The Impact of SARS-COV-2 on two Colorectal Cancer screening centres.

BowelScreen paused activity in March 2020 to prioritise the response to the COVID-19 pandemic. The aim of this study was to examine the impact of this delay. Cases affected by the pause and subsequently completed were compared to the same period in 2019. Endoscopy and histology data were obtained from the BowelScreen database and patient records. One-hundred and seven colonoscopies were performed during the study period. This compared with 224 colonoscopies during the same period in 2019. Median lead time to colonoscopy in 2020 was 74 days compared to 34 days in 2019. Adenoma detection rate was 59% for both periods. Advanced adenoma and cancer detection rates were similar in both periods. While there was a marked reduction in activity and significant delays for BowelScreen patients during the first wave of the COVID-19 pandemic, this does not appear to have impacted on clinical outcomes for patients who attended for screening colonoscopy.

National Survey of CT Colonography Practice in Ireland.

CT Colonography was first introduced to Ireland in 1999. Our aim of this study is to review current CT Colonography practices in the Republic of Ireland. A questionnaire on CT Colonography practice was sent to all non-maternity adult radiology departments in the Republic of Ireland with a CT scanner. The results are interpreted in the context of the recommendations on CT Colonography quality standards as published by the European Society of Gastrointestinal and Abdominal Radiology (ESGAR) consensus statement in the journal of European Radiology in 2013. Thirty centres provide CT Colonography; 21 of which responded (70%). Each centre performs median 90 studies per year; the majority follow accepted patient preparation and image acquisition protocols. Seventy-six percent of the centres repsonded that the majority of patients imaged are symptomatic. Of the 51 consultant radiologists reading CT Colonography, 37 (73%) have attended a CT Colonography course. In 17 (81%) of the centres the studies are single read although 81% of the centres have access to a second radiologist's opinion. Fourteen (67%) of the centres reported limited access to CT scanner time as the major limiting factor to expanding their service. CT Colonography is widely available in Ireland and is largely performed in accordance with European recommendations.

Prognostic significance of neuroepithelial transforming gene 1 in adenocarcinoma of the oesophagogastric junction.

BACKGROUND: Neuroepithelial transforming gene 1 (NET1) mediates tumour invasion and metastasis in a number of cancers, including gastric adenocarcinoma. It is an indicator of poor prognosis in breast cancer and glioma. This study examined NET1 expression and its prognostic significance in patients with adenocarcinoma of the oesophagogastric junction (AOG). METHODS: NET1 expression was measured by immunohistochemistry in a tissue microarray, constructed from biobanked tissue collected over a 10-year interval, and linked to a prospectively maintained clinical database. RESULTS: Using the Siewert classification for AOG, type I tumours expressed significantly higher levels of NET1, with lowest expression in type III and intermediate levels in type II (P = 0.001). In patients with AOG type III, NET1-positive patients were more likely to be female (P = 0.043), have advanced stage cancer (P = 0.035), had a higher number of transmural cancers (P = 0.006) and had a significantly higher median number of positive lymph nodes (P = 0.029). In this subgroup, NET1-positive patients had worse median overall (15 versus 23 months; P = 0·025) and disease-free (11 versus 36 per cent; P = 0.025) survival compared with NET1-negative patients. CONCLUSION: Although existing data show differences in clinical and prognostic indices across AOG subtypes, there are no studies showing differences in tumour biology. These data suggest NET1, a known mediator of an aggressive tumour phenotype in a number of gastrointestinal cancers, is expressed differentially across AOG subtypes and may be of prognostic significance in the clinical management of this condition.

Knowledge of the indications for endoscopic ultrasound (EUS) among gastroenterologists and non-gastroenterologists.

