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.

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.

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.

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.

Early neoplasias of the gallbladder and bile duct: an "unstable" biliary epithelium?

Benign tumours of the biliary tree are rare. In particular, only anecdotal cases of intraductal villous adenomas have been reported. The polyp-cancer sequence has not been observed in the biliary epithelium, in contrast to the paradigm of colorectal carcinogenesis. This report presents the case of a 64-year-old woman with a past history of cholelithiasis who had two early neoplasias involving the biliary epithelium: an adenocarcinoma in situ of the gallbladder and a common bile duct (CBD) villous adenoma with high-grade dysplasia. The tumours presented 4 years apart. The clinical features and combined radiological, cytological, and surgical modalities leading to the diagnosis of intraductal villous adenoma are presented. The endoscopic ultrasound (EUS) characteristics of villous adenoma of the CBD are described. While the prognosis on both occasions appears excellent following curative resections of both tumours detected at an early stage, it is possible that further neoplasia involving the biliary tree may recur. There are currently no data on optimal surveillance modalities. It may be hypothesized that the gallbladder and biliary epithelium share a similar mechanism for carcinogenesis to that observed in the colonic adenomacarcinoma sequence.

Lipoxin A(4) and aspirin-triggered 15-epi-lipoxin A(4) antagonize TNF-alpha-stimulated neutrophil-enterocyte interactions in vitro and attenuate TNF-alpha-induced chemokine release and colonocyte apoptosis in human intestinal mucosa ex vivo.

Lipoxins (LXs) are lipoxygenase-derived eicosanoids and putative endogenous braking signals for inflammation in the gastrointestinal tract and other organs. Aspirin triggers the production of 15-epimers during cell-cell interaction in a cytokine-primed milieu, and aspirin-triggered 15-epi-5(S),6(R),15(S)-trihydroxy-7,9,13-trans-11-cis-eicosatetraenoic acid (15-epi-LXA(4)) may contribute to the bioactivity profile of this prototype nonsteroidal anti-inflammatory drug in vivo. We determined the effect of LXA(4), 15-(R/S)-methyl-11,12-dehydro-LXA(4) methyl ester (15-(R/S)-methyl-LXA(4)), and stable analogs of LXA(4) on TNF-alpha-stimulated neutrophil-enterocyte interaction in vitro and TNF-alpha-stimulated chemokine release, changes in mucosal architecture, and enterocyte apoptosis in cytokine-activated intact human colonic mucosa ex vivo. LXA(4), 15-(R/S)-epi-LXA(4), and 16-phenoxy-11,12-dehydro-17,18,19,20-tetranor-LXA(4) methyl ester (16-phenoxy-LXA(4)) inhibited TNF-alpha-stimulated neutrophil adherence to epithelial monolayers at nanomolar concentrations. In parallel experiments involving human colonic mucosa ex vivo, LXA(4)potently attenuated TNF-alpha-stimulated release of the C-X-C chemokine IL-8, and the C-C chemokines monocyte-chemoattractant protein-1 (MCP-1) and RANTES. Exposure of strips of normal human colonic mucosa to TNF-alpha induced disruption of mucosa architecture and enhanced colonocyte apoptosis via a caspase-3-independent mechanism. Prior exposure of the mucosa strips to 15-(R/S)-methyl-LXA(4) attenuated TNF-alpha-stimulated colonocyte apoptosis and protected the mucosa against TNF-alpha-induced mucosal damage. In aggregate, our data demonstrate that lipoxins and aspirin-triggered 15-epi-LXA(4) are potent antagonists of TNF-alpha-mediated neutrophil-enterocyte interactions in vitro, attenuate TNF-alpha-triggered chemokine release and colonocyte apoptosis, and are protective against TNF-alpha-induced morphological disruption in human colonic strips ex vivo. Our observations further expand the anti-inflammatory profile of these lipoxygenase-derived eicosanoids and suggest new therapeutic approaches for the treatment of inflammatory bowel disease.

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.

Tumour-derived mutated K-ras codon 12 expression in regional lymph nodes of stage II colorectal cancer patients is not associated with increased risk of cancer-related death.

