Outcome of repeat ERCP after initial failed use of a needle knife for biliary access.

INTRODUCTION: A needle knife is often used to gain bile duct access when standard techniques have failed. If unsuccessful, the next step may involve either radiological- or endoscopic ultrasound-guided biliary access. However, repeat endoscopic retrograde cholangiopancreatography (ERCP) may be an option if the patient's clinical condition permits. AIM: To determine the success of repeat ERCP after failed use of a needle knife to gain biliary access. METHODS: Retrospective analysis of all patients who underwent initial unsuccessful biliary cannulation after use of a needle knife between 2007 and 2010. RESULTS: Seventy five patients were identified. Of these, 51 (68%) underwent repeat ERCP, and biliary cannulation was successful in 38 (75%). The median time to repeat ERCP was 7.7 days (range 1-28 days). Complications developed in two (4%) patients. These included one case each of wire-guided perforation and mild pancreatitis, both of which were resolved by conservative management. CONCLUSIONS: Repeat ERCP within a few days after failed use of a needle knife for biliary access is associated with acceptable success and acceptable incidence of complications, and therefore obviates the need for alternative approaches for biliary access for most patients.

Colonic stenting in 2011.

Self expanding metal stents (SEMS) are an established treatment in the management of malignant obstructing lesions throughout the gastrointestinal tract. SEMS have been utilized both as palliation in and as a bridge to surgical resection for malignant colonic obstruction. Many studies have demonstrated that placement of SEMS for malignant colonic obstruction is both efficacious, with high technical and clinical success rates, and safe with a low complication rate. In contrast, there is a paucity of data on the role of SEMS in the management of benign colonic obstruction, an indication which remains controversial. This review outlines the most recent developments in colonic stenting, their current indications, and the evidence to support their use in these indications.

Blood group O and vWf expression may be involved in development of peptic ulcer disease secondary to Helicobacter pylori infection.

Helicobacter pylori is a gram negative organism involved in peptic ulcer disease and has been linked to a number of extra-intestinal diseases. There is a large body of evidence describing the link between blood group O/non-secretor phenotypes with H. pylori infection and the risk of peptic ulcer disease. Blood group O individuals also have a higher risk of bleeding disorders due to low levels of the circulating plasma protein von Willebrand factor (vWf). vWf is one of the main proteins that binds platelets during platelet activation and aggregation. The mechanisms of how ulcers develop during H. pylori infection are not fully understood. There is however recent evidence of vWf involvement in platelet aggregation in H. pylori infection. Our new hypothesis states that H. pylori bacteria present in blood group O/non-secretor individuals are binding the available vWf to promote adhesion and subsequent platelet aggregation within the microvasculature. This in turn may deplete any available vWf for wound repair to take place leading to an increased risk of peptic ulceration and bleeding and eventually leading to an ulcer.

The fate of patients who undergo "preoperative" ERCP to clear known or suspected bile duct stones.

BACKGROUND: There is debate as to whether recurrent biliary complications are more common in patients who do not have elective cholecystectomy after endoscopic retrograde cholangiopancreatography (ERCP) management of common bile duct (CBD) stones. The aim of this study was to determine the fate of patients with intact gallbladders who have had CBD stones removed at ERCP, and to assess their risk of recurrent biliary symptoms. METHODS: We retrospectively identified all patients in our large tertiary center population with intact gallbladders who had an ERCP for CBD stones from December 1999 to March 2002. We determined which patients had subsequent elective cholecystectomy, and the outcomes of patients who did not have elective surgery. RESULTS: 309 patients had CBD stones at ERCP during the study period, of which 139 had intact gallbladders at the time of ERCP. Of these 139 patients 59 had subsequent elective cholecystectomy, 11 by open operation and 48 laparoscopically. Of these 139 patients, 27 had cholecystectomy planned; 47 patients were managed with a wait-and-see strategy, 30 of whom were poor surgical candidates. Of these 47 patients in whom a wait-and-see policy was adopted, 9 (19%) developed complications including recurrent pain and/or abnormal liver function tests (LFTs), recurrent biliary colic, and pancreatitis. Eight of these nine patients were from the poor surgical candidate group. Sphincterotomy had been performed at initial ERCP in all patients. CONCLUSIONS: Over half of our population of 139 patients with CBD stones at ERCP and intact gallbladders had actual or planned elective cholecystectomy. For those patients in whom a decision to wait-and-see was made, almost 20% developed complications. Elective cholecystectomy after a finding of choledocholithiasis is supported by many and is a common strategy in our experience. Recurrent biliary complications are relatively common in those who do not undergo elective cholecystectomy, especially those patients who represent a high operative risk.

