Antegrade double balloon enteroscopy for continued obscure gastrointestinal bleeding following push enteroscopy: is there a role?

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.

Microscopic colitis: an underdiagnosed cause of chronic diarrhoea--the clue is in the biopsies.

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.

Assessment and relevance of enzyme-linked immunosorbent assay for antibodies to Saccharomyces cerevisiae in Australian patients with inflammatory bowel disease.

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.

Early Australian experience with infliximab, a chimeric antibody against tumour necrosis factor-alpha, in the treatment of Crohn's disease: is its efficacy augmented by steroid-sparing immunosuppressive therapy? The Infliximab User Group.

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.

Use of 6-mercaptopurine in patients with inflammatory bowel disease previously intolerant of azathioprine.

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.

Persistent mucosal abnormalities in coeliac disease are not related to the ingestion of trace amounts of gluten.

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.

Dietary analysis in symptomatic patients with coeliac disease on a gluten-free diet: the role of trace amounts of gluten and non-gluten food intolerances.

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.

Video push enteroscopy in the investigation of small bowel disease: defining clinical indications and outcomes.

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.

Biliary strictures after liver transplantation: clinical picture, correlates and outcomes.

We retrospectively examined 154 adults to ascertain the frequency, site of and pre-disposing factors for biliary strictures after liver transplantation, as well as their management and clinical outcome. Twenty patients (12.5%) were identified with biliary strictures; 16 were non-anastomotic and four were anastomotic strictures. The median time from transplantation to stricture diagnosis was 17 weeks (range 3-366). Of the 16 non-anastomotic strictures, six were intrahepatic, eight hilar and two extrahepatic (donor bile duct). A control group (n = 32) of patients transplanted immediately before and after index cases was used to examine for correlates in patients with non-anastomotic strictures. At the time of diagnosis in the non-anastomotic index cases, there was a higher incidence of: (i) biliary sludge (63 vs 0%; P < 0.001); and (ii) clinical cholangitis (75 vs 0%; P < 0.001) compared with controls. Primary sclerosing cholangitis was more often the diagnosis in index patients with non-anastomotic strictures compared with controls (31 vs 9%; P < 0.05). There were no differences between index patients and controls (non-anastomotic group) in ABO blood group non-identity, cold allograft ischaemia time, use of OKT3 (murine monoclonal antibody to CD3) and hepatic artery thrombosis. Of 15 patients treated with balloon dilatation, seven required stent insertion although none have required surgery. As determined by liver function tests, there was evidence of persisting graft dysfunction in index patients compared with controls (SAP 381 vs 112 U/L, P < 0.001; GGT 529 vs 80 U/L, P < 0.001), but there was no difference in survival during a median follow-up time of 16 months (range: 3-48 months) from stricture diagnosis. In conclusion, biliary strictures tend to occur within 6 months of transplantation and are an important cause of ongoing graft dysfunction. Non-anastomotic strictures were more common in patients requiring transplantation for primary sclerosing cholangitis.

Upper gastrointestinal haemorrhage following coronary artery bypass grafting.

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.

Bacteremia and bacterascites after endoscopic sclerotherapy for bleeding esophageal varices and prevention by intravenous cefotaxime: a randomized trial.

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.

Transjugular intrahepatic portosystemic stent-shunt (TIPSS) for variceal haemorrhage: initial results in 28 patients.

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.

Anti-neutrophil cytoplasmic antibody: a prognostic indicator in primary sclerosing cholangitis.

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.

Sclerosing cholangitis and biliary tract calculi--primary or secondary?

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.

Antibiotic-associated colitis and cystic fibrosis.

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.