This study examined the frequency of lymph node micrometastases detected by expression of mutant K-ras oncogene present in the respective primary tumour. The study population consisted of consecutive patients with stage II colorectal cancer (CRC) undergoing curative resection and with disease-free survival of 60 months or longer or CRC-related death. Of 27 patients found to have K-ras mutations at codon 12, 17 had genomic DNA suitable for PCR recovered from corresponding regional lymph node tissue. The same K-ras mutation was identified in the lymph nodes of 13 patients (76%), four of whom (30%) died of CRC recurrence within 5 years. A single patient in the negative group (25%) also died. Lymph node micrometastases detected by this technique thus show no relationship to mortality in stage II CRC. Further study of this technique is necessary before it can be used in the selection of patients for adjuvant chemotherapy.

Aggressive multiple myeloma presenting as mesenteric panniculitis.

Mesenteric panniculitis is a rare disease of the bowel mesentery, characterized by tumor-like infiltration by chronic inflammatory cells, fat necrosis, and fibrosis. Reported cases cited clinical presentation ranging from abdominal pain to fever of unknown origin, the majority of which were idiopathic and associated with a benign prognosis. We report the case of a 43-yr-old male who presented with malaise, weight loss, microcytic anemia, and a high erythrocyte sedimentation rate. Radiographic and histological investigations revealed typical features of mesenteric panniculitis. Initial treatment with high-dose oral prednisolone led to rapid and complete resolution of symptomatology, radiographic, and laboratory anomalies. Within 6 months, the patient presented again with anemia, renal failure, and hypercalcemia. A diagnosis of IgA kappa chain myeloma was made. Despite chemotherapy and restoration of normocalcemia, he died from refractory pulmonary edema. This is the first report of a hematological malignancy initially presenting with features of mesenteric panniculitis culminating in an aggressive course and a fatal outcome.

MR cholangiopancreatography of pancreaticobiliary diseases: comparison of single-shot RARE and multislice HASTE sequences.

AIMS: We prospectively compared two breath-hold magnetic resonance cholangiopancreatography (MRCP) sequences: single-shot rapid acquisition with relaxation enhancement (RARE) and multislice half-Fourier acquisition single-shot turbo spin echo (HASTE) in imaging the pancreaticobiliary system. PATIENTS AND METHODS: The diagnostic accuracy of single-shot RARE and multislice HASTE was studied in 34 subjects who had undergone conventional cholangiopancreatography. Overall image quality, duct conspicuity, image artifact, signal intensity and contrast-to-noise ratios were assessed independently by two radiologists who were unaware of the underlying diagnosis. RESULTS: Both sequences had comparable diagnostic accuracy regarding a normal biliary system, choledocholithiasis, extra-hepatic and intra-hepatic strictures. Single-shot RARE was superior to multislice HASTE in diagnosing a normal pancreatic system, pancreatic and intrahepatic duct strictures, while providing significantly better image quality (mean +/- SE 3.7 +/- 0.07 vs 3.3 +/- 0.08: P = 0.02) and significantly less image artifact (mean +/- SE 3.6 +/- 0.07 vs 3.2 +/- 0.08: P = 0.01). Single-shot RARE provided significantly better duct conspicuity regarding the pancreatic duct within the body (2.7 +/- 0.2 vs 2.1 +/- 0.2: P = 0.003) and tail (2.4 +/- 0.2 vs 1.6 +/- 0.2;P = 0.0001), as well as the intrahepatic ducts (3.0 +/- 0.1 vs 2.6 +/- 0.1: P = 0.004) but there was no significant difference regarding the remainder of the biliary tree. CONCLUSION: Single-shot RARE provides superior image quality, duct conspicuity with the added advantage of less image artifact and shorter acquisition time. However, volume averaging can cause common bile duct stones to be missed. Therefore, multislice HASTE sequences should still be acquired if choledocholithiasis is suspected. Larger studies are required to assess the diagnostic efficacy of single-shot RARE sequences in pancreatic duct and intra-hepatic duct disease.Morrin, M. M. (2000). Clinical Radiology55, 866-873.

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.

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.

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.