The level of awareness among Irish doctors of the appropriate indications for endoscopic ultrasound (EUS) is unknown. This study assessed knowledge of EUS indications among consultants and trainees in 3 Irish teaching hospitals. A questionnaire was designed to test knowledge of EUS indications in 4 organ systems: oesophagus, gastroduodenum, hepatopancreatobiliary system and colorectum. The questionnaire was distributed to consultants and trainees (both gastroenterology and non-gastroenterology) in 3 major Irish teaching hospitals. The survey was distributed to 86 doctors, all of whom replied: 18 consultants (11 gastroenterologists,) 40 registrars (28 gastroenterology) and 26 SHOs/interns. Knowledge of appropriate EUS indications was best among consultant gastroenterologists (82%) and GI registrars (79%), compared with non-GI consultants (74%), non-GI registrars (72%) and SHOs/interns (68%). Among gastroenterologists and GI registrars, knowledge levels of oesophageal (89%, 85%) and gastroduodenal applications (92%, 95%) was best while knowledge of colorectal applications (75%, 71%) was poorest. GI consultants and GI registrars display good knowledge of appropriate EUS indications although their knowledge of applications for colorectal disease is poorest. Future studies focusing on the education of non-gastroenterologists of the role of EUS would be helpful.

NET1-mediated RhoA activation facilitates lysophosphatidic acid-induced cell migration and invasion in gastric cancer.

The most lethal aspects of gastric adenocarcinoma (GA) are its invasive and metastatic properties. This aggressive phenotype remains poorly understood. We have recently identified neuroepithelial cell transforming gene 1 (NET1), a guanine exchange factor (GEF), as a novel GA-associated gene. Neuroepithelial cell transforming gene 1 expression is enhanced in GA and it is of functional importance in cell invasion. In this study, we demonstrate the activity of NET1 in driving cytoskeletal rearrangement, a key pathological mechanism in gastric tumour cell migration and invasion. Neuroepithelial cell transforming gene 1 expression was increased 10-fold in response to treatment with lysophosphatidic acid (LPA), resulting in an increase in active levels of RhoA and a 2-fold increase in cell invasion. Lysophosphatidic acid-induced cell invasion and migration were significantly inhibited using either NET1 siRNA or a RhoA inhibitor (C3 exoenzyme), thus indicating the activity of both NET1 and RhoA in gastric cancer progression. Furthermore, LPA-induced invasion and migration were also significantly reduced in the presence of cytochalasin D, an inhibitor of cytoskeletal rearrangements. Neuroepithelial cell transforming gene 1 knockdown resulted in AGS cell rounding and a loss of actin filament organisation, demonstrating the function of NET1 in actin organisation. These data highlight the importance of NET1 as a driver of tumour cell invasion, an activity mediated by RhoA activation and cytoskeletal reorganisation.

Endoscopic pneumatic dilation versus botulinum toxin injection in the management of primary achalasia.

BACKGROUND: Achalasia is an oesophageal motility disorder, of unknown cause, which results in increased lower oesophageal sphincter (LOS) tone and symptoms of difficulty swallowing. Treatments are aimed at reducing the LOS tone. Current endoscopic therapeutic options include pneumatic dilation (PD) or botulinum toxin injection (BTX). OBJECTIVES: The objective of this review was to compare the efficacy and safety of two endoscopic treatments, pneumatic dilatation and intrasphincteric botulinum toxin injection, in the treatment of oesophageal achalasia. SEARCH STRATEGY: We searched the Cochrane Upper Gastrointestinal and Pancreatic Diseases Group trials register, the Cochrane Central Register of Controlled Trials, MEDLINE (1966 to Oct 2005), EMBASE (1980 to Oct 2005), BIOSIS (1969 to Oct 2005) and Web of Science (1955 to October 2005). We also searched abstracts from significant Gastroenterology meetings (DDW, UEGW) and reference lists of articles. SELECTION CRITERIA: Randomised controlled trials comparing PD to BTX injection in patients with primary achalasia. DATA COLLECTION AND ANALYSIS: Two review authors independently performed quality assessment and data extraction. MAIN RESULTS: Six studies involving 178 participants were included. Two studies were excluded from the meta-analysis of remission rates on the basis of clinical heterogeneity of the initial endoscopic protocols. There was no significant difference in remission between PD or BTX treatment within four weeks of the initial intervention, with a relative risk of remission of 1.15 (95% CI 0.95 to 1.38, P = 0.39) for PD compared to BTX. There was also no significant difference in the mean oesophageal pressures between the treatment groups; weighted mean difference for PD of -0.77 (95% CI -2.44 to 0.91, P = 0.37). Data on remission rates following the initial endoscopic treatment was available for two studies at six months and three studies at 12 months. At six months 22 of 29 PD participants were in remission compared to 7 of 27 in the BTX group, giving a relative risk of 2.90 (95% CI 1.48 to 5.67, P = 0.002); whilst at 12 months 33 of 47 PD participants were in remission compared to 11 of 43 BTX participants, relative risk of 2.67 (95% CI 1.58 to 4.52, P = 0.0002). No serious adverse outcomes occurred in participants receiving BTX, whilst PD was complicated by perforation in three cases. AUTHORS' CONCLUSIONS: The results of this meta-analysis would suggest that PD is the more effective endoscopic treatment in the long term (greater than six months) for patients with achalasia.

