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Background: Advancements in endoscopic technology have increased the ability to distinguish neoplastic polyps during colonoscopy. If a minimum accuracy can be achieved, then a resect-and-discard model can be implemented, although studies to date have demonstrated limited success, especially in the assessment of serrated polyps., Objective: To perform a proof-of-principle study assessing the accuracy of narrow-band imaging with near focus in predicting polyp histology including serrated polyps and to determine whether the minimum requirements can be achieved for a resect-and-discard policy., Design: Dual-center, prospective case series., Setting: Two tertiary-care referral endoscopic centers in Australia., Patients: Two hundred consecutive patients undergoing colonoscopy for routine indications were recruited., Interventions: Any polyps identified were assessed by using standard white light followed by narrow-band imaging with near focus for Kudo pit patterns and modified Sano capillary patterns. Based on this assessment and the macroscopic appearance, the polyp histology was predicted and subsequently compared with histopathology results., Main Outcome Measurements: Correlation in postpolypectomy surveillance intervals between endoscopic and pathologic assessments as well as negative predictive value for rectosigmoid hyperplastic polyps., Results: There was a 96% agreement for surveillance intervals between endoscopic assessment and histology by using the American Society for Gastrointestinal Endoscopy guidelines. There was a 96% negative predictive value in assessing rectosigmoid hyperplastic polyps., Limitations: Because this was a proof-of-principle study, there was no control arm, and there were small numbers, especially in assessing subgroups. The results have limited generalizability with the training requirements for polyp recognition, with confidence to be determined., Conclusion: Narrow-band imaging with near focus can predict polyp histology (including serrated polyps) accurately in the hands of trained endoscopists. Further studies with larger numbers are required to further validate this practice., (Copyright © 2015 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background & Aims: The burden of ulcerative colitis (UC) in relation to disease severity is not well documented. This study quantitatively evaluated the relationship between disease activity and quality of life (QoL), as well as health care utilization, cost, and work-related impairment associated with UC in an Australian population., Methods: A cross-sectional, noninterventional, observational study was performed in patients with a wide range of disease severity recruited during routine specialist consultations. Evaluations included the Assessment of Quality of Life-8-dimension (AQoL-8D), EuroQol 5-dimension, 5-level (EQ-5D-5L), the disease-specific Inflammatory Bowel Disease Questionnaire (IBDQ), and the Work Productivity and Activity Impairment (WPAI) instrument. The 3-item Partial Mayo Score was used to assess disease severity. Health care resource utilization was assessed by chart review and patient questionnaires., Results: In 175 patients, mean (SD) AQoL-8D and EQ-5D-5L scores were greater for patients in remission (0.80 [0.19] and 0.81 [0.18], respectively) than for patients with active disease (0.70 [0.20] and 0.72 [0.19], respectively, both Ps<0.001). IBDQ correlated with both AQoL-8D (r=0.73; P<0.0001) and EQ-5D-5L (0.69; P<0.0001). Mean 3-month UC-related health care cost per patient was AUD $2914 (SD=$3447 [mean for patients in remission=$1970; mild disease=$3736; moderate/severe disease=$4162]). Patients in remission had the least work and activity impairment., Conclusions: More severe UC disease was associated with poorer QoL. Substantial health care utilization, costs, and work productivity impairments were found in this sample of patients with UC. Moreover, greater disease activity was associated with greater health care costs and impairment in work productivity and daily activities., (Copyright © 2013 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.)

Background: Melanoma is the most common tumor to metastasize to the GI tract, where it mainly involves the small bowel., Objective: To compare capsule endoscopy (CE) and (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET)-CT scanning, the current standard and most sensitive investigation modality, in detecting small-bowel metastases in patients with metastatic melanoma., Design: A prospective study of patients with metastatic melanoma who were undergoing FDG PET-CT scanning. CE was performed and the results read by two independent observers without knowledge of the other investigation results., Setting: Tertiary care centers., Patients: This study involved 21 patients with a median age of 52 years (range 22-88 years)., Intervention: CE., Main Outcome Measurements: Detection of small-bowel melanoma., Results: FDG PET-CT scanning showed increased abdominal uptake in 12 patients, but only 5 of these patients were found to have small-bowel melanoma on CE. Importantly, in 1 patient with a bleeding small-bowel tumor on CE, the FDG PET-CT scan result was negative. One patient with positive FDG PET-CT scan results and negative CE results subsequently developed symptomatic small-bowel melanoma 10 months after CE., Limitations: Small-bowel melanoma could not be excluded entirely in 7 patients with positive FDG PET-CT scan results and negative CE results, and follow-up is ongoing. The number of patients in this study was small., Conclusion: CE was better than FDG PET-CT scanning in localizing small-bowel melanoma. This study suggests that CE is an ideal complementary investigation modality for patients with known metastatic melanoma undergoing preoperative work-ups and in those with unexplained anemia or GI symptoms., (Copyright © 2011 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.)

