asymptomatic colorectal cancer in patients with inflammatory bowel disease

Abstract: Patients with ulcerative colitis (UC) are at increased risk of colorectal carcinoma.1,2 Many clinicians practice colonoscopic surveillance in these patients in the hope of detecting dysplasia or an early cancer at a surgically curable stage. However, a recent audit of gastroenterologists showed such surveillance to be disorganised and inconsistent.3 Much debate surrounds the efficacy and cost effectiveness of surveillance programmes in UC4–6 because they were introduced without benefit of randomised controlled trials. The following guidelines should bring uniformity to the process and be of help to both surgeons and physicians. The colorectal cancer risk in patients with colonic Crohn’s disease is similar to that in UC7,8 and thus the guidelines for UC should be equally applicable to such patients with Crohn’s disease. 1. Surveillance colonoscopies should be performed when the disease is in remission. (Recommendation Grade: C). 2. All patients should have a screening colonoscopy after 8–10 years that will also clarify disease extent. (Recommendation Grade: C). 3. Regular surveillance should begin after 8–10 years (from onset of symptoms) for pancolitis and after 15–20 years for left sided disease. (Recommendation Grade: C). 4. As the risk of cancer increases exponentially with time, there should be a decrease in the screening interval with increasing disease duration. For patients with pancolitis, in the second decade of disease a colonoscopy should be conducted every three years, every two years in the third decade, and yearly by the fourth decade of disease. (Recommendation Grade: C). 5. Two to four random biopsy specimens every 10 cm from the entire colon should be taken with additional samples of suspicious areas. (Recommendation Grade: C). Patients with primary sclerosing cholangitis (including those with an orthotopic liver transplant) represent a subgroup at higher risk of cancer and they should have annual colonoscopy. (Recommendation Grade: C). Although it …

Duodenal cancer in patients with familial adenomatous polyposis (FAP): results of a 10 year prospective study

Abstract: Background: Duodenal cancer is one of the leading causes of death in familial adenomatous polyposis (FAP) patients. An endoscopic surveillance programme was therefore initiated in 1988, the outcome of which is described in this paper. Methods: We report the 10 year follow up of 114 patients with FAP who were prospectively screened for the presence and severity of duodenal adenomas. Results: Six of 114 patients (median age 67 years) developed duodenal adenocarcinoma. Four of these were from 11 patients who originally had Spigelman stage IV disease (advanced duodenal polyposis), which gives a 36% risk within this group of developing cancer. One case of duodenal cancer arose from 41 patients who originally had stage III disease (2%) and one cancer arose from 44 patients with original stage II disease (2%). All six patients have died: five were inoperable and one had recurrence three years after a pancreaticoduodenectomy. There was no association between duodenal cancer and site of germline mutation of the APC gene. Conclusions: Surveillance for duodenal adenocarcinoma and subsequent early referral for curative surgery has not been effective. Selection of patients with advanced but benign (Spigelman stage IV) duodenal polyposis for prophylactic pancreaticoduodenectomy should therefore be considered and can now be justified on the basis of these results. More comprehensive endoscopic surveillance of high risk (stage III and IV) patients is needed in an attempt to avoid underestimating the severity of duodenal polyposis, and to evaluate the role of endoscopic therapy in preventing advanced disease.

Increased mucosal tumour necrosis factor alpha production in Crohn's disease can be downregulated ex vivo by probiotic bacteria.

Abstract: Background and aims: Tumour necrosis factor α (TNF-α) plays a key role in the pathogenesis of intestinal inflammation in Crohn’s disease. The effect of bacteria on TNF-α release by intestinal mucosa was investigated. Methods: Ileal specimens were obtained at surgery from 10 patients with Crohn’s disease (ileal stricture) and five disease controls undergoing right hemicolectomy (caecal cancer). Mucosal explants from each specimen were cultured for 24 hours with either non-pathogenic Escherichia coli, Lactobacillus casei DN-114001, L bulgaricus LB10, or L crispatus (each study contained blank wells with no bacteria). Tissue and bacterial viability was confirmed by lactate dehydrogenase (LDH) release and culture. Concentrations of TNF-α were measured in supernatants and the phenotype of the intestinal lymphocytes was analysed by flow cytometry. Results: Coculture of mucosa with bacteria did not modify LDH release. Release of TNF-α by inflamed Crohn’s disease mucosa was significantly reduced by coculture with L casei or L bulgaricus; changes induced by L crispatus or E coli were not significant. The effect of L casei and L bulgaricus was not prevented by protease inhibitors. Coculture with L casei and L bulgaricus reduced the number of CD4 cells as well as TNF-α expression among intraepithelial lymphocytes from Crohn’s disease mucosa. None of the bacteria induced changes in non-inflamed mucosa. Conclusions: Probiotics interact with immunocompetent cells using the mucosal interface and modulate locally the production of proinflammatory cytokines.