Hepatic arterial and portal venous components of liver blood flow: a dynamic scintigraphic study.

Assessment of liver hemodynamics can be obtained by analysis of first pass flow studies through the liver and spleen using 99mTc compounds which are not actually trapped by these organs. This study examines new and existing methods for determining the relevant contribution made by the hepatic artery and portal vein to total liver blood flow, from these first pass studies. Eighty-two studies were performed in 56 patients with both normal and abnormal liver function. Using region of interest analysis, time-activity curves were obtained for the lungs, liver, spleen, and left kidney. These curves were analyzed by four different methods. Two of these methods are based upon measurement of the slopes of the uptake and washout curves from the liver and spleen and the other two methods employ deconvolution analysis to permit area measurement under the deconvolved curves as an indicator of blood flow. All four methods showed a small intraobserver variation after reanalysis. In 11 patients who underwent repeat studies, the correlation between the deconvolution based methods (r = 0.79-0.89) was significantly better than that for the slope based methods (r = 0.55-0.58). The deconvolution based methods provided the most significant separation between normals and patients with various liver disorders and would appear to be the most suitable techniques for monitoring the effects of various drugs and surgical procedures on the relative arterial/portal contribution to hepatic blood flow.

Mechanisms and consequences of portal hypertension.

Portal hypertension is characterised by alterations in the splanchnic and systemic circulation resulting in the development of portosystemic collateral channels, the most important of which are found in the lower oesophagus and stomach. The major clinical complication of gastro-oesophageal varices is bleeding and over the last decade there has been considerable interest in the pharmacological management of this complication. The factors currently implicated in the development of gastro-oesophageal varices in patients with cirrhosis include a) increased portal vascular resistance, b) splanchnic and systemic vasodilatation and c) changes in the lower oesophageal venous anatomy [palisade and perforating venous zones]. In a patient with gastrointestinal bleeding, endoscopic examination of the upper gastrointestinal tract will confirm the diagnosis of portal hypertension by confirming the presence of gastro-oesophageal varices. Cirrhosis is the most common aetiological factor for gastro-oesophageal varices, but imaging techniques, including Doppler ultrasound, computerised tomography and venous phase angiography, may be required to exclude extrahepatic portal venous obstruction from the differential diagnosis. Although the pathogenesis of variceal rupture remains unclear, several risk factors for variceal haemorrhage have been identified, including a) increased size, b) high intravariceal-portal pressure, c) increased varix wall tension characterised by the presence of red spots observed at endoscopy (particularly in large varices since wall tension is related to variceal size), and d) poor liver function. Although oesophagitis may be observed at endoscopy, an erosive mechanism is no longer considered to be of pathogenic significance. A high portal pressure in the immediate postbleeding period is now recognised as predictive of rebleeding. Periodic elevations in intravariceal pressure, associated with the release of enhanced endogenous vasoactive compounds, or beta-adrenergic-mediated stress-related increases in portal pressure, may contribute to the rupture mechanism. Consequently, portal hypertension is now being more widely considered as a multiorgan disorder associated with changes in blood flow within both systemic and splanchnic vascular beds. This article reviews the factors currently implicated in the development of portal hypertension and the approach to diagnosis. The pathogenesis of variceal bleeding will also be considered.

The effect of calcium channel blockade with nifedipine on splanchnic and systemic haemodynamics in cirrhosis.