Objective: Lesions missed by capsule endoscopy (CE) have been reported and this may be partly because of the properties of the capsule. We aimed to compare the ability of Pillcam SB1, SB2, ESO1 and ESO2 to identify the ampulla of Vater (AoV)., Methods: Patients were divided into four groups: SB1 [single head capsule, 2 frames per second (fps), a 140° field of view, n=50], SB2 (single head, 2 fps, a wider field of view of 156°, n=50), ESO1 (double head, 14 fps, a 140° field of view, n=8) and ESO2 (double head, 18 fps, an extra wide field of view of 169°, n=12). Metoclopramide was administered in 25 out of 50 patients in SB1 group and all patients in SB2 group before CE., Results: The AoV was not detected in any patients having SB1, irrespective of the use of metoclopramide. The AoV was identified in only nine out of 50 (18%) patients in the SB2 group confirming the benefit of a widened field of view, however, showed that even this capsule failed to visualize the AoV in more than three-quarters of cases. Double-headed capsules with faster frame rates did not improve the detection rate, the AoV was visualized in only one out of 12 (8%) patients in the ESO2 group but none in the ESO1 studies., Conclusion: Currently, CE is not reliable to visualize the AoV and by inference the proximal duodenum. This is most likely related to the speed at which the capsule passes through the fixed second part of the duodenum. Faster frame rates plus a wider field of view do not overcome this limitation, which could account for missed lesions elsewhere in the small bowel.

Aim: To study the significance of cap-fitted colonoscopy in improving cecal intubation time and polyp detection rate., Methods: This study was a prospective randomized controlled trial conducted from March 2008 to February 2009 in a tertiary referral hospital at Sydney. The primary end point was cecal intubation time and the secondary endpoint was polyp detection rate. Consecutive cases of total colonoscopy over a 1-year period were recruited. Randomization into either standard colonoscopy (SC) or cap-assisted colonoscopy (CAC) was performed after consent was obtained. For cases randomized to CAC, one of the three sizes of cap was used: D-201-15004 (with a diameter of 15.3 mm), D-201-14304 (14.6 mm) and D-201-12704 (13.0 mm). All of these caps were produced by Olympus Medical Systems, Japan. Independent predictors for faster cecal time and better polyp detection rate were also determined from this study., Results: There were 200 cases in each group. There was no significant difference in terms of demographic characteristics between the two groups. CAC, when compared to the SC group, had no significant difference in terms of cecal intubation rate (96.0% vs 97.0%, P = 0.40) and time (9.94 +/- 7.05 min vs 10.34 +/- 6.82 min, P = 0.21), or polyp detection rate (32.8% vs 31.3%, P = 0.75). On the subgroup analysis, there was no significant difference in terms of cecal intubation time by trainees (88.1% vs 84.8%, P = 0.40), ileal intubation rate (82.5% vs 79.0%, P = 0.38) or total colonoscopy time (23.24 +/- 13.95 min vs 22.56 +/- 9.94 min, P = 0.88). On multivariate analysis, the independent determinants of faster cecal time were consultant-performed procedures (P < 0.001), male patients (P < 0.001), non-usage of hyoscine (P < 0.001) and better bowel preparation (P = 0.01). The determinants of better polyp detection rate were older age (P < 0.001), no history of previous abdominal surgery (P = 0.04), patients not having esophagogastroduodenoscopy in the same setting (P = 0.003), trainee-performed procedures (P = 0.01), usage of hyoscine (P = 0.01) and procedures performed for polyp follow-up (P = 0.01). The limitations of the study were that it was a single-center experience, no blinding was possible, and there were a large number of endoscopists., Conclusion: CAC did not significantly different from SC in term of cecal intubation time and polyp detection rate.

Background: The benefit of double balloon endoscopy (DBE) over push enteroscopy (PE) for the proximal small bowel in patients with obscure gastrointestinal bleeding remains unclear., Aim: To quantify the benefit of DBE if PE fails to benefit patients with obscure gastrointestinal bleeding., Methods: This retrospective DBE database review between July 2004 and April 2008 was conducted at a tertiary university hospital in Australia. Thirty-three patients with obscure gastrointestinal bleeding who had undergone PE for proximal small bowel lesions were identified from a DBE database of 280 patients. Mean age was 68.6 (range 30-91) years, and 17 were men. In group A (n = 15) the target lesion was not reached by PE, and in group B (n = 18) an abnormality was found by PE (angioectasia in 17 and red spots in 1) but the patient had ongoing bleeding. Mean follow-up for the cohort was 19.2 (range 5-39) months. DBE interventions were performed as appropriate., Results: An abnormality was found at DBE in 28/33 (85%) patients. DBE found an abnormality in 12/15 (80%) in group A and 16/18 (89%) in group B. Endoscopic intervention was performed in 23/33 patients (70%). In 27/33 (82%) patients a clinical benefit was seen following DBE. Six patients (18%) had no clinical benefit from DBE., Conclusions: In patients with obscure gastrointestinal bleeding and proximal small bowel lesions who fail to benefit from PE, DBE offers a very high benefit in finding and treating lesions with good long-term outcomes.