Aberrant composition of gut microbiota of allergic infants: a target of bifidobacterial therapy at weaning?

Abstract: Background: Recent data have outlined a relationship between the composition of the intestinal microflora and allergic inflammation, and demonstrated the competence of probiotics in downregulation of such inflammation Aims: Our aims were to characterise the relationship between gut microbes and the extent of allergic sensitisation and to assess whether the efficacy of bifidobacterial supplementation in the treatment of allergy could relate to modulation of the intestinal microbiota Methods: This randomised study included 21 infants with early onset atopic eczema of whom eight were intolerant (highly sensitised group (HSG)) and 13 tolerant (sensitised group (SG)) to extensively hydrolysed whey formula (EHF) In the SG, six were weaned to EHF without (placebo group (PG)) and seven to EHF with Bifidobacterium lactis Bb-12 supplementation (bifidobacteria treated group (BbG)) The faecal microflora of infants in the HSG was analysed only before weaning whereas in the SG the faecal microflora was analysed both before and after weaning Results: Infants in the HSG had greater numbers of lactobacilli/enterococci than those in the SG Serum total IgE concentration correlated directly with Escherichia coli counts in all infants and with bacteroides counts in the HSG, indicating that the presence of these bacteria is associated with the extent of atopic sensitisation The effect of supplementation was characterised as a decrease in the numbers of Escherichia coli and protection against an increase in bacteroides numbers during weaning Conclusions: These data indicate that bifidobacterial supplementation appears to modify the gut microbiota in a manner that may alleviate allergic inflammation Further studies are needed to confirm this conclusion

Pancreatic stellate cells respond to inflammatory cytokines: potential role in chronic pancreatitis

Abstract: Background: It is now generally accepted that chronic pancreatic injury and fibrosis may result from repeated episodes of acute pancreatic necroinflammation (the necrosis-fibrosis sequence). Recent studies suggest that pancreatic stellate cells (PSCs), when activated, may play an important role in the development of pancreatic fibrosis. Factors that may influence PSC activation during pancreatic necroinflammation include cytokines known to be important in the pathogenesis of acute pancreatitis, such as tumour necrosis factor α (TNF-α), and the interleukins 1, 6, and 10 (IL-1, IL-6, and IL-10). Aim: To determine the effects of these cytokines on PSC activation, as assessed by cell proliferation, α smooth muscle actin (α-SMA) expression, and collagen synthesis. Methods: Cultured rat PSCs were incubated with cytokines for 24 hours. Cell proliferation was assessed by measuring 3H thymidine incorporation into cellular DNA, α-SMA expression by western blotting, and collagen synthesis by incorporation of 14C proline into collagenase sensitive protein. mRNA levels for procollagen α1(1) in PSCs were determined by northern and dot blotting methods. Results: Expression of α-SMA by PSCs was increased on exposure to each of the cytokines used in the study. Stellate cell proliferation was stimulated by TNF-α but inhibited by IL-6, while IL-1 and IL-10 had no effect on PSC proliferation. Collagen synthesis by PSCs was stimulated by TNF-α and IL-10, inhibited in response to IL-6, and unaltered by IL-1. Changes in collagen protein synthesis in response to TNF-α, IL-10, and IL-6 were not regulated at the mRNA level in the cells. Conclusion: This study has demonstrated that PSCs have the capacity to respond to cytokines known to be upregulated during acute pancreatitis. Persistent activation of PSCs by cytokines during acute pancreatitis may be a factor involved in the progression from acute pancreatitis to chronic pancreatic injury and fibrosis.

Hepatopulmonary syndrome: prevalence and predictive value of various cut offs for arterial oxygenation and their clinical consequences.