The use of infliximab for treatment of hospitalized patients with acute severe ulcerative colitis.

BACKGROUND/AIM: The use of infliximab in severe ulcerative colitis (UC) is established; however, its role in severe acute UC requires clarification. The present multicentre case series evaluated infliximab in hospitalized patients with steroid-refractory severe UC. METHODS: Patients from six hospitals were retrospectively evaluated. Data collection included demographics, duration of disease and previous treatments. The primary end point was response to in-hospital infliximab; defined as discharge without colectomy. RESULTS: Twenty-one patients (median age 26 years) were admitted between May 2006 and May 2008 with severe UC requiring intravenous steroids and given infliximab (median time to infusion eight days). Sixteen (76%) patients were discharged home without colectomy; three of these underwent colectomy at a later date. Of the remaining 13 patients (62%), all but two did not require further courses of steroids; six patients had infliximab as a bridge to azathioprine and seven patients were maintained on regular infliximab. Five patients required in-hospital colectomy after the initial infliximab. CONCLUSIONS: In this real-life experience of infliximab in patients with steroid-refractory severe UC, infliximab appears to be a viable rescue therapy. The majority of patients were discharged without surgery and 62% maintained response either as a bridge to azathioprine or maintenance infliximab.

Liver biochemistry abnormalities in a quaternary care lipid clinic database.

BACKGROUND: The metabolic syndrome and non-alcoholic fatty liver disease are increasing at alarming rates. AIMS: To determine the effect of HMG-CoA reductase inhibitors (statins) on elevated liver enzymes in patients with hyperlipidemia. PATIENTS: Patients with AST above 60 U/L prior to or during treatment with statin therapy at a quaternary care lipid clinic were reviewed. METHODS: A retrospective analysis was conducted. Patients were separated into two groups: Group 1--elevated AST prior to statin therapy; and Group 2--elevated AST during statin therapy. RESULTS: Forty six patients with one or more measurements of AST >60 U/L remained after exclusion criteria were applied. Ten of 13 (77%) group 1 patients had reduced AST levels after initiation of statin therapy. Thirty two of 33 patients (97%) in group 2 had transient AST elevations while on statin therapy; one patient had persistently elevated AST after initiation of treatment. There were no significant adverse events reported. CONCLUSION: Use of HMG-CoA reductase inhibitors in patients with elevated AST resulted in normalization of AST levels. HMG-CoA reductase inhibitors were safe in patients with mildly elevated AST. This may translate to use of HMG-CoA reductase inhibitors in diseases such as non-alcoholic fatty liver disease and non-alcoholic steatohepatitis.

Endoscopic ultrasound and computer tomography are inaccurate methods of classifying cystic pancreatic lesions.

BACKGROUND: Despite advances in imaging modalities, preoperative diagnosis of pancreatic cystic lesions remains difficult. AIM: To assess the accuracy of endoscopic ultrasound and computer tomography to preoperatively distinguish benign from potentially malignant and malignant pancreatic cystic lesions. METHODS: Photograph series obtained from endoscopic ultrasound examinations of 66 patients with cystic pancreatic lesions were blindly reviewed by three endoscopic ultrasonographers. Forty-one of those 66 patients also underwent a computer tomography scan at our institution, which was blindly reviewed by a single radiologist. Computer tomography and endoscopic ultrasound classification into benign and malignant and potentially malignant pancreatic cystic lesions was correlated with the final diagnosis, which was established by surgical pathology (n = 43), diagnostic fine needle aspiration (n = 13) or follow-up imaging (n = 10). Interobserver agreement was measured using kappa statistics. RESULTS: Endoscopic ultrasound classification by the three examiners into benign versus malignant or potentially malignant cystic lesions was correct in 65-67%. Interobserver agreement was 50%. Kappa values for pairs of endoscopic ultrasound examiners were 0.16, 0.43 and 0.53. Computer tomography classification was correct in 71% and in agreement with the endoscopic ultrasound classification in 56-61% (kappa 0.12 to 0.27). CONCLUSIONS: Endoscopic ultrasound and computer tomography cannot accurately distinguish between benign pancreatic cystic lesions and malignant or potentially malignant ones. There is poor-to-modest interobserver agreement in classifying these lesions.