Background: In August 2002, an application for the listing on the Medicare Benefits Schedule (MBS) of PillCam Capsule Endoscopy (formally M2A) as a diagnostic procedure for obscure gastrointestinal bleeding (OGIB) was made to the Medical Services Advisory Committee (MSAC). As a result of this application, in May 2004 PillCam Capsule Endoscopy was approved with interim funding until April 2007. This funding was conditional on the collection of Australian data on the long-term safety, effectiveness, and cost-effectiveness of capsule endoscopy., Methods: A review was conducted of how the data were collected, the methodological difficulties associated with the collection and analysis of the data, and the outcomes of the data., Results: The PillCam Capsule Endoscopy Register ran from 2004 to 2007 and amassed data on 4,099 patients forming the largest database on PillCam in the world. Based on these data, in November 2007, MSAC recommended that full public funding be supported under the current MBS Item Number 11820 as capsule endoscopy is as safe as and more effective than comparable diagnostic tests. It is the preferred choice of patients and has the potential to reduce the number and cost of previous investigations., Conclusions: This form of CED proved to be ideally suited to PillCam Capsule Endoscopy. The PillCam Capsule Endoscopy Register provided data that made it possible to validate assumptions used in the economic modeling in the assessment carried out for MSAC in response to the application for funding., Discussion: The use of interim funding requires both risk and cost sharing among the key players: industry, government, the medical profession, and the hospitals. Although the characteristics of PillCam Capsule Endoscopy proved to be suited to data collection, this may not be the case with other emerging health technologies. If interim funding coupled with data collection is to become an effective mechanism for bridging the evidence gap, work needs to be carried out by health technology assessment agencies to provide guidance on the design of registers so that they cater for the unique characteristics of individual procedures.

Objective: To determine whether including the study questionnaire with a letter of invitation improves the response rate in a telephone-based survey., Study Design and Setting: This randomized controlled trial was part of a larger study to assess patient preferences for novel and controversial treatments for inflammatory bowel disease at Royal Prince Alfred Hospital, a tertiary referral teaching hospital in Sydney, Australia., Results: Of 270 eligible patients, 124 (46%) were randomized to receive the questionnaire plus invitation whereas 146 (54%) were in the control group receiving a letter of invitation only. The consent rate was 26% for those receiving the questionnaire and 36% for the control group. The odds ratio for consent to participate among those sent the questionnaire to those not sent the questionnaire was 0.63 (95% CI=0.37-1.07)., Conclusion: This study found that the advance mailing of a questionnaire to potential participants in a telephone survey reduced the likelihood of their participation.

Background: Although small bowel (SB) involvement is found at postmortem in 50-60% of melanoma patients, diagnosis is only made during life in 10% of cases. This study reports the findings of capsule endoscopy (CE) in melanoma patients referred for investigation of suspected SB involvement., Methods and Subjects: Eight men and five women with known or previous melanoma were referred for CE between December 2003 and September 2006. The indications were gastrointestinal bleeding (three), anemia (six), positive fecal occult blood test (one), abnormal imaging (two), and abdominal pain (one)., Results: CE showed SB metastases in five patients and excluded SB involvement in eight. All patients had previous investigations with either endoscopy, push enteroscopy, SB follow-through, CT scan, and/or PET scan. CE showed new lesions not detected by other investigation modalities. CE also ruled out SB metastases when other tests were nondiagnostic. All five patients with SB metastases detected underwent surgical resection. At follow-up after CE of a mean 8.4 months (1-23 months) and 4.9 months (0.25-10 months) after surgery, five patients had died, including three of those who had undergone resection of SB metastases. Seven patients were still alive, including two who had SB surgery. One patient was lost to follow-up., Conclusions: CE may detect the presence and extent of SB metastases in patients with melanoma more reliably than conventional investigations. It should be considered in the workup of melanoma patients with suspected SB disease.

Objective: The objective of the study was to examine diagnosis and outcome in a series of patients with small bowel tumors detected by capsule endoscopy (CE) in three Australian centers., Methods: Review of prospectively collected data from 416 CEs identified 27 tumors in 26 patients. Clinical parameters, tumor histology, and follow-up are reported., Results: Twenty-seven tumors were identified in 26 patients (mean age 61 +/- 13.7 yr). Indications for CE were obscure gastrointestinal (GI) bleeding (21), suspected tumor (3), abdominal pain (1), diarrhea (1). Prior radiology found a possible lesion in 8 of 23 (35%). Nine tumors were proven benign: hamartoma (4), cystic lymphangioma (1), primary amyloid (1), lipoma (1). Two lesions were non-neoplastic: heterotopic gastric mucosa and inflammatory fibroid polyp. Seventeen tumors were malignant: five adenocarcinomas, six carcinoids, two melanoma metastases, two gastrointestinal stromal tumors (GIST), one colon carcinoma metastasis, one non-Hodgkin's lymphoma. Tumors were surgically resected in 23 patients. Resection was considered curative in 12 (52%). Mean duration of follow-up was 26 +/- 13.7 months. Of the five patients with primary adenocarcinoma only one remains disease free. Three of the six with carcinoid tumors have had no recurrence up to 51 months postresection. Both patients with GIST are disease free. Anemia resolved after surgery in the patients with melanoma., Conclusions: Small bowel tumors are a significant finding at CE and are often missed by other methods of investigation. In many patients, detection of a tumor alters management and improves outcome. Even in malignant lesions, treatment is potentially curative in the absence of metastatic disease.

