Gallstone pancreatitis--who really needs an ERCP?
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Acute Disease↗
Biomedical subjects
M F Byrne
Publications and source records attributed to M F Byrne.
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.
Adult↗
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.
Adolescent↗
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.
Aged↗
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.
Adult↗
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.
Aged↗
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.
Acute 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.
6-Ketoprostaglandin F1 alpha↗
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.
Barium Sulfate↗
Predicting the likelihood of therapeutic ERCP. A suggested 'model' to limit the number of purely diagnostic ERCPs.
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Cholangiopancreatography, Endoscopic Retrograde↗
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.
Blotting, Western↗
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.
Adolescent↗
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.
Cell Adhesion↗
Successful endoscopic management of subacute intestinal obstruction presenting 3 years after lodgement of a coin in the duodenal cap.
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Duodenum↗
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.
Adult↗
Assessment of Crohn's disease activity by Doppler sonography of the superior mesenteric artery, clinical evaluation and the Crohn's disease activity index: a prospective study.
AIM: Recent data have shown that superior mesenteric artery (SMA) flow rates are significantly increased in active Crohn's disease, suggesting that SMA flow may be a useful, non-invasive index of disease activity. The aim of this prospective study was to evaluate the use of SMA Doppler sonography as an indicator of Crohn's disease activity and to compare with clinical evaluation and the Crohn's disease activity index (CDAI). MATERIALS AND METHODS: Patients with active Crohn's (n = 19), inactive Crohn's (n = 17) and control subjects (n = 17) were evaluated. Categorization of disease activity was based on a reference standard. CDAI scores were also calculated independently. The SMA flow parameters evaluated were resistive index, pulsatility index, end diastolic velocity, peak systolic velocity, time averaged maximum velocity, cross-sectional area and maximum flow volume. RESULTS: Using a three-group ANOVA for each of peak systolic velocity (PSV) (P = 0.01), end-diastolic velocity (EDV) (P = 0.04), pulsatility index (PI) (P = 0.003), time-averaged maximum velocity (TAMV) (P = 0.05), and maximum flow volume (TAMV.CSA) (P = 0.01), there was a significant effect of group. Using post-hoc tests, only EDV (P = 0.01), TAMV (P = 0.02) and TAMV.CSA (P = 0.003) were significantly different between active and inactive Crohn's disease, though with considerable overlap of values for EDV and TAMV. The mean CDAI scores were significantly different between patients with active Crohn's (287) and inactive Crohn's (71) (P = 0.0001) and correlated well with the reference standard. CONCLUSION: Only three of several parameters previously described as allowing Crohn's disease activity assessment actually did so in our study. However, for two of these parameters (EDV, TAMV), there was overlap between the measurements in the active and inactive groups, thus limiting the ability to discriminate disease activity in practice. The degree of overlap for maximum flow volume (TAMV.CSA) between active and inactive disease was considerably less and this parameter may be more discriminatory of disease activity. On the other hand, we found CDAI scores to be accurate in disease categorization. We agree that there appear to be hyperdynamic changes in active Crohn's disease but suggest that Doppler ultrasound assessment does not reliably assess disease activity in routine clinical practice.
Adult↗
Formulary management of proton pump inhibitors.
The management of dyspepsia has been radically altered by the discovery of the role of Helicobacter pylori and the advent of proton pump inhibitors (PPIs). The use of PPIs alone as antisecretory agents and as part of triple therapy regimens for H. pylori eradication accounts for a significant percentage of any healthcare system's drug budget. Thus, it is important to take into account a variety of factors when devising a formulary and considering which PPIs to include. Consideration of 3 factors are particularly crucial in this process, namely therapeutic efficacy, tolerability and cost but several other clinical and economic parameters should also be considered. The mechanisms of action of all 4 PPIs currently available (omeprazole, lansoprazole, pantoprazole and rabeprazole) are very similar, with any small differences in pharmacological properties unlikely to be of clinical significance. Therapeutic efficacy in patients with acute reflux oesophagitis is again very similar for all 4 PPIs at their standard dosages; all agents are superior to H2-antagonists. Data on maintenance therapy for reflux oesophagitis also suggest similar efficacy for omeprazole and lansoprazole; data on pantoprazole and rabeprazole are awaited. For the treatment of H. pylori-related ulcers, the consensus at present is for PPI-based triple therapy. Again, all PPIs seem equally efficacious for this indication but pantoprazole and rabeprazole have yet to receive licences for H. pylori eradication therapy (HPET) in most countries. Drug tolerability is another critical issue to consider in formulary inclusion decisions. As a class, the PPIs are well tolerated. Minor drug interactions are reported for omeprazole, lansoprazole and rabeprazole but not for pantoprazole. However, whether or not this is significant in clinical practice is open to debate. Most of the pharmacoeconomic data in these indicators, to date, relate to omeprazole and, to a lesser extent, lansoprazole. Certainly, the studies on these 2 drugs confirm the superior cost effectiveness of PPIs over H2-antagonists in the treatment of reflux oesophagitis and peptic ulceration in both the short and long-terms. Although data are awaited, there is no reason to suggest that this will be any different for pantoprazole and rabeprazole. PPI-based triple therapy for H. pylori eradication appears to be the most cost-effective treatment option for H. pylori-related peptic ulcer disease. It is clear that PPIs are superior in several regards to previously used medications in the treatment of dyspepsia. Which PPI(s) to include in a particular formulary is a more difficult decision. On review of many criteria involved in formulary decisions, differences between the individual PPIs appear minimal. The relative acquisition costs of the PPIs vary nationally and internationally and this may be a critical factor in formulary inclusion decisions. However, one should not ignore non-economic factors, as these should form the basis of any sound drug policies.
Anti-Ulcer Agents↗
Food intake in baboons: effects of diazepam.
Food intake of four adult male baboons (Papio c. anubis) was monitored during daily experimental sessions lasting 22 h. Food was available under a two-component operant schedule. Following completion of the first "procurement component" response requirement, access to food, i.e., a meal, became available under the second "consumption component" during which each response produced a 1-g food pellet. After a 10-min interval in which no response occurred, the consumption component was terminated. The effects of diazepam (DZP: 0.12-4.0 mg/kg) were determined by having the baboons drink a dose on Tuesdays and Fridays 45-60 min before the daily session. DZP produced dose-dependent increases in food intake in three of the four baboons. DZP increased the size of the first two meals and total duration of eating, but had no effect on eating rate or the number of meals within a session. The effect of DZP on the topography of feeding of baboons differs from previous reports on the effects of benzodiazepines on the topography of feeding in rodents. This suggests that species or procedural differences influence the effects of DZP on food intake.
Animals↗