The splanchnic and systemic haemodynamic effects of a single sublingual dose of nifedipine (slow calcium channel blocker) in nine patients with cirrhosis of the liver and portal hypertension were studied. Nifedipine produced a significant reduction in the mean arterial blood pressure (98 +/- 5.3 vs. 86 +/- 5 mmHg, P less than 0.05) but did not alter the mean heart rate, portal venous pressure or total liver blood flow. The systemic antihypertensive effect of nifedipine can be achieved without altering liver blood-flow in patients with chronic liver disease and portal hypertension.

Primary hepatic lymphoma in a man with chronic hepatitis C.

We report the case of a middle-aged man who presented de novo with abdominal pain and hepatomegaly and was found to have positive serology for hepatitis C and subsequently a primary hepatic lymphoma. An increased incidence of primary hepatocellular cancer is well characterized in both cirrhotic and non-cirrhotic cases of chronic hepatitis C. The relationship between chronic hepatitis C and primary hepatic lymphoma remains obscure. It has been established that hepatitis C can sustain the clonal B-cell expansion that occurs in associated cryoglobulinaemia, and hepatitis C RNA has been detected within extrahepatic lymphoma tissue. Viral aetiologies for lymphoma are well characterized, such as Epstein-Barr virus (EBV) and human T-cell leukaemia virus (HTLV) I and II. Existing models of chronic infection causing lymphoma within the gastrointestinal tract include that of Helicobacter pylori and mucosa-associated lymphoid tumour of the stomach. Given the relatively low frequency of occurrence it may be prudent to perform a retrospective analysis on past cases of primary hepatic lymphoma in order to determine whether or not hepatitis C was present.

The detection of cytokeratins in lymph nodes of Duke's B colorectal cancer subjects predicts a poor outcome.

OBJECTIVES: The objectives of this study were to examine the frequency of lymph node micrometastases detected by keratin immunohistochemistry and their relationship with survival behaviour. METHODS: A total of 133 consecutive patients staged as Duke's B, who had curative resection for colorectal cancer (CRC), comprised the study population. Patients who had died of a non-CRC-related cause or who became lost to follow-up were excluded, resulting in an amended population of 100. Study end-points were defined as disease-free survival of 5 years or CRC-related death. Paraffin-embedded lymph node sections were stained with a commercial cytokeratin antibody using a standard avidin-biotin technique. RESULTS: One quarter of subjects had micrometastases. Fifty-six per cent of subjects with positive lymph nodes had an adverse outcome, compared with 11% of subjects with negative nodes. A highly significant association was found between lymph node cytokeratin expression and mortality in both the univariate (log rank P = 0.0001) and multivariate (Cox proportional hazards P = 0.0123) analysis. CONCLUSIONS: Lymph node micrometastases detected by this inexpensive and simple technique are significantly associated with mortality in Duke's B CRC. This technique may be used to select patients for adjuvant chemotherapy.

Effects of chronic treatment with amiodarone on hepatic demethylation and cytochrome P450.

The effect of chronic treatment with amiodarone on hepatic oxidative metabolism using an in-vivo [14C]aminopyrine breath test and on hepatic cytochrome P450 was examined in Wistar rats. Aminopyrine demethylation was significantly impaired but returned to pretreatment values following amiodarone for 4 weeks. In contrast the levels of cytochrome P450 were significantly depressed during treatment and at 4 weeks following treatment. While an inhibitory effect on oxidative metabolism may explain the reported drug interactions with amiodarone, the discrepancy between its in-vivo effects and cytochrome P450 levels may suggest the development of 'compensatory' extra-hepatic site of drug metabolism.

Immunohistochemical detection of mutant p53 protein in regional lymph nodes is associated with adverse outcome in stage II colorectal cancer.

Epidemiologic data identifies a cohort of Duke's B (CRC) patients whose survival more closely matches that of Duke's C. Lymph node micrometastases may account for this discrepancy. Lymph node expression of mutant p53 protein (Mp53P) has been linked to a reduction in survival in Japanese Duke's B patients. We aimed to determine the significance of nodal p53 expression in European Duke's B patients using immunohistochemistry. The study comprised 134 consecutive patients who had resections for CRC between 1984 and 1991. End points were 5 year disease free survival or CRC related death. Thirty-four subjects did not achieve end points and were excluded. We examined tumour and nodal sections for Mp53P by immunohistochemistry and correlated this with survival using a Kaplan-Meier (KM) and a Cox Proportional hazards model (CPHT). Five year survival was 73%. Fifty-eight percent of primary tumours expressed Mp53P. Tumour p53 expression did modulate survival behavior. Twenty-six percent of subjects' lymph nodes expressed Mp53P. Fifty-three per cent of those with positive and 17% of those with negative lymph nodes died of recurrence. The relative risk for nodal Mp53P expression was 3.1. There was a significant univariate relationship between lymph node p53 expression and mortality. (Log Rank p = 0.028). Multivariate analysis also showed a significant relationship with mortality. (CPHT p = .03). We conclude that lymph node expression of Mp53P is associated with increased mortality in Duke's B CRC.