Microscopic forms of colitis (collagenous colitis and lymphocytic colitis) are uncommon but important causes of chronic diarrhoea that are often overlooked. The clinical features of these disorders are similar, and they are more common in middle-aged females, although the female predominance is greater in collagenous colitis. Although their cause is unclear, both are associated with a variety of autoimmune diseases. Colonoscopy and barium enema are typically normal, so that the diagnosis depends on the demonstration of characteristic changes on histopathological examination of colorectal biopsies. These should be taken in all patients undergoing colonoscopy for the investigation of chronic diarrhoea. There are no large controlled trials of therapy available. Treatment is empirical, generally using the same agents as for inflammatory bowel -disease. Assessment of therapy is also difficult as spontaneous remissions occur often.

Objectives: Appendectomy has been shown to protect against the development of ulcerative colitis. The objective of this study was to examine the effect of appendectomy on the clinical features and natural history of colitis., Methods: A total of 259 consecutive adults patients with ulcerative colitis were studied. Of the patients, 20 had undergone appendectomy (12 before onset of colitis and eight after diagnosis)., Results: The frequency of appendectomy was significantly less than in a group of 280 controls, which comprised partners of the patients and a group from the community (OR = 0.25; 95% CI = 0.14-0.44). This was even more significant if only the 12 patients who underwent surgery before the onset of colitis were considered (OR = 0.15; 95% CI = 0.07-0.28). Patients with prior appendectomy developed symptoms of ulcerative colitis for the first time at a significantly later age than those without appendectomy (42.5 +/- 6.5 vs 32.1 +/- 0.8 yr; p < 0.01) or those who had appendectomy after the onset of colitis (24.6 +/- 3.4 yr; p < 0.05). Appendectomy did not influence disease extent, need for immunosuppressive treatment with azathioprine or 6-mercaptopurine (as a marker of resistant disease), or the likelihood of colectomy. Five patients in the appendectomy group had clinical evidence of primary sclerosing cholangitis (25%). This was more common than in those without appendectomy (8%; OR = 4.09; 95% CI = 1.04-13.60)., Conclusions: These results indicate that although appendectomy may delay onset of colitis, it does not influence its course. However, it is associated with the development of primary sclerosing cholangitis. Appendectomy is unlikely to be of benefit in established ulcerative colitis.

The frequency of antibodies to Saccharomyces cerevisiae (ASCA) in Crohn's disease, ulcerative colitis and non-inflammatory bowel disease controls has been compared using two commercially available assays. The Medizym test resulted in sensitivity of 50% and specificity of 93% for Crohn's disease. The corresponding figures for the QUANTA Lite assay were 79% and 74%, respectively. Using ASCA and perinuclear antineutrophil cytoplasmic antibody (pANCA) in combination, the sensitivity and specificity of ASCA+/pANCA- for Crohn's disease using the Medizym kit were 50% and 100%, respectively, compared with 79% and 93% using QUANTA Lite. ASCA-/pANCA+ was 100% specific for ulcerative colitis with either assay. ASCA can be found in Australian patients with Crohn's disease at a similar frequency to that reported overseas.

Background: Tumour necrosis factor-alpha (TNF-alpha) plays an important role in the pathology of Crohn's disease. Infliximab, a chimeric antibody against TNF-alpha, has been shown in controlled clinical trials to be effective in two-thirds of patients with refractory or fistulating Crohn's disease. The factors that determine a clinical response in some patients but not others are unknown., Aims: To document the early Australian experience with infliximab treatment for Crohn's disease and to identify factors that may determine a beneficial clinical response., Methods: Gastroenterologists known to have used infliximab for Crohn's disease according to a compassionate use protocol were asked to complete a spreadsheet that included demographic information, Crohn's disease site, severity, other medical or surgical treatments and a global clinical assessment of Crohn's disease outcome, judged by participating physicians as complete and sustained (remission for the duration of the study), complete but unsustained (remission at 4 weeks but not for the whole study) or partial clinical improvement (sustained or unsustained)., Results: Fifty-seven patients were able to be evaluated, with a median follow-up time of 16.4 (4-70) weeks, including 23 patients with fistulae. There were 21 adverse events, including four serious events. Fifty-one patients (89%) had a positive clinical response for a median duration (range) of 11 (2-70) weeks. Thirty patients (52%) had a remission at 4 weeks, 10 of whom had remission for longer than 12 weeks. Forty-two per cent of fistulae closed. Sustained remission (P = 0.065), remission at 4 weeks (P = 0.033) and a positive clinical response of any sort (P = 0.004) were more likely in patients on immunosuppressive therapy, despite there being more smokers in this group., Conclusion: This review of the first Australian experience with infliximab corroborates the reported speed and efficacy of this treatment for Crohn's disease. The excellent response appears enhanced by the concomitant use of conventional steroid-sparing immunosuppressive therapy.