Abstract: Background: The hepatopulmonary syndrome (HPS) is defined as the triad of liver disease, arterial deoxygenation, and pulmonary vascular dilatation. The reported prevalence of HPS in cirrhotic patients varies between 4% and 19%, and various threshold values defining arterial deoxygenation have been used and recommended previously. However, it is not known how the prevalence of HPS differs using different cut off values for arterial deoxygenation. Methods: We studied 127 patients for the presence of HPS using transthoracic contrast echocardiography for detection of pulmonary vasodilation, pulmonary function tests, and blood gas analysis. Results: Ninety eight patients were included in the study, of whom 33 (34%) had a positive contrast echocardiography. Using an increased alveolar-arterial difference for the partial pressure of oxygen (AaDO2) as an indication of hypoxaemia, the prevalence of HPS was considerably higher (>15 mm Hg, 32%; >20 mm Hg, 31%; and >age related threshold, 28%) than using reduced partial pressure of arterial oxygen (PaO2) as a threshold (<80 mm Hg, 19%; <70 mm Hg, 15%; and

Effect of weight reduction on liver histology and biochemistry in patients with chronic hepatitis C

Abstract: Background: Steatosis occurs in more than 50% of patients with chronic hepatitis C and is associated with increased hepatic fibrosis. In many of these patients the pathogenesis of steatosis appears to be the same as for patients with non-alcoholic fatty liver disease—that is, related to visceral adiposity and obesity. Methods: The effect of a three month weight reduction programme on liver biochemistry and metabolic parameters was examined in 19 subjects with steatosis and chronic hepatitis C. Paired liver biopsies were performed in 10 subjects, prior to and 3–6 months following the intervention, to determine the effect of weight loss on liver histology. Results: There was a mean weight loss of 5.9 (3.2) kg and a mean reduction in waist circumference of 9.0 (5.0) cm. In 16 of the 19 patients, serum alanine aminotransferase levels fell progressively with weight loss. Mean fasting insulin fell from 16 (7) to 11 (4) mmol/l (p<0.002). Nine of 10 patients with paired liver biopsies had a reduction in steatosis irrespective of viral genotype. In these subjects the median modified Knodell fibrosis score decreased from 3 to 1 (p=0.04) and activated stellate cells significantly decreased (p<0.004). Conclusions: Weight loss in patients with chronic hepatitis C may be associated with a reduction in steatosis and abnormal liver enzymes and an improvement in fibrosis, despite the persistence of the virus. Weight reduction may provide an important adjunct treatment strategy for patients with chronic hepatitis C.

Surveillance guidelines after removal of colorectal adenomatous polyps.

Abstract: Most colon cancers are assumed to have a premalignant adenomatous polyp phase, therefore colonoscopic detection and polypectomy provides the opportunity for cancer prevention. Some patients who have undergone colonoscopy and have had adenomas removed are at increased risk of developing colorectal cancer (CRC) in the future, and therefore might benefit from colonoscopic surveillance. However, it is important to appreciate that colonoscopy is an invasive and costly procedure with some associated morbidity. It is also an under-resourced procedure in the UK, with a serious lack of fully trained endoscopists. Around one third of the population will develop an adenoma by age 60. Most adenomas are asymptomatic and remain undiagnosed. If colorectal screening is introduced this situation will change dramatically. There are few data on the benefits of colonoscopic surveillance in preventing colorectal cancer after a baseline clearing colonoscopy. It is therefore important that this practice is applied judiciously, balancing the risks and benefits in each individual case. Using published evidence, this guideline recommends appropriate surveillance after adenoma removal. The decision to perform each follow up colonoscopy should also depend on the patient’s wishes, the presence of comorbidity, the patient’s age, and the presence of other risk factors. ### Risk of colorectal cancer and adenomas with advanced pathology (≥1 cm or severely dysplastic) (see fig 1) Figure 1 Surveillance after adenoma removal. Risk can be stratified according to findings at baseline and refined at each subsequent surveillance examination. (Recommendation Grade B) #### Low risk Patients with only 1–2, small (<1 cm) adenomas. Recommendation: no follow up or five yearly until one negative examination . #### Intermediate risk Patients with 3–4 small adenomas or at least one >1 cm Recommendation: three yearly until two consecutive negative examinations . #### High risk If either of the following are detected at any single examination (at baseline or follow up): ≥5 adenomas or ≥3 adenomas at least one of which is ≥1 cm. Recommendation: An extra examination should be undertaken at 12 months before returning …