Yield of endoscopic ultrasound-guided fine-needle aspiration of bile duct lesions.

BACKGROUND AND STUDY AIMS: It is still difficult to differentiate reliably between benign and malignant biliary tract lesions. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has added to the diagnostic power of EUS for other gastrointestinal tumors. A retrospective analysis of experience with FNA sampling of bile duct lesions was therefore carried out. PATIENTS AND METHODS: All EUS-FNA procedures for bile duct masses or strictures were analyzed at our tertiary referral center from May 2000 through October 2002. Data for EUS findings, the results of EUS-FNA, and tissue sampling at surgery were included. EUS-FNA procedures were carried out using a 22-gauge needle. An experienced cytopathologist was present during FNA in all but three cases. Clinical follow-up details were recorded when available for patients in whom a suitable diagnostic gold standard was not available for comparison. RESULTS: A total of 35 patients underwent EUS-FNA of bile duct lesions during the study period. There were no complications. Data for EUS-FNA of bile duct masses or strictures and tissue obtained at surgery were available for 23 patients. If positive cytology at surgical pathology is taken as the gold standard, EUS-FNA has a diagnostic yield for cancer of 100 % (if atypia/inconclusive findings in the FNA sample are regarded as benign). Eleven patients had a definite malignancy on surgical pathology. Of these 11 patients, five had a finding of malignancy on EUS-FNA, giving a sensitivity of 45 % (if FNA cytology reported as atypia/inconclusive is regarded as benign). Twelve patients had findings of no malignancy from tissue obtained at surgery. Of these 12 patients, nine had benign pathology and three had atypia/inconclusive findings in the EUS-FNA sample (specificity of 100 % if atypia/inconclusive findings are considered benign). A further 12 patients did not have surgical specimens for comparison with EUS-FNA results. Four patients had definite findings of malignancy on EUS-FNA alone, and one patient had FNA findings suspicious for malignancy. Seven patients had negative or equivocal EUS-FNA results. These 12 patients are described but excluded from further analysis, as a gold standard was not available for comparison. However, clinical follow-up data were available for eight of these 12 patients, and in each case the follow-up findings were compatible with previous benign or malignant EUS-FNA findings. CONCLUSIONS: The practice of EUS-FNA has improved the diagnostic yield of EUS. These results suggest that it is a safe and useful procedure for investigating biliary masses or strictures that have hitherto caused considerable diagnostic confusion, especially in patients with negative brush cytology findings. The possibility of false-negative findings remains, but core biopsy needles may improve the situation. The results of further studies are awaited.

Cyclooxygenase-2 expression in primary human colorectal cancers and bone marrow micrometastases.

BACKGROUND: Both the expressions of the inducible form of cyclooxygenase-2 and the presence of bone marrow micrometastases are poor prognostic markers in patients with colorectal carcinoma. AIMS: As cyclooxygenase-2 expression in these tumours is associated with increased metastatic potential in vitro, our objectives were to determine the relationship between cyclooxygenase-2 and haematogenous spread to bone marrow. PATIENTS AND METHODS: Thirty-two patients with resection of colorectal carcinoma were evaluated (median age: 69.5 years). Bone marrow was obtained from all patients from both iliac crests before manipulation of the primary tumour. The tumours were of varying stages at diagnosis (5 Dukes' A, 14 Dukes' B, 11 Dukes' C and 2 Dukes' D). Tumour sections were stained for cyclooxygenase-2 using the avidin-biotin immunohistochemical technique. Extent of staining was graded depending on the percentage of epithelial cells staining positive for cyclooxygenase-2. Micrometastases were detected by staining contaminant cytokeratin-18 positive cells in the bone marrow aspirates by either immunohistochemical (ARAAP) or immunological (flow cytometry) methods. Fisher's exact probability test was used to calculate statistical significance. RESULTS: Cyclooxygenase-2 expression in the primary tumour was detected in 72% of the patients. Twelve (38%) patients had bone marrow micrometastases detected by either immunohistochemistry or flow cytometry. Of the 12 patients who had bone marrow micrometastases, 8 tumours demonstrated increased expression of cyclooxygenase-2 protein (66.6%). In contrast, 9 out of the 20 (45%) patients in whom micrometastases were not detected expressed increased levels of cyclooxygenase-2 (P = 0.29). When dividing the patients into subgroups of localised (Dukes' A and B) versus disseminated (Dukes' C and D) disease, there was no further association between cyclooxygenase-2 expression and bone marrow micrometastases (P = 0.179 and 1.0). CONCLUSION: In this pilot study, there was no association between cyclooxygenase-2 expression and bone marrow micrometastases in patients with otherwise localised or disseminated disease.