Both azathioprine and its active metabolite, 6-mercaptopurine, are of benefit in the treatment of inflammatory bowel disease, either in resistant cases, or for their steroid-sparing effect. Azathioprine treatment is limited in some patients by hypersensitivity reactions or other side effects. We report our experience in 11 patients previously unable to tolerate azathioprine for a variety of reasons, who were switched to 6-mercaptopurine. Of seven patients with ulcerative colitis and four patients with Crohn's disease who were treated with 6-mercaptopurine following failed azathioprine therapy, six were able to successfully tolerate the substitute medication, with good response. Where patients have previously been intolerant of azathioprine yet ongoing indications for immunosuppressive therapy remain, a trial of 6-mercatopurine may be warranted. Given the similar efficacies of the two drugs in inflammatory bowel disease, these findings also favor the use of 6-mercaptopurine rather than the parent compound as initial therapy.

Background: It is expected that in patients with coeliac disease the small-bowel mucosal mucosa will return to normal if they adhere to a gluten-free diet (GFD). However, in many this is not the case. This study aims to determine whether this persistent villous atrophy (VA) could be due to continued ingestion of the trace amounts of gluten in 'gluten-free' foods, as defined by the WHO/FAO Codex Alimentarius., Methods: Duodenal biopsy specimens from 89 adults with long-standing coeliac disease were examined, and the findings correlated with their form of gluten-free diet., Results: In 51 subjects the duodenal specimen was normal, whereas in 38 there was villous atrophy (partial, 28; subtotal, 8; total, 2). There was no relationship between the presence or absence of VA and ingestion of either a GFD as defined by the Codex Alimentarius (Codex-GFD; 39 patients) or a GFD that contained no detectable gluten (NDG diet: 50 patients). Intraepithelial lymphocyte counts were higher, and lactase levels lower, in subjects with an abnormal biopsy specimen than in those in whom it was normal. However, within each of these biopsy groups there was no difference in these variables between patients on a Codex-GFD and those on an NDG-GFD. IgA antigliadin antibody was detected in 4 of 29 patients on a Codex-GFD and in 3 of 13 on a NDG-GFD (NS)., Conclusion: The persistent mucosal abnormalities seen in patients with coeliac disease on a GFD are not due to the ingestion of trace amounts of gluten. The consequences of these abnormalities have yet to be determined.

Background: Whereas many people with coeliac disease (CD) are asymptomatic when consuming a gluten-free diet (GFD), a proportion continues to experience symptoms. The reasons for this are unclear., Methods: Thirty-nine adult members of The Coeliac Society of New South Wales, all of whom had persistent gastrointestinal symptoms despite adhering to a GFD, were evaluated. Dietary analysis indicated that 22 (56%) were consuming a GFD as defined by the WHO/FAO Codex Alimentarius (Codex-GFD), in which foods containing up to 0.3% of protein from gluten-containing grains can be labelled as 'gluten free'. The remaining 17 were following a no detectable gluten diet (NDG)-GFD, as defined by Food Standards Australia. All subjects were required to follow a NDG-GFD during the study. Those in whom symptoms persisted after changing from a Codex-GFD and those who entered the study already on a NDG-GFD began an elimination diet followed by open and double-blind challenges to identify specific non-gluten food or food chemical intolerances., Results: Of 22 patients who switched to a NDG-GFD symptoms resolved in 5 (23%) and were reduced in 10 others (45%). Thirty-one subjects commenced the elimination diet. Symptomatic improvement was experienced in 24 (77%). Subsequent food or food chemical challenges resulted in a mean of five positive challenges per individual. Diarrhoea was the most commonly provoked symptom, followed by headache, nausea, and flatulence. Symptoms were especially provoked by amine, salicylate and soy., Conclusion: The consumption of trace amounts of gluten, traditionally allowed in a Codex-GFD, may be responsible for the continuing symptoms seen in some patients with CD. Further investigation for non-gluten food intolerances should follow if symptoms persist after adherence to a NDG-GFD.