Effect of faecal occult blood screening on mortality from colorectal cancer: results from a randomised controlled trial

Abstract: Background: Three large randomised trials have shown that screening for colorectal cancer using faecal occult blood (FOB) tests can reduce the mortality from this disease. Two national pilot studies have recently been launched in the UK to investigate the feasibility of population screening for colorectal cancer in the National Health Service. The largest of the randomised trials was conducted in Nottingham and randomised 152 850 individuals between the ages of 45 and 74 years to receive biennial Haemoccult (FOB) test kit (intervention group) or to a control group. Aims: We have compared the mortality in the intervention group compared with the control group. Methods: The 152 850 randomised individuals were followed up through local health records and central flagging (Office for National Statistics) over a median follow up period of 11 years. Results: At a median follow up of 11 years there was a 13% reduction in colorectal cancer mortality (95% confidence interval 3–22%) in the intervention group despite an uptake at first invitation of only approximately 50%. The mortality reduction for those accepting screening was 27%. The reduction in mortality was independent of sex and site of tumour. There was no significant difference in mortality from causes other than colorectal cancer between the intervention and control groups. Conclusions: Although the reduction in colorectal cancer mortality was sustained, further follow up of this population is required to determine whether a significant reduction in the incidence of colorectal cancer will be achieved.

A role for inflammation in irritable bowel syndrome

Abstract: Attention has been directed to the putative role of low grade mucosal inflammation in irritable bowel syndrome (IBS) on the basis of evidence showing that some patients with IBS have an increased number of inflammatory cells in the colonic and ileal mucosa. Previous episodes of infectious enteritis, genetic factors, undiagnosed food allergies, and changes in bacterial microflora may all play a role in promoting and perpetuating this low grade inflammatory process. Human and animal studies support the concept that inflammation may perturb gastrointestinal reflexes and activate the visceral sensory system even when the inflammatory response is minimal and confined to the mucosa. Thus abnormal neuroimmune interactions may contribute to the altered gastrointestinal physiology and hypersensitivity that underlies IBS. A brief review of the human and animal studies that have focused on the putative role of intestinal inflammation and infections in the pathogenesis of IBS is given.

The non-H pylori helicobacters: their expanding role in gastrointestinal and systemic diseases

Abstract: The number of species in the genus Helicobacter has rapidly expanded over the past decade. The genus now includes at least 24 formally named species as well as numerous other helicobacters awaiting formal naming. This review highlights the expanding role that other helicobacters, although not as well known as H pylori, play in gastrointestinal and systemic disease in humans.

Prognosis of malignant intraductal papillary mucinous tumours of the pancreas after surgical resection. Comparison with pancreatic ductal adenocarcinoma

Abstract: Background: Although the prognosis in malignant resectable intraductal papillary mucinous tumours of the pancreas (IPMT) is often considered more favourable than for ordinary pancreatic ductal adenocarcinoma, the long term outcome remains ill defined. Aims: To assess prognostic factors in patients with malignant IPMT after surgical resection, and to compare long term survival rates with those of patients surgically treated for ductal adenocarcinoma. Methods: Seventy three patients underwent surgery for malignant IPMT in four French centres. Clinical, biochemical, and pathological features and follow up after resection were recorded. Patients with invasive malignant IPMT were matched with patients with pancreatic ductal adenocarcinoma, according to age and TNM stages; survival rates after resection were compared. Results: Surgical treatment for IPMT were pancreaticoduodenectomy (n=46), distal (n=14), total (n=11), or segmentary (n=2) pancreatectomy. The operative mortality rate was 4%. IPMT corresponded to in situ (n=22) or invasive carcinoma (n=51). In the latter group, 17 had lymph node metastases. Overall median survival was 47 months. Five year survival rates in patients with in situ and invasive carcinoma were 88% and 36%, respectively. On univariate analysis, abdominal pain, preoperative high serum carbohydrate antigen 19.9 concentrations, caudal localisation, invasive carcinoma, lymph node metastases, peripancreatic extension, and malignant relapse were associated with a fatal outcome. Using multivariate analysis, lymph node metastases were the only prognostic factor (OR 7.5; 95% CI: 3.4 to 16.4). Overall five year survival rate was higher in patients with malignant invasive IPMT compared with those with pancreatic ductal carcinoma (36 v 21%, p=0.03), but was similar in the subset of stage II/III tumours. Conclusions: The prognosis of patients with resected in situ/invasive stage I malignant IPMT is excellent. In contrast, prognosis of locally advanced forms is as poor as in patients with pancreatic ductal adenocarcinoma.