Determination of the ketone body ratio in fulminant hepatic failure.

The ratio of acetoacetate to beta-hydroxybutyrate, the ketone body ratio, was measured in arterial blood from 28 patients with fulminant hepatic failure as an index of the hepatic energy charge. The ketone body ratio was significantly reduced in the total group of patients with fulminant hepatic failure as compared with control subjects (0.27 +/- 0.03 SE as compared with 0.48 +/- 0.03; p less than 0.001). Patients who survived had significantly less reduction of the ketone body ratio on admission than those who died (0.39 +/- 0.06, n = 10 as compared with 0.20 +/- 0.02, n = 19; p less than 0.02). In seven patients who died, in whom ketone body ratio was measured less than 12 hours before death there was a significant decrease in ketone body ratio as compared with that on admission (0.24 +/- 0.05 to 0.15 +/- 0.04; p less than 0.05). In contrast, in seven patients who survived there was no significant change in ketone body ratio when measured within 12 hours of regaining consciousness as compared with the figures on admission. Measurement of arterial ketone body ratio may give an indication of prognosis, and may be of use in testing the efficacy of treatments which aim to enhance hepatic regeneration or to remove toxic substances that may reduce the hepatic energy charge.

Palliative stenting of recurrent malignancy at gastrojejunostomy anastomotic sites.

BACKGROUND: Surgical bypass procedures often provide excellent palliation in cases of malignant gastric outlet obstruction. Not uncommonly outlet obstruction can recur due to tumour involvement of the gastroenterostomy site. A further surgical procedure may not be feasible in these circumstances. AIMS: To report on the successful use of expandable metal stents in two such cases.

Endoscopic management of common duct stones with laparoscopic cholecystectomy.

In the first year from October 1990 since starting the procedure 65 laparoscopic cholecystectomies were carried out on one surgical service. There were 4 planned open cholecystectomies and 8 laparoscopic procedures converted during the same period: 7 of these were in the first 3 months with only 1 of the last 53 being opened. Surgery was carried out during the same admission in 22 patients presenting as emergencies: acute cholecystitis (9), colic (6), pancreatitis (3), jaundice (4). Two patients had later laparotomies for complications; one patient bled from the umbilical stab and with ongoing peritonism had a pelvic haematoma drained on day 5 and a second was opened following a bile leak caused by a displaced cystic duct clip--both recovered uneventfully. Peroperative cholangiography was performed in 13 patients; 2 were positive (15%) and had ERCP papillotomy 3 days post op without complication. One patient who presented with pancreatitis had ERCP performed post-op without incident. Seven patients had laparoscopic cholecystectomy following papillotomy for common duct stones. The gallbladder was extracted per umbilicus in 45 (3 wound infections) and per right subcostal stab in 20 (no infections). Mean hospital stay was 48 hours (1-4 days) in uncomplicated cases. In conclusion, the learning curve is associated with higher conversion rates. Extraction through pliable hypochondrial muscles is easier and may be safer and less traumatic. Perioperative endoscopic papillotomy is safe and effective for choledochal stones.

The role of surgery and laser ablation in oesophageal carcinoma.