Background: Push enteroscopy is a new technique for investigation of the small intestine. The clinical indications are still being defined. It also offers the potential for therapeutic intervention in suitable cases., Aims: To evaluate further the role of push enteroscopy in the diagnosis and treatment of patients with suspected or known small bowel disease., Methods: A prospective record was kept of all patients having enteroscopy at Royal Prince Alfred Hospital between March 1995 and July 1997. The procedure was performed 73 times in 68 patients. Indications and diagnoses were noted. The outcome in patients with obscure gastrointestinal bleeding or anaemia in whom a vascular lesion was treated with a heater probe was also determined., Results: Enteroscopy was performed in 23 patients for gastrointestinal bleeding of obscure origin. An active or possible bleeding source was found in 13 (57%). The commonest of these was jejunal angiodysplasia. In the 21 patients with chronic iron deficiency anaemia a lesion was found in ten (48%). The majority of these were in the stomach, as described by others. The diagnostic yield in the 16 patients having enteroscopy for known or suspected small bowel disease was 56%. One patient underwent balloon dilatation of a postoperative jejunal stricture. Eleven patients with obscure bleeding or anaemia had ablation of a vascular lesion with a heater probe. Transfusion requirements fell after this procedure, particularly in those with active bleeding at the time of the examination. In five of the 11 no further transfusions were required in over six months of follow-up., Conclusions: The most common indications for enteroscopy are obscure gastrointestinal bleeding, chronic anaemia and known or suspected small bowel disease. A positive result can be expected in over 50% of patients. The treatment of vascular lesions via the enteroscope has a significant impact of subsequent transfusion requirements.

Background: Upper gastrointestinal (UGI) bleeding is a relatively common and potentially fatal complication of coronary artery bypass graft (CABG) surgery. However, little is known of this problem, including its incidence, predisposing factors and safety of endoscopy in these patients., Aim: To document the incidence, site, predisposing factors and outcome of UGI bleeding following CABG surgery. Also, to assess the safety of UGI endoscopy in these patients., Method: Retrospective study of UGI haemorrhage following CABG at one institution between 1976 and 1991., Results: Fifty-five of 10,573 patients (0.5%) suffered a major UGI haemorrhage (as defined by need for transfusion or presence of melaena or haematemesis associated with hypotension). Of 51 patients undergoing endoscopy or laparotomy, 42 (82%) bled from duodenal ulceration. Five patients bled from gastric ulcers and one each from oesophagitis and Mallory Weiss tear. Nine patients underwent endoscopic therapy, which initially arrested haemorrhage in eight patients. However, three patients rebled and required surgery. Eight patients underwent surgery as initial therapy, resulting in an overall surgical rate of 20%. One patient died due to multi system failure following surgery. There were no complications from endoscopy. Patients who bled were more likely to have received inotropic support post-operatively prior to the haemorrhage (p < 0.05) and tended to be older than controls (mean age 65.6 years vs 58.7 years, p < 0.01). Twenty-one of the patients (38%) who bled had a past history of peptic ulceration or dyspepsia compared with 9% of controls (p < 0.001). Seven (12.5%) had previously bled from peptic ulceration. Patients who bled were less likely to have received H2-receptor antagonists in the perioperative period than controls (4% vs 20%, p < 0.05)., Conclusion: Upper GI haemorrhage following CABG is relatively frequent. It is usually secondary to duodenal ulceration. Endoscopy is a safe procedure in this patient group. Mortality did not differ between index patients who suffered a UGI haemorrhage and controls undergoing CABG who did not bleed.

Thirty-one patients were randomized during 39 episodes of bleeding to receive either 1 g of intravenous cefotaxime (19 patients) or no antibiotic (20 patients) immediately before emergency endoscopic sclerotherapy. Blood was obtained for culture before and at 5 minutes, 4 hours, and 24 hours after the procedure. Specimens for culture were taken from the endoscope tip and channel, water bottle, and injection needle after sclerotherapy. When ascites was present (5 patients in the antibiotic group, 7 in the control group), fluid was obtained by paracentesis before endoscopy and at 4 and 24 hours. Bacteremia occurred in 1 of 19 patients in the antibiotic group (5.3%), compared with 6 of 19 in the control group (31.6%; p = .04). The cultured organisms were oral flora and usually also contaminated the endoscope and needle. No bacteria were cultured from ascitic fluid in any patient nor was the ascitic fluid white cell count elevated. Clinical infection attributable to sclerotherapy did not develop in any patient. In conclusion, the frequency of bacteremia after endoscopic sclerotherapy for bleeding esophageal varices can be reduced by prophylactic administration of intravenous cefotaxime. However, this may not be clinically relevant, given the absence of bacterascites and infection in this study. These findings do not support the routine use of antibiotics before sclerotherapy.

Background: Endoscopic sclerotherapy is an effective form of treatment of bleeding varices in patients with cirrhosis. However, the mortality in patients who rebleed is high. Recently, transjugular intrahepatic portosystemic stent-shunt (TIPSS) has been developed as an alternative to surgical shunt formation in patients who have failed sclerotherapy., Aim: To review the early experience with TIPSS at a teaching hospital., Methods: Twenty-eight patients underwent TIPSS on 30 occasions between September 1991 and June 1993 for bleeding oesophageal or gastric varices. The majority had alcoholic liver disease., Results: TIPSS was performed successfully in all patients. Immediate control of bleeding was achieved, but one patient rebled within 24 hours. Complications related to the procedure occurred in 30%, but no patient died from these. Thirty-day mortality was 11% (three of 28), two patients dying from progressive liver failure and one from sepsis. A further three patients died from six weeks to two months following TIPSS, due to liver failure in one, spontaneous bacterial peritonitis in the second and in the third after a fall. This represents an overall mortality of 21%. Three patients have rebled at mean follow-up of 11.3 months. One of these had repeat TIPSS while the other two had balloon dilatation of the stent with control of bleeding. Four patients developed mild chronic encephalopathy which was readily controlled with medical therapy., Conclusions: TIPSS is an effective means for control of bleeding from oesophageal and/or gastric varices not responding to other methods. Further follow-up is required with regard to rates of rebleeding, encephalopathy and survival.