Complications of pancreaticoduodenectomy after neoadjuvant chemoradiation in patients with and without preoperative biliary drainage.

BACKGROUND: It has been suggested that preoperative biliary drainage increases the risk of infectious complications of pancreaticoduodenectomy. AIMS: The aim of this study was to assess complications related to biliary stents/drains and postoperative morbidity in patients undergoing neoadjuvant chemoradiotherapy for periampullary cancer. PATIENTS: One hundred and eighty-four patients with periampullary neoplasms were prospectively selected for neoadjuvant external beam radiation therapy and 5-fluorouracil-based chemotherapy between 1995 and 2002. METHODS: The data were retrospectively completed and analysed with respect to biliary drainage, efficacy and complications of endoscopic biliary stents and postoperative morbidity. Patients who had undergone a surgical biliary bypass were excluded. RESULTS: Data were completed in 168 patients. One hundred and nineteen patients were treated with endoscopic biliary stents, 18 patients had a percutaneous biliary drain and 31 patients did not require biliary drainage. Hospitalisation for stent-related complications was necessary in 15% of the patients with endoscopic biliary stents. Seventy-two patients underwent pancreaticoduodenectomy. There was no significant difference in the rate of wound infections, intra-abdominal abscesses and overall complications between the groups with and without preoperative biliary drainage. CONCLUSIONS: Postoperative infectious complications are common in patients both with and without preoperative biliary drainage. A statistically significant difference in complication rates was not observed between these groups.

Combined terminal ileoscopy and biopsy is superior to small bowel follow-through in detecting terminal ileal pathology.

BACKGROUND: Several studies have compared small bowel barium examination with ileoscopy in assessment of terminal ileal disease. Some suggest that ileoscopy is superior in detection of terminal ileal disease whereas others suggest similar disease detection rates for both techniques. AIMS: The aim of this retrospective study was to determine if small bowel follow-through and ileoscopy with terminal ileum biopsy compare favourably at detecting pathology in the terminal ileum. PATIENTS AND METHODS: All colonoscopies with terminal ileoscopy performed over a 16-month period were reviewed. We determined which of these patients had also had small bowel follow-through studies within 2 weeks of colonoscopy. We compared the diagnoses of terminal ileum pathology using ileoscopy with terminal ileal biopsy versus small bowel follow-through. RESULTS: Forty-six patients had both terminal ileoscopy with biopsy and small bowel follow-through. In 19 patients, the terminal ileum was abnormal at ileoscopy and/or biopsy but normal at small bowel follow-through. In 27 patients, terminal ileum findings at small bowel follow-through and at ileoscopy and/or biopsy were compatible. CONCLUSIONS: This study suggests that examination of the terminal ileum by combined ileoscopy and biopsy may be superior to small bowel follow-through at detecting terminal ileal pathology. In our series, many patients received effective treatment that otherwise would not have been offered based on the small bowel follow-through results alone. Using combined ileoscopy and biopsy, microscopic inflammatory changes, otherwise missed without biopsy, can be detected. Retrograde ileoscopy is recommended in patients with a clinical history of organic diarrhoea and/or abdominal pain even in the presence of a normal small bowel follow-through.

Helicobacter pylori induces cyclooxygenase-1 and cyclooxygenase-2 expression in vascular endothelial cells.