Photodynamic therapy for cancer of the pancreas

Abstract: Background: Few pancreatic cancers are suitable for surgery and few respond to chemoradiation. Photodynamic therapy produces local necrosis of tissue with light after prior administration of a photosensitising agent, and in experimental studies can be tolerated by the pancreas and surrounding normal tissue. Aims: To undertake a phase I study of photodynamic therapy for cancer of the pancreas. Patients: Sixteen patients with inoperable adenocarcinomas (2.5–6 cm in diameter) localised to the region of the head of the pancreas were studied. All presented with obstructive jaundice which was relieved by biliary stenting prior to further treatment. Methods: Patients were photosensitised with 0.15 mg/kg meso-tetrahydroxyphenyl chlorin intravenously. Three days later, light was delivered to the cancer percutaneously using fibres positioned under computerised tomographic guidance. Three had subsequent chemotherapy. Results: All patients had substantial tumour necrosis on scans after treatment. Fourteen of 16 left hospital within 10 days. Eleven had a Karnofsky performance status of 100 prior to treatment. In 10 it returned to 100 at one month. Two patients with tumour involving the gastroduodenal artery had significant gastrointestinal bleeds (controlled without surgery). Three patients developed duodenal obstruction during follow up that may have been related to treatment. There was no treatment related mortality. The median survival time after photodynamic therapy was 9.5 months (range 4–30). Seven of 16 patients (44%) were alive one year after photodynamic therapy. Conclusions: Photodynamic therapy can produce necrosis in pancreatic cancers with an acceptable morbidity although care is required for tumours invading the duodenal wall or involving the gastroduodenal artery. Further studies are indicated to assess its influence on the course of the disease, alone or in combination with chemoradiation.

Advancing donor liver age and rapid fibrosis progression following transplantation for hepatitis C

Abstract: Background and aims: Cirrhosis with liver failure due to hepatitis C virus (HCV) infection is the most common indication for liver transplantation (LT). Reinfection of the transplanted liver by HCV is inevitable, and aggressive hepatitis with accelerated progression to graft cirrhosis may be observed. Of concern, recent reports suggest that the outcome of LT for HCV may have deteriorated in recent years. Determinants of rate of progression to cirrhosis in the immunocompetent non-transplant patient are well defined, and the most powerful determinant is patient age at the time of infection. Following LT for HCV, recipient age does not affect outcome of HCV reinfection. However, the impact of donor age on graft fibrosis progression rate following LT has not been examined. Methods: We have examined post-transplant biopsies to assess histological activity, including fibrosis stage (scored 0–6 units, 6 representing established cirrhosis), and to calculate fibrosis progression rates in 101 post-transplant specimens from 56 HCV infected LT patients. Univariate and multivariate analyses examined the impact of parameters including recipient and donor age and sex on fibrosis progression rate, and on predicted time to cirrhosis. Results: For the cohort, median fibrosis progression rate was 0.78 units/year, and median interval from transplantation to development of cirrhosis was 7.7 years. In multivariate analysis, donor age (not recipient age) was a powerful determinant (p=0.02) of fibrosis progression rate. When the liver donor was younger than 40 years, median progression rate was 0.6 units/year and interval to cirrhosis was 10 years. When the donor was aged 50 years or more, median progression rate was 2.7 units/year and interval to cirrhosis only 2.2 years. During the observation period there has been a significant increase in donor age (p=0.01) but date of transplantation per se is not a determinant of progression rate when included in multivariate analyses. Conclusions: Donor age has a major influence on graft outcome following transplantation for HCV. The changing organ donor profile will affect the long term results of LT for HCV. These observations have important implications for donor liver allocation.