Considerable variability has been reported in the frequency and specificity of anti-neutrophil cytoplasmic antibody with a perinuclear staining pattern (pANCA) in patients with chronic liver disease, especially in primary sclerosing cholangitis (PSC), and in inflammatory bowel disease. This study examines the presence of pANCA in patients with these disorders, in particular those with PSC complicated by other biliary disease, and also patients who had undergone orthotopic liver transplantation. An indirect immunofluorescent technique was used to measure pANCA with serum diluted 1:20. Ten of 39 (26%) patients with PSC had detectable pANCA, as did two of nine (22%) with autoimmune chronic active hepatitis (AICAH) but none of the 51 patients with other forms of chronic liver disease. The presence of pANCA was significantly more frequent in patients who had PSC with biliary tract complications, in particular calculi (seven of 16 with vs three of 23 without; P = 0.03). Eight of the 12 pANCA-positive patients with PSC or AICAH had undergone hepatic transplantation. This was more likely than in patients with PSC or AICAH who were pANCA negative (10 of 36; P = 0.02). To date, pANCA has been detected after transplantation in four patients with PSC and one with AICAH. In patients with PSC or AICAH, pANCA should be sought as a marker of prognosis.

The clinical features of 61 patients with sclerosing cholangitis were reviewed. This group included 23 patients with biliary tract calculi, commonly considered as excluding the diagnosis of primary sclerosing cholangitis. The aim of this study was to compare these 23 patients (group A) with 38 patients with sclerosing cholangitis free of calculi (group B). Both groups had the following features in common: (i) age at presentation, (ii) incidence of inflammatory bowel disease, (iii) extent of radiological disease, (iv) prevalence of HLA-B8 and DR3 haplotype, (v) incidence of cholangiocarcinoma, and (vi) progression to hepatic transplantation (mean follow up 49.9 months). All patients in group A were symptomatic at diagnosis compared with 23 of the 38 patients (61%) in group B. Recurrent ascending cholangitis occurred in 12 patients in group A (52%) and two patients (5%) in group B. The similarity between the two groups was maintained when the nine patients in group A who developed calculi after sclerosing cholangitis was diagnosed were excluded. It is concluded that choledocholithiasis is part of the spectrum of primary sclerosing cholangitis and that it is not necessary to invoke choledocholithiasis as the initial lesion of the bile ducts in such patients.

The use of antibiotics in patients with cystic fibrosis is widespread, and fecal carriage of Clostridium difficile occurs in up to 50% of these patients; however, antibiotic-associated colitis appears to be a rare occurrence. The reasons why this is so remain unknown. A case of antibiotic-associated colitis occurring in a patient with cystic fibrosis is described. Possible mechanisms for the rarity of antibiotic-associated colitis are reviewed and implications for prompt diagnosis and therapy are discussed.

Lymphocytes rosetting with sheep red blood cells (SRBC) have been quantitated in the peripheral blood of patients with ulcerative colitis (UC) or Crohn's disease (CD) and the results compared with those from healthy control subjects. In contrast with previous studies, normal populations of total (SRBC: lymphocyte, 60:1) and avid (8:1) rosetting lymphocytes were found in the patient groups. Analysis of these cells, using monoclonal antibodies, showed that the proportions of OKT3+, OKT4+ and OKT8+ cells were similar in the two rosetting populations. However, for patients with UC, there was a significant increase in OKT4+ cells in the total rosette forming population when compared with healthy subjects. It is concluded that avid rosette forming cells are unlikely to form a functionally distinct population of T lymphocytes and this population, which is thymosin-dependent, is not deficient in patients with UC or CD.

HLA-DR-positive histiocytes in the lamina propria of the human intestine have been characterised using combined histochemical and immunohistological techniques. In the small intestine, 80-90% of the HLA-DR+ histiocytes had irregular surfaces with stellate processes, and exhibited strong membrane adenosine triphosphatase (ATPase) activity, but weak acid phosphatase (ACP) and non-specific esterase (NSE) activities (HLA-DR+ ACP+/- NSA+/- ATP++; type 1 cell). In contrast, in the lamina propria of the colon the majority (60-70%) of HLA-DR+ cells were large, round cells with strong ACP and NSE activities but no detectable ATPase activity (HLA-DR+ ACP++ NSE++ ATP+/-; type 2 cell). The colon also contained a population of type 1 cells (30-40%). In active inflammatory bowel disease affecting the colon a third population of HLA-DR+ histiocytes was seen. These cells were irregular in outline, with many processes, and were ACP++ NSE+ ATP+/- (type 3 cell). The type 3 cells appeared to replace type 2 cells. After treatment, the appearances returned to normal. These findings suggest that the different populations of HLA-DR+ histiocytes in the human intestine may have several functions, reflecting the different forms of antigen present in the intestine. The alterations in inflammatory bowel disease may represent activation in response to an invading antigen.