BACKGROUND: Helicobacter pylori induces cyclooxygenase activity in the stomach, although the COX isoform and cellular source are unclear. A potential source is the vascular endothelial cell, which plays a role in regulating mucosal blood flow and inflammatory cell infiltration. METHODS: We examined the effect of four strains (toxigenic and non-toxigenic) of H. pylori on COX isoform expression in vascular endothelial cells. Prostaglandin synthesis was measured by enzyme immunoassay and COX isozyme expression determined by Western blot and RT-PCR. Gene induction was examined using 5' deletion constructs of the COX-1 and COX-2 promoters coupled with luciferase. RESULTS: All H. pylori strains induced prostaglandin generation and expression of both COX-1 and COX-2 in HUVEC, although this was most pronounced with the highly toxigenic strain H. pylori 60190. Treatment of the cells with selective COX inhibitors demonstrated that COX-1 was predominantly responsible for the enhanced generation of prostacyclin induced by H. pylori 60190. Similar results were seen with H. pylori broth culture filtrates, suggesting that a secreted product was responsible. Induction of COX-2 reflected both enhanced gene expression and stabilization of the mRNA. CONCLUSIONS: H. pylori increased both COX-1 and COX-2 activity in vascular endothelial cells. This increased generation of endothelial cell prostacyclin may play a role in modulating mucosal blood flow, platelet function and inflammatory cell infiltration in response to H. pylori infection. The regulation of COX-1 at the transcriptional level by H. pylori described in this study is a novel finding and calls into question the traditional description of COX-1 as a purely constitutive, housekeeping gene.

Colonoscopy or barium enema for population colorectal cancer screening?

There is good evidence from faecal occult blood testing trials that detection and removal of non-advanced colorectal neoplasms can achieve a reduction in colorectal cancer mortality. Both colonoscopy and barium enema have potential advantages and disadvantages if implemented for population screening. The relative merits of each are discussed.

Pancreatitis.

In the past decade, our understanding of the genetic basis, pathogenesis, and natural history of pancreatitis has grown strikingly. In severe acute pancreatitis, intensive medical support and non-surgical intervention for complications keeps patients alive; surgical drainage (necrosectomy) is reserved for patients with infected necrosis for whom supportive measures have failed. Enteral feeding has largely replaced the parenteral route; controversy remains with respect to use of prophylactic antibiotics. Although gene therapy for chronic pancreatitis is years away, our understanding of the roles of gene mutations in hereditary and sporadic pancreatitis offers tantalising clues about the disorder's pathogenesis. The division between acute and chronic pancreatitis has always been blurred: now, genetics of the disorder suggest a continuous range of disease rather than two separate entities. With recognition of pancreatic intraepithelial neoplasia, we see that chronic pancreatitis is a premalignant disorder in some patients. Magnetic resonance cholangiopancreatography and endoscopic ultrasound are destined to replace endoscopic retrograde cholangiopancreatography for many diagnostic indications in pancreatic disease.

Effect of H. pylori infection on the expression of cyclooxygenase-2 in human gastric mucosa.

Cyclooxygenase-1 is the primary isoform responsible for the production of cytoprotective prostaglandins (PGE(2) and PGI(2)) in the stomach. In contrast COX-2 is induced at the sites of inflammation. Using Helicobacter pylori infection as a model of inflammation, this study was designed to evaluate the effects of H. pylori infection on prostanoid synthesis and expression of COX-2 in human gastric mucosa. Prostaglandin (PGE(2)) and prostacyclin (PGI(2)) synthesis in gastric biopsies obtained from 21 patients undergoing diagnostic endoscopy, were determined. H. pylori was detected by CLO test, histology and culture. Biopsy samples were incubated either with NS-398, selective COX-2 inhibitor or aspirin. Samples were also treated with endotoxin (LPS) in order to induce COX-2 expression. Tissue was also analysed for COX-2 expression in vivo by immunohistochemistry. In 15 out of 21 patients, H. pylori was detected by at least two of the three methods. Higher levels of PGE(2) and PGI(2) were seen in patients infected with H. pylori (191+/-30 and 245+/-88ng/mg protein, respectively) compared with non-infected patients (77+/-17 and 120+/-36ng/mg protein, respectively). There was significant inhibition of PGE(2) and PGI(2) with aspirin in both H. pylori infected (28+/-6.6 and 53+/-43ng/mg, respectively) and in non-infected patients (16+/-7 and 12.5+/-3.5ng/mg protein, respectively). However, NS-398 and LPS did not alter prostaglandin function significantly. Immunohistochemistry in all patients irrespective of Hp status demonstrated expression of COX-2.Lower concentration of constitutive expression of COX-2 was detected in human gastric mucosa by immunohistochemistry, however, H. pylori infection failed to induce COX-2 protein. In addition, increased prostaglandin synthesis in Hp-infected patients appears to be COX-1 mediated rather than COX-2. Furthermore, failure of endotoxaemia-treated sample to produce more PGE(2) in the face of enhanced COX-2 expression in gastric mucosa further suggests that increased prostanoids in human gastric stomach are COX-1 mediated.