Between January 1990 and December 1994 oesophagectomy was carried out in 42 patients and comparison made with 38 who had palliative laser therapy. Apart from six patients referred after being unresectable at surgical exploration there were no agreed selection criteria, although the laser patients were in general older (mean 64 V 73 year) with a higher proportion of cardiorespiratory co-morbidity (14 per cent V 18 per cent). Lateral margins were involved in 14 per cent of known palliative resections with 50 per cent having positive nodes. The mean operating time was three hours and two chest drains inserted electively were removed after 3.6 days with mean drainage of 817 ml. The mean ICU stay was 5.4 days and 3 had radiological leaks; all but one settled conservatively. The 90 day mortality was 11.9 per cent for surgery and 34 per cent for laser patients. Twenty-three patients (61 per cent) required further courses of laser-therapy for benign anastomotic stenosis. Including the initial treatment of both groups 6.0 procedures per patient year were required in the laser groups compared with 1.1 for surgery. The 1, 2 and 3 year survival was 60 per cent, 31 per cent, 39 per cent for surgery compared with 24 per cent, 8 per cent, 3 per cent for laser--12 surgical patients are still alive and well at mean of 29 months (range 16-68). Surgery where possible with acceptable morbidity and mortality offers good palliation and long-term survival is possible; selection criteria for palliation only need to be defined.

Hepatitis C among drug users: consensus guidelines on management in general practice.

BACKGROUND: Hepatitis C (HCV) is a common cause of morbidity among patients who attend general practitioners (GPs) in Ireland for methadone maintenance treatment. AIMS: To describe the development and content of guidelines for the management of HCV among current or former opiate users in the Eastern Regional Health Authority area attending GPs for methadone treatment. METHODS: The guidelines were produced in five stages: identification of key stakeholders; development of evidence-based draft guidelines; discussion of content; determination of 'Delphi'-facilitated consensus and review by a sample of GPs for whom the guidelines would be intended. RESULTS: The guidelines contain advice for GPs on all aspects of care of patients at risk of HCV, including general and preventative care, care of other bloodborne and hepatotoxic viruses, and the factors to be considered and appropriate evaluation prior to referring a patient for assessment at a hepatology unit. CONCLUSIONS: GPs have an important role to play in the care of patients at risk of, or infected with, HCV.

Antenatal hepatitis B screening - is there a need for a national policy?

Routine antenatal testing for hepatitis B carriage with maternal consent was introduced at the Rotunda in January 1998. The uptake of testing has been excellent; 99.98% of women presenting for antenatal care accepted hepatitis B (HBV) screening in the 30-months from January 1998 through June 2000. The prevalence of HBV carriage was 0.35% (58 pregnancies of 16,222 tested) increasing from 0.25% in 1998 (16 of 6227) to 0.45% in the first six months of 2000 (16 of 3484). Fifty-five women had 58 pregnancies (three women had two pregnancies). Two of these were e-antigen positive. HBV carrier status was previously unknown in 48 (87%). Two additional women had acute HBV infection in pregnancy. Forty-five infants have been born to mothers included in this screening programme. Audit of infant outcome reveals excellent compliance with immunisation and follow-up: 29 (64%) have completed the 3 dose HBV vaccination schedule to date. Thirteen infants (31%) are still attending; three are lost to follow-up including one whose family has emigrated. Routine antenatal screening for hepatitis B carriage is cost-effective and should be considered a standard of care in maternity practice.

Net1 and Myeov: computationally identified mediators of gastric cancer.

Gastric adenocarcinoma (GA) is a significant cause of mortality worldwide. The molecular mechanisms of GA remain poorly characterised. Our aim was to characterise the functional activity of the computationally identified genes, NET 1 and MYEOV in GA. Digital Differential Display was used to identify genes altered expression in GA-derived EST libraries. mRNA levels of a subset of genes were quantitated by qPCR in a panel of cell lines and tumour tissue. The effect of pro- and anti-inflammatory stimuli on gene expression was investigated. Cell proliferation and invasion were measured using in an in-vitro GA model following inhibition of expression using siRNA. In all, 23 genes not previously reported in association with GA were identified. Two genes, Net1 and Myeov, were selected for further analysis and increased expression was detected in GA tissue compared to paired normal tissue using quantitative PCR. siRNA-mediated downregulation of Net1 and Myeov resulted in decreased proliferation and invasion of gastric cancer cells in vitro. These functional studies highlight a putative role for NET1 and Myeov in the development and progression of gastric cancer. These genes may provide important targets for intervention in GA, evidenced by their role in promoting invasion and proliferation, key phenotypic hallmarks of cancer cells.