Intraepithelial lymphocytes (IEL) of the normal human stomach, small intestine, and large intestine have been characterised in tissue sections by a double marker immunofluorescent technique. A panel of reagents was used in combination, including antisera to T lymphocyte antigen (HuTLA), Ia-like (p28, 33) antigens and immunoglobulin subclasses, as well as a mouse monoclonal antibody to a human leucocyte antigen (HLe-1). In stomach and proximal small intestine over 95% of IEL were T lymphocytes (HLe-1+, HuTLA+). The proportion was slightly lower in the colon and rectum (85--95%). IEL rarely expressed Ia-like antigens. B lymphocytes were not seen within the epithelium of any of the tissues examined. The functions of IEL must be assessed in the light of the finding that they are predominantly T cells.

Six hundred and eighty-one patients with ulcerative colitis who attend the outpatient clinic in Oxford have been screened for the presence of persistently abnormal liver function tests. Of the 21 patients (3.0 per cent) found with abnormal liver function 17 (2.4 per cent) were shown by cholangiography to have primary sclerosing cholangitis. The liver biopsies from those patients demonstrated a wide range of histological features and were diagnostic of primary sclerosing cholangitis in only 50 per cent of the patients. When persistently abnormal liver function tests are demonstrated in patients with ulcerative colitis it is likely that primary sclerosing cholangitis will be present (81 per cent of patients in this study), and in order to make a reliable diagnosis it is necessary to perform cholangiography in addition to liver biopsy. A close association with primary sclerosing cholangitis and histocompatibility antigens HLA B8 and DR3 is also reported.

The proportions of T cell subsets and Leu 7+ cells and the spontaneous cell-mediated cytotoxicity (SCMC) of isolated mononuclear cells have been determined across the mesenteric vascular bed and along the intestinal mucosal-mesenteric lymph node (MLN) axis in patients undergoing abdominal surgery. Whereas the proportion of T4+ and T8+ cells were similar in simultaneously taken PVB and mesenteric venous blood (MVB), the proportion of Leu 7+ cells was higher in MVB in 16 of 17 studies (15.4 +/- 6.8%, 10.8 +/- 5.1%). Additional studies showed that the proportions of lymphocyte subsets in peripheral arterial blood are the same as those in PVB. Thus, an enrichment of Leu 7+ cells occurs across the mesenteric vascular bed. Isolated intestinal and MLN mononuclear cells contained similarly high proportions of T4+ and T8+ cells as in PVB but Leu 7+ cells made up a minority subpopulation in intestinal (1.3 +/- 0.8%) and MLN mononuclear cells (1.0 +/- 0.9%). The SCMC of intestinal and MLN mononuclear cells was low and paralleled the proportion of Leu 7+ cells. Despite the higher proportions of Leu 7+ cells in MVB, the SCMC was less than that of PVB in eight patients with inflamed intestine and not significantly different from PVB in seven patients with normal intestines. These paradoxical findings were at least in part due to inhibitory factors in mesenteric plasma. In conclusion, NK cells appear to be largely confined within the vascular system and the enrichment of Leu 7+ cells across the mesenteric vascular bed suggests that this compartmentalization may be due to differences in the traffic of lymphocyte subpopulations through the intestinal mucosa and MLN.

T lymphocytes in the normal human intestinal tract have been analysed in tissue sections by a double-marker immunofluorescence technique, combining antiserum to T lymphocyte antigen (HuTLA) with a monoclonal antibody detecting T cells of suppressor-cytotoxic phenotype (OKT8). The distribution of HLA-A -B, -C and Ia-like antigens in intestinal mucosa was also examined by a similar method. In small and large intestine 67 to 90% (mean 70%) of intraepithelial T lymphocytes were of suppressor-cytotoxic phenotype (OKT8+). In contrast, only 27 to 56% (mean 39%) of lamina propria T cells were OKT8+. Intestinal epithelial cells demonstrated strong membrane staining for HLA-A, -B, -C antigens. Ia-like antigens were detected on the epithelial cells of small intestinal villi, but not on colonic epithelial cells. Lamina propria macrophages expressed both HLA-A, -B, -C and Ia-like antigens, the latter having strong membrane and cytoplasmic fluorescence. The distribution of T cells with suppressor-cytotoxic or inducer phenotype in the intestinal epithelium and lamina propria may be related to the differential expression of Ia-like and HLA-A, -B, -C antigens in intestinal mucosa.