A prospective analysis of inpatient consultations to a gastroenterology service.

The provision of a formal consultation service for inpatients between subspecialists is little studied. We prospectively surveyed the pattern of inpatient consultations from hospital-based generalists and surgeons to the gastroenterology (GI) service for inpatients in a large urban teaching hospital over a 5 month period. There are two GI consultants/attendings and five GI registrars/fellows on the service. A formal consultation is made by the requesting team to the GI service using the hospital computer network. All referrals over a 5 month period were prospectively analysed. 242 consecutive inpatient referrals were sent to the GI service over 5 months. Average age was 56 years, 48.8% males. 32 consultants/attendings from other disciplines sent referrals. Most patients were seen within one working day. Urgent referrals were seen without delay. The commonest reasons for referral were abdominal pain (15.8%), percutaneous endoscopic gastrostomy (PEG) tube insertion (13.6%), diarrhoea (12.8%), abnormal liver blood tests (10%), nausea and vomiting (8.2%), anaemia (6.2%), and melaena (4.9%). Iatrogenic diseases accounted for 6.2% of consultations. Ongoing patient care was assumed by the GI team in 9.5% of referrals. 15.3% required a second consultation visit before discharge. 22.7% of referrals were followed in the GI outpatients' clinic after discharge. 51.2% underwent an endoscopic procedure. 13.6% of referrals were for PEG tube insertion. A quarter of these were considered unsuitable for immediate PEG tube insertion. Subspecialty consultation provides an expert opinion, encourages discussion and learning, and improves patient care. In our experience, the provision of specialist advice and reassurance often speeded up a patient's work-up and expedited discharge. However, evaluating referral patients and subsequently providing ongoing inpatient and outpatient care and provision of endoscopy for these referrals contributes significantly to the workload of the GI service.

Stimulation of adhesion molecule expression by Helicobacter pylori and increased neutrophil adhesion to human umbilical vein endothelial cells.

Helicobacter pylori upregulates endothelial adhesion molecules but the pattern is unclear. Human umbilical vein endothelial cells (HUVEC) were exposed to control medium or H. pylori 60190. Binding of monoclonal antibodies against P-selectin, E-selectin, vascular adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) was determined using enzyme-linked immunosorbent assay. Binding of polymorphonuclear leukocytes to HUVEC was determined on cells exposed as above. After 6 h exposure to H. pylori, there were 30%, 124%, 167% and 100% increases in P-selectin, E-selectin, VCAM-1 and ICAM-1 levels and a 400% increase in polymorphonuclear leukocyte adhesion in HUVEC exposed to H. pylori. Effects of incubation for other intervals between 0 and 18 h are also described. H. pylori exerts some of its effects on gastric mucosa via gastric vasculature. This study gives insight into the pattern of H. pylori-associated endothelial adhesion molecule upregulation.

Hepatitis C infection in plasmapheresis donors: an overlooked risk factor for transmission?

Hepatitis C virus infection is the leading cause of chronic liver disease worldwide and puts significant burden on health resources. Traditionally, risk factors are well recognized. Despite this, a significant percentage of people infected with hepatitis C have no identifiable mode of transmission. However, it is known that a significant number of donors at plasmapheresis have positive hepatitis C serology, thereby potentially contaminating the equipment and putting both donors and recipients at risk. Here, we describe two patients who acquired hepatitis C infection following voluntary donation at plasmapheresis abroad and suggest that this is an unusual and overlooked mode of transmission.